Download Background

Cervical Cancer
Screening Capstone Project
Concordia University, Nebraska
Laura Mischnick
April 22, 2015
CERVICAL CANCER
Page 2
Background
I have chosen to do my capstone paper on the screening methods of cervical cancer. The
population I examined was women in the United States, 21 through 65 years of age.
Papanicolaou (Pap) tests are the conventional screening tool in the United States, but Human
Papillomavirus (HPV) testing has become a secondary tool in recent years.
Cervical Cancer
Cervical cancer is the second most prevalent cancer in women worldwide. Each year
more than 500,000 new cases, and 250,000 deaths result from cervical cancer (Bengtsson et al,
2014; Zandi et al, 2010). In the United States, almost 13,000 women get cervical cancer each
year, and 4,100 will die as a result of the cancer (Inside Knowledge: Get the Facts about
Gynecologic Cancer, 2015; Pap and HPV Testing, 2014). In the United States, cervical cancer is
only the tenth most common cancer in women due to high screening participation (Bengtsson et
al, 2014).
Cervical cancer is cancer that begins in the cervix of a woman. The cervix is the lower
part of the uterus, which connects the upper part of the uterus with the vagina (Inside
Knowledge: Get the Facts about Gynecologic Cancer, 2015). It can be prevented with screening
tests, and follow-up treatments if necessary, and is very curable if found early. The five-year
survival rate is 92% if caught early (Bengtsson et al, 2014). Cervical cancer may produce
unusual vaginal discharge or bleeding, especially after sex; however, it is common for there not
to be any signs or symptoms (Inside Knowledge: Get the Facts about Gynecologic Cancer,
2015). The majority of cervical cancer is caused by HPV, but other factors can also increase the
CERVICAL CANCER
Page 3
risk: smoking, the use of birth control pills for an extended period of time, or having three or
more children. Exposure in the womb to Diethylstilbestrol (DES), a synthetic form of estrogen
prescribed until 1971 is also known to increase the risk (Inside Knowledge: Get the Facts about
Gynecologic Cancer, 2015).
Currently, 118 types of Human Papillomavirus (HPV) have been identified, 40 of which
are routinely found in the genital tract. These have been divided into low-risk types and highrisk-types. The low-risk HPV types are often found in benign, hyperplastic cervical lesions,
while high-risk HPV types can progress into cervical, vaginal or vulvar cancer. HPV-16 and
HPV-18 are the two most common types found worldwide, and are both classified as high-risk
types (Argyi et al, 2013; Zandi et al, 2010). 70% of all cervical cancer is caused by these two
types of HPV (Cervical Cancer: Screening, 2015). HPV occurs in both men and women, and is
sexually transmitted. It is thought that at least half of all sexually active people will contract
HPV sometime during their life (Inside Knowledge: Get the Facts about Gynecologic Cancer,
2015). Most infections with HPV are handled by the body’s immune system and go away before
they are clinically detected. The infections that remain for long periods of time, often years, can
cause normal cells to become abnormal, and potentially develop into cancer especially if it is a
high-risk type (Inside Knowledge: Get the Facts about Gynecologic Cancer, 2015). Figure 1
demonstrates how the virus and lesions can shift between statuses solely from the work of the
immune system (Chen et al, 2011). Two HPV vaccines are available and protect against the
HPV types that are responsible for most cancers. The vaccines are a series of three injections
and are recommended for girls 11 to 12 years old. Females who are between the ages of 13 and
26 who did not receive the entire series, or any of the shots are also encouraged to get the
vaccines (Inside Knowledge: Get the Facts about Gynecologic Cancer, 2015).
CERVICAL CANCER
Page 4
Screening
The Pap Test
The Pap test became widely utilized by doctors as a screening tool for cervical cancer in
the mid-1940s in the United States (Bengtsson et al, 2014). The test allows doctors to identify
abnormal cells in the cervix, that left untreated may develop into cervical cancer. It also can
detect some noncancerous conditions such as infections (Pap and HPV Testing, 2014).
The Pap test is performed during a pelvic exam. Using a speculum, a doctor is able to
examine the cervix and vagina and collects cells from the cervix with a small brush and spatula.
