Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Volume II Health and Economic Outcomes of Human Papillomavirus (HPV) Vaccination in Selected Countries in Latin America: A PRELIMINARY ECONOMIC ANALYSIS 2008 A collaborative project of The Sabin Vaccine Institute (Sabin), Washington, DC, USA Harvard School of Public Health, Boston, MA, USA Institut Catalá d’Oncología, Barcelona, Spain Pan American Health Organization (PAHO) Washington, DC, USA Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA Prepared by Dagna Constenla, Sue Goldie, Nelson Alvis, Meredith O’Shea, Steven Sweet, Marite Valenzuela, Gabriel Cavada, Fernando de la Hoz, Emilia Koumans, Maria N Labbo, Cait Koss, Hector Posso Disclaimer The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the U.S. Centers for Disease Control and Prevention 119 TABLE OF CONTENTS VOLUME II EXECUTIVE SUMMARY CHAPTER 1 INTRODUCTION 1.1 BACKGROUND 1.2 STUDY AIMS CHAPTER 2 METHODS 2.1 ECONOMIC LITERATURE REVIEW 2.2 COST-EFFECTIVENESS ANALYSIS 2.2.1 ANALYTIC OVERVIEW 2.2.2 OVERVIEW OF MODELS 2.2.3 PERSPECTIVE AND SCOPE OF THE ANALYSIS 2.2.4 MODEL INPUTS 2.2.5 SENSITIVITY ANALYSIS CHAPTER 3 RESULTS 3.1 DESCRIPTION OF ECONOMIC PAPERS REVIEWED 3.2 COST ANALYSIS 3.2.1 COSTS OF TREATING PRECANCEROUS LESIONS AND CERVICAL CANCER 3.2.2 DIRECT NONMEDICAL COSTS ASSOCIATED WITH PRECANCEROUS LESIONS AND CERVICAL CANCER 3.2.3 OVERALL CANCER TREATMENT COSTS 3.2.4 ECONOMIC EVALUATION 3.2.5 HEALTH OUTCOMES FOR ADOLESCENT HPV 16 AND 18 VACCINATION 3.2.6 COST-EFFECTIVENESS OF VACCINATION 3.2.7 FINANCIAL IMPLICATIONS OF HPV 16 AND 18 VACCINATION CHAPTER 4 DISCUSSION 4.1 MAIN FINDINGS 4.2 REGIONAL CONTEXT 4.3 LIMITATION OF THE LITERATURE REVIEW 4.4 LIMITATIONS OF THE EPIDEMIOLOGICAL DATA 4.5 LIMITATIONS OF THE ECONOMIC STUDY REFERENCES 120 APPENDIXES Appendix A. Model comparison validation: Impact of HPV 16 and 18 vaccination on mean reduction in lifetime risk of cervical cancer_____________________________ 178 Appendix B. Epidemiological parameters (Appendix Tables 1 and 2) ____________ 180 Appendix C. List of physicians interviewed _________________________________ 181 Appendix D. Sample expert interview survey ________________________________ 184 Appendix E. Summary of screening strategies across studied countries1 _________ 195 Appendix F. Summary of treatment of precancerous lesions across studied countries1 ___________________________________________________________________ 199 Appendix G. Diagnostic and staging procedures and treatment modalities of invasive cervical cancer by stage across studied countries1 ___________________________ 208 Appendix H. Unit costs associated with the detection and treatment of precancerous lesions and treatment of cervical cancer by stage and country __________________ 225 Appendix I. Costs of transportation and lost work time associated with precervical cancer and invasive cervical cancer by stage and country ___________________________ 273 Appendix J. Vaccination cost per vaccinated girl and components of cost, expressed in different currencies by country ___________________________________________ 276 121 TABLES AND FIGURES Table 1. Treatment costs associated with precancerous lesions and cervical cancer (International dollars, 2005) _____________________________________________ 150 Table 2. Direct nonmedical costs of precancerous lesions and cervical cancer (International dollars, 2005) _____________________________________________ 151 Table 3. 2005) Cancer treatment cost estimates and model inputs (International dollars, 152 Table 4. Adolescent HPV 16 and 18 vaccination: health outcomes _____________ 153 Figure 1. Impact of HPV 16 and 18 vaccination on deaths averted for multiple birth cohorts for six Latin American countries (Argentina, Brazil, Chile, Colombia, Mexico, and Peru) ______________________________________________________________ 154 Table 5. Adolescent HPV 16 and 18 vaccination: CEA with assumption of lower-bound cancer costs and vaccine cost of I$25 (~I$5 per dose)* _______________________ 155 Table 6. Adolescent HPV 16 and 18 vaccination: CEA with assumption of upper-bound cancer costs and vaccine cost of I$25 (~I$5 per dose)* _______________________ 155 Table 7. Adolescent HPV 16 and 18 vaccination: CEA with assumption of lower-bound cancer costs and vaccine cost of I$50 (~I$12 per dose)* ______________________ 155 Table 8. Adolescent HPV 16 and 18 vaccination: CEA with assumption of upper-bound cancer costs and vaccine cost of I$50 (~I$12 per dose)* ______________________ 156 Table 9. Adolescent HPV 16 and 18 vaccination: CEA with assumption of lower-bound cancer costs and vaccine cost of I$75 (~I$20 per dose)* ______________________ 157 Table 10. Adolescent HPV 16 and 18 vaccination: CEA with assumption of upperbound cancer costs and vaccine cost of I$75 (~I$20 per dose)* _________________ 157 Table 11. Affordability and budget implications of HPV 16 and 18 vaccination based on varying costs per vaccinated girl for 70% coverage of five birth cohorts ___________ 158 122 ABBREVIATIONS CDC Centers for Disease Control and Prevention CEA Cost-Effectiveness Analysis CIN Cervical intraepithelial neoplasia CI5C Cancer Incidence in Five Continents DALY Disability-Adjusted Life Year GDP Growth Domestic Product GLOBOCAN Global Burden of Cancer IRAC International Agency for Research on Cancer HPV Human Papillomavirus HPV DNA Human Papillomavirus Deoxyribonucleic Acid (Screening Test) ICER Incremental Cost-Effectiveness Ratio I$ International Dollar LAC Latin America and the Caribbean LEEP Loop Electrosurgical Excision Procedure MeSH Medical Subject Headings PAHO Pan American Health Organization PPP Purchasing Power Parity QALY Quality-Adjusted Life-Year SVI Sabin Vaccine Institute VIA Visual Inspection using Acetic Acid (Screening Method) VILI Visual Inspection using Lugol’s Iodine (Screening Method) WHO World Health Organization 123 YLD Years Lived with Disability YLL Years of Life Lost YLS Years of Life Saved 124 EXECUTIVE SUMMARY Background and Aim Human Papillomavirus (HPV) is a virus associated with cervical cancer and other malignancies. Although high-risk HPV types 16 and 18 are two of the most common cancer-causing HPV types, responsible for more than 70% of invasive cervical cancer, variation exists both in the age-related prevalence of HPV and in the proportions of HPV 16 and 18 associated with cancer. Recently, vaccines against HPV types 16 and 18 have created opportunities for primary prevention in areas where organized secondary prevention with screening has been difficult. The aim of this document is to provide estimates of the health and economic outcomes of HPV vaccination in selected countries in Latin America. The findings will be used to inform national health authorities about the burden of HPV and the economic value of implementing an HPV vaccination program in selected countries of the region. This document is the second of a two-part report; the first part is a meta-analysis of the burden of HPV in Latin America and the Caribbean; this second part is a cost-effectiveness study of HPV vaccination. This document complements the meta-analysis (described elsewhere) and provides specific economic information for six selected countries in Latin America. Although some of the epidemiologic estimates from the two documents may differ because of differences in methods, the reports should be viewed as complementary in aiding understanding of HPV infection and its financial and human cost in Latin American and Caribbean countries. Methods We synthesized available data to estimate the cost-effectiveness of vaccination for HPV 16 and HPV 18 in six selected countries in Latin America (Argentina, Brazil, Chile, Colombia, Mexico, and Peru). We conducted a comprehensive literature review of epidemiologic data in countries of the region to gain information about age-specific rates of cervical cancer incidence and mortality and about distribution of HPV 16 and HPV 18 associated with cervical cancer. We researched national treatment guidelines to establish treatment practices for precancerous lesions and cervical cancer in each country. To further determine cervical cancer treatment by stage and cost of care, we conducted surveys in several countries of the region in person and by telephone or e-mail. These surveys contained specific questions about screening for precancerous lesions and about diagnosis and treatment of cervical cancer. In addition, surveys were conducted from which we derived assumptions about the costs required to vaccinate preadolescent girls against HPV. 125 To conduct the cost-effectiveness projections, we used an Excel-based model developed as a companion model to a previously validated microsimulation model of HPV infection and cervical cancer. The Excel-based model relies on simplified assumptions to explore the costs and benefits of vaccination and is less data intensive than a comprehensive microsimulation model; as such, it is an appropriate tool if its use is restricted to generating broad qualitative insights into the potential benefits of vaccination against HPV 16 and HPV 18 for preadolescent girls in the six selected countries. This model cannot compare screening costs and benefits with those of vaccination. To provide contextual insights into the benefits and cost-effectiveness of vaccination compared with screening and of vaccination combined with screening, we also show results from previously published models developed by Goldie et al. for selected countries for which adequate epidemiologic data were available to conduct empirical calibration. These previously published models evaluate the cost-effectiveness of prevention strategies that include both vaccination and screening. Model outcomes include the following measures: reduction in lifetime risk for cervical cancer, number of averted cervical cancer cases and deaths from cervical cancer, number of years of life saved (YLS), number of averted disability-adjusted life years (DALYs), and lifetime costs. Although not age-weighted, DALYs reflect the disability weight and duration estimates for cervical cancer as provided in the Global Burden of Disease study conducted by the World Health Organization (WHO) [119]. This report describes the performance of vaccination strategies by using incremental costeffectiveness ratios, which are defined as the additional cost of a specific strategy, divided by its additional benefit (life expectancy gain per woman). Each cost-effectiveness ratio is compared with that of the next most costly strategy. Results are presented in International dollars (I$, 2005) for broad comparison across countries, and financial costs are also expressed in local currency and U.S. dollars for use by local and regional decision makers. We followed recommendations from several published sources for economic evaluations and adopted a modified societal perspective and discounted future costs and life years by 3% annually. To enable country-specific payors to differentiate cost-effectiveness results (i.e., information on value for money from a long-term perspective) and affordability (i.e., information on financial costs and budget limitations over a short time), we provide crude estimates of the financial costs of vaccination. 126 Findings HPV is a relatively common infection affecting an estimated 20 million people in the United States and causing annually nearly half a million cases of cervical cancer worldwide. Cervical caner is caused by certain types of HPV, mainly types 16 and 18. According to the World Health Organization, cervical cancer accounts for more than 2.5 million years of life lost (YLL) each year. Based on available data for six countries, the total direct medical cost per case for screening ranged from I$10 to I$81 per woman and from I$534 to I$1,402 per woman for treatment of precancerous lesions. Highest screening costs occurred in Argentina, and highest treatment costs occurred in Brazil. These costs were mainly attributed to the cost of specialist consultation (in the case of screening) and hospital stay (in the case of treating precancerous lesions). The cost of cervical cancer treatment was much higher than precancerous lesion treatment and ranged from I$3,745 (Peru) to I$14,438 (Argentina) per woman, with highest costs for more advanced stages of cervical cancer. The majority of this treatment cost was attributed to the costs of hospital stay and palliative care. Using an Excel-based model to evaluate the clinical benefits of vaccination in the six selected countries of the region and assuming 70% vaccination coverage by 12 years of age, lifelong immunity, and 100% efficacy against HPV types 16 and 18, we found that HPV vaccination reduced cancer incidence by approximately 40% in Mexico and Chile, and by more than 50% in Argentina. With vaccination, almost 45,000 cancer deaths and 74,000 cervical cancer cases could be averted over the lifetime of a single birth cohort, compared to outcomes with no intervention. Most averted cases and deaths would appear in Brazil, where cervical cancer is more common than in other countries of the region. When 10 birth cohorts are considered, assuming 70% coverage, we would expect to prevent nearly half a million deaths over the lifetime of the vaccinated girls in the region. If cancer costs were reduced and cost per vaccinated girl were I$100, the Excel model’s assessment of the cost-effectiveness ratio for preadolescent vaccination, compared with no intervention (no screening or vaccination), shows that the cost per saved life-year from a societal perspective would range from I$670 (Chile) to I$1,500 (Mexico). At lower costs of I$75 per vaccinated girl (I$20 per dose), I$50 per vaccinated girl (I$12 per dose), and I$25 per vaccinated girl (I$5 per dose), the cost per saved year of life would range from I$420 (Chile) to I$1,040 (Mexico), I$180 (Chile) to I$580 (Mexico), and I$10 (Brazil) to I$160 (Peru), respectively. At I$25 per vaccinated girl (I$5 per dose), vaccination was cost saving in Chile and Argentina. Because these results were generated for vaccination only, the incremental ratios appear more attractive 127 than they would if the baseline for comparison was screening. For example, previously published independent models that include screening as well as vaccination show that as the cost per vaccinated girl approximates I$100, vaccination plus screening (at ages 35, 40, and 45) is more effective than vaccination alone, although the incremental cost-effectiveness ratio increases (i.e., becomes less attractive) with higher vaccine costs. For example, in Mexico, a combined vaccination and screening strategy at I$75, I$100, and I$360 per vaccinated girl (using 2-visit HPV DNA testing) results in costs of I$1,530, I$1,780, and I$7,070 per YLS, respectively, compared with cost-effectiveness ratios of the next best strategy. According to published data, at the vaccine price of I$360 per girl (the approximate current 2008 U.S. vaccine price) screening, with or without vaccination, used as the main cervical cancer prevention option in countries able to provide screening, was generally more cost-effective than vaccination alone. As the cost per vaccinated girl declines, however, preadolescent vaccination followed by screening three times per lifetime may be the most effective option in countries able to provide both. In the poorest countries in this region, vaccination alone, if available for a markedly reduced price and if widespread coverage of young girls is achievable, may be the most feasible option to reduce cervical cancer. Although vaccination appears to be cost-effective according to the criterion of the incremental cost-effectiveness ratio being less than the per capita Gross Domestic Product (GDP) of a specific country, vaccination may not be affordable. Even an intervention that provides good value for invested resources may have prohibitive financial requirements that cannot be met by the health care systems of countries studied. For those six countries, the financial costs would be $270 million (present value discounted 3% annually) to vaccinate five birth cohorts at 70% coverage with a cost per vaccinated girl of I$25. At a cost of I$50 per vaccinated girl, the financial costs of vaccinating just five birth cohorts at 70% coverage would be nearly $600 million; at a cost of I$360 per vaccinated girl, the cost would be more than $4 billion. These estimates of costs for broad coverage show the important difference between cost-effectiveness and affordability. Limitations of this analysis include gaps in our understanding of the natural history of HPV, uncertainties about the epidemiology and temporal trends of cervical cancer in many countries, lack of high-quality data on screening, costs associated with HPV-related diseases, and access to and costs of cervical cancer treatment for many countries. Data are lacking on the cost of initiating, enhancing, and maintaining a new adolescent vaccination program and on the longterm efficacy of the vaccine (i.e., whether it will provide life-long immunity). For countries with ongoing screening, the cost-effectiveness of vaccination strategies, either alone or combined with screening, is heavily dependent on assumptions about the quality, coverage, effectiveness, and 128 costs of screening. Collecting these data will be critical for facilitating evidence-based vaccine decisions. 129 CHAPTER 1 INTRODUCTION 1.1 Background According to the Centers for Disease Control and Prevention (CDC), approximately 20 million people are currently infected with Human Papillomavirus (HPV) [105]. HPV is a virus that causes genital warts and has been associated with cervical cancer and other malignancies. Cervical cancer is the second most frequent malignant neoplasia affecting women worldwide, accounting for approximately 10% of overall cancer incidence among women [106]. Cervical cancer is also the primary cause of cancer-related deaths among women. In 2000, 470,606 cases and 233,372 deaths associated with cervical cancer were reported [2,107–109]. The majority (80%) of this burden arises in less developed countries, where cervical cancer is the leading malignancy in women [107,108,110]. Recent estimates from the World Health Organization (WHO) suggest that in the Latin American and Caribbean region, cervical cancer accounts for 2.5 million years of life lost (YLL) [2], 72,000 cases, and 38,000 deaths. The estimated age-adjusted incidence rates for cervical cancer are 32.6 per 100,000 women in the Caribbean, 30.6 per 100,000 women in Central America, and 28.6 per 100,000 women in South America [2]. Cervical cancer is fully preventable when early detection and screening programs are available. However, despite these programs’ effectiveness and low cost, they have proven to be relatively unsuccessful in Latin America and the Caribbean (LAC). This lack of success is due in part to the apparent absence of well-organized screening programs, which are difficult to implement in lowresource settings [111]. Another reason these programs are unsuccessful is because women with abnormal cytology results are not always tracked [111]. In Mexico, fewer than 13 percent of potentially preventable cases have been averted despite having a screening program in place for more than 20 years. Costa Rica is another country where screening programs have met with limited success. Only a small number of prevented cases have been reported since national screening programs were established forty years ago. The potential benefits of HPV vaccination are considerable. Currently, two vaccines are available that are designed to protect against the two most aggressive types of HPV. The first vaccine, Gardasil® (quadrivalent) (Merck & Co., Inc., Whitehouse Station, New Jersey, USA), was approved by the U.S. Food and Drug Administration in 2006. The second vaccine, Cervarix® (bivalent) (GlaxoSmithKline [GSK] Biologicals, Inc., Rixensart, Belgium), was approved in Australia by the Therapeutic Goods Administration of Australia in 2007. Persons most likely to benefit from these vaccines are young girls and preadolescents (starting at age 9) who have not yet become sexually active. 130 However, even if women are vaccinated with these recently approved vaccines, they will still need a regular Papanicolaou (Pap) smear and, depending on their age, an HPV DNA test because HPV vaccines do not reduce the risk for cervical cancer completely. Approximately 15 types of the HPV virus can cause cervical cancer. Gardasil® and Cervarix® are designed to protect against two HPV types that are responsible for 70% of all cervical cancers [112]. Gardasil® also protects against HPV types 6 and 11, which cause genital warts. Researchers in a 2006 study published in the online edition of Lancet found that Cervarix® also prevented infection with HPV strains 31 and 45, which, together with strains 16 and 18, cause more than 80% of cervical cancer cases [9]. Recently GSK announced that it would begin a trial to determine whether Cervarix® provides better protection against cervical cancer than Gardasil® [113]. 1.2 Study aims The aims of this report are to briefly review the economic evidence for cervical cancer screening and HPV vaccination, to provide an estimate of the cost of cervical cancer screening and treatment in six selected countries of the LAC region (Argentina, Brazil, Chile, Colombia, Mexico, and Peru), and to estimate the health and economic outcomes of HPV vaccination. This study is the second part of a two-part report available to policy makers for evaluating the feasibility of implementing an HPV vaccination program in these countries. The first part of the report focuses on a meta-analysis of the burden of HPV in Latin America and the Caribbean. Available data, not necessarily derived only from the meta-analysis, were used to develop projections of the costeffectiveness of HPV vaccination; hence, differences may be observed in number of cases and deaths in the two parts of the report. 131 CHAPTER 2 METHODS This section begins with a description of the economic literature review, including the search strategy. The literature review description is followed by a brief discussion of the methods and model framework, perspective and scope of the analysis, model inputs, and sensitivity analyses. 2.1 Economic literature review We conducted an economic literature review simultaneously with the systematic review of epidemiologic studies described in the first part of this report. References with relevant economic data were included to provide a critical overview of the economic issues related to HPV and to assess the implications for prevention strategies (e.g., screening and vaccination). We identified relevant studies, including general economics papers, studies on the burden or cost of illness, economic evaluations, and official reports from countries in the region. Most of these papers were published in English or Spanish from 2003 through 2007. Much of the published literature and some of the completed study reports in the public domain were obtained from the PubMedMEDLINE, Bireme-MEDLINE, Bireme-LILACS, SciELO, and the COCHRANE library databases. Manual bibliographic searches revealed additional articles. Articles that were not true economic evaluations (e.g., reviews of applied studies, commentaries, or editorials without original data) were excluded, as were some articles that substantially replicated results from other articles. Due to the limited range of published studies originating in LAC, studies from North America and Europe were included. We also considered studies containing only abstracts as well as work in the process of being published. The medical subject heading (MeSH) terms used to survey the literature on the cost of HPV included “costs”, “cost analysis”, “cost of illness”, “cost-benefit analysis”. MeSH terms used to survey the literature on the economics of vaccines included “costs”, “cost analysis”, “cost of illness”, “hospital costs”, “cost control”, “cost-effectiveness analysis”, “cost-benefit analysis”, “cost savings”, “delivery of health care”, “drug costs”, “economic value of life”, “healthcare costs”, “HPV and vaccination”. Based on predefined inclusion and exclusion criteria, we abstracted full-text peer-reviewed studies for the final economic analysis. We reviewed the selected studies for country of evaluation, publication year, vaccine strategies assessed, study design, method of evaluation, cost measures, perspective, and period of analysis used. We report results are as they were 132 presented in the literature. That is, no adjustments of expenditures or savings to present value were made. 2.2 2.2.1 Cost-effectiveness analysis Analytic overview We synthesized the available data to estimate the incremental cost-effectiveness ratios (ICERs) of HPV vaccination for six countries in Latin America (Argentina, Brazil, Chile, Colombia, Mexico, and Peru). These countries were selected because of their available epidemiologic and economic data and their willingness and ability to participate. Each country’s economic, social, and political climates were also considered, although these factors did not necessarily affect inclusion. The models we used integrated health burden estimates and economic burden estimates generated by this study to develop country-level estimates of the value for money represented by the investment in and use of the existing HPV vaccines (Gardasil® and Cervarix®). These vaccines are the only ones that may help guard against diseases caused by HPV types 16 and 18, which together cause 70% of cervical cancer cases [3]. Both are given as three injections over six months. Gardasil® is recommended for use in girls and young women 9–26 years of age, and Cervarix® is recommended for use in girls and young women 10-25 years of age. We conducted a comprehensive literature review of epidemiologic data in countries in the region to gather information about age-specific cervical cancer incidence rates and the distribution of HPV 16 and HPV 18 in cervical cancer cases [11]. We describe the performance of vaccination strategies by using incremental cost-effectiveness ratios, defined as the additional cost of a specific strategy, divided by its additional benefit (per life expectancy gain per woman), compared with the next most costly strategy. Results are presented in international dollars (2005) for purposes of broad comparison across countries, and financial costs are also expressed in local currency and U.S. dollars to assist local and regional decision makers. All future costs and health benefits were discounted at an annual rate of 3% [114]. To provide information that enables country-specific payors to differentiate cost-effectiveness results (i.e., information on value for money from a long-term perspective) and affordability (i.e., information on financial costs and budget limitations over a short time horizon), we provide crude estimates of the financial costs of vaccination. 133 As an approximate benchmark and for comparison purposes only, we used the per capita Gross Domestic Product (GDP) as a threshold and assumed that vaccination strategies costing less than a country’s per capita GDP might be cost-effective. 2.2.2 Overview of models To conduct the cost-effectiveness projections, we used an Excel-based model developed as a companion model to a previously validated microsimulation model of HPV infection and cervical cancer [115]. The Excel-based model relies on simplified assumptions identified as reasonable by comparing results of this model’s projected benefits and cost-effectiveness to those generated by the more complex microsimulation model. An exercise to demonstrate the validity of comparing simplified assumptions appears in Appendix A and has been published [11]. The Excel-based model may be used to explore the costs and benefits of vaccination and is less data intensive than the comprehensive microsimulation model; as such, the Excel-based model is an appropriate tool provided its use is restricted to generating broad qualitative insights into the potential benefits of vaccinating preadolescent girls against HPV 16 and HPV 18. The Excelbased model follows cohorts from birth to death (100 years). The microsimulation model is described elsewhere [115]. Model outcomes include reductions in the lifetime risk for cervical cancer, the number of averted deaths from cervical cancer, and lifetime costs. Outcomes also include increases in number of averted cases of cervical cancer, years of life saved (YLS), and disability-adjusted life years (DALYs) averted. DALYs reflect the disability weight and duration estimates for cervical cancer as provided in WHO’s Global Burden of Disease study [121], although the DALYs are not age weighted. After integrating the epidemiologic data, we assumed the following: (1) the overall mean duration of time between development of invasive cancer and death is 6 years but may vary from 2 to 10 years; (2) distribution of cervical cancer by stage in an unscreened population is 30% local, 40% regional, and 30% distant, although stage distribution varied in sensitivity analyses; (3) ratio of mortality to incidence varies by country, with the poorest countries (e.g., Haiti) having mortality to incidence ratios of 80% (range, 60%–90%) and other countries having ratios of about 60% (range, 40%–80%); and (4) cancer incidence has not appreciably changed with low levels of effective cervical cytology screening. Because our goal is to identify the avertable burden and potential cost-effectiveness of vaccination against HPV 16 and 18 and because the model did not include screening, we do not examine strategies that include both vaccination and screening. For 134 practical reasons, we assumed that scaling up cervical cytology to a high coverage level and a high-quality screening program are not realistic options. We also assumed the following about the performance of the HPV 16 + 18 vaccine: (1) the vaccine effectively prevents HPV 16 and 18 in girls without previous infection and provides longlasting protection against HPV 16 and 18; (2) the vaccine, even at high coverage rates, does not alter the risk of cervical cancer associated with HPV types other than 16 and 18; and (3) successful coverage is defined as completion of a three-dose course by a girl. We assumed 70% population coverage, although we varied coverage from 0% to 90%. Results are presented for a strategy for 2007 of 70% vaccination of a single birth cohort of preadolescent girls (i.e., 12 years old), using a 100% effective vaccine at a cost ranging from I$25 to I$360 per vaccinated girl. To provide insights into the benefits and cost-effectiveness of vaccination relative to screening and of vaccination combined with screening, we summarized selected results from previously published models developed by Goldie et al. for a few countries with adequate epidemiologic data to conduct empirical calibration. These previously published models evaluated the costeffectiveness of strategies that included both vaccination and screening [11]. 2.2.3 Perspective and scope of the analysis We performed the analysis from a modified societal perspective, which considered all direct medical and nonmedical costs borne by governments and families (costs for cancer treatment included women’s time and transportation costs). We also considered the health care system in the base case analysis and included costs borne by medical facilities, providers of health care, and other facilities and providers of vaccine-related services. 2.2.4 Model inputs Health outcomes The primary outcome measures considered for both models were the total health-care and nonhealth-care costs of cervical cancer and the disease burden and societal costs averted by vaccination. Number of cases of cervical cancer, number of deaths from cervical cancer, YLSs, disability-adjusted life years (DALYs) averted, and lifetime costs (in 2005 international dollars) were also calculated. 135 ICERs compare the difference in cost with and without HPV vaccination over the difference in health outcome with and without HPV vaccination. For the cost-effectiveness analyses, medical costs averted by vaccination were subtracted from costs invested in vaccination and then divided by the health outcome. An example of the relationship between cost and health outcome is described by the following ICER: ICER = Vaccine related costs – averted disease costs DALYs averted by vaccination Epidemiologic data For our companion Excel-based model, which is intended to provide broad qualitative insight into the potential benefits of HPV 16 + 18 vaccination, we used cervical cancer incidence rates and prevalence of HPV 16 and 18 among women with cervical cancer. Cervical cancer incidence rates were drawn from GLOBOCAN 2002 (the WHO database containing estimates of incidence and mortality for the year 2002) [119] or from cancer registry data available in Cancer Incidence in Five Continents (CI5C) [110]. CI5C incidence data cover entire national populations or samples of these populations from selected regions. We applied data hierarchically according to quality, with the best data considered to be those from CI5C followed by data from GLOBOCAN 2002 (see Appendix B for rates). We used a meta1 analysis to estimate the proportion of HPV 16 and HPV 18 in cervical cancer cases [116]. For those countries with specific information in the meta-analysis, we used the provided estimate or the pool of estimates for the country if more than one citation was included. For those countries without specific information, we devised a regional pool. Smith et al. include both single- and multiple-type HPV infections [116]; women with multiple HPV types are counted more than once, so the overall prevalence of HPV types totals more than 100%. Specifically, women with both HPV 16 and 18 are counted twice; therefore, the HPV 16 and 18 distribution is inflated. To avoid that overestimate, we used a hierarchical classification in which multiple types are assigned according to the most common type, and women are counted only once. For example, a woman with both HPV types 16 and 18 is classified as HPV 16. This classification implies that the prevalence of HPV 16 remains the same, but the prevalence of HPV 18 decreases, thus altering the HPV16/18 distribution. The prevalence of HPV 18 was corrected for cervical cancer cases 136 with multiple types 16 and 18 when this information was reported (provided by the International Agency for Research on Cancer). The final prevalence of HPV 18 that we report is the prevalence presented in the Smith et al. meta-analysis less the prevalence of women with both types. For those studies with multiple types but no specific information, we used a 3.3% correction (i.e., overall average of prevalences from articles with available information on multiple types 16 and 18). Because cancer prevalence is thought to be underestimated in some of these data sources, we conducted sensitivity analyses to explore the implications of underreporting and underestimation. The model relies on detailed population data by age for each country. Demographic estimates for age-group–specific population size and age-group–specific life expectancy were drawn from United Nations World Population Prospects 2004 data [117] and from 2004 WHO life tables [118]. We assumed that the average age at initiation of sexual activity and the levels of other risk factors remained constant over the time horizon. DALYs In addition to estimating numbers of cases and deaths, we expressed the disease burden in DALYs, which provide a standardized measure of disease burden that allows for cross-disease comparisons of burden [119]. DALY estimate includes two components: YLL due to premature mortality and years lived with disability (YLD). Calculations of YLL were based on country-specific mean life expectancies for girls 9 and 12 years of age (Excel model) [118]. For the calculation of YLD, we considered morbidity only from disease severe enough to require medical care. We calculated YLD by using default disability weights from WHO’s Global Burden of Disease study [119] and WHO’s guidelines for cost-effectiveness studies [120]. The calculated DALYs reflect the disability weight and duration estimates for cervical cancer as provided in the Global Burden of Disease [121]. This calculation is not age weighted and uses an annual discount rate of 3%. Use of health services for early detection of precancerous lesions and treatment of cervical cancer National guidelines for the detection of precervical cancer and treatment of cervical cancer were available for each of the six selected countries. Most of these guidelines were published by government-sponsored institutions that focused on early detection and treatment of cervical 1 Estimates of the proportion of HPV 16 and HPV 18 in cervical cancer derived from the Sabin Vaccine Institute metaanalysis were not available at the time of the analysis. 137 2 cancer in each country. We used these guidelines to derive resource-use profiles for each country. We used the resource-use profiles to learn about treatment practices in each country and to help identify the level of input of each resource in the treatment of precancerous lesions and cervical cancer. National guidelines generally included what, in theory, is provided to and for patients who are at risk for precancerous lesions or who are diagnosed with cervical cancer. The information in these guidelines was not always complete. To augment this information, we contacted HPV researchers in nine countries and asked them to respond to a survey. We visited some of these researchers in Argentina, Brazil, Chile, and Colombia and corresponded with others by telephone or e-mail. We surveyed health care providers to determine HPV treatment by stage and cost of care. In addition, we reviewed conference abstracts, and, with the help of the Pan American Health Organization (PAHO), we contacted national Ministries of Health in nine countries in the region to identify additional information about cervical cancer treatment. The survey sent to health researchers contained specific questions about screening for precancerous lesions and about the diagnosis and treatment of cervical cancer. Most of the experts interviewed were obstetricians, oncologists, or primary care physicians working in the public sector, but we also interviewed physicians working in the private sector. Fourteen physicians responded to the surveys. Appendix C provides a list of all physicians interviewed. Surveys were originally developed in English and were translated into Spanish and Portuguese to facilitate physicians’ responses. Appendix D contains an example of the Spanish version of the survey. The surveys contained two sets of questions: the first set addressed practices used in the early detection of precancerous lesions; the second set addressed diagnosis and treatment practices (acute and long-term care) for invasive cervical cancer by stage (i.e., stages IA1, IA2, IB1, IB2, IIA, IIB, IIIA-IIIB, IVA, and IVB). Although we were unable to include a comparative screening strategy for the Excel-based model, we made a substantial effort to identify screening information (e.g., coverage, protocols, guidelines, and costs) for the following reasons: (1) to provide qualitative comparisons to vaccination outcomes, (2) to conduct future cost-effectiveness analyses using more complex models that can accommodate simulation of primary and secondary prevention, and (3) to 2 Resource use profiles included diagnosis for precervical cancer, treatment for precervical cancer, diagnosis and staging for invasive cervical cancer, treatment of invasive cervical cancer by stage, follow-up treatment by stage, and palliative care by stage. 138 provide useful information to countries for comparison of financial costs associated with screening with financial costs required for vaccination. We reviewed studies including both screening and vaccination. We also summarize selected results from previously published models developed by Goldie et al. for some countries having adequate epidemiologic data for conducting empirical calibration. These previously published models evaluated the cost-effectiveness of strategies that included both vaccination and screening [11]. The information we gathered from the surveys regarding screening strategies was consistent with the information provided in the national guidelines. For example, in Argentina, women undergo cervical cytology (with Pap smears) during their first screening visit and return for results in a second visit. If results are negative, women are screened once every three years. If results are positive, women are screened every six months for three years. In Brazil, women undergo initial screening in the first visit; those with positive results undergo colposcopy/biopsy in a second visit, which is followed by treatment of abnormalities at a tertiary clinical site in a third visit. In Chile, cervical cytology is performed in the majority of women every six months to rule out falsenegative results.Women with negative screens are screened every three years. In Colombia, women undergo a Pap smear every three years. Screen-negative women undergo a second Pap smear a year later to confirm a negative result. If the second Pap smear is negative, a Pap smear is scheduled every three years after the second negative test. However, if the second Pap smear is positive, women undergo a Pap smear three times a year. Women in Mexico are offered a screening protocol similar to Argentina’s. In Peru, women undergo a screening test (90%, Pap smear; 5%, HPV DNA testing; 3%, visual inspection using acetic acid [VIA]; and 2%, visual inspection using Lugol’s iodine [VILI]). Those women with positive results undergo a screening test every six months. The test is repeated again and, if results are negative, a test is scheduled once every three years thereafter. Appendix E summarizes the screening recommendations and current practices of studied countries. Treatment of precancerous lesions depends on the lesions’ size and type and may include cryosurgery, loop electrosurgical excision procedure (LEEP), cold knife conization, or simple hysterectomy. According to information from the surveys, precancerous lesions are generally treated on an outpatient basis. The classification system of cervical intraepithelial neoplasia (CIN) is used in the studied countries to provide information about the precancerous condition of the cervix. After initial screening, screen-positive women generally undergo a gynecological exam, colposcopy, and directed biopsy to determine whether they are suitable for follow-up or same-day treatment such as cryosurgery or LEEP. Biopsy-confirmed CIN 1 lesions are generally followed by colposcopy and cytology every six months until the lesion regresses to normal or until evidence of progression appears. Only a small proportion of women in these countries with CIN 1 139 lesions require treatment. In contrast, all biopsy-confirmed CIN 2 and 3 lesions in the studied countries require treatment because of the potential of these lesions to progress to invasive cervical cancer. Women undergoing treatment for CIN 2 and 3 lesions are generally treated as outpatients; however, certain procedures such as cold knife conization require general or regional anesthesia, and women undergoing these procedures may need to be admitted to a hospital. Treatment of complications resulting from procedures such as cold knife conization is also reported in these countries. Women treated for precancerous lesions in the studied countries generally return for a follow-up visit two to six weeks after treatment for a gynecological examination and discussion of results of histopathology (in cases involving LEEP and cold knife conization) and at six and twelve months for a screening test and coloscopy and directed biopsy (in cases of persistent lesions). Appendix F summarizes the treatment of precancerous lesions in studied countries. Staging is required for women who have a histologic diagnosis of cervical cancer. For the studied countries, the International Federation of Gynecology and Obstetrics staging system is recommended for staging invasive cervical cancer. This classification system is based on tumor size and on the extent of spread of disease in the pelvis and distant organs. Like precancerous lesions, treatment of invasive cervical cancer depends on lesion size and type. The most common tests and procedures performed for staging and treatment of invasive cervical cancer in the studied countries included vaginal and rectal examination, abdominal ultrasound, cystoscopy, proctoscopy, cone biopsy, chest x-ray, computerized tomography scan of abdomen and pelvis, magnetic resonance imaging of pelvis, and blood tests. Appendix G describes methods used for cervical cancer staging in the studied countries. Once the extent of the cancer’s growth is assessed, several treatment modalities can be performed, including surgery, radiotherapy, and chemotherapy. For the studied countries, the most commonly reported surgical procedures include simple abdominal hysterectomy for treatment of stage IA1 and radical hysterectomy or pelvic lymphadenectomy or both for treatment of stages IA2 to IIA. Length of stay in the hospital for a surgical procedure varies by country but averages seven to ten days. Surgical procedures are generally performed in a tertiary-level hospital and require about two to three hours. Most of these procedures were performed to effect a cure, but most countries (Brazil, Chile, Colombia, Mexico, and Peru) reported palliative surgery to relieve symptoms, particularly at advanced stages of cervical cancer. Radiotherapy (teletherapy, brachytherapy) was commonly reported for treatment of stages IB1 through IVB. However, in countries like Brazil, Chile, and Colombia, use of radiotherapy was 140 reported for treatment as early as stages IA1 and IA2. For treatment of stages IA1 through IIA, radiotherapy was sometimes used concurrently with surgery. For bulkier tumors and for women with extensive lymph node involvement, radiotherapy was used as the sole treatment. Teletherapy was generally used in addition to brachytherapy. Radiotherapy sessions were generally given five days a week for about five weeks in a tertiary-level hospital. Women receiving radiotherapy were either admitted to a hospital or were treated as outpatients. For women admitted to a hospital for radiotherapy, the length of stay varied between two and three days, depending on the dose rate. For all studied countries, palliative therapy was commonly reported to relieve symptoms. A third treatment modality for invasive cervical cancer is chemotherapy. The most commonly used drug in the studied countries was cisplatin. Chemotherapy was generally given for the treatment of bulkier tumors; however, in Brazil, Chile, and Colombia, chemotherapy was reported as being used in early stages of cervical cancer, specifically stage IA2 (Brazil) and stage IB2 (Chile and Colombia). Cisplatin is generally given concurrently with surgery or radiation or both. Five to six cycles of chemotherapy were generally administered to women who undergo chemotehrapy. Women treated with surgery or radiotherapy generally return for follow-up visits every three months for the first two years. Several tests are performed during these follow-up visits, including vaginal and rectal examination and Pap smears. Appendix G provides a summary of the treatment modalities of invasive cervical cancer by stage and country. Costs associated with precancerous lesions and cervical cancer treatment Low estimates for treatment costs were determined by using methods of indirect estimation previously used by others in the absence of primary data [115,122]. We compared these estimates to the data we collected in our study sites: Argentina, Brazil, Chile, Colombia, Mexico, and Peru. The costs for cervical cancer treatment represent an average treatment cost per case and are assumed to be realized at around median survival time after cancer onset. Every detected cancer case is assumed to incur cancer treatment costs. The base case value was estimated by using data collected separately. Because we accepted the favorable assumption that women with detected cancer have access to care in the latter estimation procedure, we refer to the treatment cost of all detected cases as the upper treatment cost estimate, and we vary it widely in sensitivity analyses. Methods of collecting cost data and of conducting surveys to assess clinical practice assumptions are documented below. 141 Costs are presented in 2005 international dollars, a currency that provides a means of translating and comparing costs among countries, taking into account differences in purchasing power. Costs are also presented in local currency and in U.S. dollars for local and regional decision makers. For the latter, we needed to distinguish tradable from nontradable goods. Vaccine, wastage, and freight are considered tradable goods. Whether expressed in local currency units or in U.S. dollars, they are converted by using exchange rates of the U.S. dollar to local currency units. Administration and vaccine support are considered local nontradable goods. To express nontradable goods in local currency units, we converted them from international dollars by using purchasing power parity (PPP) exchange rates. When expressing administration and vaccine support in U.S. dollars, the local currency units are converted by using U.S. dollar exchange rates. Health care costs Cost-generating events were estimated based on two main sources: country-specific management guidelines and expert surveys. The unit cost for detection of precancerous lesions and treatment of invasive cervical cancer was based on estimates provided by the finance departments of local hospitals and national administrative data in each studied country. Unit cost estimates associated with the detection and treatment of precancerous lesions and the treatment of cervical cancer by stage and by country are summarized in Appendix H. The cost per stay as an inpatient was calculated by multiplying the per diem rate by length of stay and adding the cost of diagnostics and medications. The per diem rate includes the accommodation and administration costs (i.e., costs of the bed, building, utilities, maintenance, administration, and equipment), food, and personnel. Mean hospital lengths of stay were derived from combined physician surveys and varied by stage: 1.17 and 2.67 days for precancerous lesions CIN1 and CIN2, respectively; 2.50 days for stage IA1; 3.30 days for stages IA2 and IB1; 5.17 days for stage IB2; 4.17 days for stage IIA; 3.67 days for stage IIB; 2.00 days for stages IIIA–IIIB; 1.83 days for stage IVA; and 2.83 days for stage IVB. The cost per outpatient visit was based on the cost of visiting a general practitioner, a nurse, or a specialist (obstetrician or oncologist). According to physicians surveyed, 50% of women with precancerous lesions have an average of one to two outpatient visits with a general practitioner, 66% are seen by the nurse once or twice, and 78% are seen once or twice by the obstetrician or oncologist. An estimated 79% of women with invasive cervical cancer are seen in the outpatient setting. The majority (99%) of this outpatient care is for staging of cervical cancer, 56% is for treatment, and 100% is for follow-up and palliative care. An average of 2.67, 4.26, 4.50, 12.67, 142 6.50, 7, 17.67, 20.17, 21.17, and 22.00 outpatient visits were reported for cervical cancer screening, stage CIN1, stage CIN2, stage IA1, stage IA2, stage IB1, stage IB2, stage IIA, stage IIB, and stages IIIA–IV, respectively. The majority of these outpatient visits were for palliative care treatment. Unit cost estimates for outpatient visits were based on the average provided by the finance departments of public institutions and administrative sources. The total screening and diagnostic cost per woman was calculated by first multiplying the number of each test used by the frequency of its use, multiplying that number by each test’s unit cost, and then summing the total cost for all tests administered to each woman. Unit cost estimates for screening and diagnostic tests were based on the average given by the finance departments of public institutions and administrative sources described previously. Costs associated with surgery were based on data from finance departments of hospitals and national administrative data. The total average cost of surgery was calculated by multiplying the cost per surgery performed by the proportion of cervical cancer patients who had the surgery and the frequency with which the surgery was performed; this total was then summed to calculate the total cost for all the surgeries performed per woman. The costs associated with radiotherapy and chemotherapy were calculated in a similar manner. Costs associated with medications were based on national formularies and prices quoted by the finance departments of hospitals and local pharmacies. The total medication cost per patient was calculated by multiplying the cost per dose of each medication used by the number of doses administered and then summing the total cost for all the medications administered to a single patient. Societal costs In addition to health care costs, transportation costs to health care facilities were also included in the cost calculations. For the base case analysis, these costs were based on assumptions made about the number of trips to and from the doctor’s office and/or the hospital and the cost of each trip. The number of trips to and from the doctor’s office and/or hospital was based on the number of outpatient visits and hospital admissions reported by physicians in the studied countries. The cost of each trip was derived directly from the National Association of Transport Services of each country [123,124]. Indirect costs associated with lost time from paid work were also calculated for women. For the base case analysis, these costs were calculated by using 1) the number of days off work (one 143 outpatient consultation or one day in the hospital was assumed to be the same as one day off work); 2) an average 2005 minimum monthly salary in Argentina, Brazil, Chile, Colombia, Mexico and Peru of I$765.6 [125,126], I$337.5 [127], I$1,856.8 [128], I$308 (Personal communication, Nelson Alvis, September 2007), I$1,636.8 [126], and I$728.19 [126], respectively; and 3) an assumption of 22 days of work per month. Appendix I summarizes the average direct nonmedical and indirect costs of precancerous lesions and cervical cancer by stage and country. Vaccination costs Vaccination costs include several components: (1) the cost (or price) of three doses; (2) costs associated with vaccine wastage, freight into the country, supplies and administration; (3) programmatic costs (i.e., vaccine support costs) associated with immunization support, such as training, social mobilization, transportation within the country, monitoring and surveillance, cold chain equipment and maintenance, waste management, and injection safety. Because the price for the HPV vaccine for different countries is not established and the associated vaccination programmatic and support costs are uncertain, we varied a hypothetical cost per vaccinated girl from I$10 to I$360. Similar to other studies, we assumed for each composite cost a distribution of component costs. For example, at I$25 per vaccinated girl, we assumed three doses of vaccine at I$5 each, wastage of I$2.25, freight and supplies of I$1.31, administration of I$1.50, immunization support costs of I$2.94, and incremental costs of a new adolescent program of I$2. For comparison, we also conducted an analysis that assumes that the price of the vaccine is similar to the U.S. price. Appendix J shows an example conversion of a cost of I$25 per vaccinated girl into countryspecific currencies. Vaccine efficacy and coverage Clinical trials of HPV vaccine have been conducted in Latin America, North America, Europe, and Asia; hence, we used estimates of the effectiveness of the bivalent HPV vaccine conducted in North America (Canada and the United States) and Brazil because these trials were considered to be most applicable to the population being considered. Vaccine efficacy estimates against HPV 16 and 18 were assumed to be 100%[129,130]. Vaccination coverage was assumed to be 70%, and dose completion rates were assumed to be 100%. 144 2.2.5 Sensitivity analysis The models described above require country-specific data concerning the epidemiology of the disease, the economic costs associated with different outcomes, and vaccine efficacy. Although some of these data are available, the quality and representativeness are severely limited in some instances. These data limitations create uncertainties regarding final estimates of economic burden and cost-effectiveness, but these preliminary results will hopefully begin a dialogue about the relative cost-effectiveness of vaccination. We conducted sensitivity analyses around many of the most notable uncertainties to identify those assumptions and parameters that are most influential for results. RESULTS Results are presented in three sections. Section 3.1 summarizes the economic papers reviewed. Section 3.2 presents the results of the cost analyses by country. Section 3.3 presents the results of the cost-effectiveness analyses by country. 2.3 Description of economic papers reviewed A recent chapter [11] provides an in-depth view of the economics of HPV 16 and 18 vaccination in LAC countries. We will focus our attention here on citing some of the more salient points of recent publications that address modeling the impact of HPV vaccines and cervical cancer screening strategies in developed and developing countries. This information serves as an introduction to the recent publication. Various modeling studies have explored the potential benefits of cervical cancer screening and/or HPV vaccination of preadolescent girls at the population level [115,131–137]. Most of these studies are based on state-transition disease models that focus on cervical cancer screening options in high-income countries. Issues addressed in these studies include (a) choice of screening interval, (b) age for starting and stopping screening, (c) enhancements to conventional cytology, and (d) integration of HPV DNA testing into cytology-based screening programs as a primary screening test or as a triage for equivocal cytology results for women older than 30 years of age [132]. Despite differences in model structures and assumptions, these studies indicate several general conclusions, which have been highlighted by Goldie and colleagues in a 2006 paper [133]. One conclusion is that the cost-effectiveness of screening in the general population becomes less 145 favorable when screening is performed more frequently than every 2–3 years. According to Goldie et al., this decrease in feasibility of screening is due to the almost linear increase in screening costs when screening tests are performed frequently; simultaneously, incremental gains in benefits rapidly diminish with increased cost [133]. In addition, screening at a very young age is not considered beneficial and could even be harmful when unnecessary procedures such as colposcopy are performed among younger populations. A policy of starting screening at 20–25 years of age and stopping at around 60–65 years of age is considered by most experts to be acceptable as benefits of screening decline rapidly after age 65 due to the natural history of the disease [138]. Experts note, however, that screening older women who have not previously been screened may be cost-effective because of the high risk of disease in older, unscreened populations [133]. Another notable trend is the small incremental benefit of using screening tests that have higher sensitivity than conventional Pap smears (e.g., primary screening with HPV DNA testing among older women). According to experts, using screening tests with higher sensitivity results in little incremental benefit and is generally associated with high ICERs due to increased costs of frequent screening tests [139]. However, similar strategies with more sensitive screening tests appear to be cost-effective in the context of screening every 3–5 years [134,140–142]. Experts note that small changes in the specificity of screening tests can have an important impact on the cost-effectiveness of screening in settings where frequent screening and aggressive follow-up strategies are performed [143]. With frequent screening, the impact on costs is much greater, an important consideration because, compared to the Pap smear, HPV DNA testing has, on average, 20%–30% greater sensitivity and 5%–10% lower specificity for detecting high-grade cancer lesions when combined testing of all women is performed. Specificity of screening has a greater impact in settings with high coverage rates. Moreover, combining cytology and HPV DNA testing in a screening program could help lengthen testing intervals from 1–3 years to 3–5 years. The combination of these two tests reaches sensitivity and negative predictive values that approach 100% [133]. Few modeling studies on screening in developing countries have been identified [132,144–150]. Many of these studies, including the earlier one by Sherlaw-Johnson and colleagues [146], showed that screening efforts should focus on using a combination of cytology and HPV DNA testing on women 30–59 years of age at least once during their lifetimes to reduce lifetime risk of cervical cancer by up to 30%. Goldie and colleagues conducted a comprehensive assessment of novel cervical cancer screening strategies in five countries and concluded that lifetime cancer risk 146 can potentially be reduced by about 25% when one-visit VIA or two-visit HPV DNA testing targeted women 35–40 years of age [132]. When screening strategies were increased to 2–3 times during a lifetime, the risk reduction was nearly doubled. In all five developing countries, a one-visit screening strategy was as cost-effective as hepatitis B immunization, second-line treatment for tuberculosis, and malaria prevention with bed nets [132]. Early modeling studies explored the impact of an HPV vaccine using conservative efficacy levels that mirrored those of HIV and genital herpes vaccines [151]. Based on the assumption of limited vaccine protection, Hughes and colleagues projected a moderate HPV vaccine impact. These researchers identified concerns about increased progression of high-risk types other than HPV 16 and 18 and about reduced cross-immunity. These concerns were shared by Goldie and colleagues in their study using a cohort model calibrated to data from Costa Rica [136]. These researchers assumed a vaccine efficacy of 98%, which yielded a 51% reduction in lifetime risk of invasive cancer [136]. In another study, Goldie and colleagues found that vaccination against HPV types 16 and 18 resulted in a small incremental increase in the number of cervical cancer cases attributable to types other than HPV 16 and 18 [135]. They also found that the costeffectiveness of a combined primary and secondary prevention program depended on various factors, including the age at which vaccination occurred, age at which screening was initiated, and screening frequency. These findings were consistent with those reported by Kulasingam and Myers [137]. Models also explored the added benefits and impact of costs of HPV vaccination on cervical cancer incidence in males and older women [151-154]. Preliminary findings of these studies suggest that direct protection of males against certain HPV-related conditions may be achieved. In their study in which no type-specific immunity was assumed, Taira and colleagues found little benefit in vaccinating boys [152]. However, the impact of vaccinating girls alone was high. Similar results were found in another study in which long-lasting type-specific immunity was assumed [153]. Indirect protection of women may result from reduced HPV transmission. Modeling studies have shown that little additional reduction in cervical cancer can be gained by vaccinating males when high HPV vaccination coverage of females is achieved because HPV vaccination directly protects women from cervical cancer [131,153,154]. At lower coverage of women, vaccinating boys may contribute to controlling infection, but more gains may be derived by vaccinating girls instead of boys. Studies also find that direct protection of a woman may be reduced as age at vaccination increases because older women may have already been exposed to HPV infection [131,153,154]. 147 Despite differences in methodology, the state-transition modeling studies yield remarkably similar results. The study conducted by Barnabas and colleagues, for example, found that a 90% coverage rate of preadolescent girls results in a 91% reduction in HPV type-specific cervical cancer incidence [153]. Other studies reported similar findings [135,136,151]. Scientists agree that state-transition models using cohort or Monte Carlo simulation can be adequate tools for projecting the vaccine impact on cervical cancer. Models of transmission dynamics are being used increasingly to estimate the potential benefits of HPV vaccination [152,153,154]. These models are based on assumptions that a person’s acquisition of infection depends on that person’s sexual behavior and on the distribution of the infection within the population [131]. In the context of middle-income countries like Brazil, findings of modeling studies based on transmission dynamics suggest that adding HPV vaccination to routine screening strategies (e.g., 1–3 times per lifetime) would be cost-effective provided vaccine price is low [115]. With an assumed coverage rate of 100%, the projected reduction in cancer incidence with vaccination alone was estimated to be 61%; with vaccination and screening three times in a lifetime, reduced incidence was approximately 75%. Moreover, the ICERs associated with non-dominated strategies are most influenced by vaccination costs. As the cost of the vaccine increased, the ICERs associated with vaccination plus screening increased as well [115]. Models of HPV transmission dynamics find that the impact of the HPV 16 and 18 vaccine on both prevalence of infection and infection-related disease is greatest in the absence of screening. When screening is compared with vaccination, the impact of screening on cancer incidence reduction is much lower than the impact of vaccination. These models have also shown that the age at vaccination is important for outcomes. According to these models, the strategy that has the best long-term outcome is vaccinating girls before exposure to potential HPV infection. However, scientists agree that many factors need to be considered when adapting a vaccination strategy, including the age at which sexual behavior is common and the extent to which the vaccine is replacing naturally derived protection. The findings of these complex models need to be validated with long-term field implementation studies. A few issues should be considered, such as cost of the vaccine, which is currently over $100 per dose, and administration costs, which are expected to be higher than for routine vaccination schedules. Also, because most countries do not have an HPV vaccine program, barriers to the introduction of HPV vaccine exist, which include but are not limited to adapting or 148 building an adolescent vaccination program and targeting preadolescent girls only instead of both girls and boys. The literature points to various factors that affect the applicability of cost-effectiveness studies of cervical cancer prevention and screening. These factors include age-specific cancer incidence; all-cause life expectancy; temporal trends of major epidemics; age structure of populations; availability, effectiveness, and costs of cancer treatment; and health system costs of the prevention or screening intervention. 2.4 Cost analysis The results presented here provide insight into the costs associated with precancerous lesions and cervical cancer by stage and by country. These costs are considered to be the best available estimates for the countries studied. 2.4.1 Costs of treating precancerous lesions and cervical cancer Estimates of total costs per case associated with precancerous lesions and cervical cancer are provided in Table 1. These costs (in 2005 international dollars) are presented by stage and country and are calculated by using national treatment guidelines and physician surveys, which were described previously. The total direct medical cost per case for screening and treatment of precancerous lesions ranged from I$10 to US$81 per woman and from I$534 to I$1,402 per woman, respectively, with highest costs incurred in Argentina (screening) and Brazil (treatment of precancerous lesions). In all countries, most of the cost was attributed to the cost of specialist consultation (for screening) and hospital stay (for treatment of precancerous lesions). For cervical cancer treatment, the total cost per case was between I$3,745 and I$14,438 per woman; highest costs were incurred in Argentina due to higher palliative care costs. Disease progression considerably affected the cost of treatment. As expected, treatment costs associated with invasive cervical cancer were found to be the most resource intensive. Treatment costs increased as cervical cancer progressed and curative treatment was no longer an option. 149 Table 1. Treatment costs associated with precancerous lesions and cervical cancer (International dollars, 2005) Cost per event Argentina Brazil Chile Colombia Mexico Peru a Event Screening 81 10 33 37 52 15 CIN 1 534 864 553 974 648 595 CIN 2 1,094 1,402 969 1,252 1,159 729 IA1 5,157 5,169 5,267 4,823 4,900 3,745 IA2 10,031 8,447 5,738 6,540 7,988 7,407 IB1 13,350 8,633 7,301 6,648 7,954 7,918 IB2 13,424 9,026 7,655 6,984 7,981 7,884 IIA 13,577 8,145 8,486 7,232 8,073 8,086 IIB 13,616 8,350 8,836 7,380 8,559 8,148 IIIA–IIIB 14,039 8,739 9,422 7,734 8,895 8,486 IVA 14,061 8,851 10,078 8,028 9,149 8,550 IVB 14,438 9,042 10,534 8,455 9,528 8,660 a CIN, Cervical intraepithelial neoplasia; IA1–IVB, stages of invasive cervical cancer For economic evaluations, the most important consideration is that the relative costs of the different items are consistent within each country’s column. For example, one would expect that the treatment cost of more advanced stages of cervical cancer would be more costly than the treatment cost of early stage cervical cancer and that the latter would be more costly than the cost of treating precancerous lesions. This relationship was apparent in all countries and is a direct result of including palliative treatment costs. Comparison of costs among countries was of less interest here than country-specific costs. However, because the costs are applied to a set of resource-use data derived from various centers in six countries, consistency of definition of items being costed was necessary. Overall, levels of health care expenditure and absolute price levels for health care resources varied among the six Latin American countries. Generally, one would expect the unit costs for all items to show the same relationship between two countries; for example, unit costs in Mexico would be expected to be higher than those in Peru. This study shows that such a relationship among countries exists except for certain procedures and follow-up treatment. In these cases, the differences could arise from genuine differences in the relative costs for these items, from differences in financial responsibilities between health and nonhealth agencies, or from different definitions of the item or service being used. When such differences appeared, they were checked to ensure that they were genuine relative cost differences rather than inconsistencies in the cost measurement. 