In a conventional Pap test, the brushings are smeared across a microscope slide. The slide is
stained, and then the cells are viewed under a microscope (Bengstsson et al, 2014; Cervical
Cancer: Screening, 2015). Liquid based cytology (LBC) preparatory methods, such as ThinPrep,
have been developed more recently. The brush used to collect the cervical cellular sample is
CERVICAL CANCER
Page 5
immersed in a liquid. At a lab, the liquid goes through a series of procedures before being put on
a slide, stained, and then examined (Bengstsson et al, 2014; Cervical Cancer: Screening, 2015).
Although more costly to perform, LBC preparations allow for better visual and machine analysis
because the specimen sample is spread in a thinner, more uniform layer on the slide (Bengstsson
et al, 2014; The ThinPrep Test, 2010). The LBC preparation also permits co-testing for HPV
(Pap and HPV Testing, 2014). The cost to prepare a slide during the conventional Pap test
ranges between $1 and $2 (U.S.), while liquid based tests are at least $10 (Bengstsson et al,
2014).
Pap Test Results
The results of a Pap test typically come back one of three ways: “normal, “unclear,” or
“abnormal.” Normal is another term for a negative result, no abnormal cellular changes were
detected. Unclear, equivocal, or inconclusive, mean that there could be some abnormal cells. In
this case, the doctor cannot tell if the changes are due to HPV, menopause, sex, or another type
of infection. Abnormal test results signify that there are cellular changes- but does not mean that
it is automatically cervical cancer. Many of these changes can reverse back to normal, but it is
imperative that the individual follows-up with their doctor for additional tests or procedures
(Inside Knowledge: Get the Facts about Gynecological Cancer, 2015; Pap and HPV Testing,
2014; Pap Test Procedure, Test Results, What Abnormal Results Mean and More, 2015). The
majority of labs in the United States report results using a standard rubric called, The Bethesda
System (Cervical Cancer: Screening, 2015; Pap and HPV Testing, 2014).
HPV Testing
Two HPV tests are currently in use, one is a HPV ribonucleic acid (RNA) test, and the
other is a HPV deoxyribonucleic acid (DNA). Both tests, determine if there is any HPV in the
CERVICAL CANCER
Page 6
sample, and if so, which genotypes. The results tend to be reported as either positive or negative.
Positive results refer to high-risk types of HPV being present, while negative results refer to no
HPV present, or only low-risk types (Cervical Cancer: Screening, 2014).
Alternative Screening for Limited Resource Settings
A screening method gaining traction in countries with very limited resources is the onetime visual inspection of the cervix with acetic acid (VIA). If a lesion is discovered, immediate
treatment is usually performed, making the screening and treatment available all in one trip
(Cervical Cancer: Screening, 2014).
Current Policies Nationwide
In 2012, the U.S. Preventive Services Task Force (USPSTF), American Cancer Society
(ACS), American Society for Colposcopy and Cervical Pathology (ASCCP), and the American
Society for Clinical Pathology (ASCP), came out with their new guidelines and
recommendations for cervical cancer screening. Their suggestion is to not start screening before
the age of 21, due to higher rates of false-positives, and that cervical cancer is very rare in
females under 21 years old. In this age group, HPV infections and any abnormal cells usually go
away on their own, without medical intervention and the concern is that unnecessary procedures
would be performed (Cervical Cancer: Screening, 2015). Current recommendations are for all
women ages 21 to 65 to have a Pap test every three years starting at age 21. Women 30 to 65
years of age should have HPV and Pap co-testing done every five years (or a Pap test alone every
three years) (Cervical Cancer: Screening, 2015; Inside Knowledge: Get the Facts about
Gynecological Cancer, 2015; Pap and HPV Testing, 2014). Women with certain risk factors
such as being human immunodeficiency virus (HIV) positive, immunosuppressed, exposed to
CERVICAL CANCER
Page 7
diethylstilbestrol in the womb, or been treated for a precancerous cervical lesion or cervical
cancer may need to have more regular screening, or past the age of 65 (Pap and HPV Testing,
2014). Women who have had a hysterectomy (and the cervix was removed), don’t need to
continue screening unless the surgery was done to treat cervical cancer (Cervical Cancer:
Screening, 2015; Pap and HPV Testing, 2014). It is highly recommended that women who have
been vaccinated for HPV still follow the general screening guidelines (Cervical Cancer:
Screening, 2015; Inside Knowledge: Get the Facts about Gynecological Cancer, 2015). Most
cervical cancer occurs in women who have never had a Pap test, or one in the last five years
(Inside Knowledge: Get the Facts about Gynecological Cancer, 2015).