150 2.4.2 Direct nonmedical costs associated with precancerous lesions and cervical cancer Table 2 provides estimates of direct nonmedical costs for patients undergoing screening and for patients with precancerous lesions and cervical cancer. The average cost to transport a woman undergoing screening for cervical cancer ranged from I$2 to I$7. The average cost to transport a woman with precancerous lesions ranged from I$12 to I$33. For women with a confirmed diagnosis of cervical cancer, the average transportation cost ranged from I$15 to I$112; the highest transportation costs were incurred in Chile. The nonmedical costs associated with lost wages for women with cervical cancer (I$3,460) were much higher than those for women with precancerous lesions (I$61). This difference occurs because more women with cervical cancer lost time from work than women with precancerous lesions (85% versus 35%). Table 2. Direct nonmedical costs of precancerous lesions and cervical cancer (International dollars, 2005) Argentina Brazil Chile Colombia Transp Time Transp Time Transp Time Transp Time costs loss costs loss costs loss costs loss Screening 7 70 6 31 5 169 5 28 CIN 1 24 244 13 61 19 591 13 70 CIN 2 20 209 13 61 33 1,013 19 102 IA1 27 278 51 245 69 2,110 55 294 IA2 34 348 48 230 69 2,110 57 308 IB1 34 348 48 230 60 1,857 36 196 IB2 47 487 102 491 88 2,701 91 490 IIA 44 452 99 476 112 3,460 75 406 IIB 51 522 90 430 93 2,870 81 434 IIIA–IIIB 91 940 90 430 82 2,532 81 434 IVA 91 940 86 414 93 2,870 81 434 IVB 95 974 90 430 93 2,870 83 448 a CIN, Cervical intraepithelial neoplasia; IA1–IVB, stages of invasive cervical cancer Eventa 2.4.3 Mexico Transp Time costs loss 2 74 12 446 16 595 22 818 19 707 15 558 19 707 61 2,232 61 2,232 61 2,232 61 2,232 61 2,232 Peru Transp Time costs loss 5 66 21 265 19 240 36 463 39 496 39 496 75 960 75 960 77 993 80 1,026 80 1,026 80 1,026 Overall cancer treatment costs Table 3 provides cancer cost estimates for stages I–IV. The first set of cost estimates (lower bound) was estimated by using methods that indirectly estimate cancer treatment costs based on extrapolating from primary data in one country to another [115,122]. These estimates include both direct medical and direct nonmedical costs such as cost of transportation. The second set of cost estimates (upper bound) was based on country-specific physician surveys described earlier. This set of costs includes only direct medical costs. 151 The derived cancer cost estimates are much lower than in-country estimates because palliative care costs are included in the latter estimates. Of importance is that for the lower bound estimates, the costs for treating stages II–IV are consistently lower than for stage I. In contrast, the upper bound estimates have a reversed effect; treating more advanced stages of disease is always more costly than treating the early stages of the illness because palliative (long-term) care, which is the focus in the later stages of the illness, is accounted for in the upper-bound estimates but not in the lower-bound estimates. Another important consideration is that Argentina incurs the highest cancer treatment costs in both the lower-bound and upper-bound estimates due to the higher costs of treatment. Table 3. Cancer treatment cost estimates and model inputs (International dollars, 2005) Country Derived estimates (Lower Bound) In-country data collection (Upper Bound) Stage I Stages II–IV Stage I Stages II–IV Argentina 5,107.37 4,301.72 9,894.72 14,516.96 Brazil 3,834.30 3,229.46 7,416.14 8,755.72 Chile 4,388.56 3,696.30 6,095.07 9,442.39 Colombia 3,444.84 2,901.44 6,003.79 7,787.16 Mexico 4,368.55 3,679.44 7,313.91 9,295.52 Peru 2,749.07 2,315.42 6,425.95 8,507.53 2.4.4 Economic evaluation In this section, we make projections of the health and economic outcomes of HPV vaccination compared with outcomes for no vaccination. 2.4.5 Health outcomes for adolescent HPV 16 and 18 vaccination Table 4 provides estimates of the health outcomes for adolescent HPV 16 and HPV 18 vaccination. Results shown are for a single birth cohort assumed to have 70% coverage by 12 years of age. The lifetime reduction in cancer ranges from 39% to 54%; the lowest reduction in cancer rates occurs in Chile, and the highest reduction occurs in Argentina. Vaccinating 70% of the 12-year-old girls would prevent between 2,767 (Chile) and 35,363 (Brazil) cervical cancer cases over a cohort’s lifetime and between 1,660 (Chile) and 21,218 deaths (Brazil). 152 Table 4. Adolescent HPV 16 and 18 vaccination: health outcomes Country Cancer Incidence Lifetime Reduction in Cancer, % Cases of cancer averted Cancer deaths averted % of cases/deaths across the region Years of life saved (YLS) Argentina 23.2 53.86 5,796 3,478 6% 86,921 Brazil 23.4 48.17 35,363 21,218 35% 474,912 Chile 25.8 39.41 2,767 1,660 3% 48,461 Colombia 36.4 40.30 9,512 5,707 10% 140,264 Mexico 29.5 39.60 15,213 9,128 16% 215,813 Peru 48.2 47.46 5,218 3,131 5% 69,046 73,869 44,322 75% 97,984 58,791 100% Total for 6 countries Total for 33 countries Figure 1 presents the impact of adolescent HPV 16 and 18 vaccination on the number of deaths averted for multiple birth cohorts, with an assumption of an average coverage of 70% in the six studied countries. For example, in a 10-year vaccination program in which we vaccinate 70% of 12-year-old girls for 10 consecutive calendar years in these six countries, we would expect to prevent nearly half a million deaths. When we assumed a 30%–50% underestimation of cancer burden in the registries used for our cancer incidence estimates, the averted burden increased by the same degree of magnitude. Further, when we also accounted for both future population growth and explored the implication of temporal trends resulting in increased rates of cancer, a 10-year program would easily avert more than one million deaths over the lifetime of the vaccinated girls. 600,000 Cancer Deaths Averted 500,000 400,000 300,000 200,000 100,000 0 10 birth cohorts 5 birth cohorts 3 birth cohorts 1 birth cohort 153 Figure 1. Impact of HPV 16 and 18 vaccination on deaths averted for multiple birth cohorts for six Latin American countries (Argentina, Brazil, Chile, Colombia, Mexico, and Peru) Cost-effectiveness of vaccination Table 5 summarizes the incremental costs and ICERs of adolescent HPV 16 and HPV 18 vaccination. The cost per YLS from a societal perspective would range from I$10 (Brazil) to I$160 (Peru), and vaccination would be cost saving in Argentina and Chile compared with costs of outcomes with no vaccination. This analysis assumes that all women with detected invasive cervical cancer are treated; the costs are derived indirectly (as previously described) and are therefore considered lower-bound estimates. The incremental costs include a strategy of vaccination of 70% for a single birth cohort of preadolescent girls (i.e., 12-year-olds) in 2007 with a 100% effective vaccine at a cost per vaccinated girl of I$25 (~I$5 per dose) and are compared with costs of outcomes with no vaccination. 154 Table 5. Adolescent HPV 16 and 18 vaccination: CEA with assumption of lowerbound cancer costs and vaccine cost of I$25 (~I$5 per dose)* Country Cancer Incidence Incremental Costs (I$) ICER (I$/YLS) ICER (I$/DALY) Argentina 23.2 -593,233 Saving (-40) Saving (-30) Brazil 23.4 648,421 10 10 Chile 25.8 -629,952 Saving (-70) Saving (-70) Colombia 36.4 1,101,643 40 40 Mexico 29.5 4,865,009 120 110 Peru 48.2 2,117,122 160 160 * CEA, cost-effectiveness analysis; cancer incidence source: Globocan 2002 [109]; ICER, Incremental costeffectiveness ratio; I$, International dollars; YLS, years of life saved; DALY, disability-adjusted life years. Table 6 summarizes the incremental costs and ICERs of HPV vaccination when upper-bound cancer costs (in-country estimates) are assumed. Adolescent HPV 16 and 18 vaccination is cost saving in all countries if upper-bound costs are assumed. This analysis uses the same assumptions as the previous analysis except that costs are based on protocols collected as part of a cost survey instead of being derived indirectly. Table 6. Adolescent HPV 16 and 18 vaccination: CEA with assumption of upperbound cancer costs and vaccine cost of I$25 (~I$5 per dose)* Cancer Incremental Costs ICER ICER Country Incidence (I$) (I$/YLS) (I$/DALY) Argentina 23.2 -12,834,602 Saving (-770) Saving (-740) Brazil 23.4 -41,301,364 Saving (-450) Saving (-440) Chile 25.8 -4,031,630 Saving (-430) Saving (-420) Colombia 36.4 -8,476,018 Saving (-330) Saving (-320) Mexico 29.5 -12,712,279 Saving (-310) Saving (-300) Peru 48.2 -4,659,049 Saving (-360) Saving (-340) * CEA, cost-effectiveness analysis; cancer incidence source: Globocan 2002 [109]; ICER, Incremental costeffectiveness ratio; I$, International dollars; YLS, years of life saved; DALY, disability-adjusted life years. Table 7 summarizes the incremental costs and ICERs of HPV vaccination if lower-bound cancer costs are assumed and using a cost per vaccinated girl of I$50 (~I$12 per dose), compared with the cost of outcomes with no vaccination. The vaccination program is no longer cost saving when the cost per vaccinated girl is higher than I$50, but it may still be considered cost-effective in all countries. Table 7. Adolescent HPV 16 and 18 vaccination: CEA with assumption of lower-bound cancer costs and vaccine cost of I$50 (~I$12 per dose)* 155 Cancer Incidence Incremental Costs(I$) ICER (I$/YLS) ICER (I$/DALY) Argentina 23.2 5,290,582 320 310 Brazil 23.4 30,244,666 330 320 Chile 25.8 1,668,953 180 170 Colombia 36.4 9,212,000 360 340 Mexico 29.5 23,917,014 580 560 Peru 48.2 7,281,810 560 530 Country * CEA, cost-effectiveness analysis; cancer incidence source: Globocan 2002 [109]; ICER, Incremental cost-effectiveness ratio; I$, International dollars; YLS, years of life saved; DALY, disability-adjusted life years. Table 8 summarizes the incremental costs and ICERs of HPV vaccination with the assumption of upper-bound cancer costs and a cost per vaccinated girl of I$50 (~I$12 per dose), compared with the costs of outcomes with no vaccination. The vaccination program is cost saving in all countries except Mexico and Peru, where vaccination costs I$150 per YLS and I$40 per YLS, respectively. Of great importance in reviewing these results is that the estimates for vaccination are compared with costs of outcomes resulting from doing nothing, i.e., neither screening nor vaccinating. In countries such as Mexico and Peru, where some level of screening occurs, the most appropriate analysis will compare the ICER of each strategy (vaccination alone, screening alone, and combined vaccination and screening) with the ICER of the next best strategy. Even so, these ratios provide a contextual basis for the potential cost-effectiveness of HPV 16 and 18 vaccination relative to other vaccines that have been adopted or are under consideration in this region of the world. Table 8. Adolescent HPV 16 and 18 vaccination: CEA with assumption of upper-bound cancer costs and vaccine cost of I$50 (~I$12 per dose)* Cancer Incremental Costs ICER ICER Country Incidence (I$) (I$/YLS) (I$/DALY) Argentina 23.2 -6,950,787 Saving (-420) Saving (-400) Brazil 23.4 -11,705,119 Saving (-130) Saving (-120) Chile 25.8 -1,732,725 Saving (-190) Saving (-180) Colombia 36.4 -365,661 Saving (-10) Saving (-10) Mexico 29.5 6,339,726 150 150 Peru 48.2 505,639 40 40 * CEA, cost-effectiveness analysis; cancer incidence source: Globocan 2002 [109]; ICER, Incremental cost-effectiveness ratio; I$, International dollars; YLS, years of life saved; DALY, disability-adjusted life years. Table 9 summarizes the incremental costs and ICERs with the assumption of lower-bound cancer costs and a cost per vaccinated girl of I$75 (~I$20 per dose), compared with costs of outcomes with no vaccination. The cost per YLS from a societal perspective would range from I$420 (Chile) to I$1,040 (Mexico). 156 Table 9. Adolescent HPV 16 and 18 vaccination: CEA with assumption of lower-bound cancer costs and vaccine cost of I$75 (~I$20 per dose)* Cancer Incremental Costs ICER ICER Country Incidence (I$) (I$/YLS) (I$/DALY) Argentina 23.2 11,174,397 670 640 Brazil 23.4 59,840,911 660 630 Chile 25.8 3,967,858 420 410 Colombia 36.4 17,322,358 670 650 Mexico 29.5 42,969,019 1,040 1,000 Peru 48.2 12,446,497 950 910 * CEA, cost-effectiveness analysis; cancer incidence source: Globocan 2002 [109]; ICER, Incremental cost-effectiveness ratio; I$, International dollars; YLS, years of life saved; DALY, disability-adjusted life years. Table 10 summarizes the incremental costs and ICERs with the assumption of upper-bound cancer costs and vaccine cost of I$75 (~I$20 per dose) per vaccinated girl, compared to costs resulting from no vaccination. The cost per YLS from a societal perspective would range from I$60 (Chile) to I$610 (Mexico) and would be cost saving in Argentina. Table 10. Adolescent HPV 16 and 18 vaccination: CEA with assumption of upper-bound cancer costs and vaccine cost of I$75 (~I$20 per dose)* Cancer Incremental ICER ICER Country Incidence Costs (I$) (I$/YLS) (I$/DALY) Argentina 23.2 -1,066,972 Saving (-60) Saving (-60) Brazil 23.4 17,891,126 200 190 Chile 25.8 566,180 60 60 Colombia 36.4 7,744,697 300 290 Mexico 29.5 25,391,731 610 590 Peru 48.2 5,670,326 430 420 * CEA, cost-effectiveness analysis; cancer incidence source: Globocan 2002 [109]; ICER, Incremental cost-effectiveness ratio; I$, International dollars; YLS, years of life saved; DALY, disability-adjusted life years. Because these results were generated for vaccination only, the incremental ratios appear more attractive than they would be if the baseline for comparison is screening. For example, according to previously published independent models that include screening as well as vaccination [11], as the cost per vaccinated girl approximates I$100, vaccination plus screening (at ages 35, 40, and 45) is preferable to vaccination alone, although the incremental cost-effectiveness ratio increases (i.e., becomes less attractive) with higher vaccine costs. For example, in Mexico, a combined vaccination and screening strategy that costs I$75, I$100, and I$360 per vaccinated girl and that uses 2-visit HPV DNA testing costs I$1,530, I$1,780, and I$7,070 per YLS, respectively, compared with cost outcomes of the next best strategy. 157 A previous analysis in Brazil [115], using the empirically-calibrated models mentioned above, showed that when the vaccine cost rose above I$75 per vaccinated girl, vaccination alone was no longer preferred; instead, vaccination plus screening three times in a woman’s lifetime (at ages 35, 40 and 45 years) was preferable. In Brazil, this combined vaccination and screening strategy, costing I$75, I$100, and I$450 per vaccinated girl and using 2-visit HPV DNA testing, costs I$1,100, I$1,700, and I$9,600 per YLS, respectively, compared with costs of screening alone. 2.4.6 Financial implications of HPV 16 and 18 vaccination Cost-effectiveness analysis, which is about value for money and opportunity costs of not investing the dollars elsewhere, is not the same as affordability (which is about impact on the current budget) and financial costs over a short time horizon. Table 11 shows the financial costs for the six studied countries. According to a threshold of each country’s GDP per capita, vaccination would be cost-effective in all countries evaluated if the cost per vaccinated girl is less than I$75 (implied cost per dose of I$20). However, the financial costs of vaccinating five birth cohorts at 70% coverage would be $270 million (2008 value discounted 3% annually) at I$25 per vaccinated girl, almost $600 million at I$50 per vaccinated girl, and more than $4 billion at I$360 per vaccinated girl; thus, whether HPV vaccination is affordable as well as cost-effective in these countries is uncertain. Table 11. Affordability and budget implications of HPV 16 and 18 vaccination based on varying costs per vaccinated girl for 70% coverage of five birth cohorts Cost per vaccinated girl I$25 I$50 I$360 Argentina $22,802,814 $50,239,204 $389,371,186 Brazil $120,678,403 $262,951,492 $2,022,107,977 Chile $7,746,554 $18,174,568 $146,857,377 Colombia $28,258,592 $66,316,739 $535,955,252 Mexico $67,664,604 $155,995,259 $1,246,481,871 Peru $19,783,465 $43,893,204 $341,846,289 All 6 countries $266,934,432 $597,570,466 $4,682,619,952 158 CHAPTER 3 DISCUSSION 3.1 Main findings HPV infection is a common sexually transmitted disease; an estimated 20 million people are currently infected. Most HPV-related cancer deaths are due to cervical cancer. Of the half million cervical cancer cases reported annually worldwide, LAC countries account for 72,000 cases and 38,000 deaths. Cervical cancer results in significant illness as well as economic burden in the studied countries. In Latin America, scientists have contributed to the goal of preventing cervical cancer through multidisciplinary research and cooperative projects with pharmaceutical and biotechnology companies. Examples of these projects are major molecular epidemiologic studies conducted in Mexico, Costa Rica, Panama, and Colombia and HPV prevalence and screening studies conducted in Costa Rica, Brazil, Mexico, and Colombia. In addition, several countries in the region have well-established cancer registries that provide essential cancer information. The region has also had a strong presence in the case-control studies of the International Agency for Research on Cancer (IRAC) and has recruited a large number of female participants in vaccination trials. In recent years, models have been developed to explore the transmission dynamics of HPV and the cost-effectiveness of vaccination and screening strategies in middleincome countries like Brazil. The current collaboration, led by the Albert B. Sabin Vaccine Institute and assisted by many organizations, including the Harvard School of Public Health, the Institut Catalá d’Oncología, PAHO, and CDC, is further testimony of the scientific community’s continuing commitment to improving awareness of HPV in the region. Findings of the economic literature have consistently shown that vaccination with current bivalent and quadrivalent HPV vaccines can have a substantial impact in settings lacking effective screening programs. If the cost of vaccination per girl is under I$75, vaccination has the potential to be cost-effective when the per capita GPD criterion is used as an approximate indicator of monetary resource constraints. HPV vaccination may, in some cases, be cost saving. In countries with established ongoing screening programs, vaccination may be cost-effective if screening programs are modified. Modelling studies show that vaccinating boys in addition to girls may not be as cost-effective as vaccinating girls alone. Scientists agree that further collection of empirical data needs to be carried out to parameterize and validate these models. 159 The vast majority of studies of screening in high-income countries or in countries with existing screening programs have focused their attention on identifying optimal screening intervals and appropriate ages for starting and stopping screening and on enhancing conventional cytology programs. In low-income countries with infrequent or no screening, studies have focused on finding alternative noncytologic tests and strategies that enhance the link between treatment and screening and on targeting older women (35–45 years) for screening one, two, or three times during their lifetimes. Findings from these studies are consistent. Based on the available data, the total direct medical cost per case for screening and treatment of precancerous lesions ranged from I$10 (Brazil) to I$81 (Argentina) per woman and from I$534 (Argentina) to I$1,402 (Brazil) per woman, respectively. Higher treatment costs were incurred in Brazil due to higher treatment costs of precancerous lesions. The cost of cervical cancer treatment was much higher than for precancerous lesions and ranged from I$3,745 (Peru) to I$14,438 (Argentina) per woman; higher costs were incurred in the more advanced stages of cervical cancer. HPV vaccines have been shown to be effective in preventing infection and disease related to HPV genotypes 16 and 18 in healthy women. Assuming 70% vaccination coverage by 12 years of age and 100% efficacy against types 16 and 18 in six selected countries of the region (Argentina, Brazil, Chile, Colombia, Mexico, and Peru), we found that almost 45,000 cancer deaths and 74,000 cervical cancer cases would be averted over the lifetime of a single birth cohort. Most of the cases and deaths averted were in Brazil, where cervical cancer is more common than in other countries of the region. When 10 birth cohorts with 70% coverage are considered, we would expect to prevent nearly half a million deaths over the lifetime of the vaccinated girls. These results emphasize the importance of HPV vaccination as a cost-effective intervention for preventing women’s death. If the vaccine cost approaches the price of I$100 per dose and if vaccination coverage for a single birth cohort of preadolescent girls (i.e., 12-year-olds) in the six countries studied was 70%, then vaccination is no longer preferable to screening if we assume lower-bound costs for cancer treatment. At lower costs of I$75 per vaccinated girl (I$20 per dose), the cost per YLS would range from I$420 (Chile) to I$1,040 (Mexico). At costs of I$50 per vaccinated girl (I$12 per dose), the cost per YLS would range from I$180 (Chile) to I$580 (Mexico), respectively. Based on published data, screening, with or without vaccination, as the main cervical cancer prevention option in countries able to provide screening, was generally more cost-effective than vaccination alone if the vaccine cost was I$360 per girl. As the cost per vaccinated girl declines, 160 however, preadolescent vaccination, followed by screening three times per lifetime, may be the most cost-effective option in countries able to provide both. In the poorest countries in this region, vaccination alone, if available for a markedly reduced price and if widespread coverage is achievable in young girls, may be the most feasible option to reduce cancer. Cost-effectiveness analysis, which is about value for money and opportunity costs of not investing the dollars elsewhere, is not the same as affordability (which is about impact on the current budget) and financial costs over a short time horizon. When compared to WHO benchmarks for cost-effectiveness, HPV vaccination meets the criteria, provided the cost per vaccinated girl is less than I$75 (implied cost per dose of I$20). However, the financial requirements for vaccinating five birth cohorts at 70% coverage would be $267 million at I$25 per vaccinated girl, almost $600 million at I$50 per vaccinated girl, and over $4 billion at I$360 per vaccinated girl, making HPV vaccination expensive. Clearly, given national financial constraints, decision makers faced with many cost-effective interventions will need to consider affordability as well as programmatic capacity and sustainability. Although averted treatment costs can partially offset costs of vaccination, in some health systems, distributions of costs and savings may not be equitable; hence, the impact of averted treatment costs on affordability of interventions may be less than presented in this analysis. 3.2 Regional context This analysis supports the conclusion that cervical cancer poses a sizable burden in the six countries studied and results annually in 72,000 cases and 38,000 deaths in the LAC region. Establishing the burden of disease is a first step to accelerating vaccine introduction. Several large-scale programs are contributing to improved awareness of HPV and cervical cancer and are setting the stage for more widespread use of the HPV vaccine in the region. In 2007, an International Symposium on Clinical and Scientific Aspects of HPV was held in Medellin, Colombia, where important information concerning the latest progress on prevention and control strategies for cervical cancer was presented. Several studies around the world are currently being conducted to learn more about the burden of cervical cancer and the economics of various treatment and vaccination strategies. The findings of this study and those of the meta-analysis (Volume I), which report on the economics of HPV vaccination and the burden of HPV infection, respectively, were presented in Mexico City in May 2008. 161 Our epidemiologic estimates (projected cases and deaths) differed from the meta-analysis estimates (discussed separately) in several respects. Our scope was narrower in that we focused on only six countries rather than the region as a whole. In addition, we used estimates from the Globocan 2002 and CI5C databases rather than estimates derived from the meta-analysis, which included wide variations in study methodology. 3.3 Limitation of the literature review Due to our limited timeframe, we did not review in detail all economic studies on cervical cancer screening and vaccination, nor did we explicitly assess study quality. We included the most recently published review papers on screening and vaccination rather than investigating each paper separately. Additionally, we incorporated information from key disease experts who have local knowledge of the HPV disease burden that may not be published in the literature. 3.4 Limitations of the epidemiological data Cancer registries and GLOBOCAN 2002 provide data by calendar year and age group. In this economic analysis, we modeled a member of a birth cohort forward through her entire life, not for a calendar year. Cancer data are analyzed to provide age-specific rates for five-year age groups, and these rates are applied in the model to the appropriate age groups and superimposed on the population age structure data to calculate number of cases and deaths. Observed differences in estimates result from changes in methods and should not be interpreted as a time-trend effect. The degree of detail and quality of cancer data may vary considerably as they are derived from many countries through the registration of vital events. In addition, cancer data may not always be the most recent data, as these data are collected and compiled after the events to which they relate. While the cancer incidence data used in the analysis were considered the most recent estimates at the time of analysis, more recent estimates may be available directly from local sources. Caution must be exercised when comparing these estimates with previously published estimates, as sources of data are continuously improving in quality and extent. The age-standardized rate (world standard) is calculated by using the five age groups 0–14, 15– 44, 45–54, 55–64, and 65+. The result may slightly differ from that computed by using the same data categorized according to traditional five-year age groups. 162 Our understanding of the natural history of HPV infection has many gaps. For instance, we do not know whether HPV infections become latent and undetectable in the basal epithelial layer and whether infections are acquired or reactivated later in life. Also, uncertainties exist about the epidemiology and temporal trends of cervical cancer in many countries. Estimates from extensively populated areas and information about HPV type distributions in individual countries still need to be researched. The role of HPV in cervical cancer also is uncertain, and risk factors for progression to invasive cancer are unknown. Also unknown is the role of upstream cofactors that may contribute to HPV infection and downstream cofactors that may result from HPV infection. HPV epidemiology also has uncertainties. For example, we do not know the geographical differences in risk factors among HPV types, nor do we know the distribution of HPV types in precancerous lesions for planning new HPV assays. The meta-analysis (Volume 1) discusses risk factors and HPV epidemiology and may help clarify some of these uncertainties. 3.5 Limitations of the economic study Screening and treatment strategies inputs Although the field of HPV diagnostics is progressing at a considerable rate and has provided valuable information about the usefulness of typing, high-quality data on screening is still lacking. Also, strategies to achieve high coverage and eliminate disparities still need to be developed. In addition, gaps in knowledge exist concerning screening algorithms among HPV-vaccinated women and the effectiveness of VIA in combination with screen-and-treat and other methods. Surveys were conducted in each country to provide information about screening and treatment strategies. Vaccination inputs We used vaccine efficacy data from the bivalent HPV vaccine trials conducted in North America (Canada and the United States) and in Brazil, as these trials were considered to be most applicable to the population under consideration. Because these trials were not conducted in other countries of the region, the vaccine efficacy data may not be generalizable to the Latin American countries studied. 163 We assumed that 70% of preadolescents were fully vaccinated, so we did not adjust for potential protection provided by incomplete vaccination (e.g., receiving only one or two doses of HPV vaccine). Such protective effects may increase vaccine cost-effectiveness. Our vaccination coverage estimate was based on coverage of 70% overall. We assumed that all groups within a country would have equal likelihood of vaccination and would be vaccinated at the recommended time. If high-risk populations are missed or vaccination is delayed, the effectiveness may be reduced. Some questions remain concerning long-term efficacy, protection indicators, strategies, optimal vaccination age, and ways to go about vaccinating the Latin American populations that need it most to achieve broad protection. We did not estimate the benefits of cross protection or examine the uncertainty of waning immunity, as these issues were beyond the scope of the study. Due to methodological difficulties and time constraints, we did not consider the potential indirect protective effect of herd immunity on people who are not vaccinated. Herd immunity could offset gaps in delivery of full-course, on-time vaccination as well as prevent disease in nontargeted populations and improve the cost-effectiveness of HPV vaccination. Finally, we evaluated the effect of a vaccine that protects against HPV types 16 and 18 and focused only on cervical cancer outcomes (mortality and cases). We did not include outcomes of HPV types 6 and 11, as they were beyond the scope of the analysis. These outcomes are reported in published U.S. analyses. [131,152,153] Population inputs We did not consider other groups aside from preadolescent girls in the analysis. Other target groups (e.g., boys and younger girls) should be considered in future analyses once the epidemiology of HPV, the natural history and transmission of HPV infection, and the mechanism and duration of protection by HPV vaccines are better understood. Cost inputs Our estimates of resource use, medical treatment costs, and indirect costs were developed using physician and caregiver interviews and data from selected facilities in each of six countries. 164 These estimates are based on public system costs only and could be improved with patient-level data and larger samples. We did not consider costs borne by families for treatment of cervical cancer in less formal settings (i.e., treatment at home or by traditional healers). Several questions remain regarding costs associated with HPV-related diseases as well as access to and costs of cervical cancer treatment for many countries. Because the price of HPV vaccine for different countries is still not established and the associated vaccination programmatic and support costs are also uncertain, we made assumptions about vaccination costs by expressing a composite value, the cost per vaccinated girl, and varied it from I$10 to I$360. Future studies should focus on the cost of adolescent vaccination programs, particularly the cost of the vaccine itself, as this cost is likely to be a major determinant of the cost and affordability of any vaccine program. Data are unavailable on the cost of initiating, scaling up, and maintaining a new adolescent vaccination program; the cost of reaching adolescents; and the programs needed to achieve high coverage. Our economic analysis is based on an assumption of the cost of an adolescent vaccination program because no standard cost exists. Administration costs for HPV vaccination are expected to be higher than for traditional vaccines because few countries have routine vaccination programs for preadolescents. Model limitations The Excel-based model used in this analysis was simple and helped to generate estimates of avertable burden and cost-effectiveness (and affordability) estimates of HPV vaccination. Ongoing research uses more complex models that assess vaccination and screening (including screening algorithms that consider various screening tests, ages at which to begin screening, age-specific screening strategies, and screening frequency). Vaccine research also incorporates multiple HPV types beyond HPV 16 and 18, which are targeted by the current vaccines, and thereby address the possibility of type replacement in the context of vaccination. The research also reflects uncertainty of outcomes in a more sophisticated manner by simulating individual women, tracking each woman’s health history, and allowing her history of screening, vaccination, health, and behavior to affect her future risk. Also, HPV vaccine research includes dynamic transmission considerations necessary to address questions of male vaccination and herd immunity, as well as issues surrounding the duration of protection of the vaccine (i.e., the extent 165 to which the vaccine provides lifelong protection and the impact of a waning vaccine/booster dose on cost-effectiveness results). 166 REFERENCES 1. Muñoz N, BX, de Sanjosé S, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer [comment]. N Engl J Med. 2003;348:518–27. 2. Lewis MJ. Análisis de la situación del cáncer cervicouterino en America Latina y el Caribe. Organización Panamericana de la Salud. Washington D.C.: OMS; 2004, 3. WHO/ICO, Human Papillomavirus and Cervical Cancer 2007. Instituto Oncológico Catalá Barcelona: OMS. 4. De Sanjose S, et al., Worldwide prevalence and genotype distribution of cervical human papillomavirus DNA in women with normal cytology: a meta-analysis. Lancet Infect Dis. 2007;7:453–9. 5. Ferreccio C, et al. Population-based prevalence and age distribution of human papillomavirus among women in Santiago, Chile. Cancer Epidemiology, Biomarkers & Prevention. 2004;13(12):2271. 6. Lazcano Ponce, E.C. Epidemiology of HPV among Mexican women with normal cervical cytology. International Journal Cancer. 2001; 91:412–20. 7. Matos E, et al. Prevalence of human papillomavirus infection among women in Concordia, Argentina: a population-based study. Sexually Transmitted Diseases. 2003;30(8):593. 8. Molano M, et al. Low grade squamous intra-epithelial lesions and human papillomavirus infection in Colombian women. British Journal of Cancer. 2002; 87(12):1417. 9. Abba MC, et al. Human papillomavirus genotype distribution in cervical infections among woman in La Plata, Argentina. [Spanish]. Revista Argentina de Microbiologia. 2003;35(2):74. 10. Ferrera A, et al. Human papillomavirus infection, cervical dysplasia and invasive cervical cancer in Honduras: a case-control study. International Journal of Cancer. 1999;82(6):799. 11. Goldie SJ, Diaz M, Constenla D, Alvis N, Andrus JK, Kim SY. Mathematical models of cervical cancer prevention in Latin America and the Caribbean. Vaccine. 2008;26(S11):L59 –72. 12. Giuliano AR, et al. Human papillomavirus infection at the United States-Mexico border: implications for cervical cancer prevention and control. Cancer Epidemiology, Biomarkers & Prevention. 2001;10(11):1129. 13. González-Losa MD, et al. Molecular variants of HPV type 16 E6 among Mexican women with LSIL and invasive cancer. Journal of Clinical Virology. 2004;29(2):95. 167 14. Herrero R, et al. Population-based study of human papillomavirus infection and cervical neoplasia in rural Costa Rica. Journal of the National Cancer Institute. 2000;92(6):464. 15. Rattray C, S.H.D.E.C.C.B.B.C.M.A.S.M.H.P.J.M.H.B.B.W.A. Type-specific prevalence of human papillomavirus DNA among Jamaican colposcopy patients. J Infect Dis. 1996;173(3):718. 16. Strickler HD, et al. Adeno-associated virus and development of cervical neoplasia. Journal of Medical Virology. 1999;59(1):60. 17. Tonon SA, et al. Human papillomavirus cervical infection and associated risk factors in a region of Argentina with a high incidence of cervical carcinoma. Infectious Diseases in Obstetrics & Gynecology. 1999;7(5):237. 18. Tortolero-Luna G, et al. A case-control study of human papillomavirus and cervical squamous intraepithelial lesions (SIL) in Harris County, Texas: differences among racial/ethnic groups Environmental and occupational cancer in Latin America. Cadernos de Saúde Pública. 1998;14(Suppl3):149. 19. Bosch FX, et al. Human papillomavirus and cervical intraepithelial neoplasia grade III/carcinoma in situ: a case-control study in Spain and Colombia. Cancer Epidemiology, Biomarkers & Prevention. 1993;2(5):415. 20. Camara GNL, et al. Prevalence of human papillomavirus types in women with preneoplastic and neoplastic cervical lesions in the Federal District of Brazil. Mem. Inst. Oswaldo Cruz. 2003;98(7):879. 21. Golijow CD, et al. Chlamydia trachomatis and Human papillomavirus infections in cervical disease in Argentine women. Gynecologic Oncology. 2005; 96(1):181. 22. González-Losa MD, et al. High prevalence of human papillomavirus type 58 in Mexican colposcopy patients. Journal of Clinical Virology. 2004;29(3):202. 23. Herrero R, et al. Epidemiologic profile of type-specific human papillomavirus infection and cervical neoplasia in Guanacaste, Costa Rica. Journal of Infectious Diseases. 2005; 191(11):1796. 24. Parkin M, Bray F. The birden of HPV relates cancers. Vaccine. 2006;24(S3):11–25. 25. Bruzzi P, et al. Estimating the population attributable risk for multiple risk factors using case control data. Am J Epidemiol. 1958;122(5):904–14. 26. D'Souza G, et al. Case control study og human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007;356:194–56. 27. Munger K, Edwards KM, Hayakawa H, Nguyen CL., Owens M, et al. Mechanisms of Human Papillomavirusvirus-induced oncogenesis. J Virol. 2004;78:11451–60. 28. Walboomers JM, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;Sep189(1):9–12. 168 29. F X Bosch, Muñoz N, Meijer C J L M, Shah K V. The causal relation between HPV and Cervical cancer. J.Clin.Pathol. 2002; 55(4):244–65. 30. PATH, Preventing cervical cancer in low-resource settings. Outlook. 2000;18(1):1–8. 31. Herrington, C. Do HPV-negative cervical carcinomas exist? revisited. J Pathol. 1999; Sep;189(1):1–3. 32. Bekkers LM, Bulten J, Melchers WJG. Epidemiological and clinical aspects of human papillomavirus detection in the prevention of cervical cancer. Rev. Med. Virol. 2004;14(2):95–105. 33. G. Böhmer, A.v.d.B., O. Brummer, C. Meijer, K. Petry. No confirmed case of human papillomavirus DNA-negative cervical intraepithelial neoplasia grade 3 or invasive primary cancer of the uterine cervix among 511 patients. Am J Obstet Gynecol. 2003;189(1):118 –20. 34. Franceschi S. The IARC commitment to cancer prevention: the example of papillomavirus and cervical cancer. Recent Results Cancer Res. 2005;66:277–97. 35. Huang LW, C.S., Chen PH, et al. Multiple HPV genotypes in cervical carcinomas: improved DNA detection and typing in archival tissues. J Clin Virol. 2004;29(4):271–6. 36. Bosch FX, M.M., Muñoz N, Sherman M, et al. Prevalence of human papillomavirus in cervical cancer: A worldwide perspective. J Nat cancer Inst. 1995;87:796–802. 37. Jacobs MV, S.P., van den Brule AJ, Helmerhorst TJ, Meijer CJ, Walboomers JM. A general primer GP5+/GP6(+)-mediated PCR-enzyme immunoassay method for rapid detection of 14 high-risk and 6 low-risk human papillomavirus genotypes in cervical scrapings. J Clin Microbiol. 1997;35:791–5. 38. Nindl I, L.A., Mielzynska I, et al. Human papillomavirus detection in cervical intraepithelial neoplasia by the second-generation hybrid capture microplate test, comparing two different cervical specimen collection methods. Clin Microbiol. 1992;30:2122–8. 39. De Villiers E, F.C., Broker T, Bernard H, zur Hausen H. Classification of papillomavirus. Virology. 2004;324:17–27. 40. Cogliano V, B.R., Straif K, Grosse Y, Secretan B, El Ghissassi F; WHO International Agency for Research on Cancer. Carcinogenicity of human papillomaviruses. Lancet Oncol. 2005;6:204. 41. Hiller T, P.S., Stubenrauch F, Iftner T. Comparative Analysis of 19 Genital Human Papillomavirus Types with Regard to p53 Degradation, Immortalization, Phylogeny, and Epidemiologic Risk Classification. Cancer Epidemiol Biomarkers Prev. 2006;15(7):1262– 7. 42. Schiffman, M., et al. The carcinogenicity of human papillomavirus types reflects viral evolution. Virology. 2005;337(1):76. 169 43. Wieland U, P.H. Papillomavirus in human pathology: Epidemiology, pathogenesis and oncogenic role. In: Gross G, Barrasso R. Human Papilloma Virus Infection.U. Mosby, Editor.Alemania; 1997. p. 1–16. 44. Holowaty P, M.A., Rohan T, et al. Natural history of dysplasia of the uterine cervix. . Journal of the National Cancer Institute. 1999;91(3):252–8 45. IH., F. Prevention of cervical cancer through papillomavirus vaccination. Nat Rev Immunol. 2004;4(1):46–54. 46. Goodman A, W.D. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 32-2003. A 37-year-old woman with atypical squamous cells on a Papanicolaou smear. N Engl J Med. 2003;1555–64. 47. Pagliusi SR, T.A.M., Efficacy and other milestones for human papillomavirus vaccine introduction. Vaccine. 2004;23(5):569–78. 48. Franco EL, H.D. Vaccination against human papillomavirus infection: a new paradigm in cervical cancer control. Vaccine. 2005;23:2388–94. 49. Beutner KR, T.S. Human papillomavirus and human disease. Am J Med. 1997;5(102(5A)):9–15. 50. Nielsen A., et al. Type-Specific HPV infection an multiple HPV types: Prevalence and risk factor in nearly 12.000 younger older Danish women. Sexually Transmitted Diseases. 2007;13(Epub ahead of print). 51. Winer, R.L., et al. Genital human papillomavirus infection: incidence and risk factors in a cohort of female university students. Am J Epidemiol. 2003;157(3): 218–26. 52. Castellsague X, B.F., Munoz N. Environmental co-factors in HPV carcinogenesis. Virus Res. 2002;89(2):191–9. 53. Matsumoto K, Y.T., Nakagawa S, et al. Human papillomavirus type 16 E6 variants and HLA class II alleles among Japanese women with cervical cancer. Int J Cancer. 2003; 106(6):919–22. 54. Daling JR, M.M., Schwartz SM, et al. A population-based study of squamous cell vaginal cancer: HPV and cofactors. Gynecol Oncol. 2002;84(2):263–70. 55. Plummer M, H.R., Franceschi Set al. Smoking and cervical cancer: pooled analysis of the IARC multi-centric case--control study. Cancer Causes Control. 2003;14(9):805–14. 56. Castellsague X, M.N., Chapter 3: Cofactors in human papillomavirus carcinogenesis--role of parity, oral contraceptives, and tobacco smoking. J Natl Cancer Inst Monogr. 2003;(31): 20–8. 57. Thomas DB, R.R., Qin Q. WHO Collaborative Study of Neoplasia and Steroid Contraceptives. Risk factors for progression of squamous cell cervical carcinoma in-situ to invasive cervical cancer: results of a multinational study. Cancer Causes Control. 2002;13(7):683–90. 170 58. IARC. Globocan 2002. Lyon: International Agency for Research on Cancer; 2002. 59. Bosch, F.X., et al. Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. Journal of the National Cancer Institute. 1995;87(11):796. 60. Eluf-Neto, J., et al. Human papillomavirus and invasive cervical cancer in Brazil. British Journal of Cancer. 1994;69(1):114. 61. Rabelo-Santos, S.H., et al. Human papillomavirus prevalence among women with cervical intraepithelial neoplasia III and invasive cervical cancer from Goiƒnia, Brazil. Mem. Inst. Oswaldo Cruz. 2003;98(2):181. 62. Rolon, P.A., et al. Human papillomavirus infection and invasive cervical cancer in Paraguay. International Journal of Cancer. 2000;85(4):486. 63. Santos, C., et al. HPV types and cofactors causing cervical cancer in Peru. British Journal of Cancer. 2001;85(7):966. 64. Alonio, L.V., et al. Ha-ras oncogene mutation associated to progression of papillomavirus induced lesions of uterine cervix. J Clin Virol. 2003;27(3):263–9. 65. Bryan, J.T., et al., Detection of specific human papillomavirus types in paraffin-embedded sections of cervical carcinomas. J Med Virol. 2006;78(1):117–24. 66. Burger, R.A., et al. Human papillomavirus type 18: association with poor prognosis in early stage cervical cancer. J Natl Cancer Inst. 1996;88(19):1361–8. 67. Duggan, M.A., et al. adenocarcinoma: a The human papillomavirus clinicopathological and status outcome of invasive analysis. Hum cervical Pathol. 1995;26(3):319–25. 68. Ferguson, A.W., Svoboda-Newman S.M., and Frank T.S., Analysis of human papillomavirus infection and molecular alterations in adenocarcinoma of the cervix. Mod Pathol. 1998;11(1):11–8. 69. Lorenzato, F., et al. The use of human papillomavirus typing in detection of cervical neoplasia in Recife (Brazil). Int J Gynecol Cancer. 2000;10(2):143–150. 70. Meyer, T., et al. Association of rare human papillomavirus types with genital premalignant and malignant lesions. J Infect Dis. 1998;178(1):252–5. 71. Paquette, R.L., et al. Mutations of p53 and human papillomavirus infection in cervical carcinoma. Cancer. 1993;72(4):1272–80. 72. Report of the Type-specific HPV Prevalence in High Grade lesions or Cervical Cancer in Latin America and the Caribbean: a Systematic Review of Epidemiological Studies. Beijing: Congreso de Beijing; 2007. 73. Davey, D. Cervical Citology classification and the Bethesda System Cancer. Cancer J. 2003;(9):327–34. 74. Solomon, D. Terminology for reporting results of cervical cytology. JAMA. 2002;287:2114. 171 75. Sanderson S., T.I., Higgings J. Tools for assesing quality and susceptibility to bias in observational studies in epidemiology: a systematic review and annotated bibliography. Int J Epidemiol. 2007;36(3):666–76. 76. Tooth L., W.R., Bain C., Pudie D., Dobson A. Quality of reporting of observational longitudinal research. Am J Med. 2005;161:280–8. 77. Berlin J., L.N., Sacks H,. Chalmers T. A Comparison of Statistical method for combining event rates from clinical trial. Statistics in Medicine. 1989;8:141–51. 78. Sterne J., B.M., Egger M. Metaanalysis in Stata TM . In chapter 18 Systematica Reviews. 2001. p. 347. Available from;URL: www.sytematicreviews.com. 79. De Villiers E, F.C., Broker T, Bernard H, zur Hausen H. Classification of papillomavirus. Virology. 2004;324:17–27. 80. Daling JR, M.M., Jonhson LG, Schwartz SM, Shera KA, Wurscher MA, et al. Human papillomavirus, smoking and sexual practices in the etiology of anal cancer. Cancer. 2004;101(2):270–80. 81. Long FX, C.C., Wheeler CM, Koutsky LA, Galloway DA, Kuypers J, et al. Risk of anal carcinoma in Situ in relation to human papillomavirus type 16 variants. Cancer Research. 1998;58:3839–44. 82. Carter JJ, M.M., Shera KA, Schwartz SM, Cushing-Haugen KL, Wipf GC, et al. Human papillomavirus 16 and 18 L1 serology compared across anogenital cancer sites. Cancer Research. 2001;61:1934–40. 83. Kreimer AR, C.G., Boyle P, Franceschi S. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Epidemiology, Biomarkers and Prevention. 2005;14(2):467–75. 84. Schwartz SM, D.J., Doody DR, Wipf GC, Carter JJ, Madeleine MM, et al. Oral cancer risk in relation to sexual history and evidence of human papillomavirus infection. Journal of the National Cancer Institute. 1998;90(21):1626–36. 85. Herrero R, C.X., Pawlita M, Lissowska J, Kee F, Balaram P, et al. Human papillomavirus and oral cancer: the International Agency for Reseach in Cancer multicenter study. . Journal of the National Cancer Institute. 1998;95(23):1772–83. 86. D´Souza G, F.A., Viscidi R, Pawlita M, Fakhry C, Koch WM, et al. Case-Control study of human papillomavirus and oropharyngeal cancer. . New England Journal of Medicine. 2007;356(19):1944–56. 87. Frisch M, F.C., Van den Brule AJC, Sorensen Per, Meijer C, Walboomers J, et al. Variants of squamous cell carcinoma of the anal canal and perianal skin and their relation to human papillomaviruses. Cancer Reseach. 1999;59:753–7. 172 88. Bjørge T, E.A., Luostarinen T, Mork J, Gislefoss RE, Jellum E, et al. Human papillomavirus infection as a risk factor for anal and perianal skin cancer in a prospective study. British Journal of Cancer. 2002;87:61–4. 89. Heideman DA, W.T., Pawlita M, Diemen PD, Nindl I, Leijte J, et al. Human papillomavirus-16 is the predominant type etiologically involved in penile squamous cell carcinoma. Journal Of Clinical Oncology. 2007;25(29):4550–6. 90. Hildesheim A, C.-L.H., Brinton L, Kurman L, Schiller J. Human papillomavirus type 16 and risk of preinvasive and invasive vulvar cancer: results from a seroepidemiological casecontrol study. Obstetrics & Ginecology. 1997;90(5):748–54. 91. Madeleine MM, D.J., Carter JJ, Wipf GC, Schwartz SM, McKnight B, et al. Cofactors With human papillomavirus in a population-based study of vulvar cancer. Journal of the National Cancer Institute. 1997;89(20):1516–23. 92. Sun Y, H.A., Brinton L, Nasca P, Trimble C, Kurman R, et al. Human papillomavirusspecific serologic response in vulvar neoplasia. Gynecologic Oncology. 1996;63:200–03. 93. Pan American Healh Organization. Health Analysis and Statistic Unit. [cited February 6, 2008]. Available from URL: http://www.paho.org/english/dd/ais/coredata.htm. 94. Salud Sexual y Reproductiva en Colombia: Encuesta Nacional de Demografia y Salud 2005. [cited November 13, 2007]. Available from URL: www.profamilia.org.co/encuestas. 95. Centers for Disease Control and Prevention. Global Youth Tobacco Surveillance, 2000–2007. MMWR 2008;57(No. SS-1). 96. Mackay J and Eriksen M. The Tobacco Atlas. Geneva: World Health Organization; 2002. [Cited November 13, 2007]. Available from URL: http://www.who.int/tobacco/statistics/tobacco_atlas/en/. 97. Centers for Disease Control and Prevention and United States Agency for International Development. Reproductive, Maternal and Child Health in Central America: Trends and Challenges Facing Women and Children: El Salvador, Guatemala, Honduras, Nicaragua. Atlanta: CDC; 2005. 98. Clifford G., R.R., Franceschi S., Smith JS. Human Papillomavirus Genotype Distribution in Low Grade Cervical lesions: Comparison by Geographic region and with Cervical Lesions. . Cancer Epidemiol Biomarkers Prev. 2005;14:1157–64. 99. Clifford GM., S.J., Aguado T. and Franceschi S. Comparison of HPV type distribution in high-grade cervical lesiosn and cervical cancer: a metaanalysis. British Jour Cancer. 2003;89:101–5. 100. Clifford GM., S.J., Plummer M., Muñoz N., Franceschi S. Human Papillomavirus types in invasive cervical cancer worldwide: a meta-analysis. British Jour Cancer. 2003;88:63–73. 101. Smith J., et al. Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: A meta-analysis update. Int. J. Cancer. 2007;121:621–32. 173 102. Cogliano V, B.R., Straif K, Grosse Y, Secretan B, El Ghissassi F. WHO International Agency for Research on Cancer. Carcinogenicity of human papillomaviruses. Lancet Oncol. 2005;6:204. 103. Jacobs MV, S.P., van den Brule AJ, Helmerhorst TJ, Meijer CJ, Walboomers JM. A general primer GP5+/GP6(+)-mediated PCR-enzyme immunoassay method for rapid detection of 14 high-risk and 6 low-risk human papillomavirus genotypes in cervical scrapings. J Clin Microbiol. 1997;35:791–5. 104. Nindl I, L.A., Mielzynska I, Petry U, Baur S, Kirchmayr R, Michels W, Schneider A. Human papillomavirus detection in cervical intraepithelial neoplasia by the secondgeneration hybrid capture microplate test, comparing two different cervical specimen collection methods. Clin Diagn Virol. 1998;10(1):49–56. 105. Centers for Disease Control. How common is HPV? in: Genital HPV Infection. CDC Fact Sheet. 2007 [cited Oct 2007]; Available from URL: http://www.cdc.gov/std/HPV/STDFact-HPV.htm. 106. Villa, L.L. Vacunas contra infección y enfermedad causadas por papilomavirus. Rev Chil Infectol. 2006;23(2):157. 107. Parkin DM, B.F., Ferlay J, Pisani P. Estimating the world cancer burden: Globocan 2000. Int J Cancer. 2001;94:153–6. 108. Parkin DM, B.F., Devesa SS. Cancer burden in the year 2000. The global picture. Eur J Cancer. 2001;37(suppl 8):S4–66. 109. Ferlay J, B.F., Pisani P. GLOBOCAN 2002: cancer incidence, mortality and prevalence worldwide. Lyon, France: IRAC; 2004. 110. Parkin DM, et al., eds. Cancer Incidence in Five Continents Vol. VIII, No. 155, IARC Scientific Publications. Lyon, France: IRAC; 2002: 111. Murillo, R. Cytology-based cervical cancer screening programmes in Latin America. HPV Today. 2007;12(6). 112. Immunization., N.A.C.O. Statement on human papillomavirus vaccine. Can Commun Dis Rep. 2007; 33(ACS-2):1–31. 113. Kaiser Daily Women's Health Policy Report. 2007. Available from URL: http://www.kaisernetwork.org/daily_reports/rep_index.cfm?hint=2&DR_ID=44452. 114. Gold MR, et al. Cost-effectiveness in health and medicine. NewYork: Oxford University Press; 1996. 115. Goldie, S.J., et al. Cost-effectiveness of HPV 16, 18 vaccination in Brazil. Vaccine. 2007; 25(33):6257–70. 116. Smith, J.S., et al. Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: a meta-analysis update. Int J Cancer. 2007;121(3):621–32. 174 117. Nations, U. UN World Population Prospects: The 2004 Revision 2004. Available from URL: http://www.un.org/esa/population/publications/WPP2004/wpp2004.htm. 118. WHOSIS. W.S.I.S. 2004 Life Tables for WHO Member States 2004. Available from URL: http://www.who.int/whosis/database/life_tables/life_tables.cfm. 119. Murray CJL, Lopez AD, and (eds). The Global Burden of Disease. Vol. 1 of Global Burden of Disease and Injury Series. Cambridge, MA: Harvard University Press;1996. 120. Murray, C.J., et al. Development of WHO guidelines on generalized cost-effectiveness analysis. Health Econ. 2000;9(3):235–51. 121. World Health Organization. The Global Burden of Disease: A comprehensive assessment of mortality and disability from diseases, injuries, and risk factors in 1990 and projected to 2020. Volume I. Geneva, WHO; 1990. 122. Goldie, S.J., et al. Global Cervical Cancer/HPV Vaccine Policy Model: Brazil Supplementary Appendix. 2007. Available from URL: http://www.sciencedirect.com/science/MiamiMultiMediaURL/B6TD4-4P00K0J-2/B6TD44P00K0J-2-C/5188/72ed62388e82574122d55627c360d864/f.pdf. 123. Urbanos, A.N.d.E.d.T. Associação Nacional das Empresas de Transportes Urbanos NTU (IGP-DI/FGV, 2006). 2004. 124. Urbanos, A.N.d.E.d.T., Asociacion Nacional de Empresas de Transportes Urbanos. 2005. 125. Direccion Central de Estudios y Formulacion de Politicas de Empleo. 2006. 126. Organization, I.L. International Labor Organization. 2004. Available from URL: http://laborsta.ilo.org 127. Banco Central do Brasil. 2006. [cited July 14, 2007]. Available from URL: http/www. bcb.gov.br/ 128. Estadisticas del Trabajo y Prevision. 2005. 129. Harper, D.M., et al. Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial. Lancet. 2006;367(9518):1247. 130. Harper, D.M., et al. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: A randomised controlled trial. Lancet. 2004;364(9447):1757. 131. Garnett, G.P., et al. Chapter 21: Modelling the impact of HPV vaccines on cervical cancer and screening programmes. Vaccine. 2006;24(Suppl 3):S178–86. 132. Goldie, S.J., et al. Cost-effectiveness of cervical-cancer screening in five developing countries. N Engl J Med. 2005;353(20):2158–68. 133. Goldie, S.J., Kim J.J., Myers E. Chapter 19: Cost-effectiveness of cervical cancer screening. Vaccine. 2006;24(Suppl 3):S164–70. 175 134. Goldie, S.J., Kim J.J., Wright T.C. Cost-effectiveness of human papillomavirus DNA testing for cervical cancer screening in women aged 30 years or more. Obstet Gynecol. 2004;103(4):619–31. 135. Goldie, S.J., et al. Projected clinical benefits and cost-effectiveness of a human papillomavirus 16/18 vaccine. J Natl Cancer Inst. 2004;96(8):604–15. 136. Goldie SJ, G.D., Kohli M, Wright TC, Weinstein M, Franco E. A comprehensive natural history model of HPV infection and cervical cancer to estimate teh clinical impact of a prophylactic HPV-16/18 vaccine. Int J Cancer. 2003;106(6):896–904. 137. Kulasingam, S.L., Myers E.R. Potential health and economic impact of adding a human papillomavirus vaccine to screening programs. JAMA. 2003;290(6):781–9. 138. Mandelblatt J, L.W., Yi B, King J. The balance of harms, benefits, and costs of screening for cervical cancer in older women: the case for continued screening. Arch Intern Med. 2004;164(3):245–7. 139. Mandelblatt, J.S., et al. Benefits and costs of using HPV testing to screen for cervical cancer. JAMA. 2002;287(18):2372–81. 140. Kim, J.J., Wright T.C., Goldie S.J. Cost-effectiveness of human papillomavirus DNA testing in the United Kingdom, The Netherlands, France, and Italy. J Natl Cancer Inst. 2005;97(12):888–95. 141. Legood, R., et al. Lifetime effects, costs, and cost effectiveness of testing for human papillomavirus to manage low grade cytological abnormalities: results of the NHS pilot studies. Br Med J. 2006;332(7533):79–85. 142. Sherlaw-Johnson C, P.Z. An evaluation of liquid-based cytology and human papillomavirus testing within the UK cervical cancer screening programme. Br J Cancer. 2004;91(1):84–91. 143. Myers ER, M.D., Subramanian S, McCall N, Nanda K, Datta S, et al. Setting the target for a better cervical screening test: characteristics of a cost-effective test for cervical neoplasia screening. Obstet Gynecol. 2000;96(5 Pt 1):645–52. 144. Goldie, S.J., et al. Policy analysis of cervical cancer screening strategies in low-resource settings: clinical benefits and cost-effectiveness. JAMA. 2001;285(24):3107–15. 145. Suba EJ, N.C., Nguyen BD, Raab SS. De novo establishment and cost-effectiveness of Papanicolaou cytology screening services in the Socialist Republic of Vietnam. Cancer. 2001;91(5):928–39. 146. Sherlaw-Johnson C, G.S., Jenkins D. Evaluating cervical cancer screening programmes for developing countries. Int J Cancer. 1997;72(2):210–6. 147. Mandelblatt JS, L.W., Gaffikin L, Limpahayom KK, Lumbiganon P, Warakamin S, et al. Costs and benefits of different strategies to screen for cervical cancer in less-developed countries. J Natl Cancer Inst. 2002;94(19):1469–83. 176 148. Diaz M, Kim JJ, Albero G, de Sanjosé S, Clifford G, Bosch FX, Goldie SJ. Health and economic impact of HPV 16 and 18 vaccination and cervical cancer screening in India. Br J Cancer.2008;99(2):230-8. 149. Goldie SJ, O'Shea MK, Campos NG, Diaz M, Sweet SJ, Kim SY. Health and economic outcomes of HPV 16,18 vaccination in 72 GAVI-eligible countries. Vaccine. 2008;26(32):4080-93. 150. Kim JJ, Kobus KE, Diaz M, O'Shea M, Van Minh H, Goldie SJ. Exploring the costeffectiveness of HPV vaccination in Vietnam: insights for evidence-based cervical cancer prevention policy. Vaccine. 2008;26(32):4015-24. 151. Hughes JP, G.G., Koutsky L. The theoretical population-level impact of a prophylactic human papilloma virus vaccine. Epidemiology. 2002;13(6):631–9. 152. Taira, A.V., Neukermans, C.P, Sanders G.D. Evaluating human papillomavirus vaccination programs. Emerg Infect Dis. 2004;10(11):1915–23. 153. Barnabas, R.V., et al. Epidemiology of HPV 16 and cervical cancer in Finland and the potential impact of vaccination: mathematical modelling analyses. PLoS Med. 2006;3(5): e138. 154. Kim JJ, Andres-Beck B, Goldie SJ. The value of including boys in an HPV vaccination programme: a cost-effectiveness analysis in a low-resource setting. Br J Cancer. 2007; 97(9):1322–8. 155. Goldhaber-Fiebert JD, Stout NK, Salomon JA, Kuntz KM, Goldie SJ. Cost-effectiveness of cervical cancer screening with human papillomavirus DNA testing and HPV-16,18 vaccination. J Natl Cancer Inst. 2008;100(5):308–20. 156. Kim JJ, Goldie SJ. Health and economic implications of HPV vaccination in the United States. N Engl J Med. 2008;359(8):821–32 177 Appendix A. Model comparison validation: Impact of HPV 16 and 18 vaccination on mean reduction in lifetime risk of cervical cancer Shown is the mean reduction (thick grey line) in lifetime risk of cervical cancer with HPV 16 and 18 vaccination of 70% of a 12-year-old birth cohort generated by using empirically calibrated models for Argentina, Brazil, Chile, Colombia, Peru, and Mexico. The range (orange rectangles) represents the minimum and maximum reductions across the good-fitting parameter sets for each country-specific model. The stars indicate the average reduction predicted with the Excel-based companion model. 178 Source: Goldie SJ, Diaz M, Constenla D, Alvis N, Andrus JK, Kim SY. Mathematical models of cervical cancer prevention in Latin America and the Caribbean. Vaccine. 2008;26(S11):L59–72. 179 Appendix B. Epidemiological parameters (Appendix Tables 1 and 2) Table 1. Cervical cancer incidence rates by data source and age group for studied countries Data 10– 15– 20– 25– 30– 35– Country 0–4 5–9 40–44 45–49 50–54 55–59 60–64 65–69 70–74 75–79 80 Sources 14 19 24 29 34 39 Argentina CI5C 0.00 0.00 0.00 0.66 3.23 9.27 32.29 46.53 51.24 59.02 49.00 33.07 49.75 31.16 48.96 41.94 41 Brazil CI5C 0.00 0.00 0.07 0.36 2.49 9.57 24.22 40.57 64.50 89.04 94.40 105.74 104.91 111.22 104.19 104.19 104 Chile CI5C 0.00 0.00 0.08 0.61 3.93 17.92 53.46 77.75 106.00 123.64 117.02 119.34 116.17 103.72 78.66 56.94 75 Colombia CI5C 0.00 0.00 0.00 0.08 2.19 12.10 28.79 53.98 75.33 101.40 115.47 126.86 146.03 144.55 142.40 135.63 135 Globocan Mexico 0.00 0.00 0.00 14.00 14.00 14.00 14.00 14.00 14.00 80.36 80.36 84.71 84.71 112.07 112.07 112.07 112 2002 Peru CI5C 0.00 0.00 0.12 0.33 1.50 6.28 15.94 35.55 49.29 73.76 90.96 110.90 99.32 111.53 112.62 119.09 111 Sources: Globocan 2002. International Agency for Research on Cancer (IRAC). Parkin DM, et al., Editors. Cancer Incidence in Five Continents Vol. VIII, No. 155. Lyon, France: IARC Scientific Publications; 2002.. Table 2. Estimates of prevalence of HPV 16/18 in cervical cancer by country and source Country/Region % HPV 16/18 Estimate from Smith 2007 meta-analysis [101] Argentina Brazil Chile Colombia Mexico Peru 76.9 68.8 56.3 57.6 56.6 67.8 Argentina pool Brazil pool Chile Colombia pool Mexico pool Peru 180 Appendix C. List of physicians interviewed Argentina Jorge A. Gomez, Ph.D. Epidemiologic Advisor for Vaccines (HPV) Latin America & Caribbean GlaxoSmithKline Biologicals Carlos Casares 3690, (B1644BCD), Buenos Aires Argentina Tel: 54-11- 4725-8995 E-mail: [email protected] Dr. Silvio Tatti Sociedad Argentina de Colposcopía Universidad de Buenos Aires Argentina E-mail: [email protected] Brazil Dr. Nelson Vespa Junior Instituto Brasileiro de Controle do Câncer / IBCC Sao Paulo, Brazil E-mail: [email protected] Dr. Francisco Galdo Coelho Instituto Brasileiro de Controle do Câncer / IBCC Sao Paulo, Brazil Tel: +55 11 9908-3220 E-mail: [email protected] Dr. Ronaldo Rangel Costa Instituto Brasileiro de Controle do Câncer / IBCC Sao Paulo, Brazil E-mail: [email protected] Chile Sra. Marta Prieto Coordinadora Programa de Cáncer Cervicouterino Ministerio de Salud Santiago, Chile E-mail: [email protected] Dr. Hugo Salinas Portillo Red Hospital Clínico Universidad de Chile Chile E-mail: [email protected] Colombia Martha Patricia Velandia Gonzalez Encargada del Programa Ampliado de Inmunización Bogotá Colombia E-mail: [email protected] Dr. Orlando Borre Liga contra el Cancer Cartgena de Indias Colombia E-mail: [email protected] Dra. Celia Castillo Directora Profamilia Cartagena de Indias Colombia E-mail: [email protected] Dra. Elizaberth Lopez Decana de la Facultad de Medicina Universidad de Cartagena Colombia E-mail: [email protected] y [email protected] Dr. Luis Alzamora Liga contra el Cancer/ Departamento de Ginecologia y Obstetricia de la Clínica Maternidad Rafael Calvo (Hospital Universitario) Universidad de Cartagena 181 Cartgena de Indias Colombia Colombia E-mail: [email protected] Dr. David Romero Liga contra el Cancer/ Departamento de Ginecologia y Obstetricia de la Clínica Materidad Rafael Calvo (Hospital Universitario) Universidad de Cartagena Cartgena de Indias Colombia Dr. Julio Faciolince Liga contra el Cancer/ Departamento de Ginecologia y Obstetricia de la Clínica Materidad Rafael Calvo (Hospital Universitario) Universidad de Cartagena Cartgena de Indias Colombia Honduras Hilda Lourdes Aguilar Cantarero Programa Nacional para el Control del Cáncer Secretaría de Salud, segundo piso Apartado Postal 3102 Tegucigalpa, M.D.C. Honduras E-mail: [email protected] Dr. Sergio Girado Liga contra el Cancer/ Departamento de Ginecologia y Obstetricia de la Clínica Materidad Rafael Calvo (Hospital Universitario) Universidad de Cartagena Cartgena de Indias Colombia Dominican Republic Dra. Elizabeth Gomez, Epidemiologa Directora Direccion General de Epidemiologia Secretaria de Estado de Salud Publica Republica Dominicana Tel: 809-686-9140 Fax 809-689-8395 E-mail [email protected] ; [email protected] Jamaica Professor Horace Fletcher University of the West Indies Dept. Obstetrics/Gynaecology Mona Kingston, Jamaica E-mail: [email protected] Dr. Nestor Martinez Liga contra el Cancer/ Departamento de Ginecologia y Obstetricia de la Clínica Materidad Rafael Calvo (Hospital Universitario) Universidad de Cartagena Cartgena de Indias Guyana Dr. Janice Woolford EPI Manager/MCH Director Ministry of Health Brickdam Georgetown, Guyana Mexico Dr. Eduardo Lazcano Ponce Director del Centro de Investigación en Salud Poblacional Instituto Nacional de Salud Pública de México Tel. 01 777 3293003 Fax 01 777 3111148 Email: [email protected] 182 Dra. Vesta Richardson Director General del Centro Nacional para la Salud de la Infancia y la Adolescencia (CENSIA) Ciudad de México Mexico E-mail: [email protected] Alejandro Garcia Carranca Instituto Nacional de Cancerología Av San Fernando 22, Col Toriello Guerra del Tialpan, México DF CP 14080 E-mail: [email protected] 183 Appendix D. Sample expert interview survey ENCUESTA SOBRE LA DETECCIÓN TEMPRANA Y TRATAMIENTO DEL CÁNCER CERVICOUTERINO INFORMACIÓN GENERAL 1. Nombre del entrevistado ___________________________ 2. Tipo de especialidad del entrevistado______________________________ 3. País ___________________________ 4. Fecha de finalización de la encuesta: |___|___| día |___|___| mes |___|___| año DETECCIÓN TEMPRANA DEL CÁNCER CERVICOUTERINO En primer lugar, tenemos algunas preguntas sobre la detección temprana del cáncer cervicouterino. Sírvase responder de acuerdo con su experiencia y conocimientos especializados. 5. ¿Existe en su país un programa para la prevención (screening) y el control del cáncer cervicouterino con metas y objetivos definidos? SÍ / NO (Sírvase marcar uno) En caso afirmativo, sírvase responder a las preguntas a partir de la número 6. Si no hay un programa para la prevención (screening) y el control del cáncer cervicouterino en su país, sírvase pasar a la pregunta 34. 6. ¿En qué nivel está estructurado este programa en relación con su administración y la prestación de servicios? (Sírvase indicar) Nivel primario de atención Nivel secundario de atención Nivel terciario de atención Otro, sírvase indicar: __________________________ 7. ¿Quién está a cargo de la coordinación de este programa de prevención (screening) del cáncer cervicouterino? (Sírvase indicar) Médicos Enfermeras Otro, sírvase indicar: __________________________ 8. Aproximadamente, ¿cuál es la cobertura actual de este programa de prevención (screening) (porcentaje de mujeres evaluadas en la población beneficiaria)? (Sírvase indicar) < 10% 10-25% 26-50% 51-75% 76-85% > = 86% 9. De las mujeres que son detectadas con el cáncer cuellouterino, ¿aproximadamente cuál es el porcentaje de mujeres que reciben diagnóstico y tratamiento de seguimiento? (Sírvase indicar) < 10% 10-25% 26-50% 51-75% 76-85% > = 86% 10. ¿Está funcionando algún sistema de vigilancia de las mujeres detectadas que requieren seguimiento? 184 SÍ / NO (Sírvase marcar uno) 11. ¿Tienen que pagar de su bolsillo las mujeres por las medidas de prevención (citología - prueba de Papanicolaou, análisis del VPH, ADN) que son realizadas ? (Sírvase indicar) Sí No 12. ¿Cuánto pagan por estos exámenes de detección del cáncer cuello uterino? (Sírvase indicar) Pago total Pago parcial No se paga 13. ¿Tienen que pagar de su bolsillo las mujeres por el diagnóstico (colposcopía y biopsia)? (Sírvase indicar) Sí No 14. ¿Cuánto pagan por el diagnóstico (colposcopía y biopsia)? (Sírvase indicar) Pago total Pago parcial No se paga 15. ¿Tienen las mujeres que pagar de su bolsillo por el tratamiento de lesiones pre cancerosas? (Sírvase indicar) Sí No 16. ¿Cuánto pagan por el tratamiento de lesiones pre cancerosas? (Sírvase indicar) Pago total Pago parcial No se paga 17. ¿Tienen las mujeres que pagar de su bolsillo por el tratamiento del cáncer cervicouterino? (Sírvase indicar) Sí No 18. ¿Cuánto pagan por el tratamiento del cáncer cervicouterino? (Sírvase indicar) Pago total Pago parcial No se paga Si respondió afirmativamente a cualquiera de las preguntas 11, 13, 15 y 17, sírvase pasar a la pregunta 19 y continúe con la encuesta. De lo contrario, sírvase pasar a la pregunta 23. 19. Aproximadamente, ¿cuánto cuesta en promedio por paciente los exámenes realizados para la detección temprana del cáncer cuello uterino? Sírvase incluir los costos de los exámenes de laboratorio (citología - prueba de Papanicolaou, análisis del VPH, ADN) que se realizan para la detección temprana del cáncer cuello uterino. |__|__|__|__|__|__| por paciente (expresar en moneda nacional) (coloque 0 si no lo sabe) 20. Aproximadamente, ¿cuánto cuesta en promedio por paciente el diagnóstico (colposcopía y biopsia)? |__|__|__|__|__|__| (expresar en moneda nacional) (coloque 0 si no lo sabe) 21. Aproximadamente, ¿cuánto cuesta en promedio por paciente el tratamiento de lesiones pre cancerosas? 185 |__|__|__|__|__|__| (expresar en moneda nacional) (coloque 0 si no lo sabe) 22. Aproximadamente, ¿cuánto cuesta en promedio por paciente el tratamiento de cáncer cervicouterino? |__|__|__|__|__|__| (expresar en moneda nacional) (coloque 0 si no lo sabe) 23. ¿A qué edad se suele comenzar a detectar (screen) a las pacientes en relación con el cáncer cervicouterino? (Sírvase indicar) < = 9 años 10 a 12 años 13 a 15 años 16 a 19 años +20 años Otro grupo de edad, sírvase indicar:________________________ 24. ¿Con qué frecuencia se realiza la detección de cáncer cervicouterino por lo general? (sírvase indicar) Anualmente Año de por medio Cada dos años Cada tres años Nunca 25. ¿Qué exámenes se realizan para detectar el cáncer cuellouterino por lo general? (sírvase indicar) Citología (prueba de Papanicolaou) Análisis del VPH, ADN Otro análisis, sírvase indicar: _____________________________________ 26. ¿Cuántas de estas pruebas se realizan por año por lo general? (sírvase indicar el tipo de pruebas y además mencione el número de pruebas por año por paciente) Citología (prueba de Papanicolaou): ________________ por año Análisis del VPH, ADN :___________________ por año Otro, sírvase indicar: ______________________, _________________ por año 27. ¿Dónde suelen realizarse estas pruebas por lo general? (sírvase indicar) Consultorio para pacientes ambulatorios Consultorio de detección para el cáncer cuello uterino Consultorio de planificación familiar Consultorio médico Otro, sírvase indicar: ________________________________________________ 28. ¿Cómo se realizan estas pruebas por lo general? (sírvase indicar) Como parte de los servicios preventivos sistemáticos de salud Como parte de los servicios de salud materno infantil Como una campaña especial para la prevención del cáncer cervicouterino Otro, sírvase indicar: _________________________________________________ 29. ¿Quién realizará por lo general estas pruebas? (Sírvase indicar) Técnicos de laboratorio Ginecólogos Médicos de cabecera y comunitarios Enfermeros Otro, sírvase indicar: ___________________________________________ 186 30. ¿Dónde se analizan e interpretan estas pruebas por lo general? (Sírvase indicar) Laboratorio de patología Consultorio médico Hospital Centros oncológicos Otro, sírvase indicar: _____________________________________________ 31. ¿Cuál es el tiempo promedio que transcurre entre el momento en que se realiza las pruebas de detección y el momento en que se entregan los resultados a la mujer? (Sírvase indicar) < 1 semana 1 a 2 semanas 2 a 3 semanas > 3 semanas 32. ¿Cómo se notifica a la mujer el resultado de estas pruebas? (Sírvase indicar) En persona en el consultorio médico Por teléfono Por correo Otro, sírvase indicar: _____________________________________________ 33. ¿Qué ocurre si una mujer tiene una evaluación anormal? (Sírvase indicar) Se le pide que regrese a realizarse más pruebas en el lapso de seis meses Se repite la prueba en la próxima consulta médica Regresa para una colposcopía o una biopsia de inmediato Otro, sírvase indicar: _____________________________________________ TRATAMIENTO EN LA ETAPA PREVIA AL CÁNCER A continuación se mencionan algunas preguntas sobre la manera en que usted tratará por lo general a los pacientes en el estadio previo al cáncer (CIN 1 o CIN 2/3). Sírvase responder de acuerdo con su experiencia y conocimientos especializados. 34. ¿Cuál es el porcentaje de pacientes con CIN 1 que por lo general será sometido a los siguientes procedimientos e intervenciones? (Sírvase escribir la respuesta en la segunda columna del cuadro en la página siguiente). 35. ¿Cuál es el porcentaje de pacientes con CIN por lo general tratados en los servicios ambulatorios? (Sírvase escribir la respuesta en la tercera columna del cuadro a continuación. Indique el número de consultas ambulatorias). 36. ¿Cuál es el porcentaje de pacientes con CIN por lo general tratados en el hospital? (Sírvase escribir la respuesta en la cuarta columna del cuadro a continuación. Indique el número de días en el hospital). 