Application of Screening Tools
The U.S. Patient Protection and Affordable Care Act of 2010 made it mandatory for
health insurance plans to cover preventative care without requiring deductibles or copayments
(Habbema et al, 2012). Evidence has shown that preventative care is cost-effective. This is only
the case if the services are being implemented according to guidelines and recommendations.
Implementation of participation in the preventative medicine is left mostly to a woman’s
individual physician, especially their obstetricians and gynecologists (Habbema et al, 2012). In a
study done by the Centers for Disease Control and Prevention’s (CDC) National Breast and
Cervical Cancer Early Detection Program (NBCCEDP), half of the physicians reported that they
usually screened all women yearly. They cited the fear that at a three-year screening interval,
more women would not return for their next test, (Habbema et al, 2012). A yearly Pap test is
unnecessary for the majority of women since cervical cancer progresses so slowly that if it is not
CERVICAL CANCER
Page 8
caught one test, it will be caught in time for treatment on the next test (Cervical Cancer:
Screening, 2015).
Even though there is no authority overseeing the implementation of the cervical cancer
screening guidelines in the United States, the five-year coverage rates for women ages 30 to 64
was between 80 and 90 percent (Habbema et al, 2012).
Validity & Bias in Application of Screening Tools
The Pap test has a rather low sensitivity rate, but its specificity is extremely good. The
sensitivity rate ranges from 36-55% for the Pap test, while the specificity was 97%. HPV tests
have been shown to have a sensitivity rate between 91-95%, and a specificity rate of 94-98.6%
(Cervical Cancer: Screening, 2015; Mukhdelger et al, 2014; Zandi et al, 2010). Together, the
Pap test and HPV test had 100% sensitivity which is why they work best together (Cervical
Cancer: Screening, 2015).
Co-testing for HPV along with the Pap test also allows for a lower false-negative rate
than the Pap test alone (Pap and HPV Testing, 2014). It is also thought that the detection rate of
glandular cell abnormalities is enhanced with co-testing. The Pap test is better at sensing
squamous cell abnormalities than glandular cell abnormalities, which are much less common
(Geldenhuys et al, 2007; Pap and HPV Testing, 2014).
CERVICAL CANCER
Page 9
Ethical Considerations
The characteristics of HPV, the appearance and disappearance of infection, can
potentially cause a woman to undergo treatment for a condition that may have gone away on its
own. Treatment and worry cause stress on most individuals, which could have been unnecessary
(Pap and HPV Testing, 2014). There is a disparity in the mortality rates between black and
white women. In women under the age of 65, the cervical cancer mortality rate in black women
is 40% higher than their white counterparts. Over the age of 65, the same mortality rate jumps to
over 150% more than white women. However, both rates are very low in women who receive
regular screenings (Cervical Cancer: Screening, 2015). The mortality rate in Hispanic women is
50% greater than in their non-Hispanic counterparts (Daley et al, 2013).
Another ethical consideration is to remember that all screening methods, and treatment
require the examination of a very private area of a women’s body. Respect and utmost discretion
are paramount when performing these screening tests for all women. Cultural and religious
beliefs may make some women apprehensive of participating in the screenings.
Recommendations
Participation
The United States has a currently has a good participation rate in the screening of cervical
cancer. However, it is clear that there is a great amount of misunderstanding among women as
to what the screening tests actually test for and what is excluded (Daley et al, 2013; Bertram et
al, 2007). It is essential that doctors explain what Pap smears and HPV tests are to their
patients, and what the differences between them are. Sexual education and health classes in
schools need to do a better job of explaining cervical cancer and HPV, how they are related,
CERVICAL CANCER
Page 10
screened for, and treated. Cervical cancer is a very treatable disease if it is caught early.
Education about the need to be screened for young women and minorities will go a long way in
saving their lives. Women ought to know that HPV is incredibly common in both men and
women, and that they should not be ashamed if they have it. The HPV vaccine is a great
preventative measure, and young girls should be highly encouraged to have it (Cervical Cancer:
Screening, 2014). It has also recently been approved for use in males, which would help with
decreasing the rate of transmission for both males and females (Inside Knowledge: Get the Facts
about Gynecological Cancer, 2015). Programs and funding need to be lobbied for to provide the
vaccine to young women of lower socioeconomic means due to its relatively high cost.