37. ¿Cuál es la tasa general de complicaciones menores y mayores que resultan de estos procedimientos o intervenciones? (Sírvase escribir la respuesta en la quinta y sexta columnas del cuadro a continuación). La complicación menor se define como algo que requiere intervención clínica breve de hospitalización (aspirina, antibióticos de administración oral, refulgeración, relleno vaginal). Una complicación grave se define como algo que requiere hospitalización (transfusión sanguínea intravenosa, administración intravenosa de antibióticos, etc.). 187 ¿% de pacientes con CIN 1 que reciben intervencion es? ¿% tratado ambulatoria -mente? (Además indicar el número de consultas) ¿% tratado en el hospital? (Además indicar el número de días) ¿% con complicacion es menores? ¿% con complicacio nes graves? Crioterapia Electrocauteriz ación con colposcopía LEEP Cono de láser Conización fría con bisturí Histerectomía simple Otro, indicar: ____________ ___ Otro, indicar: ____________ ___ 38. ¿Qué porcentaje de las complicaciones graves en general requiere las siguientes intervenciones: (Sírvase marcar e indicar el porcentaje y el número de días) Sutura e intervención quirúrgica _________% Antibióticos por vía intravenosa y hospitalización ____% ¿Cuántos días de hospitalización? ____días Transfusión sanguínea intravenosa y hospitalización ___% ¿Cuántos días de hospitalización?___ días Otra intervención, sírvase indicar: ______________________________, ______% 39. ¿Qué porcentaje de todas las complicaciones en general requiere el cuidado de: (sírvase marcar e indicar el porcentaje) Un médico _________% Un enfermero _________% Otro tipo de atención, sírvase indicar: _____________________________, ______% 40. ¿Cuál es el porcentaje de pacientes con CIN 2/3 que por lo general será sometido a las siguientes intervenciones? (Sírvase escribir la respuesta en la segunda columna del cuadro a continuación). 41. ¿Cuál es el porcentaje de pacientes con CIN 2/3 por lo general tratado en los servicios ambulatorios? (Sírvase escribir la respuesta en la tercera columna del cuadro a continuación. Indique el número de consultas ambulatorias). 42. ¿Cuál es el porcentaje de pacientes con CIN 2/3 por lo general tratado en el hospital? (Sírvase escribir la respuesta en la cuarta columna del cuadro a continuación. Indique el número de días en el hospital). 43. ¿Cuál es la tasa general de complicaciones menores y graves que resultan de este tratamiento? (Sírvase escribir la respuesta en la quinta y sexta columnas del cuadro a continuación). Una complicación menor se define como algo que requiere intervención clínica breve de hospitalización (aspirina, antibióticos de administración oral, refulgeración, relleno vaginal). Una complicación grave se 188 define como algo que requiere hospitalización (transfusión sanguínea intravenosa, administración intravenosa de antibióticos, etc.). ¿% de ¿% tratado ¿% tratado ¿% con ¿% con lesiones pre ambulatoria en el complicacion complicacancerosas -mente? hospital? es menores? ciones con inter(Además (Además graves? venciones? indicar el indicar el número de número de consultas) días) LEEP Cono de láser Conización fría con bisturí Histerectomía simple Otro, indicar: ____________ ___ Otro, indicar: ____________ ___ 44. ¿Qué porcentaje de las complicaciones graves en general requiere las siguientes intervenciones: (sírvase marcar e indicar el porcentaje y el número de días) Sutura e intervención quirúrgica _________% Antibióticos por vía intravenosa y hospitalización _______% ¿Cuántos días de hospitalización? _____días Transfusión sanguínea intravenosa y hospitalización ____% ¿Cuántos días de hospitalización?_____ días Otra, sírvase indicar: ______________________________, ______% 45. ¿Qué porcentaje de todas las complicaciones en general requiere el cuidado de: (sírvase marcar e indicar el porcentaje) Un médico _________% Un enfermero _________% Otro tipo de atención, sírvase indicar: _____________________________, ______% TRATAMIENTO DEL CÁNCER A continuación se hacen algunas preguntas sobre la clasificación en estadios del cáncer y el tratamiento sistemático para el cáncer cervicouterino. 46. ¿Dónde se realiza por lo general la clasificación en estadios del cáncer cervicouterino? (Sírvase indicar) Hospital de primer nivel Hospital de nivel secundario Hospital de nivel terciario Hospital de oncología Otro, sírvase indicar: ___________________ 47. ¿Cuáles son las pruebas y los procedimientos de diagnóstico habituales para determinar clínicamente los estudios del cáncer cervicouterino? (sírvase indicar) Análisis sanguíneos Radiografías Biopsia Exploración con tomografía computarizada 189 Pruebas de medicina nuclear Otro, sírvase indicar: _________________ Otro, sírvase indicar: _________________ 48. ¿Con qué frecuencia se realizan estas pruebas y procedimientos de diagnóstico durante la clasificación en estadios del cáncer cervicouterino? (Sírvase marcar e indicar el número de pruebas o procedimientos realizados) Análisis sanguíneos # _____________ Radiografías # _____________ Biopsia # _____________ Exploración con tomografía computarizada # _____________ Pruebas de medicina nuclear Otro, sírvase indicar: _________________ # _____________ Otro, sírvase indicar: _________________ # _____________ 49. ¿Quién atiende por lo general a las mujeres en el estadio 1a a 2a del cáncer cervicouterino en el entorno ambulatorio? (Sírvase marcar cada una que se aplique e indique el número de consultas ambulatorias.) Oncólogo experto en ginecología, sírvase indicar el número de consultas: ____________ consultas Oncólogo médico, sírvase indicar el número de consultas: ________________ consultas Oncólogo experto en radiación médica. Sírvase indicar el número de consultas: ________ consultas Otro, sírvase indicar: ______________________: ________________ consultas Las mujeres en el estadio 1a a 2a de cáncer cervicouterino no son atendidas en el entorno ambulatorio. 50. ¿Donde se hospitaliza por lo general a las mujeres que padecen cáncer cervicouterino en el estadio 1a a 2a? (Sírvase marcar cada una que se aplique e indique la duración de la estadía) Pabellón de oncología, sírvase especificar la duración de la estadía: ________________ días Pabellón médico general y quirúrgico. Sírvase indicar la duración de la estadía: ____________ días Otro, sírvase indicar: ______________________________: ________________ días Las mujeres en el estadio 1a a 2a del cáncer cervicouterino no son hospitalizadas. 51. ¿Quién atiende por lo general a las mujeres en el estadio 2b a 3b del cáncer cervicouterino en el entorno ambulatorio? (Sírvase marcar cada una que se aplique e indique el número de consultas ambulatorias correspondientes) Oncólogo experto en ginecología. Sírvase indicar el número de consultas: ____________ consultas Oncólogo médico. Sírvase indicar el número de consultas: ________________ consultas Oncólogo experto en radiación médica. Sírvase indicar el número de consultas: ________ consultas Otro, sírvase indicar: ______________________: ________________ consultas Las mujeres con el estadio 2b a 3b del cáncer cervicouterino no son atendidas en el entorno ambulatorio. 52. ¿Donde se hospitaliza por lo general a las mujeres que padecen cáncer cervicouterino en el estadio 2b a 3b? (sírvase marcar cada una que se aplique e indique la duración de la estadía correspondiente) Pabellón de oncología, sírvase especificar la duración de la estadía: ________________ días 190 Pabellón médico general y quirúrgico, sírvase indicar la duración de la estadía: ____________ días Otro, sírvase indicar: ______________________________: ________________ días Las mujeres en el estadio 2b a 3b del cáncer cervicouterino no son hospitalizadas. 53. ¿Quién atiende por lo general a las mujeres en el estadio 4a a 4b del cáncer cervicouterino en el entorno ambulatorio? (Sírvase marcar cada una que se aplique e indique el número de consultas ambulatorias correspondientes.) Oncólogo experto en ginecología. Sírvase indicar el número de consultas: ____________ consultas Oncólogo médico. Sírvase indicar el número de consultas: ________________ consultas Oncólogo experto en radiación médica. Sírvase indicar el número de consultas: ________ consultas Otro, sírvase indicar: ______________________: ________________ consultas Las mujeres en el estadio 4a-b del cáncer cervicouterino no son atendidas en el entorno ambulatorio. 54. ¿Donde se hospitaliza por lo general a las mujeres que padecen cáncer cervicouterino en el estadio 4a-b? (Sírvase marcar cada una que se aplique e indique la duración de la estadía correspondiente.) Pabellón de oncología. Sírvase especificar la duración de la estadía: ________________ días Pabellón médico general y quirúrgico. Sírvase indicar la duración de la estadía: ____________ días Otro, sírvase indicar: ______________________________: ________________ días Las mujeres en el estadio 4a-b del cáncer cervicouterino no son hospitalizadas. 55. ¿Se trata a las mujeres que padecen cáncer cervicouterino con quimioterapia? SÍ / NO (sírvase marcar uno) 56. ¿Cuándo reciben quimioterapia por lo general las mujeres que padecen cáncer cervicouterino? (Sírvase indicar) Estadio 1a-2a Estadio 2b-3b Estadio 4a-b Las mujeres que padecen cáncer cervicouterino no son tratadas con quimioterapia. 57. ¿Dónde se administra por lo general la quimioterapia en mujeres que padecen cáncer cervicouterino? (Sírvase indicar) Hospital de primer nivel Hospital de nivel secundario Hospital de nivel terciario Hospital de oncología Otro, sírvase indicar: ___________________ Las mujeres que padecen cáncer cervicouterino no son tratadas con quimioterapia. 58. ¿Se trata a las mujeres que padecen cáncer cervicouterino con una histerectomía simple? SÍ / NO (sírvase marcar uno) 59. ¿Cuándo por lo general se trata a las mujeres que padecen cáncer cervicouterino con una histerectomía simple? (Sírvase indicar) Estadio 1a-2a Estadio 2b-3b 191 Estadio 4a-b Las mujeres que padecen cáncer cervicouterino no son tratadas con una histerectomía simple. 60. ¿Dónde suele realizarse por lo general una histerectomía simple? (sírvase indicar) Hospital de primer nivel Hospital de nivel secundario Hospital de nivel terciario Hospital de oncología Otro, sírvase indicar: ___________________ Las mujeres que padecen cáncer cervicouterino no son tratadas con una histerectomía simple. 61. ¿Se trata a las mujeres que padecen cáncer cervicouterino con una histerectomía radical? SÍ / NO (Sírvase marcar uno) 62. ¿Cuándo por lo general se trata a las mujeres que padecen cáncer cervicouterino con una histerectomía radical? (Sírvase indicar) Estadio 2b-3b Estadio 4a-b Las mujeres que padecen cáncer cervicouterino no son tratadas con una histerectomía radical. 63. ¿Dónde suele realizarse por lo general una histerectomía radical? (sírvase indicar) Hospital de primer nivel Hospital de nivel secundario Hospital de nivel terciario Hospital de oncología Otro, sírvase indicar: ___________________ Las mujeres que padecen cáncer cervicouterino no son tratadas con una histerectomía simple. 192 64. Piense en los tipos de fármacos que usted suministra por lo general en este establecimiento (como quimioterapia) para el cáncer cervicouterino por estadio. Al responder a la pregunta, sírvase tener en cuenta el abastecimiento usual de fármacos y responda a las preguntas en el cuadro a continuación. Sólo declare varios fármacos si más de uno sería suministrado por lo general al mismo tiempo. ¿Cuántas ¿Qué fármacos ¿Qué vía? ¿Dosis ¿Durante veces por suministraría por lo (IV, IM, por kg? cuántos días día general en este oral) la recetaría? (mg / recomendarí establecimiento ml) a que se para esta afección? tome? 1a-2ª 2b-3b 4a-b 65. Piense en la radioterapia (XRT) que por lo general reciben las mujeres que padecen cáncer cervicouterino por estadio en este establecimiento. Sírvase responder a las preguntas en el cuadro a continuación por estadio. ¿Intervalo de ¿Tipo de XRT ¿Unidades de ¿Número de CXRT? (¿cada recibida por XRT? (Rads, XRT? cuanto estadio del Centigreys) tiempo? cáncer cervicouterino? 1a-2ª 2b-3b 4a-b 66. Piense sobre los tipos de procedimientos e intervenciones que por lo general realiza para el cáncer cervicouterino por estadio. Cuando responda a la pregunta, tenga en cuenta el tipo de procedimiento y la intervención realizada por estadio, el número de procedimientos realizados por estadio y el lugar en que se realizaron estos procedimientos. 193 ¿Tipo de procedimiento o intervención realizada? ¿Número medio de procedimientos e intervenciones realizadas? ¿Lugar donde se realizaron los procedimientos y las intervenciones? 1a-2ª 2b-3b 4a-b 194 Appendix E. Summary of screening strategies across studied countries1 Screening Argentina2 Brazil3 Chile4 What tests 1 pap smear with 1 pap smear (100%) Pap smear (98%) are cytobrush (100%) VPH DNA test (2% performed? in the private sector) Where are 2 outpatient services 2 outpatient visits 2 outpatient visits tests visits with required with general required with general performed? gynecologist physician and/or physician, family nurse at the family planning clinic, or planning clinic, or cervical cancer cervical cancer screening outreach screening outreach clinic clinic How often If pap (-), once every If pap (-), once every If pap (-), repeat test are tests 3 years 3 years every six months for performed? If pap (+), perform pap If pap (+), perform the first year to confirm a non false-positive. every 6 months for 3 pap every 4 months years for 3 years Pap should be done every 3 years after the third PAP (-) If pap (+), repeat pap smear every 4 months At what age are tests performed? By whom are tests performed? Age ≥35 years <35 years if sexually active Gynecologist Nurse Paramedic Age ≥20 years <20 years if sexually active Gynecologist Primary care physician 25–64 years <25 years if sexually active Registered midwife (public sector) Gynecologist or Colombia5 1 pap smear (100%) Dominican Republic6 1 pap smear (100%) 1–2 outpatient visits required with general physician, family planning clinics, or cervical cancer screening outreach clinic 2 outpatient services visits If pap (-), once every 3 years Follow the 1-1-3 protocol: if PAP is (-), a second PAP should be done one year later to confirm a non false-positive. If second PAP (-), schedule PAP every three years after that 25–69 years <25 years if sexually active Gynecologist Primary care physician If Pap (-) once for the first year and after second pap (-), once every 3 years If PAP (+), repeat pap every 4–6 months, followed by a biopsy with colposcopy 35–64 years <35 years if sexually active Gynecologist Nurse Paramedic 195 Nurse Where are Pathology laboratory results analyzed/ interpreted? Pathology laboratory gynecologistoncologist or primary care physician (private sector) Pathology laboratory Nurse Pathology laboratory Pathology laboratory 1 Screening for cervical cancer is based on expert interviews and national treatment guidelines. Source: Federación Argentina de Sociedades de Ginecología y Obstetricia (FASGO) – Guía de Práctica Clínica, 2002; Subprograma Nacional de Detección Precoz de Cancer de Cuello Uterino, Ministerio de Salud 2006; expert opinion (Interview with one local oncologist). 3 Source: Condutas do Instituto Nacional de Cancer/ Ministério da Saúde, (INCA/MS), 2006; 5ª Edição – UICC, 1997; Ministério da Saúde, 1998; expert opinion (Interviews with three local oncologists). 4 Source: Ministerio de Salud. Guía Clínica Cáncer Cervicouterino. Serie guías clínicas MINSAL NºXX, 3ª edición. Santiago: Minsal, 2006; expert opinion (Interview with one expert in charge of the National Cervical Cancer Program, Cancer Unit, MINSAL). 5 Source: Instituto Nacional de Cancerología. Guías de Práctica Clínicas en Enfermedades Neoplásicas, 2ª edición. Bogotá D.C. – Colombia 2007; Servicio de Salud Colombia. Norma Técnica para la detección temprana del cáncer de cuello uterino y guía de atención de lesiones preneoplásicas de cuello uterino, Resolución Número 00412 de 2000; expert opinión (Interviews with three experts in charge of National Institute of Cancer. 6 Source: Secretaria de Estado de Salud Pública y Asistencia Social (SESPAS). Normas Nacionales para la Detección, diagnostico temprano y tratamiento de cáncer cervico uterino, 2006; expert opinion (Interview with one expert in charge of the National Cervical Cancer Program). 2 196 Appendix E. Summary of screening strategies across studied countries (continued)1 Screening Honduras7 Jamaica8 Mexico9 Peru10 What tests 1 Pap smear (100%) 1 Pap smear (95%) 1 Pap smear (95%) 1 pap smear (90%) are 1 visual inspection – VIA VPH DNA-based test (5%) VPH DNA-based test (5%) performed? (only 5%) Visual inspection – VIA (3%) Visual inspection – VILI (2%) Where are 2 outpatient visits required 2 outpatient visits 1 outpatient visits required 2 outpatient visits required tests with general physician, with general physician, with general physician, performed? family planning clinics, or family planning clinics, or family planning clinics, or cervical cancer screening cervical cancer screening cervical cancer screening outreach clinic outreach clinic) outreach clinic How often If pap (-), repeat twice for Once every year for the If PAP (-), once every 3 If PAP (-), once every 3 are tests the first year and after the first three years years years performed? first year perform once Repeat pap smear if PAP If pap (+), once every 6 every 3 years (+) for the first year, and do months Repeat once for If PAP (+), repeat pap pap every three years one year if second PAP (-), every 6 months for 3 years schedule PAP every three years thereafter At what age 30–59 years 25–54 years 25–64 years ≥20 years are tests <30 years if sexually active <25 years if sexually active <25 years if sexually <20 years if sexually active performed? active By whom Gynecologist Gynecologist Register midwife (public Gynecologist are tests sector) Nurse Primary care physician Primary care physician performed? Gynecologist or Nurse Nurse gynecologist-oncologist Where are Pathology laboratory Pathology laboratory Pathology laboratory Pathology laboratory results analyzed/ interpreted? 1 Screening for cervical cancer is based on expert interviews and national treatment guidelines. 197 7 Source: Guidelines for the management of cervical cancer, Ministry of Health, 2004; expert opinion (Interview with one local primary care physician). Source: Expert opinion (Interview with one local OBGYN physician). Source: National Comprehensive Cancer Network (NCCN), Guías de Práctica Oncológica – v.1 2005; Modificación a la Norma Oficial Mexicana NOM-014-SSA2-1994, Para la Prevención, Detección, diagnóstico, tratamiento, control y vigilancia epidemiológica del cáncer cérvico uterino; expert opinion (Interview with one local primary care physician). 10 Source: Tobar A. Costo y desempeño de las pruebas de tamizaje costos del tratamiento del cancer cervicouterino en la región de San Martín (Perú), OPS/DPC/NC, 2005; expert opinion (Interview with one local OBGYN physician). 8 9 198 Appendix F. Summary of treatment of precancerous lesions across studied countries1 Argentina2 Brazil3 Chile4 Diagnosis - CIN 1 What 1 colposcopy + 2 colposcopy with 2 colposcopy with tests/procedures biopsy biopsy (acetic acid biopsy are performed? VIA) 1 endocervical 1 cryotherapy curettage 1 LEEP 1 LEEP 1 LEEP Lab tests (see Lab tests (see spreadsheet for 1 cryotherapy spreadsheet for details) details) Lab tests (see Follow-up: Follow-up: spreadsheet for Specialist details) Specialist consultation (2); Follow-up: consultation (3); nurse visit (1); nurse visit (1); Specialist colposcopy (2); colposcopy (2); consultation (4); biopsy (1); pap biopsy (2); pap smear colposcopy (2); smear (1) for the (2) for the first year. biopsy (1); pap first year. smear (1) for the first year. Colombia5 Dominican Republic6 2 colposcopy and biopsy 1 cryotherapy 1 LEEP 1 cold knife conization Lab tests (see spreadsheet for details) Follow-up: Specialist consultation (2); nurse visit (1); colposcopy (2); biopsy (1); pap smear (1) for the first year. What % receive interventions? Colposcopy with biopsy: 65% Endocervical curettage: 20% LEEP: 10% Cryotherapy: 5% 1 colposcopy with biopsy: 93% 1 LEEP: 7% Colposcopy and biopsy: 70% Cryotherapy: 10% LEEP: 20% Colposcopy and biopsy: 75% Cryotherapy: 10% LEEP: 5% Cold knife conization: 10% 2 colposcopy and biopsy Endocervical curettage Cryotherapy LEEP Lab tests (see spreadsheet for details) Follow-up: Specialist consultation (2); nurse visit (1); colposcopy (2); biopsy (1); pap smear (1) for the first year. Colposcopy and biopsy: 68% Endocervical curettage: 2% Cryotherapy: 10% LEEP: 20% What % are treated as outpatients? Endocervical curettage: 100% (1 visit) Colposcopy with biopsy: 100% (2+ visits) Colposcopy and biopsy: 100% (up to 3 visits) Colposcopy and biopsy: 100% (up to 2 visits) Colposcopy and biopsy: 100% (2+ visits) 199 (specify # visits) Argentina2 Colposcopy with biopsy: 100% (1 visit) Brazil3 Chile4 Cryotherapy: 10% (up to 3 visits) LEEP: 98% (up to 3 visits) What % are treated in hospital? (specify # days) LEEP: 100% (1 day) Cryotherapy (100%) (1 day) LEEP: 100% (2 days) Cryotherapy: 90% (2 days) LEEP: 8% (2 days) What % have minor complications? None LEEP: 1% Cryotherapy: 10% LEEP: 10% Infection (20%) None Cryotherapy: <10% LEEP: 10% What % have major complications? Colombia5 Cryotherapy: 10% (1 visit) LEEP: 10% (1 visit) Cold knife conization: 60% (1 visit) Cryotherapy: 90% (1 day) LEEP: 90% (1 day) Cold knife conization: 40% (1 day) Cryotherapy: <5% LEEP: <5% Dominican Republic6 Endocervical curettage: 100% (1 visit) None None Cryotherapy: 100% (1 day) LEEP: 100 (1 day) None 200 Appendix F. Summary of treatment of precancerous lesions across studied countries (continued)1 Management of complications – CIN 1 What treatment None is used for minor complication? What treatment Hospitalization (20%, is used for major 2 days) complication? Diagnosis - CIN 2 What 1 endocervical tests/procedures curettage are performed? 1 LEEP 1 cold knife conization 1 simple hysterectomy Lab tests (see spreadsheet for details) Follow-up: Specialist consultation (4); nurse visit (2); colposcopy (2); biopsy (1); pap smear (1) for the first year. What % receive LEEP: 60% interventions? Cold knife conization Surgical intervention and sutures (no hospital care required) None Surgical intervention and sutures Intravenous antibiotic Blood transfusion Intravenous antibiotic Blood transfusion Intravenous antibiotic Blood transfusion None Intravenous antibiotic Blood transfusion None 1 colposcopy with biopsy 1 LEEP 1 simple hysterectomy Lab tests (see spreadsheet for details) Follow-up: Specialist consultation (2); nurse visit (1); colposcopy (2); biopsy (1); pap smear (1) for the first year. 1 cryotherapy 1 LEEP 1 Cold knife conization 1 simple hysterectomy Lab tests (see spreadsheet for details) Follow-up: Specialist consultation (3); nurse visit (1); colposcopy (2); biopsy (2); pap smear (2) for the first year. 1 colposcopy with biopsy 1 cryotherapy 1 LEEP 1 cold knife conization Lab tests (see spreadsheet for details) Follow-up: Specialist consultation (3); nurse visit (1); colposcopy (2); biopsy (2); pap smear (2) for the first year. 1 LEEP 1 simple hysterectomy Lab tests (see spreadsheet for details) Follow-up: Specialist consultation (2); colposcopy (2); biopsy (2); pap smear (2) for the first year. LEEP: 95% Simple Cryotherapy: 1% LEEP: 90% Cryotherapy: 5% LEEP: 90% LEEP: 96% Simple 201 (40%) Simple hysterectomy: 7% hysterectomy: 5% What % are treated as outpatients? (specify # visits) What % are treated in hospital? (specify # days) None None What % have minor complications? None LEEP: 2% Simple hysterectomy: 3% What % have major complications? None Simple hysterectomy: 1% LEEP: 100% (1 day) LEEP: 100% (2 days) Simple hysterectomy: 100% (1 day) Simple hysterectomy: 100% Cold knife conization: (2 days) 100% (1 day) Cold knife conization: 2% Simple hysterectomy: 7% LEEP: 99% (1 visit) Cold knife conization: 5% Cryotherapy: 100% (1 day) LEEP: 1% (1 day) Cold knife conization: 100% (2 days) Simple hysterectomy: 7% (5 days) Cold knife conization: 3–4% Simple hysterectomy:10% Cold knife conization: 3–1–2% Simple hysterectomy:10% Cryotherapy: 100% (1 LEEP: 100% (2 day) days) LEEP: 90% (≤2.25 Simple days) hysterectomy: 100% (2 days) Cold knife conization: 100% (2 days) LEEP: 10% (1 visit) hysterectomy: 4% None LEEP: <10% LEEP: 1% Simple hysterectomy: 3% None Simple hysterectomy: 1% 202 Appendix F. Summary of treatment of precancerous lesions across studied countries (continued)1 Management of complications – CIN 2 What None treatment is used for minor complication? What None treatment is used for major complication? Surgical intervention and sutures Intravenous antibiotic Surgical intervention and sutures Intravenous antibiotic Blood transfusion Intravenous antibiotic Blood transfusion Intravenous antibiotic Surgical intervention and sutures Intravenous antibiotic Surgical intervention and sutures Intravenous antibiotic Blood transfusion Intravenous antibiotic Blood transfusion Intravenous antibiotic 1 Diagnosis and management of pre cervical cancer is based on expert interviews and national treatment guidelines. Source: Federación Argentina de Sociedades de Ginecología y Obstetricia (FASGO) – Guía de Práctica Clínica, 2002; Subprograma Nacional de Detección Precoz de Cancer de Cuello Uterino, Ministerio de Salud 2006; expert opinion (Interview with 1 local oncologist). 3 Source: Condutas do Instituto Nacional de Cancer/ Ministério da Saúde, (INCA/MS), 2006; 5ª Edição – UICC, 1997; Ministério da Saúde, 1998; expert opinion (Interviews with three local oncologists). 4 Source: Ministerio de Salud. Guía Clínica Cáncer Cervicouterino. Serie guías clínicas MINSAL NºXX, 3ª edición. Santiago: Minsal, 2006; expert opinion (Interview with 1 expert in charge of the National Cervical Cancer Program, Cancer Unit, MINSAL). 5 Source: Instituto Nacional de Cancerología. Guías de Práctica Clínicas en Enfermedades Neoplásicas, 2ª edición. Bogotá D.C. – Colombia 2007; Servicio de Salud Colombia. Norma Técnica para la detección temprana del cáncer de cuello uterino y guía de atención de lesiones preneoplásicas de cuello uterino, Resolución Número 00412 de 2000; expert opinion (Interviews with three local oncologists). 6 Source: Secretaria de Estado de Salud Pública y Asistencia Social (SESPAS). Normas Nacionales para la Detección, diagnostico temprano y tratamiento de cáncer cervico uterino, 2006; expert opinion (Interview with one expert in charge of the National Cervical Cancer Program). 2 203 Appendix F. Summary of treatment of precancerous lesions across studied countries (continued)1 Honduras7 Diagnosis - CIN 1 What 2 colposcopy + biopsy tests/procedures Lab tests (see are performed? spreadsheet for details) Follow-up: Specialist consultation (4); nurse visit (1); colposcopy (2); biopsy (2); pap smear (2) for the first year. Jamaica8 Mexico9 Peru10 2 colposcopy + biopsy 1 LEEP Lab tests (see spreadsheet for details) Follow-up: Specialist consultation (2); nurse visit (1); colposcopy (2); biopsy (2); pap smear (2) for the first year. 2 colposcopy + biopsy 1 cryotherapy 1 LEEP Lab tests (see spreadsheet for details) Follow-up: Specialist consultation (4); colposcopy (2); biopsy (2); pap smear (2) for the first year. Colposcopy and biopsy: 70% Cryotherapy: 10% LEEP: 20% Colposcopy and biopsy: 100% (2 visits) Cryotherapy: 10% (2 visits) LEEP: 98% (2 visits) Cryotherapy: 90% (1 day) LEEP: 2% (1 day) 2 colposcopy and biopsy 1 cryotherapy 1 LEEP Lab tests (see spreadsheet for details) Follow-up: Specialist consultation (4); nurse (1); colposcopy (4); biopsy (4); pap smear (2) for the first year. Colposcopy and biopsy: 80% Cryotherapy: 10% LEEP: 10% Colposcopy and biopsy: 100% (1 visit) Cryotherapy: 10% (1 visit) LEEP: 10% (1 visit) Cryotherapy: 10% LEEP: 10% Cryotherapy:<10% LEEP: 1% What % receive interventions? Coloscopy + biopsy: 100% LEEP: 5% Colposcopy + biopsy: 95% What % are treated as outpatients? (specify # visits) Coloscopy + biopsy: 100% (1 visit) Coloscopy + biopsy: 95% (1 visit) What % are treated in hospital? (specify # days) What % have minor complications? None LEEP: 100% (2 days) VIA with colposcopy: 5% (1 day) None LEEP: 1% Cryotherapy: 90% (1 day) LEEP: 90% (1 day) 204 Honduras7 What % have major complications? None Management of complications - CIN 1 What treatment None is used for minor complication? Treatment for major complication? None Jamaica8 None Surgical intervention and sutures (no hospital care required) None Mexico9 Cryotherapy: <1% LEEP: 1–2% Surgical intervention and sutures Intravenous antibiotic Blood transfusion Surgical intervention and sutures Intravenous antibiotic Blood transfusion Peru10 None Intravenous antibiotic Surgical intervention and sutures Intravenous antibiotic Surgical intervention and sutures 205 Appendix F. Summary of treatment of precancerous lesions across studied countries (continued)1 Diagnosis - CIN 2 What 1 LEEP tests/procedures 1 simple hysterectomy are performed? Lab tests (see spreadsheet for details) Follow-up: Specialist consultation (4); colposcopy (2); biopsy (2); pap smear (2) for the first year. 1 LEEP 1 simple hysterectomy Lab tests (see spreadsheet for details) Follow-up: Specialist consultation (4); colposcopy (2); biopsy (2); pap smear (2) for the first year. What % receive interventions? LEEP: 96% Simple hysterectomy: 4% LEEP: 95% Simple hysterectomy: 5% What % are treated as outpatients? (specify # visits) What % are treated in hospital? (specify # days) None None LEEP: 100% (≤3 days) Simple hysterectomy: 100% (≤3 days) LEEP: 100% (≤4 days) Simple hysterectomy: 100% (≤4 days) What % have minor complications? LEEP: 1% Simple hysterectomy: 3% LEEP: 2% Simple hysterectomy: 3% 1 cryotherapy 1 LEEP 1 cold knife conization 1 simple hysterectomy Lab tests (see spreadsheet for details) Follow-up: Specialist consultation (4); colposcopy (2); biopsy (2); pap smear (2) for the first year. Cryotherapy: 1% LEEP: 90% Cold knife conization: 2% Simple hysterectomy: 7% LEEP: 99% (1 visit) 1 cryotherapy 1 LEEP 1 cold knife conization 1 simple hysterectomy Lab tests (see spreadsheet for details) Follow-up: Specialist consultation (5); colposcopy (4); biopsy (4); pap smear (4) for the first year. Cryotherapy: 5% LEEP: 80% Cold knife conization: 5% Simple hysterectomy: 10% LEEP: 10% (1 visit) Cryotherapy: 100% (1 day) LEEP: 1% (1 day) Cold knife conization: 100% (1 day) Simple hysterectomy: 100% (3 days) Cold knife conization: 10% Simple hysterectomy: 10% Cryotherapy: 100% (1 day) LEEP: 90% (1 day) Cold knife conization: 100% (up to 2.25 days) Simple hysterectomy: 7% (up to 2.25 days) LEEP: 1% Simple hysterectomy: 10% 206 What % have major complications? Management of complications - CIN 2 What Intravenous antibiotic treatmentis used for minor complication? What treatment Intravenous antibiotic is used for major complication? Simple hysterectomy: 1% Cold knife conization: 1% Simple hysterectomy: 1% Simple hysterectomy: 1% Surgical intervention and sutures Intravenous antibiotic Surgical intervention and sutures Intravenous antibiotic Blood transfusion Surgical intervention and sutures Intravenous antibiotic Blood transfusion Intravenous antibiotic Surgical intervention and sutures Surgical intervention and sutures Intravenous antibiotic Intravenous antibiotic Surgical intervention and sutures 1 Diagnosis and management of pre cervical cancer is based on expert interviews and national treatment guidelines. Source: Guidelines for the management of cervical cancer, Ministry of Health, 2004; expert opinion (Interview with one local primary care physician). Source: Expert opinion (interview with a local OBGYN physician). 9 Source: National Comprehensive Cancer Network (NCCN), Guías de Práctica Oncológica – v.1 2005; Modificación a la Norma Oficial Mexicana NOM-014-SSA2-1994, Para la Prevención, Detección, diagnóstico, tratamiento, control y vigilancia epidemiológica del cáncer cérvico uterino; expert opinion (Interview with one local primary care physician). 10 Source: Tobar A. Costo y desempeño de las pruebas de tamizaje costos del tratamiento del cancer cervicouterino en la region de San Martín (Perú), OPS/DPC/NC, 2005; expert opinion (Interview with one local OBGYN physician). 7 8 207 Appendix G. Diagnostic and staging procedures and treatment modalities of invasive cervical cancer by stage across studied countries1 Argentina2 Brazil3 Chile4 Colombia5 Dominican Republic6 Diagnostic & staging for all stages7 Diagnostic & staging: Diagnostic & staging: Diagnostic & staging: Diagnostic & staging: Diagnostic & staging: Vaginal and rectal Vaginal and rectal Vaginal and rectal Vaginal and rectal 1 vaginal and rectal examination (1) examination (2) examination (2) examination (2) examination (2) Pelvic/abdominal CT Colposcopy + biopsy Colposcopy + biopsy Colposcopy + biopsy Colposcopy + biopsy or urogram, IV (2) (1) (1) (1) pyelogram (1) Chest x-ray (1) IV pyelogram (up to 2) IV pyelogram (2) Abdominal US (2) Uretrocistofibroscopy Pelvic/abdominal CT Abdominal US (up to 2) Abdominal US (2) 1 chest x-ray (1) (1) Cystoscopy/rectoscopy Chest x-ray (1) Pelvis MRI (1) Rectosigmoidoscopy Pelvis MRI (1) (1) Lab tests (see Rectosigmoidoscopy (1) Abdominal ultrasound Chest x-ray (1) spreadsheet for details (1) Chest x-ray (1) (2) Lab tests (see Specialist consultation Lab tests (see Lab tests (see Cystoscopy (1) spreadsheet for (4) spreadsheet for spreadsheet for details) details) Lab tests (see details) spreadsheet for Specialist consultation Specialist consultation Specialist consultation details) (4) (2) (3) Specialist consultation (4) Treatment by stage IA1 Treatment: Treatment: Treatment: Treatment: Treatment: 1 cold knife conization 1 cold knife conization 1 abdominal 1 cold knife conization 1 cold knife conization for continued fertility for continued fertility hysterectomy (Class I for continued fertility for continued fertility Rudledge) 8 1 simple abdominal 1 abdominal Simple hysterectomy8 1 simple abdominal hysterectomy8 hysterectomy (Class I 1 cold knife conization (abdominal/ hysterectomy8 8 (extrafascial) Rudledge) for continued fertility laparoscopy) (extrafascial) 9 9 9 Medication for Brachytherapy Brachytherapy Brachytherapy (4 Palliative care (see symptom control (see (700cGy 4 week (700cGy 4 week week course) in high spreadsheet) 208 Argentina2 spreadsheet) IA2 Treatment: 1 Wertheim hysterectomy8, Piver III or Schauta with pelvic lymphadenectomy (complete colpoanexohysterectomy) 1 external pelvic brachytherapy9 + teletherapy If tumor is 2cm, 1 complete colpoanexohysterectomy abdominal type Piver II (Massi class II) Palliative care (see spreadsheet) Brazil3 course) Palliative care (see spreadsheet) Treatment: 1 abdominal hysterectomy8 Class II Rudledge + intraoperative selective pelvic lymph node biopsy Pelvic radiotherapy (5 week course) (distant) (5,000cGy 25 fractions followed by brachy-therapy9) Chemotherapy EV 50 mg for 5 days Palliative care (see spreadsheet) Chile4 course) Palliative care (see spreadsheet) Treatment: 1 radical hysterectomy8 (Class II Rudledge) with lymphoadenectomy Brachytherapy9 (700cGy 4 week course) Palliative care (see spreadsheet) Colombia5 risk surgical patients Palliative care (see spreadsheet) Treatment: 1 radical hysterectomy + pelvic lymphadenectomy8 Teletherapy + brachytherapy9 in high risk surgical patients 1 radical hysterectomy (modified) + pelvic lymphadenectomy with vascular spaces or lymph node involvement Palliative care (see spreadsheet) Dominican Republic6 Treatment: 1 Wertheim hysterectomy8, Piver III or Schauta with pelvic lymphadenectomy (complete colpoanexohysterectomy External pelvic brachytherapy9 + radiotherapy If tumor is 2cm, complete colpoanexohysterectomy abdominal type Piver II (Massi class II) Palliative care (see spreadsheet) 209 Appendix G. Diagnostic and staging procedures and treatment modalities of invasive cervical cancer by stage across studied countries (continued)1 IB1 IB2 Treatment: 1 Wertheim hysterectomy8, Piver III or Schauta with pelvic lymphadenectomy (complete colpoanexohysterectomy External pelvic brachytherapy9 + teletherapy Surgery, medicine for symptom control (see spreadsheet) If tumor is 2cm, complete colpoanexohysterecto my abdominal type Piver II (Massi class II) Treatment: Radical hysterectomy Chemoradiotherapy (platinum 5 cycles) Teletherapy (pelvis) + brachytherapy9 Surgery, medicine for symptom control If tumor persists, 1 anexohysterectomy (extrafascial) Treatment: 1 radical abdominal hysterectomy8 class III Rudledge Radical Pelvic lymphadenectomy or nodal dissection Pelvic radiotherapy (distant) (5,000cGy 25 fractions followed by brachytherapy9) Chemotherapy EV 50 mg for 5 days Palliative care (see spreadsheet) Treatment: 1 radical hysterectomy8 (Class II + III Rudledge) with lymphoadenectomy Pelvic (external and intra cavity) radiotherapy (distant) (5,000cGy 25 fractions Palliative care (see spreadsheet) Treatment: Treatment: 1 radical 1 Wertheim hysterectomy8 + pelvic hysterectomy8, Piver III lymphadenectomy + or Schauta with pelvic paraaortic biopsy + lymphadenectomy oophorepexia in (complete colpoanexowomen 40–45 years. hysterectomy In women >45 years External pelvic bilateral oophorexia brachytherapy9 + External radiotherapy teletherapy + brachytherapy9 in If tumor is 2cm, high risk surgical complete patients colpoanexohysterecto Palliative care (see my abdominal type spreadsheet) Piver II (Massi class II) Palliative care (see spreadsheet) Treatment: 1 radical abdominal hysterectomy8 class III Rudledge + lymphadenectomy Pelvic radiotherapy (distant) (5,000cGy 25 fractions followed by brachytherapy9) Chemotherapy EV 50 mg for 5 days Treatment: Chemotherapy (cisplatin 5 cycles) Pelvic (external and intra cavity) radiotherapy (distant) (5,000cGy 25 fractions Brachytherapy9 (700cGy 4 weeks) Palliative care (see Treatment: 1 radical hysterectomy8 + pelvic lymphadenectomy + paraaortic biopsy + oophorepexia in women 40–45 years. In women >45 years bilateral oophorexia External radiotherapy + brachytherapy9 in Treatment: Chemoradiotherapy (platinum 5 cycles) Teletherapy (pelvis) + brachytherapy9 If tumor persists, 1 anexohysterectomy (extrafascial) Palliative care (see spreadsheet) 210 Palliative care (see spreadsheet) Palliative care (see spreadsheet) spreadsheet) high risk surgical patients Chemotherapy (cisplatin 40mg/m2 6 cycles) + radiotherapy (teletherapy + brachytherapy9) Palliative care (see spreadsheet) 211 Appendix G. Diagnostic and staging procedures and treatment modalities of invasive cervical cancer by stage across studied countries (continued)1 IIA Treatment Radical hysterectomy Chemoradiotherapy (platinum 5 cycles) Teletherapy (pelvis) + brachytherapy9 Surgery, medicine for symptom control If tumor is 2cm, 1 complete colpoanexohysterectomy8 abdominal type Piver II (Massi class II) If tumor persists, 1 anexohysterectomy (extrafascial) Palliative care (see spreadsheet) Treatment: 1 radical abdominal hysterectomy8 class III Rudledge + lymphadenectomy Pelvic radiotherapy (distant) (5,000cGy 25 fractions followed by brachytherapy9) Chemotherapy EV 50 mg for 5 days Palliative care (see spreadsheet) Treatment: Chemotherapy (cisplatin 5 cycles) Pelvic (external) radiotherapy (5,000cGy 25 fractions Brachytherapy9 (700cGy 4 weeks) 1 radical hysterectomy8 (Class III Rudledge) with lymphoadenectomy Palliative care (see spreadsheet) IIB Treatment Chemoradiotherapy (platinum 5 cycles) Teletherapy (pelvis) + brachytherapy9 Surgery, medicine for symptom control Lumboaortic irradiation If recurrent w/ prior radiotherapy, 1 Treatment: Pelvic radiotherapy (distant) (5,000cGy 25 fractions followed by brachytherapy9) Chemotherapy EV 50 mg for 5 days Palliative care (see spreadsheet) Treatment: Chemotherapy (cisplatin 5 cycles) Pelvic (external) radiotherapy (5,000cGy 25 fractions Brachytherapy9 (700cGy 4 weeks) Evaluation of Treatment: 1 radical hysterectomy8 + pelvic lymphadenectomy + paraaortic biopsy + oophorepexia in women 40–45 years. In women > 45 years bilateral oophorexia External radiotherapy + brachytherapy9 in high risk surgical patients Chemotherapy (cisplatin 40mg/m2 6 cycles) + radiotherapy (teletherapy + brachytherapy9) Palliative care (see spreadsheet) Treatment: 1 radical hysterectomy8 + pelvic lymphadenectomy + paraaortic biopsy + oophorepexia in women 40–45 years. In women > 45 years bilateral oophorexia External radiotherapy + Treatment Chemoradiotherapy (platinum 5 cycles) Teletherapy (pelvis) + brachytherapy9 If tumor is 2cm, 1 complete colpoanexohysterectomy8 abdominal type Piver II (Massi class II) If tumor persists, 1 anexohysterectomy (extrafascial) Palliative care (see spreadsheet) Treatment Chemoradiotherapy (platinum 5 cycles) Teletherapy (pelvis) + brachytherapy Lumboaortic irradiation If recurrent w/ prior radiotherapy, 1 translaparoscopy/retroperitonea 212 translaparoscopy/retroperitonea l minilaparatomy; if lymph peritoneal involvement – palliative care (see spreadsheet) IIIA–IIIB IVA Treatment Chemoradiotherapy (platinum 5 cycles) Teletherapy (pelvis) + brachytherapy9 Surgery, medicine for symptom control Lumboaortic irradiation If recurrent w/ prior radiotherapy, 1 translaparoscopy/retroperitonea l minilaparatomy; if lymph peritoneal involvement – palliative care (see spreadsheet) Treatment Chemoradiotherapy (platinum 5 cycles) Teletherapy (pelvis) + brachytherapy9 Surgery, medicine for hysterectomy type I Palliative care (see spreadsheet) Treatment Pelvic radiotherapy (distant) (5,000cGy 25 fractions followed by brachytherapy9) Chemotherapy EV 50 mg for 5 days Palliative care (see spreadsheet) Treatment: Chemotherapy (cisplatin 5 cycles) Pelvic (external) radiotherapy (5,000cGy 25 fractions Brachytherapy9 (700cGy 4 weeks) Palliative care (see spreadsheet) Treatment Pelvic radiotherapy (distant) (5,000cGy 25 fractions followed by brachytherapy9) Palliative care (see Treatment: Chemotherapy (cisplatin 5 cycles) Pelvic (external) radiotherapy (5,000cGy 25 brachytherapy9 in high l minilaparatomy; if risk surgical patients lymph peritoneal involvement – Chemotherapy palliative care (see (cisplatin 40mg/m2 6 spreadsheet) cycles) + radiotherapy (teletherapy + brachytherapy9) Palliative care (see spreadsheet) Treatment: Treatment External radiotherapy + Chemoradiotherapy brachytherapy9 (platinum 5 cycles) Palliative care (see Teletherapy (pelvis) + spreadsheet) brachytherapy9 Lumboaortic irradiation If recurrent w/ prior radiotherapy, 1 translaparoscopy/retroperitonea l minilaparatomy8; if lymph peritoneal involvement – palliative care (see spreadsheet) Treatment: External radiotherapy + brachytherapy9 for curative and symptom control (palliative) purposes (see Treatment Chemoradiotherapy (platinum 5 cycles) Teletherapy (pelvis) + brachytherapy9 Selectron therapy 213 symptom control Lumboaortic irradiation If recurrent w/ prior radiotherapy, 1 translaparoscopy/retroperitonea l minilaparatomy8; if lymph peritoneal involvement – palliative care (see spreadsheet) Treatment Teletherapy (5-week course) Teletherapy plus HDR or selectron plus chemotherapy plus palliative care (see spreadsheet) spreadsheet) IVB Follow-up by stage10 IA1 Follow-up: 4 ambulatory visits, 2 pap smears, 1 vaginal/rectal examination for the first year IA2 Follow-up: fractions Brachytherapy9 (700cGy 4 weeks) Palliative care (see spreadsheet) spreadsheet) Lumboaortic irradiation If recurrent w/ prior radiotherapy, 1 translaparoscopy/retroperitonea l minilaparatomy8; if lymph peritoneal involvement – palliative care (see spreadsheet) Treatment: Pelvic irradiation (teletherapy + brachytherapy)plus concurrent chemotherapy Palliative care (see spreadsheet) Treatment: Chemotherapy (cisplatin 5 cycles) Pelvic (external) radiotherapy (5,000cGy 25 fractions Brachytherapy9 (700cGy 4 weeks) Palliative radiotherapy Other palliative care (see spreadsheet) Treatment: Palliative chemotherapy Chemoradiotherapy Other palliative care (see spreadsheet) Treatment Teletherapy (5-week course) Teletherapy plus HDR or selectron plus chemotherapy plus palliative care (see spreadsheet) Follow-up: 6 ambulatory visits, 2 pap smears, 2 vaginal/rectal examination for the first year Follow-up: Follow-up: 6 ambulatory visits, 3 pap smears, 6 vaginal/rectal examination for the first year Follow-up: Follow-up: 6 ambulatory visits, 3 pap smears, 6 vaginal/rectal examination for the first year Follow-up: Follow-up: 4 ambulatory visits, 2 pap smears, 2 vaginal/rectal examination for the first year Follow-up: 214 IB1 4 ambulatory visits, 1 pap smears, 1 vaginal/rectal examination for the first year Follow-up: 4 ambulatory visits, 1 pap smears, 1 vaginal/rectal examination for the first year 6 ambulatory visits, 2 pap smears, 2 vaginal/rectal examination for the first year Follow-up: 6 ambulatory visits, 2 pap smears, 2 vaginal/rectal examination for the first year 6 ambulatory visits, 3 pap smears, 6 vaginal/rectal examination for the first year Follow-up: 6 ambulatory visits, 3 pap smears, 6 vaginal/rectal examination for the first year 6 ambulatory visits, 3 pap smears, 6 vaginal/rectal examination for the first year Follow-up: 6 ambulatory visits, 2 pap smears, 2 vaginal/rectal examination for the first year 4 ambulatory visits, 2 pap smears, 2 vaginal/rectal examination for the first year Follow-up: 4 ambulatory visits, 2 pap smears, 2 vaginal/rectal examination for the first year 215 Appendix G. Diagnostic and staging procedures and treatment modalities of invasive cervical cancer by stage across studied countries (continued)1 IB2 Follow-up: 6 ambulatory visits, 1 pap smears, 1 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 3 pap smears, 3 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 3 pap smears, 3 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 4 pap smears, 4 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 3 pap smears, 3 vaginal/rectal examination for the first year IIA Follow-up: 6 ambulatory visits, 1 pap smears, 1 vaginal/rectal examination for the first year Follow-up: 8 ambulatory visits, 2 pap smears, 2 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 2 pap smears, 2 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 2 pap smears, 2 vaginal/rectal Follow-up: 22 ambulatory visits, 3 pap smears, 3 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 4 pap smears, 4 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 4 pap smears, 4 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 6 pap smears, 12 vaginal/rectal Follow-up: 22 ambulatory visits, 3 pap smears, 3 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 3 pap smears, 3 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 3 pap smears, 3 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 6 pap smears, 12 vaginal/rectal Follow-up: 22 ambulatory visits, 3 pap smears, 3 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 3 pap smears, 6 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 3 pap smears, 3 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 6 pap smears, 12 vaginal/rectal Follow-up: 22 ambulatory visits, 3 pap smears, 3 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 3 pap smears, 3 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 3 pap smears, 3 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 6 pap smears, 6 vaginal/rectal IIB IIIA-IIIB IVA 216 IVB examinations for the first year Follow-up: 22 ambulatory visits, 2 pap smears, 2 vaginal/rectal examinations for the first year examination for the first year Follow-up: 22 ambulatory visits, 6 pap smears, 12 vaginal/rectal examination for the first year examination for the first year Follow-up: 22 ambulatory visits, 6 pap smears, 12 vaginal/rectal examination for the first year examination for the first year Follow-up: 22 ambulatory visits, 6 pap smears, 12 vaginal/rectal examination for the first year examination for the first year Follow-up: 22 ambulatory visits, 6 pap smears, 6 vaginal/rectal examination for the first year 1 Management of invasive cervical cancer is based on expert interviews and national treatment guidelines. Source: Federación Argentina de Sociedades de Ginecología y Obstetricia (FASGO) – Guía de Práctica Clínica, 2002; Subprograma Nacional de Detección Precoz de Cancer de Cuello Uterino, Ministerio de Salud 2006; expert opinion (Interview with one local oncologist). 3 Source: Condutas do Instituto Nacional de Cancer/ Ministério da Saúde, (INCA/MS), 2006; 5ª Edição – UICC, 1997; Ministério da Saúde, 1998; expert opinion (Interviews with three local oncologists). 4 Source: Ministerio de Salud. Guía Clínica Cáncer Cervicouterino. Serie guías clínicas MINSAL NºXX, 3ª edición. Santiago: Minsal, 2006; expert opinion (1 interview with the person in charge of the National Cervical Cancer Program, Cancer Unit, MINSAL). 5 Source: Instituto Nacional de Cancerología. Guías de Práctica Clínicas en Enfermedades Neoplásicas, 2ª edición. Bogotá D.C. – Colombia 2007; Servicio de Salud Colombia. Norma Técnica para la detección temprana del cáncer de cuello uterino y guía de atención de lesiones preneoplásicas de cuello uterino, Resolución Número 00412 de 2000; expert opinión (Interviews with three local oncologists). 6 Source: Secretaria de Estado de Salud Pública y Asistencia Social (SESPAS). Normas Nacionales para la Detección, diagnostico temprano y tratamiento de cáncer cervico uterino, 2006; expert opinion (one interview with the person in charge of the National Cervical Cancer Program). 7 Some assumptions made for the diagnostics and staging of invasive cervical cancer are conservative. For example, the frequency (how often they are performed) of laboratory tests (urea, hemogram, etc.) and radiography/radiology (x-ray, CT, etc.) were assumed to be the same for each country, based on expert opinion and treatment guidelines. 8 For surgical procedures, we assumed the same length of stay in the hospital (7–10 days), based on WHO guidelines (2006). 9 For brachytherapy, we assumed the same length of stay in the hospital (2 days) and the same number of outpatient visits (one lasting one hour). These assumptions were based on an average estimate (WHO guidelines, 2006). For teletherapy and chemotherapy, we assumed the same number of outpatient visits (one outpatient visit). 10 Patient follow-up was generally assumed to be for the first year. 2 217 Appendix G. Diagnostic and staging procedures and treatment modalities of invasive cervical cancer by stage across studied countries (continued)1 Honduras11 Diagnostic & staging for all stages7 Diagnostic & staging: Vaginal and rectal examination (1) Colposcopy + biopsy (1) Cystoscopy (1) Proctoscopy (1) Chest x-ray (1) Pelvis MRI (1) Rectosigmoidoscopy (1) Lab tests (see spreadsheet for details) Specialist consultation (2) Treatment by stage IA1 Treatment: 1 cold knife conization for continued fertility 1 simple abdominal hysterectomy8 (extrafascial) Palliative care (see spreadsheet) Jamaica12 Mexico13 Peru14 Diagnostic & staging: Vaginal and rectal examination (1) Colposcopy + biopsy (1) 1 Abdominal ultrasound (2) Cystoscopy (1) Proctoscopy (1) Chest x-ray (1) Pelvic MRI (1) Rectosygmoidoscopy (1) Lab tests (see spreadsheet for details) Specialist consultation (2) Diagnostic & staging: Vaginal and rectal examination (2) Colposcopy + biopsy (1) Abdominal US (2) Cystoscopy (1) Proctoscopy (1) Cone biopsy (1) Chest x-ray (1) Pelvis MRI (1) Rectosigmoidoscopy (1) Lab tests (see spreadsheet for details) Specialist consultation (4) Diagnostic & staging: Vaginal and rectal examination (2) Colposcopy + biopsy (2) Abdominal US (2) Cystoscopy (1) Proctoscopy (1) Cone biopsy (1) Chest x-ray (1) Pelvis MRI (1) Lab tests (see spreadsheet for details) Specialist consultation (4) Treatment: 1 cold knife conization for continued fertility 1 radical hysterectomy 8 Teletherapy and brachytherapy9 (Cobalt 60/cesium 5 days for 5 weeks) Chemotherapy (cisplatin or carboplatin, every 3 weeks, 6 cycles) Treatment: 1 simple abdominal hysterectomy8 (extrafascial) 1 cold knife conization for continued fertility Palliative care (see spreadsheet) Treatment: 1 cold knife conization for continued fertility Simple hysterectomy8 (abdominal/ laparoscopy) Palliative care (see spreadsheet) 218 Honduras11 IA2 Treatment: 1 Wertheim hysterectomy8, Piver III with pelvic lymphadenectomy External pelvic brachytherapy9 (4 week course) + teletherapy (5 week course) Palliative care (see spreadsheet) Jamaica12 Palliative care (see spreadsheet) Treatment: 1 radical hysterectomy 8 Teletherapy and brachytherapy9 (Cobalt 60/cesium 5 days for 5 weeks) Chemotherapy (cisplatin or carboplatin, every 3 weeks, 6 cycles) Palliative care (see spreadsheet) Mexico13 Treatment: 1 radical hysterectomy8 + pelvic lymphoadenectomy Brachytherapy9 + pelvic radiotherapy (75–80 Gy 4 week course) Palliative care (see spreadsheet) Peru14 Treatment: 1 radical hysterectomy + pelvic lymphadenectomy8 Teletherapy + brachytherapy9 Palliative care (see spreadsheet) 219 Appendix G. Diagnostic and staging procedures and treatment modalities of invasive cervical cancer by stage across studied countries (continued)1 IB1 Treatment: 1 Wertheim hysterectomy8, Piver III with pelvic lymphadenectomy External pelvic brachytherapy9 (4-week course) + teletherapy (5week course) Palliative care (see spreadsheet) IB2 Treatment: Chemoradiotherapy (platinum 5 cycles) Teletherapy (pelvis) + brachytherapy9 Palliative care (see spreadsheet) IIA Treatment: Chemoradiotherapy (platinum 5 cycles) Treatment: 1 radical abdominal hysterectomy8 class III Rudledge Radical Teletherapy and brachytherapy9 (Cobalt 60/cesium 5 days for 5 weeks) Chemotherapy (cisplatin or carboplatin, every 3 weeks, 6 cycles) Palliative care (see spreadsheet) Treatment: 1 radical abdominal hysterectomy8 class III Rudledge Teletherapy and brachytherapy9 (Cobalt 60/cesium 5 days for 5 weeks) Chemotherapy (cisplatin or carboplatin, every 3 weeks, 6 cycles) Palliative care (see spreadsheet) Treatment: 1 radical abdominal hysterectomy8 class III Treatment: 1 radical hysterectomy8 + pelvic lymphoadenectomy Pelvic radiotherapy + brachytherapy9 (80–85 Gy 4-week course) Palliative care (see spreadsheet) Treatment: 1 radical hysterectomy + pelvic lymphadenectomy8 Teletherapy + brachytherapy9 Palliative care (see spreadsheet) Treatment: 1 radical hysterectomy8 + pelvic lymphoadenectomy Pelvic radiotherapy + chemotherapy (cisplatin) + brachytherapy9 (85Gy) Pelvic radiotherapy + chemotherapy (cisplatin) + brachytherapy9 (75–80Gy) + adjuvant hysterectomy Palliative care (see spreadsheet) Treatment: 1 radical hysterectomy + pelvic lymphadenectomy8 Teletherapy + brachytherapy9 Palliative care (see spreadsheet) Treatment: Pelvic radiotherapy + chemotherapy (cisplatin) Treatment: 1 radical hysterectomy + pelvic lymphadenectomy8 220 Teletherapy (pelvis) + brachytherapy9 Palliative care (see spreadsheet) IIB Treatment: Chemoradiotherapy (platinum 5 cycles) Teletherapy (pelvis) + brachytherapy9 Palliative care (see spreadsheet) IIIA–IIIB Treatment: Chemoradiotherapy (platinum 5 cycles) Teletherapy (pelvis) + brachytherapy9 Palliative care (see spreadsheet) Rudledge Teletherapy and brachytherapy9 (Cobalt 60/cesium 5 days for 5 weeks) Chemotherapy (cisplatin or carboplatin, every 3 weeks, 6 cycles) Palliative care (see spreadsheet) Treatment: Teletherapy and brachytherapy9 (Cobalt 60/cesium 5 days for 5 weeks) Chemotherapy (cisplatin or carboplatin, every 3 weeks, 6 cycles) Palliative care (see spreadsheet) Treatment: Teletherapy and brachytherapy9 (Cobalt 60/cesium 5 days for 5 weeks) Chemotherapy (cisplatin or carboplatin, every 3 weeks, 6 cycles) Palliative care (see spreadsheet) Pelvic radiotherapy + chemotherapy (cisplatin) + brachytherapy9 (85Gy) Palliative care (see spreadsheet) Teletherapy + brachytherapy9 Chemotherapy (cisplatin 40mg/m2 6 cycles) + radiotherapy (teletherapy + brachytherapy9) Palliative care (see spreadsheet) Treatment: Pelvic radiotherapy + chemotherapy (cisplatin) Pelvic radiotherapy + chemotherapy (cisplatin) + brachytherapy9 (85Gy) Palliative care (see spreadsheet) Treatment: Teletherapy + brachytherapy9 Chemotherapy (cisplatin 40mg/m2 6 cycles) + radiotherapy (teletherapy + brachytherapy9) Palliative care (see spreadsheet) Treatment: Pelvic radiotherapy + chemotherapy (cisplatin) Pelvic radiotherapy + chemotherapy (cisplatin) + brachytherapy9 (85Gy) Palliative care (see spreadsheet) Treatment: Teletherapy + brachytherapy9 Chemotherapy (cisplatin 40mg/m2 6 cycles) + radiotherapy (teletherapy + brachytherapy9) Palliative care (see spreadsheet) 221 Appendix G. Diagnostic and staging procedures and treatment modalities of invasive cervical cancer by stage across studied countries (continued)1 IVA Treatment: Chemoradiotherapy (platinum 5 cycles) Teletherapy (pelvis) + brachytherapy9 Palliative care (see spreadsheet) IVB Treatment: Teletherapy (5-week course) Palliative care (see spreadsheet) Follow-up by stage10 IA1 Follow-up: 6 ambulatory visits, 2 pap smears, 2 vaginal/rectal examination for the first year IA2 Follow-up: 6 ambulatory visits, 1 pap smears, 1 vaginal/rectal examination for the first year Treatment: Teletherapy and brachytherapy9 (Cobalt 60/cesium 5 days for 5 weeks) Chemotherapy (cisplatin or carboplatin, every 3 weeks, 6 cycles) Palliative care (see spreadsheet) Treatment: Teletherapy and brachytherapy9 (Cobalt 60/cesium 5 days for 5 weeks) Chemotherapy (cisplatin or carboplatin, every 3 weeks, 6 cycles) Palliative care (see spreadsheet) Treatment: Pelvic radiotherapy + chemotherapy (cisplatin) Pelvic radiotherapy + chemotherapy (cisplatin) + brachytherapy9 (85Gy) Palliative care (see spreadsheet) Treatment: External radiotherapy + brachytherapy9 for curative and symptom control (palliative) purposes (see spreadsheet) Treatment: Palliative radiotherapy Palliative care (see spreadsheet) Treatment: Palliative chemotherapy Chemoradiotherapy Other palliative care (see spreadsheet) Follow-up: 4 ambulatory visits, 2 pap smears, 2 vaginal/rectal examination for the first year Follow-up: 4 ambulatory visits, 2 pap smears, 2 vaginal/rectal examination for the first year Follow-up: 6 ambulatory visits, 3 pap smears, 3 vaginal/rectal examination for the first year Follow-up: 4 ambulatory visits, 2 pap smears, 2 vaginal/rectal examination for the first year Follow-up: 6 ambulatory visits, 2 pap smears, 2 vaginal/rectal examination for the first year Follow-up: 6 ambulatory visits, 2 pap smears, 2 vaginal/rectal examination for the first year 222 IB1 IB2 IIA IIB Follow-up: 6 ambulatory visits, 2 pap smears, 2 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 3 pap smears, 3 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 3 pap smears, 3 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 3 pap smears, 3 vaginal/rectal examination for the first year Follow-up: 4 ambulatory visits, 2 pap smears, 2 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 3 pap smears, 3 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 2 pap smears, 2 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 2 pap smears, 2 vaginal/rectal examination for the first year Follow-up: 2 ambulatory visits, 2 pap smears, 1 vaginal/rectal examination for the first year Follow-up: 4 ambulatory visits, 2 pap smears, 2 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 3 pap smears, 3 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 3 pap smears, 3 vaginal/rectal examination for the first year Follow-up: 6 ambulatory visits, 2 pap smears, 2 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 3 pap smears, 3 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 2 pap smears, 2 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 3 pap smears, 3 vaginal/rectal examination for the first year 223 Appendix G. Diagnostic and staging procedures and treatment modalities of invasive cervical cancer by stage across studied countries (continued)1 IIIA–IIIB IVA IVB Follow-up: 22 ambulatory visits, 3 pap smears, 3 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 6 pap smears, 6 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 6 pap smears, 6 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 4 pap smears, 4 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 4 pap smears, 4 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 6 pap smears, 6 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 3 pap smears, 3 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 6 pap smears, 6 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 6 pap smears, 6 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 4 pap smears, 4 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 4 pap smears, 4 vaginal/rectal examination for the first year Follow-up: 22 ambulatory visits, 6 pap smears, 6 vaginal/rectal examination for the first year 1 Management of invasive cervical cancer is based on expert interviews and national treatment guidelines. The cost components associated with the management of invasive cervical cancer are described in more detail in the Cost of HPV document. 7 Some assumptions made for the diagnostics and staging of invasive cervical cancer are conservative. For example, the frequency (how often they are performed) of laboratory tests (urea, hemogram, etc.) and radiography/radiology (x-ray, CT, etc.) were assumed to be the same for each country, based on expert opinion. 8 For surgical procedures, we assumed the same length of stay in the hospital (7–10 days), based on WHO guidelines (2006). 9 For brachytherapy, we assumed the same length of stay in the hospital (2 days) and the same number of outpatient visits (one lasting one hour). These assumptions were based on an average estimate (WHO guidelines, 2006). For teletherapy and chemotherapy, we assumed the same number of outpatient visits (one outpatient visit). 10 Patient follow-up was generally assumed to be for the first year. 11 Source: Guidelines for the management of cervical cancer, Ministry of Health, 2004; expert opinion (Interview with one local primary care physician). 12 Source: Expert opinion (Interview with one local OBGYN physician). 13 Source: National Comprehensive Cancer Network (NCCN), Guías de Práctica Oncológica – v.1 2005; Modificación a la Norma Oficial Mexicana NOM-014-SSA2-1994, Para la Prevención, Detección, diagnóstico, tratamiento, control y vigilancia epidemiológica del cáncer cérvico uterino; expert opinion (interview with one local primary care physician). 14 Source: Tobar A. Costo y desempeño de las pruebas de tamizaje costos del tratamiento del cancer cervicouterino en la region de San Martín (Perú), OPS/DPC/NC, 2005; expert opinion (Interview with one local OBGYN physician). 224 Appendix H. Unit costs associated with the detection and treatment of precancerous lesions and treatment of cervical cancer by stage and country Argentina Unit cost (International $, 2005) % used1 Screening for cervical cancer Screening tests Pap smear 11.00 100% VPH DNA-based test 0% Visual inspection – VIA 0% Visual inspection – VILI 0% Follow-up General practitioner visit 17.83 0% Nurse visit 12.00 0% Specialist consultation 35.00 100% Average cost per event (screening for cervical cancer) Diagnosis, management, and follow-up of precervical cancer Diagnosis – CIN 1 Colposcopy 11.00 65% Biopsy – sample 60.00 65% Biopsy – histopathology study 23.00 65% Treatment – CIN 1 Blood typing 1.52 0% Complete blood test 2.63 70% Prothrombin time 2.19 0% Blood glucose 1.52 70% Creatinine 2.19 70% Complete urine test 2.78 70% Urine culture 1.81 0% Endocervical curettage 60.00 20% Cryotherapy 206.62 5% LEEP 170.55 10% Cold knife conization 274.08 0% Observation ward 0% Regular ward 399.37 20% ECG 0% Follow-up – CIN 1 General practitioner visit 17.83 0% Nurse visit 12.00 0% Specialist consultation 17.83 100% Colposcopy 11.00 100% Biopsy – sample 60.00 100% Biopsy – histopathology study 23.00 100% Pap smear 11.00 100% Management of complications – CIN 1 Surgical intervention/sutures 0% IV antibiotics 3.65 0% Blood transfusion 9.80 0% Regular ward 399.37 20% Average cost per event (CIN 1) Frequency2 Cost per event (International $, 2005)3 1.00 - 11.00 - 2.00 70.00 81.00 1.00 1.00 1.00 7.15 39.00 14.95 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 - 1.84 1.06 1.53 1.95 12.00 10.33 17.06 79.87 - 4.00 2.00 1.00 1.00 1.00 71.32 22.00 60.00 23.00 11.00 2.00 159.75 533.81 225 Diagnosis – CIN 2 Colposcopy 11.00 100% Biopsy – sample 60.00 100% Biopsy – histopathology study 23.00 100% Treatment – CIN 2 Blood typing 1.52 0% Complete blood test 2.63 70% Prothrombin time 2.19 0% Blood glucose 1.52 70% Creatinine 2.19 70% Complete urine test 2.78 70% Urine culture 1.81 0% Endocervical curettage 60.00 95% Cryotherapy 206.62 0% LEEP 170.55 60% Cold knife conization 274.08 40% Simple hysterectomy 1,656.00 7% Short-stay hospitalization 0% Long-stay hospitalization 399.37 60% ECG 150.00 70% Follow-up – CIN 2 General practitioner visit 17.83 0% Nurse visit 12.00 100% Specialist consultation 17.83 100% Colposcopy 11.00 100% Biopsy – sample 60.00 100% Biopsy – histopathology study 23.00 100% Pap smear 11.00 100% Management of complications – CIN 2 Surgical intervention/sutures 0% IV antibiotics 3.65 0% Blood transfusion 9.80 0% Regular ward 0% Average cost per event – CIN 2 Staging, management and follow-up of invasive cervical cancer Staging of invasive cervical cancer (all stages) Vaginal/rectal examination 829.49 100% Colposcopy 11.00 100% Biopsy – sample 60.00 100% Biopsy – histopathology study 23.00 100% Intravenous pyelogram 0% Abdominal ultrasound 0% ECG 0% Cystoscopy 0% Proctoscopy 0% Cone biopsy 0% Endocervical curettage/smear 0% Chest x-ray (front/lateral) 13.77 100% Bone scan 251.71 0% Abdomen/pelvis CT scan 185.71 100% Pelvis MRI 321.71 0% Urethrocistofibroscopy 97.82 50% Rectosigmoidoscopy 112.72 50% 2.00 1.50 1.50 22.00 90.00 34.50 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.84 1.06 1.53 1.95 57.00 102.33 109.63 115.92 239.62 105.00 2.00 4.00 2.00 1.00 1.00 1.00 24.00 71.32 22.00 60.00 23.00 11.00 - 1,093.71 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 829.49 11.00 60.00 23.00 13.77 185.71 48.91 56.36 226 Urography 75.82 Complete hemogram 12.50 Complete urine test 2.78 Urine culture 1.81 Electrolyte 5.79 Serum creatinine 2.19 Prothrombin time 2.19 Glycemia 1.52 Ionogram 1.52 HIV test 10.50 ALT serum AST (TGO) Ureic nitrogen 1.81 Nurse visit 12.00 Specialist consultation 35.00 Treatment of invasive cervical cancer by stage Surgery – IA1 Cold knife conization 170.55 Simple hysterectomy 1,656.00 Radical hysterectomy 2,566.00 Pelvic lymphadenectomy 695.75 Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate 399.37 care ward) Hospitalization (ICU) Specialist consultation 35.00 Radiotherapy – IA1 Pelvic teletherapy 3,250.00 Intravaginal brachytherapy 3,250.00 Hospitalization (intermediate 399.37 care ward) Chemotherapy – IA1 1,500.00 Palliative care – IA1 Palliative radiotherapy Palliative surgery 905.06 Palliative medicine 485.91 Palliative care (other) 47.00 Follow-up – IA1 Specialist consultation 35.00 Pap smear 11.00 Vaginal/rectal examination 829.49 Average cost per event – IA1 Surgery – IA2 Simple hysterectomy 1,656.00 Radical hysterectomy 2,566.00 Pelvic lymphadenectomy 695.75 Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate 399.37 care ward) 0% 100% 100% 100% 100% 100% 0% 100% 0% 0% 0% 0% 100% 100% 100% 5.00 1.00 1.00 6.00 1.00 1.00 1.00 1.00 2.00 3.00 62.50 2.78 1.81 34.74 2.19 1.52 1.81 24.00 105.00 100% 100% 0% 0% 0% 0% 0% 100% 1.00 1.00 2.00 170.55 1,656.00 798.74 0% 100% 1.00 35.00 0% 0% 0% - - 0% - - 0% 0% 100% 100% 0.50 1.00 242.96 47.00 100% 98% 70% 4.00 2.00 1.00 140.00 21.56 580.64 5,157.04 0% 100% 100% 0% 0% 0% 100% 1.00 1.00 2.00 2,566.00 695.75 798.74 227 Hospitalization (ICU) Specialist consultation Radiotherapy – IA2 Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IA2 Palliative care – IA2 Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IA2 Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IA2 Surgery – IB1 Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) Specialist consultation Radiotherapy – IB1 Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy - IB1 Palliative care – IB1 Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IB1 Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IB1 Surgery – IB2 Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate 35.00 0% 100% 1.00 35.00 3,250.00 3,250.00 399.37 50% 50% 50% 1.00 1.00 1.00 1,625.00 1,625.00 199.69 1,500.00 0% - - 905.06 485.91 47.00 0% 0% 50% 100% 1.00 1.00 242.96 47.00 35.00 11.00 829.49 100% 100% 70% 4.00 1.00 1.00 140.00 11.00 580.64 10,031.36 1,656.00 2,566.00 695.75 399.37 0% 100% 100% 0% 0% 0% 100% 1.00 1.00 2.00 2,566.00 695.75 798.74 35.00 0% 100% 2.00 70.00 3,250.00 3,250.00 399.37 100% 100% 100% 1.00 1.00 1.00 3,250.00 3,250.00 399.37 1,500.00 0% - - 905.06 485.91 47.00 0% 0% 50% 100% 1.00 1.00 242.96 47.00 35.00 11.00 829.49 100% 100% 50% 4.00 1.00 1.00 140.00 11.00 414.75 13,350.15 1,656.00 2,566.00 695.75 399.37 0% 50% 0% 0% 0% 0% 50% 1.00 2.00 1,283.00 399.37 228 care ward) Hospitalization (ICU) Specialist consultation Radiotherapy – IB2 Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IB2 Palliative care – IB2 Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IB2 Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IB2 Surgery – IIA Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) Specialist consultation Radiotherapy – IIA Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IIA Palliative care – IIA Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IIA Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IIA Surgery – IIB Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) 35.00 0% 100% 2.00 70.00 3,250.00 3,250.00 399.37 100% 100% 100% 1.00 1.00 3.00 3,250.00 3,250.00 1,198.11 1,500.00 100% 1.00 1,500.00 905.06 485.91 47.00 0% 0% 50% 100% 1.00 1.00 242.96 47.00 35.00 11.00 829.49 100% 100% 60% 6.00 1.00 1.00 210.00 11.00 497.69 13,423.72 1,656.00 2,566.00 695.75 399.37 0% 70% 0% 0% 0% 0% 70% 1.00 3.00 1,796.20 838.68 35.00 0% 100% 2.00 70.00 3,250.00 3,250.00 399.37 100% 100% 100% 1.00 1.00 1.00 3,250.00 3,250.00 399.37 1,500.00 100% 1.00 1,500.00 905.06 485.91 47.00 0% 0% 50% 100% 1.00 1.00 242.96 47.00 35.00 11.00 829.49 100% 100% 60% 6.00 1.00 1.00 210.00 11.00 497.69 13,577.49 1,656.00 2,566.00 695.75 - 0% 0% 0% 0% 0% 0% - 229 Hospitalization (intermediate care ward) Hospitalization (ICU) Specialist consultation Radiotherapy – IIB Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IIB Palliative care – IIB Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IIB Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IIB Surgery – IIIA–IIIB Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) Specialist consultation Radiotherapy – IIIA–IIIB Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IIIA–IIIB Palliative care – IIIA–IIIB Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IIIA–IIIB Specialist consultation Pap smear Vaginal/rectal examination Average cost per event IIIA–IIIB Surgery – IVA Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) 399.37 0% - - 35.00 0% 0% - - 3,250.00 3,250.00 399.37 100% 100% 100% 1.00 1.00 4.00 3,250.00 3,250.00 1,597.48 1,500.00 100% 1.00 1,500.00 905.06 545.80 47.00 0% 0% 100% 100% 1.00 1.00 545.80 47.00 35.00 11.00 829.49 100% 100% 100% 8.00 2.00 2.00 280.00 22.00 1,658.98 13,615.85 1,656.00 2,566.00 695.75 399.37 0% 0% 0% 0% 0% 0% 0% - - 35.00 0% 0% - - 3,250.00 3,250.00 399.37 100% 100% 100% 1.00 1.00 2.00 3,250.00 3,250.00 798.74 1,500.00 100% 1.00 1,500.00 905.06 545.80 778.66 0% 0% 100% 100% 1.00 1.00 545.80 778.66 35.00 11.00 829.49 100% 100% 100% 22.00 2.00 2.00 770.00 22.00 1,658.98 14,038.77 1,656.00 2,566.00 695.75 - 0% 0% 0% 0% 0% - - - 230 Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) Specialist consultation Radiotherapy – IVA Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IVA Palliative care – IVA Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IVA Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IVA Surgery – IVB Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) Specialist consultation Radiotherapy – IVB Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IVB Palliative care – IVB Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IVB Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IVB 399.37 0% 0% - - 35.00 0% 0% - - 3,250.00 3,250.00 399.37 100% 100% 100% 1.00 1.00 2.00 3,250.00 3,250.00 798.74 1,500.00 100% 1.00 1,500.00 905.06 545.80 778.66 0% 0% 100% 100% 1.00 1.00 545.80 778.66 35.00 11.00 829.49 100% 100% 100% 22.00 4.00 2.00 770.00 44.00 1,658.98 14,060.77 1,656.00 2,566.00 695.75 399.37 0% 0% 0% 0% 0% 0% 0% - - 35.00 0% 0% - - 3,250.00 3,250.00 399.37 100% 100% 100% 1.00 1.00 3.00 3,250.00 3,250.00 1,198.11 1,500.00 100% 1.00 1,500.00 905.06 545.80 778.66 0% 0% 100% 100% 1.00 1.00 545.80 778.66 35.00 11.00 829.49 100% 100% 100% 22.00 2.00 2.00 770.00 22.00 1,658.98 14,438.14 - 1 Proportion of treatment-related events (visits, diagnostics, medications) occurring (e.g., 100% hospitalized patients are admitted to the regular ward; 20% ambulatory patients are seen by their gynecologist; 20% hospitalized patients receive chest x-rays). 2 Number of events (visits, diagnostics, medications) occurring (e.g., the average length of stay in the hospital is 3.5 days; an average of two pap smears are performed in patients). 