Education and outreach also needs to be increased for lower socioeconomic and minority
women.
CERVICAL CANCER
Page 11
Works Cited
Argyri, E., Papaspyridakos, S., Tsimplaki, E., Michala, L., Myriokefalitaki, E., Papassideri, I., . .
. Panotopoulou, E. (2013). A cross sectional study of HPV type prevalence according to
age and cytology. BMC Infectious Diseases, 13(53). Retrieved April 21, 2015, from
Academic Search Premier.
Bengtsson, E., & Malm, P. (2014). Screening for Cervical Cancer Using Automated Analysis of
PAP-Smears. Computational and Mathematical Methods in Medicine, 1-12. Retrieved
April 18, 2015, from Academic Search Premier.
Bertram, C., & Magnussen, L. (2007). Informational Needs And The Experiences Of Women
With Abnormal Papanicolaou Smears. Journal of Lower Genital Tract Disease, 20, 455462. Retrieved April 18, 2015, from Academic Search Premier.
Cervical Cancer: Screening. (2015, March 1). Retrieved April 10, 2015, from
http://www.uspreventiveservicestaskforce.org/Page/Topic/recommendationsummary/cervical-cancer-screening
Chen, M., Hung, H., Duffy, S., Yen, A., & Chen, H. (2011). Cost-effectiveness analysis for Pap
smear screening and human papillomavirus DNA testing and vaccination. Journal of
Evaluation in Clinical Practice, 17, 1050-1058. Retrieved April 18, 2015, from Academic
Search Premier.
Daley, E., Perrin, K., Vamos, C., Hernandez, N., Anstey, E., Baker, E., . . . Ebbert, J. (2013).
Confusion About Pap Smears: Lack of Knowledge Among High-Risk Women. Journal
Of Women's Health, 22(1), 67-74. Retrieved April 18, 2015, from Academic Search
Premier.
Geldenhuys, L., & Murray, M. (2007). Sensitivity and Specificity of the Pap Smear for
Glandular Lesions of the Cervix and Endometrium. Acta Cytologica, 47-50. Retrieved
April 10, 2015, from Pubmed.
Getman, D., Aiyer, A., Dockter, J., Giachetti, C., Zhang, F., & Ginocchio, C. (2009). Efficiency
of the APTIMA® HPV Assay for detection of HPV RNA and DNA targets. Journal of
Clinical Virology, 45, S49-S54. Retrieved April 18, 2015, from Academic Search
Premier.
Habbema, D., Kok, I., & Brown, M. (2012). Cervical Cancer Screening in the United States and
the Netherlands: A Tale of Two Countries. Milbank Quarterly, 90(1), 5-37. Retrieved
April 18, 2015, from Academic Search Premier.
Inside Knowledge: Get the Facts About Gynecologic Cancer. (2015, February 23). Retrieved
April 10, 2015, from http://www.cdc.gov/cancer/knowledge
CERVICAL CANCER
Page 12
Munkhdelger, J., Kim, G., Wang, H., Lee, D., Kim, S., Choi, Y., Choi, E., Park, S., Jin, H, Park,
K., & Lee, H. (2014). Performance of HPV E6/E7 mRNA RT-qPCR for screening and
diagnosis of cervical cancer with ThinPrep Pap test Samples. Experimental & Molecular
Pathology, 97(2), 279-284. Retrieved April 18, 2015, from Academic Search Premier.
Pap test Procedure, Test Results, What Abnormal Results Mean, and More. (2015, January 29).
Retrieved April 10, 2015, from http://www.webmd.com/women/guide/pap-smear
Pap and HPV Testing. (2014, September 9). Retrieved April 10, 2015, from
http://www.cancer.gov/cancertopics/types/cervical/pap-hpv-testing-fact-sheet
The ThinPrep Pap Test. (2010). Retrieved April 10, 2015, from
http://www.thinprep.com.au/pp/pforp.html
Zandi, K., Eghbali, S., Hamkar, R., Ahamdi, S., Ramedani, E., Deilami, I., Nejad, H.,
Farshadpour, F., & Rastian, Z. (2010). Prevalence of various Human Papillomavirus
(HPV) genotypes among women who subjected to routine Pap smear test in Bushehr city
(Southwest of Iran) 2008-2009. Virology Journal, 7(65). Retrieved April 18, 2015, from
Academic Search Premier.