3 2005 World Development Indicators, 2005 international dollars (LCU per international dollar, period average vaginal/rectal examinations) for the first four years. These costs are based on an average patient who does not have 231 any special circumstances (e.g., pregnancy, menstruation, PID, or HIV). Palliative care is assumed to be given at every stage of treatment and considers only the first year of palliative therapy. Sources: 1. Federación Argentina de Sociedades de Ginecología y Obstetricia (FASGO) – Guía de Práctica Clínica, 2002; Subprograma Nacional de Detección Precoz de Cancer de Cuello Uterino, Ministerio de Salud 2006. 2. Agencia de Evaluación de Tecnologías Sanitarias (AETS/IECS), 2005. 3. Expert opinion (Interviews with 2 experts in charge of the National Cervical Cancer Program and interviews with participants of the GSK HPV project in Argentina). 232 Brazil Unit cost (International $, 2005) % used1 Screening for cervical cancer Screening tests Pap smear 5.37 100% VPH DNA-based test 0% Visual inspection – VIA 0% Visual inspection –VILI 0% Follow-up General practitioner visit 7.55 30% Nurse visit 3.54 70% Specialist consultation 7.56 0% Average cost per event (screening for cervical cancer) Diagnosis, management, and follow-up of precervical cancer Diagnosis – CIN 1 Colposcopy 45.00 93% Biopsy – sample 14.66 93% Biopsy – histopathology study 11.28 93% Treatment – CIN 1 Blood typing 3.51 70% Complete blood test 4.11 70% Prothrombin time 2.85 70% Blood glucose 1.85 70% Creatinine 3.51 70% Complete urine test 15.65 70% Urine culture 5.65 70% Endocervical curettage 141.27 0% Cryotherapy 160.42 0% LEEP 308.02 7% Cold knife conization 935.35 0% Observation ward 136.62 100% Regular ward 359.52 100% ECG 10.73 70% Follow-up – CIN 1 General practitioner visit 7.55 0% Nurse visit 3.54 100% Specialist consultation 7.56 100% Colposcopy 45.00 100% Biopsy – sample 14.66 100% Biopsy – histopathology study 11.28 100% Pap smear 5.37 100% Management of complications – CIN 1 Surgical intervention/sutures 164.09 1% IV antibiotics 0.85 0% Blood transfusion 8.09 0% Regular ward 179.76 0% Average cost per event – CIN 1 Diagnosis – CIN 2 Colposcopy 45.00 87% Biopsy – sample 14.66 87% Frequency2 Cost per event (International $, 2005)3 1.00 - 5.37 - 1.00 1.00 - 2.27 2.48 10.11 2.00 2.00 2.00 83.70 27.27 20.98 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 2.00 2.46 2.88 2.00 1.30 2.46 10.96 3.96 21.56 136.62 359.52 15.02 1.00 2.00 2.00 2.00 2.00 2.00 3.54 15.12 90.00 29.32 22.56 10.74 1.00 - 1.64 863.58 2.00 2.00 78.30 25.51 233 Biopsy – histopathology study 11.28 87% Treatment – CIN 2 Blood typing 3.51 70% Complete blood test 4.11 70% Prothrombin time 2.85 70% Blood glucose 1.85 70% Creatinine 3.51 70% Complete urine test 15.65 70% Urine culture 5.65 70% Endocervical curettage 141.27 0% Cryotherapy 160.42 0% LEEP 308.02 95% Cold knife conization 935.35 0% Simple hysterectomy 1,149.36 5% Short-stay hospitalization 136.62 0% Long-stay hospitalization 359.52 100% ECG 10.73 65% Follow-up – CIN 2 General practitioner visit 7.55 0% Nurse visit 3.54 100% Specialist consultation 7.56 100% Colposcopy 45.00 100% Biopsy – sample 14.66 100% Biopsy – histopathology study 11.28 100% Pap smear 5.37 100% Management of complications – CIN 2 Surgical intervention/sutures IV antibiotics Blood transfusion 8.09 0% Regular ward 179.76 0% Average cost per event – CIN 2 Staging, management, and follow-up of invasive cervical cancer Staging of invasive cervical cancer (all stages) Vaginal/rectal examination 26.71 100% Colposcopy 45.00 100% Biopsy – sample 14.66 100% Biopsy – histopathology study 11.28 100% Intravenous pyelogram 52.12 0% Abdominal ultrasound 54.04 70% ECG 10.73 50% Cystoscopy 31.70 50% Proctoscopy 58.84 0% Cone biopsy 935.35 0% Endocervical curettage/smear 182.31 0% Chest x-ray (front/lateral) 9.50 70% Bone scan 206.63 0% Abdomen/pelvis CT scan 138.63 70% Pelvis MRI 269.13 70% Urethrocistofibroscopy 25.62 0% Rectosigmoidoscopy 18.56 0% Urography 14.52 0% Complete hemogram 4.11 100% Complete urine test 15.65 100% 2.00 19.63 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 2.00 1.00 2.46 2.88 2.00 1.30 2.46 10.96 3.96 292.62 57.47 719.04 6.97 1.00 2.00 2.00 2.00 2.00 2.00 3.54 15.12 90.00 29.32 22.56 10.74 - 4.92 0.03 1,401.76 2.00 0.60 1.00 1.00 2.00 2.00 1.00 1.00 1.00 1.00 1.00 2.00 2.00 53.42 27.00 14.66 11.28 75.66 5.37 15.85 6.65 97.04 188.39 8.22 31.30 234 Urine culture 5.65 Electrolyte 8.75 Serum creatinine 3.51 Prothrombin time 2.85 Glycemia 1.85 Ionogram 6.48 HIV test 65.00 ALT serum 5.65 AST (TGO) 5.65 Ureic nitrogen 5.65 Nurse visit 3.54 Specialist consultation 7.56 Treatment of invasive cervical cancer by stage Surgery – IA1 Cold knife conization 935.35 Simple hysterectomy 1,149.36 Radical hysterectomy 2,966.19 Pelvic lymphadenectomy 966.19 Trachelectomy 529.87 Hospitalization (short-stay) 136.62 Hospitalization (regular ward) 248.33 Hospitalization (intermediate 359.52 care ward) Hospitalization (ICU) 636.47 Specialist consultation 7.56 Radiotherapy – IA1 Pelvic teletherapy 674.71 Intravaginal brachytherapy 556.60 Hospitalization (intermediate 520.48 care ward) Chemotherapy – IA1 355.08 Palliative care – IA1 Palliative radiotherapy 674.71 Palliative surgery 376.13 Palliative medicine Palliative care (other) 904.29 Follow-up – IA1 Specialist consultation 7.56 Pap smear 5.37 Vaginal/rectal examination 26.71 Average cost per event – IA1 Surgery – IA2 Simple hysterectomy 1,149.36 Radical hysterectomy 2,966.19 Pelvic lymphadenectomy 966.19 Trachelectomy 529.87 Hospitalization (short-stay) 136.62 Hospitalization (regular ward) 248.33 Hospitalization (intermediate 359.52 care ward) Hospitalization (ICU) 636.47 Specialist consultation 7.56 Radiotherapy – IA2 100% 100% 100% 100% 100% 0% 0% 0% 0% 0% 100% 100% 2.00 2.00 2.00 1.00 1.00 2.00 4.00 11.30 17.50 7.02 2.85 1.85 7.08 30.24 5% 95% 0% 0% 0% 0% 100% 100% 1.00 1.00 2.00 2.00 46.77 1,091.89 496.66 719.04 15% 100% 1.00 2.00 95.47 15.12 0% 100% 100% 1.00 1.00 556.60 520.48 0% - - 0% 0% 100% 100% 1.00 1.00 904.29 100% 100% 100% 6.00 2.00 2.00 45.36 10.74 53.42 5,168.51 0% 100% 100% 0% 0% 100% 100% 1.00 1.00 2.00 1.00 2,966.19 966.19 496.66 359.52 15% 100% 1.00 1.00 95.47 7.56 235 Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IA2 Palliative care – IA2 Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IA2 Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IA2 Surgery – IB1 Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) Specialist consultation Radiotherapy – IB1 Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IB1 Palliative care – IB1 Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IB1 Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IB1 Surgery – IB2 Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) Specialist consultation 674.71 556.60 520.48 100% 100% 100% 1.00 1.00 1.00 674.71 556.60 520.48 355.08 50% 1.00 177.54 674.71 376.13 unknown 904.29 0% 0% 100% 100% 1.00 1.00 904.29 7.56 5.37 26.71 100% 100% 100% 6.00 2.00 2.00 45.36 10.74 53.42 8,447.40 1,149.36 2,966.19 966.19 529.87 136.62 248.33 359.52 0% 100% 100% 0% 0% 100% 100% 1.00 1.00 2.00 1.00 2,966.19 966.19 496.66 359.52 636.47 7.56 15% 100% 1.00 2.00 95.47 15.12 674.71 556.60 520.48 100% 100% 100% 1.00 1.00 1.00 674.71 556.60 520.48 355.08 100% 1.00 355.08 674.71 376.13 904.29 0% 0% 100% 100% 1.00 1.00 904.29 7.56 5.37 26.71 100% 100% 100% 6.00 2.00 2.00 45.36 10.74 53.42 8,632.50 1,149.36 2,966.19 966.19 529.87 136.62 248.33 359.52 0% 100% 100% 0% 0% 100% 100% 1.00 1.00 3.00 1.00 2,966.19 966.19 744.99 359.52 636.47 7.56 15% 100% 1.00 1.00 95.47 7.56 236 Radiotherapy – IB2 Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IB2 Palliative care – IB2 Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IB2 Specialist consultation Pap smear Vaginal/rectal examination Average cost per event - IB2 Surgery – IIA Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) Specialist consultation Radiotherapy – IIA Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IIA Palliative care – IIA Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IIA Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IIA Surgery – IIB Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) 674.71 556.60 520.48 100% 100% 100% 1.00 1.00 1.00 674.71 556.60 520.48 355.08 100% 1.00 355.08 674.71 376.13 904.29 0% 0% 100% 100% 1.00 1.00 904.29 7.56 5.37 26.71 100% 100% 100% 22.00 3.00 3.00 166.32 16.11 80.13 9,026.31 1,149.36 2,966.19 966.19 529.87 136.62 248.33 359.52 0% 100% 100% 0% 0% 100% 100% 1.00 1.00 2.00 1.00 2,966.19 966.19 496.66 359.52 636.47 7.56 15% 100% 1.00 1.00 95.47 7.56 674.71 556.60 520.48 100% 100% 100% 1.00 1.00 1.00 674.71 556.60 520.48 355.08 100% 1.00 355.08 674.71 376.13 904.29 0% 0% 50% 30% 1.00 1.00 271.29 7.56 5.37 26.71 100% 100% 100% 22.00 3.00 3.00 166.32 16.11 80.13 8,144.98 1,149.36 2,966.19 966.19 529.87 136.62 248.33 359.52 0% 0% 0% 0% 0% 0% 0% - - 636.47 0% - - - 237 Specialist consultation Radiotherapy – IIB Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IIB Palliative care – IIB Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IIB Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IIB Surgery – IIIA–IIIB Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) Specialist consultation Radiotherapy – IIIA–IIIB Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IIIA-IIIB Palliative care – IIIA-IIIB Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IIIA–IIIB Specialist consultation Pap smear Vaginal/rectal examination Average cost per event IIIA–IIIB Surgery – IVA Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) 7.56 100% 4.00 30.24 674.71 556.60 520.48 100% 100% 100% 1.00 1.00 2.00 674.71 556.60 1,040.96 355.08 100% 1.00 355.08 674.71 376.13 904.29 0% 70% 100% 100% 1.00 1.00 5.00 263.29 4,521.45 7.56 5.37 26.71 100% 100% 100% 22.00 4.00 4.00 166.32 21.48 106.84 8,349.64 1,149.36 2,966.19 966.19 529.87 136.62 248.33 359.52 0% 0% 0% 0% 0% 0% 0% - - 636.47 7.56 0% 0% - - 674.71 556.60 520.48 100% 100% 100% 1.00 1.00 2.00 674.71 556.60 1,040.96 355.08 100% 1.00 355.08 674.71 376.13 904.29 65% 65% 100% 100% 1.00 1.00 1.00 5.00 438.56 244.48 4,521.45 7.56 5.37 26.71 100% 100% 100% 22.00 4.00 4.00 166.32 21.48 106.84 8,739.16 1,149.36 2,966.19 966.19 529.87 136.62 248.33 359.52 0% 0% 0% 0% 0% 0% 0% - - - - 238 Hospitalization (ICU) Specialist consultation Radiotherapy – IVA Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IVA Palliative care – IVA Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IVA Specialist consultation Pap smear Vaginal/rectal examination Average cost per event - IVA Surgery – IVB Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) Specialist consultation Radiotherapy – IVB Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IVB Palliative care – IVB Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IVB Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IVB 636.47 7.56 0% 0% - - 674.71 556.60 520.48 100% 100% 100% 1.00 1.00 1.00 674.71 556.60 520.48 355.08 100% 2.00 710.16 674.71 376.13 904.29 70% 70% 100% 100% 1.00 1.00 1.00 5.00 472.30 263.29 4,521.45 7.56 5.37 26.71 100% 100% 100% 22.00 6.00 12.00 166.32 32.22 320.52 8,850.72 1,149.36 2,966.19 966.19 529.87 136.62 248.33 359.52 0% 0% 0% 0% 0% 0% 0% - - 636.47 7.56 0% 0% - - 674.71 556.60 520.48 100% 100% 100% 1.00 1.00 2.00 674.71 556.60 1,040.96 355.08 100% 1.00 355.08 674.71 376.13 904.29 85% 50% 100% 100% 1.00 1.00 2.00 5.00 573.50 188.07 4,521.45 7.56 5.37 26.71 100% 100% 100% 22.00 6.00 12.00 166.32 32.22 320.52 9,042.10 - 1 Proportion of treatment-related events (visits, diagnostics, medications) occurring (e.g., 100% hospitalized patients are admitted to the regular ward; 20% ambulatory patients are seen by their gynecologist; 20% hospitalized patients receive chest x-rays). 2 Number of events (visits, diagnostics, medications) occurring (e.g., the average length of stay in the hospital is 3.5 days; an average of two pap smears are performed in patients). 3 2005 World Development Indicators, 2005 international dollars (LCU per international dollar, period average for year 2005). Costs are based on the first year of treatment and include follow-up care (e.g. ambulatory visits, vaginal/rectal examinations) for the first four years. These costs are based on an average patient who does not have any special circumstances (e.g., pregnancy, menstruation, PID, or HIV). Palliative care is assumed to be given at every stage of treatment and only considers the first year of palliative therapy. Sources: 239 1. Condutas do Instituto Nacional de Cancer/ Ministério da Saúde, (INCA/MS), 2006; 5ª Edição – UICC, 1997; Ministério da Saúde, 1998. 2.Tabela de Procedimentos o Sistema Ambulatorial e Hospitalario del Sistema Único de Salud (SIA/SUS; SIH/SUS). DATASUS, 2005. 3. Expert opinion (Interviews with three experts in charge of the National Cervical Cancer Program, Sao Paulo, Brazil. 240 Chile Unit cost (International $, 2005) % used1 Screening for cervical cancer Screening tests Pap smear 10.55 98% VPH DNA-based test 925.65 2% Visual inspection – VIA 0% Visual inspection – VILI 0% Follow-up General practitioner visit 9.24 30% Nurse visit 2.46 70% Specialist consultation 18.60 0% Average cost per event (screening for cervical cancer) Diagnosis, management and follow-up of pre-cervical cancer Diagnosis – CIN 1 Colposcopy 13.89 70% Biopsy – sample 39.39 70% Biopsy – histopathology study 21.49 70% Treatment – CIN 1 Blood typing 3.89 70% Complete blood test 4.92 70% Prothrombin time 2.40 70% Blood glucose 2.16 70% Creatinine 2.16 70% Complete urine test 3.07 70% Urine culture 5.99 20% Endocervical curettage 16.05 0% Cryotherapy 40.12 10% LEEP 82.86 20% Cold knife conization 275.26 0% Observation ward 24.41 100% Regular ward 72.74 100% ECG 10.79 70% Follow-up – CIN 1 General practitioner visit 9.24 0% Nurse visit 2.46 100% Specialist consultation 18.60 100% Colposcopy 13.89 100% Biopsy – sample 39.39 100% Biopsy – histopathology study 21.49 100% Pap smear 10.55 100% Management of complications – CIN 1 Surgical intervention/sutures 46.81 10% IV antibiotics 2.46 10% Blood transfusion 18.60 10% Regular ward 72.74 0% Average cost per event – CIN 1 Diagnosis – CIN 2 Colposcopy 13.89 100% Biopsy – sample 39.39 100% Frequency2 Cost per event (International $, 2005)3 1.00 1.00 - 10.34 18.51 - 1.00 1.00 - 2.77 1.72 33.34 2.00 2.00 2.00 19.45 55.15 30.09 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 2.00 1.00 2.72 3.45 1.68 1.51 1.51 2.15 1.20 4.01 16.57 24.41 145.47 7.55 1.00 3.00 2.00 2.00 2.00 2.00 2.46 55.81 27.78 78.78 42.98 21.09 1.00 1.00 1.00 - 4.68 0.25 1.86 552.61 2.00 2.00 27.78 78.78 241 Biopsy – histopathology study 21.49 100% Treatment – CIN 2 Blood typing 3.89 70% Complete blood test 4.92 70% Prothrombin time 2.40 70% Blood glucose 2.16 70% Creatinine 2.16 70% Complete urine test 3.07 70% Urine culture 5.99 70% Endocervical curettage 16.05 0% Cryotherapy 40.12 1% LEEP 82.86 90% Cold knife conization 275.26 2% Simple hysterectomy 839.00 7% Short-stay hospitalization 24.41 100% Long-stay hospitalization 72.74 100% ECG 10.79 70% Follow-up – CIN 2 General practitioner visit 9.24 0% Nurse visit 2.46 100% Specialist consultation 18.60 100% Colposcopy 13.89 100% Biopsy – sample 39.39 100% Biopsy – histopathology study 21.49 100% Pap smear 10.55 100% Management of complications – CIN 2 Surgical intervention/sutures 46.81 10% IV antibiotics 2.46 10% Blood transfusion 18.60 10% Regular ward 72.74 10% Average cost per event – CIN 2 Staging, management, and follow-up of invasive cervical cancer Staging of invasive cervical cancer (all stages) Vaginal/rectal examination 13.89 70% Colposcopy 13.89 100% Biopsy – sample 39.39 100% Biopsy – histopathology study 21.49 100% Intravenous pyelogram 23.25 70% Abdominal ultrasound 225.26 70% ECG 10.79 70% Cystoscopy 96.14 70% Proctoscopy 89.45 0% Cone biopsy 164.19 0% Endocervical curettage/smear 16.05 0% Chest x-ray (front/lateral) 30.12 70% Bone scan 128.57 0% Abdomen/pelvis CT scan 139.51 0% Pelvis MRI 265.32 0% Urethrocistofibroscopy 99.48 0% Rectosigmoidoscopy 119.33 0% Urography 71.61 0% Complete hemogram 4.92 100% Complete urine test 3.07 100% 2.00 42.98 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 2.00 5.00 1.00 2.72 3.45 1.68 1.51 1.51 2.15 4.19 0.40 74.57 5.51 58.73 48.81 363.68 7.55 1.00 3.00 2.00 2.00 2.00 2.00 2.46 55.81 27.78 78.78 42.98 21.09 1.00 1.00 1.00 1.00 4.68 0.25 1.86 7.27 968.98 2.00 1.00 1.00 1.00 2.00 2.00 1.00 1.00 1.00 5.00 1.00 19.45 13.89 39.39 21.49 32.55 315.36 7.55 67.30 21.09 24.62 3.07 242 Urine culture 5.99 Electrolyte 2.01 Serum creatinine 2.16 Prothrombin time 9.70 Glycemia 2.16 Ionogram 2.89 HIV test 21.49 ALT serum 2.16 AST (TGO) 2.16 Ureic nitrogen 1.88 Nurse visit 2.46 Specialist consultation 18.60 Treatment of invasive cervical cancer by stage Surgery – IA1 Cold knife conization 275.26 Simple hysterectomy 839.00 Radical hysterectomy 1,145.41 Pelvic lymphadenectomy 316.44 Trachelectomy Hospitalization (short-stay) 24.41 Hospitalization (regular ward) 72.74 Hospitalization (intermediate 146.11 care ward) Hospitalization (ICU) 302.43 Specialist consultation 18.60 Radiotherapy – IA1 Pelvic teletherapy 2,022.52 Intravaginal brachytherapy 1,834.04 Hospitalization (intermediate 146.11 care ward) Chemotherapy – IA1 598.48 Palliative care – IA1 Palliative radiotherapy 2,022.52 Palliative surgery 1,145.41 Palliative medicine 62.64 Palliative care (other) 21.06 Follow-up – IA1 Specialist consultation 18.60 Pap smear 10.55 Vaginal/rectal examination 13.89 Average cost per event – IA1 Surgery – IA2 Simple hysterectomy 839.00 Radical hysterectomy 1,145.41 Pelvic lymphadenectomy 316.44 Trachelectomy Hospitalization (short-stay) 24.41 Hospitalization (regular ward) 72.74 Hospitalization (intermediate 146.11 care ward) Hospitalization (ICU) 302.43 Specialist consultation 18.60 Radiotherapy – IA2 100% 100% 100% 100% 100% 0% 0% 0% 0% 0% 100% 100% 1.00 6.00 1.00 1.00 1.00 1.00 4.00 5.99 12.04 2.16 9.70 2.16 2.46 74.41 30% 100% 0% 0% 0% 0% 100% 100% 1.00 1.00 8.00 2.00 82.58 839.00 581.88 292.22 30% 100% 2.00 2.00 181.46 37.20 0% 100% 100% 1.00 3.00 1,834.04 438.33 0% - - 0% 0% 100% 100% 1.00 2.00 62.64 42.13 100% 98% 70% 6.00 3.00 6.00 111.61 31.01 58.34 5,267.11 0% 100% 100% 0% 0% 100% 100% 1.00 1.00 8.00 2.00 1,145.41 316.44 581.88 292.22 15% 100% 2.00 2.00 90.73 37.20 243 Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IA2 Palliative care – IA2 Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IA2 Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IA2 Surgery – IB1 Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) Specialist consultation Radiotherapy – IB1 Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IB1 Palliative care – IB1 Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IB1 Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IB1 Surgery – IB2 Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) Specialist consultation 2,022.52 1,834.04 146.11 0% 100% 100% 1.00 3.00 1,834.04 438.33 598.48 0% - - 2,022.52 1,145.41 62.64 21.06 0% 0% 100% 100% 1.00 3.00 62.64 63.19 18.60 10.55 13.89 100% 98% 70% 6.00 3.00 6.00 111.61 31.01 58.34 5,737.72 839.00 1,145.41 316.44 24.41 72.74 146.11 0% 100% 100% 0% 0% 100% 100% 1.00 1.00 8.00 2.00 1,145.41 316.44 581.88 292.22 302.43 18.60 15% 100% 2.00 2.00 90.73 37.20 2,022.52 1,834.04 146.11 100% 100% 0% 1.00 1.00 - 2,022.52 1,834.04 - 598.48 0% - - 2,022.52 1,145.41 62.64 21.06 0% 0% 100% 100% 1.00 2.00 62.64 42.13 18.60 10.55 13.89 100% 98% 70% 6.00 3.00 6.00 111.61 31.01 58.34 7,300.85 839.00 1,145.41 316.44 24.41 72.74 146.11 0% 0% 0% 0% 0% 0% 0% - - 302.43 18.60 0% 0% - 244 Radiotherapy – IB2 Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IB2 Palliative care – IB2 Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IB2 Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IB2 Surgery – IIA Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) Specialist consultation Radiotherapy – IIA Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IIA Palliative care – IIA Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IIA Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IIA Surgery – IIB Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) 2,022.52 1,834.04 146.11 100% 100% 100% 1.00 1.00 6.00 2,022.52 1,834.04 876.66 598.48 100% 1.00 598.48 2,022.52 1,145.41 62.64 131.73 0% 0% 100% 100% 2.00 8.00 125.29 1,053.86 18.60 10.55 13.89 100% 98% 70% 22.00 3.00 3.00 409.24 31.01 29.17 7,654.94 839.00 1,145.41 316.44 24.41 72.74 146.11 0% 100% 100% 0% 0% 100% 100% 1.00 1.00 8.00 2.00 1,145.41 316.44 581.88 292.22 302.43 18.60 15% 100% 1.00 1.00 45.36 18.60 2,022.52 1,834.04 146.11 100% 100% 100% 1.00 1.00 2.00 2,022.52 1,834.04 292.22 598.48 100% 1.00 598.48 2,022.52 1,145.41 62.64 131.73 0% 0% 100% 100% 1.00 1.00 62.64 131.73 18.60 10.55 13.89 100% 98% 70% 22.00 3.00 3.00 409.24 31.01 29.17 8,485.65 839.00 1,145.41 316.44 24.41 72.74 146.11 0% 0% 0% 0% 0% 0% 0% - - 302.43 0% - - - 245 Specialist consultation Radiotherapy – IIB Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IIB Palliative care – IIB Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IIB Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IIB Surgery – IIIA–IIIB Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) Specialist consultation Radiotherapy – IIIA–IIIB Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IIIA–IIIB Palliative care – IIIA–IIIB Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IIIA–IIIB Specialist consultation Pap smear Vaginal/rectal examination Average cost per event IIIA–IIIB Surgery – IVA Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) 18.60 100% 4.00 74.41 2,022.52 1,834.04 146.11 100% 100% 100% 1.00 1.00 8.00 2,022.52 1,834.04 1,168.88 598.48 100% 1.00 598.48 2,022.52 1,145.41 62.64 131.73 0% 70% 100% 100% 1.00 2.00 8.00 801.79 125.29 1,053.86 18.60 10.55 13.89 100% 100% 100% 22.00 3.00 3.00 409.24 31.64 41.67 8,836.48 839.00 1,145.41 316.44 24.41 72.74 146.11 0% 0% 0% 0% 0% 0% 0% - - 302.43 18.60 0% 0% - - 2,022.52 1,834.04 146.11 100% 100% 100% 1.00 1.00 4.00 2,022.52 1,834.04 584.44 598.48 100% 1.00 598.48 2,022.52 1,145.41 62.64 131.73 65% 65% 100% 100% 1.00 1.00 2.00 8.00 1,314.64 744.52 125.29 1,053.86 18.60 10.55 13.89 100% 98% 70% 22.00 3.00 3.00 409.24 31.01 29.17 9,421.87 839.00 1,145.41 316.44 24.41 72.74 146.11 0% 0% 0% 0% 0% 0% 0% - - - - 246 Hospitalization (ICU) Specialist consultation Radiotherapy – IVA Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IVA Palliative care –IVA Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IVA Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IVA Surgery – IVB Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) Specialist consultation Radiotherapy – IVB Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IVB Palliative care – IVB Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IVB Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IVB 302.43 18.60 0% 0% - - 2,022.52 1,834.04 146.11 100% 100% 100% 1.00 1.00 8.00 2,022.52 1,834.04 1,168.88 598.48 100% 1.00 598.48 2,022.52 1,145.41 62.64 131.73 65% 50% 100% 100% 1.00 1.00 4.00 8.00 1,314.64 572.71 250.58 1,053.86 18.60 10.55 13.89 100% 98% 70% 22.00 6.00 12.00 409.24 62.02 116.68 10,078.31 839.00 1,145.41 316.44 24.41 72.74 146.11 0% 0% 0% 0% 0% 0% 0% - - 302.43 18.60 0% 0% - - 2,022.52 1,834.04 146.11 100% 100% 100% 1.00 1.00 8.00 2,022.52 1,834.04 1,168.88 598.48 100% 1.00 598.48 2,022.52 1,145.41 62.64 131.73 85% 50% 100% 100% 1.00 1.00 4.00 8.00 1,719.14 572.71 250.58 1,053.86 18.60 10.55 13.89 100% 100% 100% 22.00 6.00 12.00 409.24 63.28 166.69 10,534.08 - 1 Proportion of treatment-related events (visits, diagnostics, medications) occurring (e.g., 100% hospitalized patients are admitted to the regular ward; 20% ambulatory patients are seen by their gynecologist; 20% hospitalized patients receive chest x-rays). 2 Number of events (visits, diagnostics, medications) occurring (e.g., the average length of stay in the hospital is 3.5 days; an average of two pap smears are performed in patients). 3 2005 World Development Indicators, 2005 international dollars (LCU per international dollar, period average for year 2005). Costs are based on the first year of treatment and include follow-up care (e.g. ambulatory visits, vaginal/rectal examinations) for the first four years. These costs are based on an average patient who does not have any special circumstances (e.g., pregnancy, menstruation, PID, or HIV). Palliative care is assumed to be given at every stage of treatment and only considers the first year of palliative therapy. Sources: 247 1. FONASA, Arancel de Prestaciones de Salud . Modalidad Libre Elección, 2005. 2. Ministerio de Salud. Guía Clínica Cáncer Cervicouterino. Serie guías clínicas MINSAL NºXX, 3ª edición. Santiago: Minsal, 2006. 3. Expert opinion (Interview with one expert in charge of the National Cervical Cancer Program, Cancer Unit, Minsal, 2006. 248 Colombia Unit cost (International $, 2005) % used1 Screening for cervical cancer Screening tests Pap smear 15.32 70% VPH DNA-based test 0% Visual inspection - VIA 0% Visual inspection - VILI 0% Follow-up General practitioner visit 19.15 60% Nurse visit 9.58 40% Specialist consultation 27.62 40% Average cost per event (screening for cervical cancer) Diagnosis, management, and follow-up of pre-cervical cancer Diagnosis – CIN 1 Colposcopy 31.92 75% Biopsy – sample 56.67 70% Biopsy – histopathology study 75.18 70% Treatment – CIN 1 Blood typing 13.41 70% Complete blood test 15.96 70% Prothrombin time 19.37 70% Blood glucose 7.98 70% Creatinine 7.63 70% Complete urine test 8.45 70% Urine culture 34.98 20% Endocervical curettage 0% Cryotherapy 56.19 10% LEEP 79.81 5% Cold knife conization 79.81 10% Observation ward 45.17 60% Regular ward 57.46 90% ECG 26.18 40% Follow-up – CIN 1 General practitioner visit 19.15 0% Nurse visit 9.58 100% Specialist consultation 27.62 100% Colposcopy 31.92 100% Biopsy – sample 56.67 100% Biopsy – histopathology study 75.18 100% Pap smear 15.32 100% Management of complications – CIN 1 Surgical intervention/sutures 0% IV antibiotics 15.96 5% Blood transfusion 126.10 5% Regular ward 57.46 0% Average cost per event – CIN 1 Diagnosis – CIN 2 Colposcopy 31.92 80% Biopsy – sample 56.67 60% Frequency2 Cost per event (International $, 2005)3 1.00 - 10.72 - 1.00 1.00 1.00 11.49 3.83 11.05 37.09 2.00 2.00 2.00 47.88 79.34 105.25 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 9.39 11.17 13.56 5.59 5.34 5.92 7.00 5.62 3.99 7.98 27.10 51.71 10.47 1.00 5.00 4.00 2.00 2.00 2.00 9.58 138.10 127.68 113.34 150.36 30.64 1.00 1.00 - 0.80 6.31 974.11 2.00 2.00 51.07 68.00 249 Biopsy – histopathology study 75.18 70% Treatment – CIN 2 Blood typing 13.41 70% Complete blood test 15.96 70% Prothrombin time 19.37 70% Blood glucose 7.98 70% Creatinine 7.63 70% Complete urine test 8.45 70% Urine culture 34.98 20% Endocervical curettage 0% Cryotherapy 56.19 5% LEEP 79.81 90% Cold knife conization 79.81 5% Simple hysterectomy 0% Short-stay hospitalization 47.89 60% Long-stay hospitalization 127.70 100% ECG 26.18 70% Follow-up – CIN 2 General practitioner visit 19.15 0% Nurse visit 9.58 100% Specialist consultation 27.62 100% Colposcopy 31.92 100% Biopsy – sample 56.67 100% Biopsy – histopathology study 75.18 100% Pap smear 15.32 100% Management of complications – CIN 2 Surgical intervention/sutures 0% IV antibiotics 15.96 10% Blood transfusion 126.10 10% Regular ward 0% Average cost per event – CIN 2 Staging, management, and follow-up of invasive cervical cancer Staging of invasive cervical cancer (all stages) Vaginal/rectal examination 27.62 70% Colposcopy 31.92 100% Biopsy – sample 56.67 100% Biopsy – histopathology study 75.18 100% Intravenous pyelogram 96.25 70% Abdominal ultrasound 124.03 70% ECG 26.18 50% Cystoscopy 95.77 50% Proctoscopy 47.89 0% Cone biopsy 389.64 0% Endocervical curettage/smear 0% Chest x-ray (front/lateral) 38.31 50% Bone scan 0% Abdomen/pelvis CT scan 366.02 0% Pelvis MRI 0% Urethrocistofibroscopy 95.77 0% Rectosigmoidoscopy 95.77 0% Urography 0% Complete hemogram 20.75 100% Complete urine test 8.45 100% 2.00 105.25 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 2.25 1.00 9.39 11.17 13.56 5.59 5.34 5.92 7.00 2.81 71.83 3.99 28.73 287.33 18.33 1.00 4.00 4.00 2.00 2.00 2.00 9.58 110.48 127.68 113.34 150.36 30.64 1.00 1.00 - 1.60 12.61 1,251.58 2.00 1.00 1.00 1.00 2.00 2.00 1.00 1.00 1.00 5.00 1.00 38.67 31.92 56.67 75.18 134.75 173.64 13.09 47.89 19.16 103.75 8.45 250 Urine culture 34.98 Electrolyte 40.73 Serum creatinine 12.32 Prothrombin time 19.37 Glycemia 7.98 Ionogram 38.26 HIV test 45.77 ALT serum AST (TGO) Ureic nitrogen 7.04 Nurse visit 9.58 Specialist consultation 27.62 Treatment of invasive cervical cancer by stage Surgery – IA1 Cold knife conization 79.81 Simple hysterectomy 1,248.26 Radical hysterectomy 1,424.65 Pelvic lymphadenectomy 1,424.65 Trachelectomy 307.92 Hospitalization (short-stay) Hospitalization (regular ward) 45.17 Hospitalization (intermediate 426.84 care ward) Hospitalization (ICU) 793.49 Specialist consultation 27.62 Radiotherapy – IA1 Pelvic teletherapy 990.31 Intravaginal brachytherapy 580.55 Hospitalization (intermediate 426.84 care ward) Chemotherapy – IA1 180.38 Palliative care – IA1 Palliative radiotherapy 473.77 Palliative surgery 1,336.38 Palliative medicine 159.62 Palliative care (other) Follow-up – IA1 Specialist consultation 27.62 Pap smear 15.32 Vaginal/rectal examination 27.62 Average cost per event – IA1 Surgery – IA2 Simple hysterectomy 1,248.26 Radical hysterectomy 1,424.65 Pelvic lymphadenectomy 1,424.65 Trachelectomy 307.92 Hospitalization (short-stay) Hospitalization (regular ward) 45.17 Hospitalization (intermediate 426.84 care ward) Hospitalization (ICU) 793.49 Specialist consultation 27.62 Radiotherapy – IA2 100% 100% 100% 100% 100% 0% 0% 0% 0% 0% 100% 100% 1.00 6.00 1.00 1.00 1.00 1.00 4.00 34.98 244.38 12.32 19.37 7.98 9.58 110.48 2% 98% 0% 0% 0% 0% 100% 100% 1.00 1.00 8.00 2.00 1.60 1,223.29 361.36 853.68 15% 100% 1.00 2.00 119.02 55.24 0% 100% 0% 1.00 - 580.55 - 0% - - 0% 0% 100% 0% 1.00 - 159.62 - 100% 98% 70% 6.00 3.00 6.00 165.72 45.04 116.00 4,823.38 0% 100% 100% 0% 0% 100% 100% 1.00 1.00 8.00 2.00 1,424.65 1,424.65 361.36 853.68 15% 100% 2.00 1.00 238.05 27.62 251 Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IA2 Palliative care – IA2 Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IA2 Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IA2 Surgery – IB1 Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) Specialist consultation Radiotherapy – IB1 Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IB1 Palliative care – IB1 Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IB1 Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IB1 Surgery – IB2 Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) Specialist consultation 990.31 580.55 426.84 0% 100% 0% 1.00 - 580.55 - 180.38 0% - - 473.77 1,336.38 159.62 - 0% 0% 100% 0% 1.00 - 159.62 - 27.62 15.32 27.62 100% 100% 70% 6.00 3.00 6.00 165.72 45.96 116.00 6,540.11 1,248.26 1,424.65 1,424.65 307.92 45.17 426.84 0% 100% 100% 0% 0% 100% 100% 1.00 1.00 2.00 1.00 1,424.65 1,424.65 90.34 426.84 793.49 27.62 15% 100% 1.00 2.00 119.02 55.24 990.31 580.55 426.84 100% 100% 0% 1.00 1.00 - 990.31 580.55 - 180.38 0% - - 473.77 1,336.38 159.62 - 0% 0% 100% 0% 1.00 - 159.62 - 27.62 15.32 27.62 100% 98% 70% 6.00 2.00 2.00 165.72 30.03 38.67 6,647.89 1,248.26 1,424.65 1,424.65 307.92 45.17 426.84 0% 100% 0% 0% 0% 100% 100% 1.00 4.00 3.00 1,424.65 180.68 1,280.52 793.49 27.62 15% 100% 2.00 1.00 238.05 27.62 252 Radiotherapy – IB2 Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IB2 Palliative care – IB2 Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IB2 Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IB2 Surgery – IIA Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) Specialist consultation Radiotherapy – IIA Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IIA Palliative care – IIA Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IIA Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IIA Surgery – IIB Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) 990.31 580.55 426.84 100% 100% 0% 1.00 1.00 - 990.31 580.55 - 180.38 100% 1.00 180.38 473.77 1,336.38 159.62 - 0% 0% 100% 0% 1.00 - 159.62 - 27.62 15.32 27.62 100% 100% 100% 22.00 4.00 4.00 607.64 61.28 110.48 6,984.03 1,248.26 1,424.65 1,424.65 307.92 45.17 426.84 0% 100% 100% 0% 0% 100% 100% 1.00 1.00 1.00 1.00 1,424.65 1,424.65 45.17 426.84 793.49 27.62 15% 100% 1.00 1.00 119.02 27.62 990.31 580.55 426.84 100% 100% 0% 1.00 1.00 - 990.31 580.55 - 180.38 100% 1.00 180.38 473.77 1,336.38 159.62 - 0% 0% 100% 0% 1.00 - 159.62 - 27.62 15.32 27.62 100% 98% 70% 22.00 3.00 3.00 607.64 45.04 58.00 7,231.75 1,248.26 1,424.65 1,424.65 307.92 45.17 426.84 0% 100% 100% 0% 0% 100% 100% 1.00 1.00 3.00 1.00 1,424.65 1,424.65 135.51 426.84 793.49 15% 1.00 119.02 253 Specialist consultation Radiotherapy – IIB Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IIB Palliative care – IIB Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IIB Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IIB Surgery – IIIA–IIIB Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) Specialist consultation Radiotherapy – IIIA–IIIB Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IIIA–IIIB Palliative care – IIIA–IIIB Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IIIA–IIIB Specialist consultation Pap smear Vaginal/rectal examination Average cost per event IIIA–IIIB Surgery – IVA Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) 27.62 100% 1.00 27.62 990.31 580.55 426.84 100% 100% 0% 1.00 1.00 - 990.31 580.55 - 180.38 100% 1.00 180.38 473.77 1,336.38 159.62 - 0% 0% 100% 0% 1.00 - 159.62 - 27.62 15.32 27.62 100% 98% 70% 22.00 3.00 6.00 607.64 45.04 116.00 7,380.09 1,248.26 1,424.65 1,424.65 307.92 45.17 426.84 0% 0% 0% 0% 0% 0% 0% - - 793.49 27.62 0% 0% - - 990.31 580.55 426.84 100% 100% 100% 1.00 1.00 5.00 990.31 580.55 2,134.20 180.38 100% 1.00 180.38 473.77 1,336.38 159.62 - 100% 100% 100% 0% 1.00 1.00 1.00 - 473.77 1,336.38 159.62 - 27.62 15.32 27.62 100% 100% 100% 22.00 3.00 3.00 607.64 45.96 82.86 7,733.92 1,248.26 1,424.65 1,424.65 307.92 45.17 426.84 0% 0% 0% 0% 0% 0% 0% - - - - 254 Hospitalization (ICU) Specialist consultation Radiotherapy – IVA Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IVA Palliative care –IVA Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IVA Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IVA Surgery – IVB Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) Specialist consultation Radiotherapy – IVB Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IVB Palliative care – IVB Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IVB Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IVB 793.49 27.62 0% 0% - - 990.31 580.55 426.84 100% 100% 100% 1.00 1.00 5.00 990.31 580.55 2,134.20 180.38 100% 1.00 180.38 473.77 1,336.38 159.62 - 100% 100% 100% 0% 1.00 1.00 1.00 - 473.77 1,336.38 159.62 - 27.62 15.32 27.62 100% 100% 100% 22.00 6.00 12.00 607.64 91.92 331.44 8,028.46 1,248.26 1,424.65 1,424.65 307.92 45.17 426.84 0% 0% 0% 0% 0% 0% 0% - - 793.49 27.62 0% 0% - - 990.31 580.55 426.84 100% 100% 100% 1.00 1.00 6.00 990.31 580.55 2,561.04 180.38 100% 1.00 180.38 473.77 1,336.38 159.62 - 100% 100% 100% 0% 1.00 1.00 1.00 - 473.77 1,336.38 159.62 - 27.62 15.32 27.62 100% 100% 100% 22.00 6.00 12.00 607.64 91.92 331.44 8,455.30 - 1 Proportion of treatment-related events (visits, diagnostics, medications) occurring (e.g., 100% hospitalized patients are admitted to the regular ward; 20% ambulatory patients are seen by their gynecologist; 20% hospitalized patients receive chest x-rays). 2 Number of events (visits, diagnostics, medications) occurring (e.g., the average length of stay in the hospital is 3.5 days; an average of two pap smears are performed in patients). 3 2005 World Development Indicators, 2005 international dollars (LCU per international dollar, period average for year 2005). Costs are based on the first year of treatment and include follow-up care (e.g. ambulatory visits, vaginal/rectal examinations) for the first four years. These costs are based on an average patient who does not have any special circumstances (e.g., pregnancy, menstruation, PID, or HIV). Palliative care is assumed to be given at every stage of treatment and only considers the first year of palliative therapy. Sources: 255 1. Decreto 2423 de 1996. Manual Tarifario ajustado a 2005. 2. Ministerio de Protección Social. Serie Guías Clínicas. 3. Expert opinion (Interviews with 3 experts in charge of the National Cervical Cancer Program, Universidad de Cartagena, Cartagena, Colombia. 256 Mexico Unit cost (International $, 2005) % used1 Screening for cervical cancer Screening tests Pap smear 22.13 95% VPH DNA-based test 187.50 5% Visual inspection – VIA 0% Visual inspection – VILI 0% Follow-up General practitioner visit 22.00 100% Nurse visit 10.81 0% Specialist consultation 32.93 0% Average cost per event (screening for cervical cancer) Diagnosis, management, and follow-up of pre-cervical cancer Diagnosis – CIN 1 Colposcopy 49.75 70% Biopsy – sample 34.25 70% Biopsy – histopathology study 0% Treatment – CIN 1 Blood typing 0% Complete blood test 2.56 100% Prothrombin time 2.56 100% Blood glucose 2.56 100% Creatinine 2.56 100% Complete urine test 2.56 100% Urine culture 2.56 100% Endocervical curettage 200.00 0% Cryotherapy 165.00 10% LEEP 133.75 20% Cold knife conization 200.00 0% Observation ward 32.93 100% Regular ward 77.75 100% ECG 0% Follow-up – CIN 1 General practitioner visit 22.00 0% Nurse visit 10.81 100% Specialist consultation 32.93 100% Colposcopy 49.75 100% Biopsy – sample 34.25 100% Biopsy – histopathology study 100% Pap smear 22.13 100% Management of complications – CIN 1 Surgical intervention/sutures 20.38 10% IV antibiotics 17.90 10% Blood transfusion 28.75 10% Regular ward 77.75 0% Average cost per event – CIN 1 Diagnosis – CIN 2 Colposcopy 49.75 100% Biopsy – sample 34.25 100% Frequency2 Cost per event (International $, 2005)3 1.00 1.00 - 21.02 9.38 - 1.00 - 22.00 52.39 2.00 2.00 - 69.65 47.95 - 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 - 2.56 2.56 2.56 2.56 2.56 2.56 16.50 26.75 32.93 77.75 - 1.00 4.00 2.00 2.00 2.00 10.81 131.72 99.50 68.50 44.25 1.00 1.00 1.00 - 2.04 1.79 2.88 648.37 2.00 2.00 99.50 68.50 257 Biopsy – histopathology study 0% Treatment – CIN 2 Blood typing 70% Complete blood test 2.56 70% Prothrombin time 2.56 70% Blood glucose 2.56 70% Creatinine 2.56 70% Complete urine test 2.56 70% Urine culture 2.56 20% Endocervical curettage 200.00 0% Cryotherapy 165.00 1% LEEP 133.75 90% Cold knife conization 200.00 2% Simple hysterectomy 1,079.75 7% Short-stay hospitalization 77.75 60% Long-stay hospitalization 510.38 25% ECG 0% Follow-up – CIN 2 General practitioner visit 22.00 0% Nurse visit 10.81 0% Specialist consultation 32.93 100% Colposcopy 49.75 100% Biopsy – sample 34.25 100% Biopsy – histopathology study 0% Pap smear 22.13 100% Management of complications – CIN 2 Surgical intervention/sutures 20.38 10% IV antibiotics 17.90 10% Blood transfusion 28.75 10% Regular ward 77.75 0% Average cost per event – CIN 2 Staging, management, and follow-up of invasive cervical cancer Staging of invasive cervical cancer (all stages) Vaginal/rectal examination 1,273.50 70% Colposcopy 49.75 100% Biopsy – sample 34.25 100% Biopsy – histopathology study 0% Intravenous pyelogram 0% Abdominal ultrasound 61.13 70% ECG 0% Cystoscopy 139.75 70% Proctoscopy 147.63 70% Cone biopsy 133.75 100% Endocervical curettage/smear 200.00 0% Chest x-ray (front/lateral) 41.75 70% Bone scan 0% Abdomen/pelvis CT scan 0% Pelvis MRI 108.88 70% Urethrocistofibroscopy 0% Rectosigmoidoscopy 84.63 70% Urography 0% Complete hemogram 2.56 100% Complete urine test 2.56 100% - - 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 3.00 - 1.79 1.79 1.79 1.79 1.79 0.51 1.65 120.38 4.00 75.58 46.65 382.78 - 4.00 2.00 2.00 2.00 131.72 99.50 68.50 44.25 1.00 1.00 1.00 - 2.04 1.79 2.88 1,159.18 2.00 1.00 1.00 2.00 1.00 1.00 1.00 1.00 1.00 1.00 4.00 1.00 1,782.90 49.75 34.25 85.58 97.83 103.34 133.75 29.23 76.21 59.24 10.24 2.56 258 Urine culture 2.56 Electrolyte 2.56 Serum creatinine 2.56 Prothrombin time 2.56 Glycemia 2.56 Ionogram HIV test ALT serum AST (TGO) Ureic nitrogen Nurse visit 10.81 Specialist consultation 32.93 Treatment of invasive cervical cancer by stage Surgery – IA1 Cold knife conization 133.75 Simple hysterectomy 1,079.75 Radical hysterectomy 1,515.38 Pelvic lymphadenectomy 1,526.75 Trachelectomy 1,310.25 Hospitalization (short-stay) Hospitalization (regular ward) 77.75 Hospitalization (intermediate 510.38 care ward) Hospitalization (ICU) Specialist consultation 32.93 Radiotherapy – IA1 Pelvic teletherapy 499.88 Intravaginal brachytherapy 744.50 Hospitalization (intermediate 510.38 care ward) Chemotherapy – IA1 365.63 Palliative care – IA1 Palliative radiotherapy 772.50 Palliative surgery 1,079.75 Palliative medicine 26.45 Palliative care (other) 32.93 Follow-up – IA1 Specialist consultation 32.93 Pap smear 22.13 Vaginal/rectal examination 123.50 Average cost per event – IA1 Surgery – IA2 Simple hysterectomy 1,079.75 Radical hysterectomy 1,515.38 Pelvic lymphadenectomy 1,526.75 Trachelectomy 1,310.25 Hospitalization (short-stay) Hospitalization (regular ward) 77.75 Hospitalization (intermediate 510.38 care ward) Hospitalization (ICU) Specialist consultation 32.93 Radiotherapy – IA2 100% 100% 100% 100% 100% 0% 0% 0% 0% 0% 100% 100% 1.00 2.00 1.00 1.00 1.00 1.00 4.00 2.56 5.12 2.56 2.56 2.56 10.81 131.72 30% 100% 0% 0% 0% 0% 0% 100% 1.00 1.00 1.00 40.13 1,079.75 510.38 0% 100% 2.00 65.86 0% 0% 0% - - 0% - - 0% 0% 100% 100% 1.00 1.00 26.45 32.93 100% 98% 70% 6.00 3.00 3.00 197.58 65.05 259.35 4,900.22 0% 100% 100% 0% 0% 0% 100% 1.00 1.00 1.00 1,515.38 1,526.75 510.38 0% 100% 1.00 32.93 259 Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IA2 Palliative care – IA2 Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up - IA2 Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IA2 Surgery – IB1 Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) Specialist consultation Radiotherapy – IB1 Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IB1 Palliative care – IB1 Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IB1 Specialist consultation Pap smear Vaginal/rectal examination Average cost per event - IB1 Surgery – IB2 Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) Specialist consultation 499.88 744.50 510.38 100% 100% 50% 1.00 1.00 0.50 499.88 744.50 127.59 365.63 0% - - 772.50 1,079.75 26.45 32.93 0% 0% 100% 100% 1.00 1.00 26.45 32.93 32.93 22.13 123.50 100% 98% 70% 4.00 2.00 2.00 131.72 43.37 172.90 7,987.51 1,079.75 1,515.38 1,526.75 1,310.25 77.75 510.38 0% 100% 100% 0% 0% 0% 100% 1.00 1.00 1.00 1,515.38 1,526.75 510.38 32.93 0% 100% 2.00 65.86 499.88 744.50 510.38 100% 100% 30% 1.00 1.00 0.50 499.88 744.50 76.56 365.63 50% 1.00 182.81 772.50 1,079.75 26.45 32.93 0% 0% 100% 100% 1.00 1.00 26.45 32.93 32.93 22.13 123.50 100% 50% 50% 2.00 2.00 1.00 65.86 22.13 61.75 7,953.97 1,079.75 1,515.38 1,526.75 1,310.25 77.75 510.38 0% 100% 100% 0% 0% 0% 60% 1.00 1.00 1.00 1,515.38 1,526.75 306.23 32.93 0% 100% 2.00 65.86 260 Radiotherapy – IB2 Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IB2 Palliative care – IB2 Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IB2 Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IB2 Surgery – IIA Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) Specialist consultation Radiotherapy – IIA Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IIA Palliative care – IIA Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IIA Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IIA Surgery – IIB Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) 499.88 744.50 510.38 100% 100% 65% 1.00 1.00 0.50 499.88 744.50 165.87 365.63 50% 1.00 182.81 772.50 1,079.75 26.45 32.93 0% 0% 5% 5% 1.00 1.00 1.32 1.65 32.93 22.13 123.50 100% 98% 70% 4.00 2.00 2.00 131.72 43.37 172.90 7,980.97 1,079.75 1,515.38 1,526.75 1,310.25 77.75 510.38 0% 0% 0% 0% 0% 0% 0% - - 32.93 0% 0% - - 699.88 944.50 510.38 100% 100% 100% 1.00 1.00 4.00 699.88 944.50 2,041.50 365.63 100% 1.00 365.63 772.50 1,079.75 26.45 32.93 0% 0% 100% 100% 4.00 4.00 105.80 131.72 32.93 22.13 123.50 100% 100% 100% 22.00 3.00 3.00 724.46 66.38 370.50 8,073.10 1,079.75 1,515.38 1,526.75 1,310.25 77.75 510.38 0% 0% 0% 0% 0% 0% 0% - - - 0% - - - 261 Specialist consultation Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IIB Palliative care – IIB Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IIB Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IIB Surgery – IIIA–IIIB Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) Specialist consultation Radiotherapy – IIIA–IIIB Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IIIA–IIIB Palliative care – IIIA–IIIB Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IIIA–IIIB Specialist consultation Pap smear Vaginal/rectal examination Average cost per event IIIA–IIIB Surgery – IVA Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) 32.93 0% Radiotherapy - IIB 699.88 100% 944.50 100% 510.38 100% - - 1.00 1.00 4.00 699.88 944.50 2,041.50 365.63 75% 1.00 274.22 772.50 1,079.75 26.45 32.93 0% 70% 100% 100% 1.00 1.00 1.00 755.83 26.45 32.93 32.93 22.13 123.50 100% 100% 100% 22.00 3.00 3.00 724.46 66.38 370.50 8,559.38 1,079.75 1,515.38 1,526.75 1,310.25 77.75 510.38 0% 0% 0% 0% 0% 0% 0% - - 32.93 0% 0% - - 699.88 944.50 510.38 100% 100% 100% 1.00 1.00 4.00 699.88 944.50 2,041.50 365.63 75% 1.00 274.22 772.50 1,079.75 26.45 32.93 65% 65% 100% 100% 1.00 1.00 1.00 1.00 502.13 701.84 26.45 32.93 32.93 22.13 123.50 100% 98% 70% 22.00 3.00 3.00 724.46 65.05 259.35 8,895.04 1,079.75 1,515.38 1,526.75 1,310.25 77.75 510.38 0% 0% 0% 0% 0% 0% 0% - - - - 262 Hospitalization (ICU) Specialist consultation Radiotherapy – IVA Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IVA Palliative care – IVA Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IVA Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IVA Surgery – IVB Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) Specialist consultation Radiotherapy – IVB Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IVB Palliative care – IVB Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IVB Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IVB 32.93 0% 0% - - 699.88 944.50 510.38 100% 100% 100% 1.00 1.00 4.00 699.88 944.50 2,041.50 365.63 100% 1.00 365.63 772.50 1,079.75 26.45 32.93 65% 50% 100% 100% 1.00 1.00 1.00 1.00 502.13 539.88 26.45 32.93 32.93 22.13 123.50 100% 98% 70% 22.00 6.00 6.00 724.46 130.10 518.70 9,148.88 1,079.75 1,515.38 1,526.75 1,310.25 77.75 510.38 0% 0% 0% 0% 0% 0% 0% - - 32.93 0% 0% - - 699.88 944.50 510.38 100% 100% 100% 1.00 1.00 4.00 699.88 944.50 2,041.50 365.63 100% 1.00 365.63 772.50 1,079.75 26.45 32.93 85% 50% 100% 100% 1.00 1.00 1.00 1.00 656.63 539.88 26.45 32.93 32.93 22.13 123.50 100% 100% 100% 22.00 6.00 6.00 724.46 132.75 741.00 9,528.34 - 1 Proportion of treatment-related events (visits, diagnostics, medications) occurring (e.g., 100% hospitalized patients are admitted to the regular ward; 20% ambulatory patients are seen by their gynecologist; 20% hospitalized patients receive chest x-rays). 2 Number of events (visits, diagnostics, medications) occurring (e.g., the average length of stay in the hospital is 3.5 days; an average of two pap smears are performed in patients). 3 2005 World Development Indicators, 2005 international dollars (LCU per international dollar, period average for year 2005). Costs are based on the first year of treatment and include follow-up care (e.g. ambulatory visits, vaginal/rectal examinations) for the first four years. These costs are based on an average patient who does not have any special circumstances (e.g., pregnancy, menstruation, PID, or HIV). Palliative care is assumed to be given at every stage of treatment and considers only the first year of palliative therapy. Sources: 263 1. National Comprehensive Cancer Network (NCCN), Guías de Práctica Oncológica – v.1 2005; Modificación a la Norma Oficial Mexicana NOM-014-SSA2-1994, Para la Prevención, Detección, diagnóstico, tratamiento, control y vigilancia epidemiológica del cáncer cérvico uterino. 2. Expert opinion (Interview with one expert in charge of the NCNN). 3. Marmolejo-Saucedo, Costos del diagnostico y tratamiento de las enfermedades relacionadas con el virus del papiloma humano en el Instituto Nacional de Cancerologia, Mexico. 264 Peru Unit cost (International $, 2005) % used1 Screening for cervical cancer Screening tests Pap smear 3.42 90% VPH DNA-based test 12.50 5% Visual inspection – VIA 0.80 3% Visual inspection – VILI 1.96 2% Follow-up General practitioner visit 2.77 80% Nurse visit 0.84 100% Specialist consultation 13.88 20% Average cost per event (screening for cervical cancer) Diagnosis, management, and follow-up of precervical cancer Diagnosis – CIN 1 Colposcopy 27.70 80% Biopsy – sample 20.70 80% Biopsy – histopathology study 38.67 0% Treatment – CIN 1 Blood typing 3.15 0% Complete blood test 2.50 100% Prothrombin time 2.50 100% Blood glucose 2.50 100% Creatinine 2.50 100% Complete urine test 2.50 100% Urine culture 2.50 100% Endocervical curettage 114.17 0% Cryotherapy 38.67 10% LEEP 48.22 10% Cold knife conization 315.27 0% Observation ward 71.35 0% Regular ward 190.50 100% ECG 8.59 0% Follow-up – CIN 1 General practitioner visit 2.77 0% Nurse visit 0.84 100% Specialist consultation 13.88 100% Colposcopy 27.70 100% Biopsy - sample 20.70 100% Biopsy - histopathology study 38.67 0% Pap smear 3.42 100% Management of complications – CIN 1 Surgical intervention/sutures 52.40 10% IV antibiotics 27.51 10% Blood transfusion 8.44 0% Regular ward 190.50 10% Average cost per event – CIN 1 Diagnosis – CIN 2 Colposcopy 27.70 100% Biopsy – sample 20.70 100% Frequency2 Cost per event (International $, 2005)3 1.00 1.00 1.00 1.00 3.08 0.63 0.02 0.04 2.00 2.00 2.00 4.43 1.68 5.55 15.43 2.00 2.00 - 44.32 33.12 - 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 - 2.50 2.50 2.50 2.50 2.50 2.50 3.87 4.82 190.50 - 1.00 4.00 4.00 4.00 2.00 0.84 55.52 110.80 82.80 6.84 1.00 1.00 2.00 5.24 2.75 38.10 594.52 2.00 2.00 55.40 41.40 265 Biopsy – histopathology study 38.67 0% Treatment – CIN 2 Blood typing 3.15 100% Complete blood test 2.50 100% Prothrombin time 2.50 100% Blood glucose 2.50 100% Creatinine 2.50 100% Complete urine test 2.50 100% Urine culture 2.50 100% Endocervical curettage 0% Cryotherapy 38.67 5% LEEP 48.22 80% Cold knife conization 315.27 5% Simple hysterectomy 1,053.93 10% Short-stay hospitalization 58.68 0% Long-stay hospitalization 190.50 40% ECG 8.59 0% Follow-up – CIN 2 General practitioner visit 2.77 0% Nurse visit 0.84 0% Specialist consultation 13.88 100% Colposcopy 27.70 100% Biopsy – sample 20.70 100% Biopsy – histopathology study 38.67 0% Pap smear 3.42 100% Management of complications – CIN 2 Surgical intervention/sutures 20.38 10% IV antibiotics 17.90 10% Blood transfusion 8.44 0% Regular ward 190.50 0% Average cost per event - CIN 2 Staging, management, and follow-up of invasive cervical cancer Staging of invasive cervical cancer (all stages) Vaginal/rectal examination 396.80 100% Colposcopy 27.70 100% Biopsy - sample 20.70 80% Biopsy - histopathology study 38.67 0% Intravenous pyelogram 32.86 0% Abdominal ultrasound 58.85 70% ECG 7.64 0% Cystoscopy 60.80 70% Proctoscopy 68.99 70% Cone biopsy 474.40 20% Endocervical curettage/smear 126.25 0% Chest x-ray (front/lateral) 21.20 100% Bone scan 114.26 0% Abdomen/pelvis CT scan 117.97 0% Pelvis MRI 178.33 70% Urethrocistofibroscopy 33.02 0% Rectosigmoidoscopy 52.62 70% Urography 15.45 0% Complete hemogram 2.50 100% Complete urine test 2.50 100% - - 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 2.25 - 3.15 2.50 2.50 2.50 2.50 2.50 2.50 1.93 38.58 15.76 105.39 171.45 - 5.00 4.00 4.00 4.00 69.40 110.80 82.80 13.68 1.00 1.00 - 2.04 1.79 728.57 2.00 2.00 2.00 2.00 1.00 1.00 1.00 1.00 1.00 1.00 5.00 1.00 793.60 55.40 33.12 82.39 42.56 48.29 94.88 21.20 124.83 36.83 12.50 2.50 266 Urine culture 2.50 Electrolyte 2.50 Serum creatinine 2.50 Prothrombin time 2.50 Glycemia 2.50 Ionogram 6.94 HIV test 33.94 ALT serum 2.47 AST (TGO) 2.47 Ureic nitrogen 3.35 Nurse visit 0.84 Specialist consultation 13.88 Treatment of invasive cervical cancer by stage Surgery – IA1 Cold knife conization 133.75 Simple hysterectomy 1,053.93 Radical hysterectomy 2,037.58 Pelvic lymphadenectomy 999.53 Trachelectomy 574.07 Hospitalization (short-stay) 58.68 Hospitalization (regular ward) 135.10 Hospitalization (intermediate 360.62 care ward) Hospitalization (ICU) 362.42 Specialist consultation 13.88 Radiotherapy – IA1 Pelvic teletherapy 869.60 Intravaginal brachytherapy 829.69 Hospitalization (intermediate 428.69 care ward) Chemotherapy – IA1 411.57 Palliative care – IA1 Palliative radiotherapy 596.67 Palliative surgery 681.38 Palliative medicine 67.96 Palliative care (other) 395.32 Follow-up – IA1 Specialist consultation 13.88 Pap smear 3.42 Vaginal/rectal examination 117.57 Average cost per event – IA1 Surgery – IA2 Simple hysterectomy 1,053.93 Radical hysterectomy 2,037.58 Pelvic lymphadenectomy 999.53 Trachelectomy 574.07 Hospitalization (short-stay) 58.68 Hospitalization (regular ward) 135.10 Hospitalization (intermediate 360.62 care ward) Hospitalization (ICU) 362.42 Specialist consultation 13.88 Radiotherapy – IA2 100% 100% 100% 100% 100% 0% 0% 0% 0% 0% 100% 100% 1.00 6.00 1.00 1.00 1.00 1.00 4.00 2.50 15.00 2.50 2.50 2.50 0.84 55.52 30% 70% 0% 0% 0% 0% 0% 100% 1.00 1.00 2.00 40.13 737.75 721.24 0% 100% 2.00 27.76 0% 0% 0% - - 0% - - 0% 0% 100% 100% 1.00 1.00 67.96 395.32 100% 100% 100% 6.00 2.00 2.00 83.28 6.84 235.14 3,744.88 0% 100% 100% 0% 0% 0% 100% 1.00 1.00 2.00 2,037.58 999.53 721.24 0% 100% 1.00 13.88 267 Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IA2 Palliative care – IA2 Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IA2 Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IA2 Surgery – IB1 Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) Specialist consultation Radiotherapy – IB1 Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IB1 Palliative care – IB1 Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IB1 Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IB1 Surgery – IB2 Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) Specialist consultation 869.60 829.69 428.69 100% 100% 50% 1.00 1.00 1.00 869.60 829.69 214.35 411.57 0% - - 596.67 681.38 67.96 395.32 0% 0% 25% 5% 1.00 1.00 16.99 19.77 13.88 3.42 117.57 100% 98% 70% 6.00 2.00 2.00 83.28 6.70 164.60 7,406.67 1,053.93 2,037.58 999.53 574.07 58.68 135.10 360.62 0% 100% 100% 0% 0% 0% 100% 1.00 1.00 2.00 2,037.58 999.53 721.24 362.42 13.88 0% 100% 2.00 27.76 869.60 829.69 428.69 100% 100% 50% 1.00 1.00 1.00 869.60 829.69 214.35 411.57 0% - - 596.67 681.38 67.96 395.32 0% 0% 100% 100% 1.00 1.00 67.96 395.32 13.88 3.42 117.57 100% 100% 100% 6.00 2.00 2.00 83.28 6.84 235.14 7,917.75 1,053.93 2,037.58 999.53 574.07 58.68 135.10 360.62 0% 100% 100% 0% 0% 0% 100% 1.00 1.00 2.00 2,037.58 999.53 721.24 362.42 13.88 0% 100% 2.00 27.76 268 Radiotherapy – IB2 Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IB2 Palliative care – IB2 Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IB2 Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IB2 Surgery – IIA Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) Specialist consultation Radiotherapy – IIA Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IIA Palliative care – IIA Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IIA Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IIA Surgery – IIB Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) 869.60 829.69 428.69 100% 100% 50% 1.00 1.00 1.00 869.60 829.69 214.35 411.57 0% - - 596.67 681.38 67.96 395.32 0% 0% 50% 50% 1.00 1.00 33.98 197.66 13.88 3.42 117.57 100% 60% 60% 22.00 3.00 3.00 305.36 6.16 211.63 7,884.00 1,053.93 2,037.58 999.53 574.07 58.68 135.10 360.62 0% 100% 100% 0% 0% 0% 100% 1.00 1.00 2.00 2,037.58 999.53 721.24 362.42 13.88 0% 0% - - 869.60 829.69 428.69 100% 100% 50% 1.00 1.00 1.00 869.60 829.69 214.35 411.57 50% 1.00 205.79 596.67 681.38 67.96 395.32 0% 0% 50% 50% 1.00 1.00 33.98 197.66 13.88 3.42 117.57 100% 100% 100% 22.00 2.00 2.00 305.36 6.84 235.14 8,086.22 1,053.93 2,037.58 999.53 574.07 58.68 135.10 360.62 0% 0% 0% 0% 0% 0% 0% - - 362.42 0% - - - 269 Specialist consultation Radiotherapy – IIB Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy - IIB Palliative care – IIB Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IIB Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IIB Surgery – IIIA–IIIB Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) Specialist consultation Radiotherapy – IIIA–IIIB Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IIIA–IIIB Palliative care – IIIA–IIIB Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IIIA–IIIB Specialist consultation Pap smear Vaginal/rectal examination Average cost per event IIIA–IIIB Surgery – IVA Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) 13.88 0% - - 869.60 829.69 428.69 100% 100% 100% 1.00 1.00 4.00 869.60 829.69 1,714.76 411.57 100% 1.00 411.57 596.67 681.38 67.96 395.32 60% 70% 100% 100% 1.00 1.00 3.00 3.00 358.00 476.97 203.88 1,185.96 13.88 3.42 117.57 100% 100% 100% 22.00 3.00 3.00 305.36 10.26 352.71 8,148.23 1,053.93 2,037.58 999.53 574.07 58.68 135.10 360.62 0% 0% 0% 0% 0% 0% 0% - - 362.42 13.88 0% 0% - - 869.60 829.69 428.69 100% 100% 100% 1.00 1.00 5.00 869.60 829.69 2,143.45 411.57 100% 1.00 411.57 596.67 681.38 67.96 395.32 85% 85% 100% 100% 1.00 1.00 2.00 2.00 507.17 579.17 135.92 790.64 13.88 3.42 117.57 100% 100% 100% 22.00 4.00 4.00 305.36 13.68 470.28 8,486.00 1,053.93 2,037.58 999.53 574.07 58.68 135.10 360.62 0% 0% 0% 0% 0% 0% 0% - - - - 270 Hospitalization (ICU) Specialist consultation Radiotherapy – IVA Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IVA Palliative care – IVA Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IVA Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IVA Surgery – IVB Simple hysterectomy Radical hysterectomy Pelvic lymphadenectomy Trachelectomy Hospitalization (short-stay) Hospitalization (regular ward) Hospitalization (intermediate care ward) Hospitalization (ICU) Specialist consultation Radiotherapy – IVB Pelvic teletherapy Intravaginal brachytherapy Hospitalization (intermediate care ward) Chemotherapy – IVB Palliative care – IVB Palliative radiotherapy Palliative surgery Palliative medicine Palliative care (other) Follow-up – IVB Specialist consultation Pap smear Vaginal/rectal examination Average cost per event – IVB 362.42 13.88 0% 0% - - 869.60 829.69 428.69 100% 100% 100% 1.00 1.00 5.00 869.60 829.69 2,143.45 411.57 100% 1.00 411.57 596.67 681.38 67.96 395.32 90% 90% 100% 100% 1.00 1.00 2.00 2.00 537.00 613.24 135.92 790.64 13.88 3.42 117.57 100% 100% 100% 22.00 4.00 4.00 305.36 13.68 470.28 8,549.90 1,053.93 2,037.58 999.53 574.07 58.68 135.10 360.62 0% 0% 0% 0% 0% 0% 0% - - 362.42 13.88 0% 0% - - 869.60 829.69 428.69 100% 100% 100% 1.00 1.00 5.00 869.60 829.69 2,143.45 411.57 100% 1.00 411.57 596.67 681.38 67.96 395.32 85% 75% 100% 100% 1.00 1.00 2.00 2.00 507.17 511.04 135.92 790.64 13.88 3.42 117.57 100% 100% 100% 22.00 6.00 6.00 305.36 20.52 705.42 8,659.84 - 1 Proportion of treatment-related events (visits, diagnostics, medications) occurring (e.g., 100% hospitalized patients are admitted to the regular ward; 20% ambulatory patients are seen by their gynecologist; 20% hospitalized patients receive chest x-rays). 2 Number of events (visits, diagnostics, medications) occurring (e.g., the average length of stay in the hospital is 3.5 days; an average of 2 pap smears are performed in patients). 3 2005 World Development Indicators, 2005 international dollars (LCU per international dollar, period average for year 2005). Costs are based on the first year of treatment and includes follow up care (e.g. ambulatory visits, vaginal/rectal examinations) for the first four years. These costs are based on an average patient who does not have any special circumstances (pregnancy, menstruation, PID, or HIV). Palliative care is assumed to be given at every stage of treatment and only considers the first year of palliative therapy. Sources: 271 1. Tobar A. Costo y desempeño de las pruebas de tamizaje costos del tratamiento del cancer cervicouterino en la region de San Martín (Perú), OPS/DPC/NC, 2005. 2. Extrapolation based on unit cost estimates from 7 countries (Argentina, Brazil, Chile, Colombia, DR, Honduras and Mexico) - population weighted average. 3. Expert opinion (Interview with one OBGYN physician). 272 Appendix I. Costs of transportation and lost work time associated with precervical cancer and invasive cervical cancer by stage and country Costs in International $ for 2005 Argentina Brazil Chile Colombia Dominican Republic Honduras Jamaica Mexico Peru (Internation 2005) Transp. P costsq Transp. costsa Patient time lossb Transp. Costsc Patient time lossd Transp. costse Patient time lossf Transp. costsg Patient time lossh Transp. costsi Patient time lossj Transp. costsk Patient time lossl Transp. costsm Patient time lossn Transp. costso Patient time lossp 6.76 69.60 6.40 30.68 5.48 168.80 5.20 28.00 4.40 56.80 3.96 42.40 5.16 66.20 2.02 74.40 5.16 23.66 243.60 12.80 61.36 19.18 590.80 13.00 70.00 6.60 85.20 11.88 127.20 10.32 132.40 12.12 446.40 20.64 20.28 208.80 12.80 61.36 32.88 1,012.80 18.85 101.50 11.00 142.00 13.86 148.40 20.64 264.80 16.16 595.20 18.71 27.04 278.40 51.20 245.45 68.50 2,110.00 54.60 294.00 15.40 198.80 19.80 212.00 20.64 264.80 22.22 818.40 36.12 Average cost per event (IA2) 33.80 348.00 48.00 230.11 68.50 2,110.00 57.20 308.00 19.80 255.60 21.78 233.20 23.22 297.90 19.19 706.80 38.70 Average cost per event (IB1) 33.80 348.00 48.00 230.11 60.28 1,856.80 36.40 196.00 19.80 255.60 19.80 212.00 25.80 331.00 15.15 558.00 38.70 Average cost per event (IB2) 47.32 487.20 102.40 490.91 87.68 2,700.80 91.00 490.00 63.80 823.60 55.44 593.60 69.66 893.69 19.19 706.80 74.82 Average cost per event (IIA) 43.94 452.40 99.20 475.57 112.34 3,460.40 75.40 406.00 59.40 766.80 55.44 593.60 72.24 926.79 60.60 2,232.00 74.82 Average cost per event (IIB) 50.70 522.00 89.60 429.55 93.16 2,869.60 80.60 434.00 61.60 795.20 55.44 593.60 74.82 959.89 60.60 2,232.00 77.40 Average cost per event (IIIA–IIIB) 91.26 939.60 89.60 429.55 82.20 2,532.00 80.60 434.00 61.60 795.20 55.44 593.60 74.82 959.89 60.60 2,232.00 79.98 Average cost per event (IVA) 91.26 939.60 86.40 414.20 93.16 2,869.60 80.60 434.00 61.60 795.20 53.46 572.40 74.82 959.89 60.60 2,232.00 79.98 Average cost per event (IVB) 94.64 974.40 89.60 429.55 93.16 2,869.60 83.20 448.00 61.60 795.20 55.44 593.60 74.82 959.89 60.60 2,232.00 79.98 Average cost per screening Average cost per event (CIN 1) Average cost per event (CIN 2) Average cost per event (IA1) 273 66 26 23 46 49 49 95 95 99 1, 1, 1, a Transportation costs were based on assumptions made about the number of trips to and from the doctor’s office and/or clinic or hospital and the cost of each trip during the first year. The number of trips to and from the doctor’s office and/or clinic or hospital was based on the number of outpatient visits and hospital admissions reported by physicians in Buenos Aires. The cost of each trip was derived from the Asociacion Nacional de Empresas de Transportes Urbanos, 2005. b Care time costs were based on the number of days off work (one outpatient consultation or one day in the hospital was assumed to be the same as one day off work), assuming an average 2005 average monthly salary in Argentina of Int. $765.60 (Direccion Central de Estudios y Formulacion de Politicas de Empleo, en base a la EPH, INDEC, 2005) and 22 days of work per month. c Transportation costs were based on assumptions made about the number of trips to and from the doctor’s office and/or clinic or hospital and the cost of each trip during the first year. The number of trips to and from the doctor’s office and/or clinic or hospital was based on the number of outpatient visits and hospital admissions reported by physicians in São Paulo. The cost of each trip was derived from the Associação Nacional das Empresas de Transportes Urbanos, 2005. d Care time costs were based on the number of days off work (one outpatient consultation or one day in the hospital was assumed to be the same as one day off work), assuming an average 2005 monthly salary in Brazil of Int. $1,083.58 (BCB, 2005) and 22 days of work per month. e Transportation costs were based on assumptions made about the number of trips to and from the doctor’s office and/or clinic or hospital and the cost of each trip during the first year. The number of trips to and from the doctor’s office and/or clinic or hospital was based on the number of outpatient visits and hospital admissions reported by physicians in Santiago. The cost of each trip was derived from the Asociacion Nacional de Empresas de Transportes Urbanos, 2005. f Care time costs were based on the number of days off work (one outpatient consultation or one day in the hospital was assumed to be the same as one day off work), assuming an average 2005 monthly salary in Chile of Int. $1856.80 (Estadisticas del Trabajo y Prevision, 2005) and 22 days of work per month. g Transportation costs were based on assumptions made about the number of trips to and from the doctor’s office and/or clinic or hospital and the cost of each trip during the first year. The number of trips to and from the doctor’s office and/or clinic or hospital was based on the number of outpatient visits and hospital admissions reported by physicians in Cartagena de Indias. The cost of each trip was derived from personal communication (Nelson Alvis). h Care time costs were based on the number of days off work (one outpatient consultation or one day in the hospital was assumed to be the same as one day off work), assuming an average 2005 monthly salary in Colombia of Int. $308.00 (personal communication, Nelson Alvis) and 22 days of work per month. i Transportation costs were based on assumptions made about the number of trips to and from the doctor’s office and/or clinic or hospital and the cost of each trip during the first year. The number of trips to and from the doctor’s office and/or clinic or hospital was based on the number of outpatient visits and hospital admissions reported by physicians in Santo Domingo. The cost of each trip was derived from personal communication (Elizabeth Gomez). j Care time costs were based on the number of days off work (one outpatient consultation or one day in the hospital was assumed to be the same as one day off work), assuming an average 2005 monthly salary in Dominican Republic of Int. $624.80 (personal communication, Nelson Alvis) and 22 days of work per month. k Transportation costs were based on assumptions made about the number of trips to and from the doctor’s office and/or clinic or hospital and the cost of each trip during the first year. The number of trips to and from the doctor’s office and/or clinic or hospital was based on the number of outpatient visits and hospital admissions reported by physicians in Tegucigalpa. The cost of each trip was derived from personal communication. l Care time costs were based on the number of days off work (one outpatient consultation or one day in the hospital was assumed to be the same as one day off work), assuming an average 2005 monthly salary in Dominican Republic of Int. $466.40 (personal communication) and 22 days of work per month. m Transportation costs were based on the number of trips to and from the doctor’s office and/or clinic or hospital from eight countries and the population weighted average cost of each trip during the first year. The number of trips to and from the doctor’s office and/or clinic or hospital was based on the number of outpatient visits and hospital admissions extrapolated from eight countries. n Care time costs were based on the number of days off work (one outpatient consultation or one day in the hospital was assumed to be the same as one day off work), assuming a population weighted average 2005 monthly salary of Int. $728.19 and 22 days of work per month. 274 o Transportation costs were based on assumptions made about the number of trips to and from the doctor’s office and/or clinic or hospital and the cost of each trip during the first year. The number of trips to and from the doctor’s office and/or clinic or hospital was based on the amount of outpatient visits and hospital admissions reported by physicians in Mexico City. The cost of each trip was derived from personal communication. p Care time costs were based on the number of days off work (one outpatient consultation or one day in the hospital was assumed to be the same as one day off work), assuming an average 2005 monthly salary in Dominican Republic of Int. $1,636.80 (personal communication) and 22 days of work per month. q Transportation costs were based on the number of trips to and from the doctor’s office and/or clinic or hospital from eight countries and the population weighted average cost of each trip during the first year. The number of trips to and from the doctor’s office and/or clinic or hospital was based on the number of outpatient visits and hospital admissions extrapolated from eight countries. r Care giver time costs were based on the number of days off work (one outpatient consultation or one day in the hospital was assumed to be the same as one day off work), assuming a population weighted average 2005 monthly salary of Int. $728.19 and 22 days of work per month. 275 Appendix J. Vaccination cost per vaccinated girl and components of cost, expressed in different currencies by country Cost per fully immunized girl in local currency units Argentina Brazil Chile Cost per vaccinated girl 25.00 60.08 53.15 12,516.41 International $ Peso Real Peso Currency Unit Vaccine cost* 15.00 43.55 36.52 8,401.35 Vaccine wastage* 2.25 6.53 5.48 1,260.20 Vaccine supplies (including wastage and freight)* 1.31 3.80 3.19 733.72 Administration** 1.50 1.44 1.86 494.05 Vaccine Support** 4.94 4.75 6.11 1,627.08 Monitoring, Programmatic, Cold chain, Injection safety, Operational costs 2.94 2.83 3.64 968.34 Incremental cost of adolescent vaccination program 2.00 1.92 2.47 658.74 Vaccine cost per dose 5.00 14.52 12.17 2800.45 276 Appendix J. Vaccination cost per vaccinated girl and components of cost, expressed in different currencies by country Cost per vaccinated girl Currency Unit Vaccine cost* Vaccine wastage* Vaccine supplies (including wastage and freight)* Administration** Vaccine Support** Monitoring, programmatic, cold chain, injection safety, operational costs Incremental cost of adolescent vaccination program Vaccine cost per dose 277 Cost per fully immunized girl in local currency units Colombia Mexico 25.00 48,563.25 250.93 International $ Peso Peso 15.00 8401.35 163.47 2.25 1,260.20 24.52 Peru 71.15 Nuevo Sol 49.44 7.42 1.31 1.50 4.94 733.72 494.05 4,210.18 14.28 11.33 37.33 4.32 2.32 7.65 2.94 2505.65 22.22 4.55 2.00 5.00 1704.53 11,604.17 15.11 54.49 3.10 16.48 Appendix J. Vaccination cost per vaccinated girl and components of cost, expressed in different currencies by country Cost per vaccinated girl Currency Unit Vaccine cost* Vaccine wastage* Vaccine supplies (including wastage and freight)* Administration** Vaccine Support** Monitoring, programmatic, cold chain, injection safety, operational costs Incremental cost of adolescent vaccination program Vaccine cost per dose 278 Cost per fully immunized girl in U.S. dollars Argentina Brazil 25.00 20.78 21.21 International $ U.S. Dollars U.S. Dollars 15.00 15.00 15.00 2.25 2.25 2.25 Chile 18.57 U.S. Dollars 15.00 2.25 1.31 1.50 4.94 1.31 0.52 1.70 1.31 0.62 2.03 1.31 0.0027 0.01 2.94 1.01 1.21 0.01 2.00 5.00 0.69 5.00 0.82 5.00 0.0036 5.00 Appendix J. Vaccination cost per vaccinated girl and components of cost, expressed in different currencies by country Cost per vaccinated girl Currency Unit Vaccine cost* Vaccine wastage* Vaccine supplies (including wastage and freight)* Administration* Vaccine Support** Monitoring, programmatic, cold chain, injection safety, operational costs Incremental cost of adolescent vaccination program Vaccine cost per dose Cost per fully immunized girl in U.S. dollars Colombia Mexico 25.00 18.56 19.15 International $ U.S. Dollars U.S. Dollars 15.00 15.00 15.00 2.25 2.25 2.25 Peru 20.51 U.S. Dollars 15.00 2.25 1.31 1.50 4.94 1.31 0.0006 0.0021 1.31 0.14 0.45 1.31 0.46 1.50 2.94 0.0013 0.27 0.89 2.00 5.00 0.0009 5.00 0.18 5.00 0.61 5.00 *Vaccine, wastage, and supplies are considered tradeable goods. Whether expressed in local currency units or in U.S. dollars, they are converted by using U.S. dollar to local currency unit exchange rates. For tradeable goods, one U.S. dollar equals one International dollar; thus, when International dollars are expressed as U.S. dollars, those costs stay the same. **Administration and vaccine support are considered local, nontradeable goods. When these costs are expressed in local currency units, they are converted from International dollars using PPP exchange rates. When these costs are expressed in U.S. dollars, the local currency units are converted by using U.S. dollar exchange rates. 279