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Cancer Screening and Immunizations in Adults Michael Adams, M.D., FACP Program Director Associate Professor of Medicine Georgetown University Medical Center Outline • Definitions • Adult Cancer Screening Guidelines • What’s new in cancer screening • Immunizations Definitions Screening: testing for disease in average (or low) risk, asymptomatic population may be considered a form of primary prevention goals: – early detection – treating to reduce morbidity or mortality no diagnostic intent average prevalence (by definition) Definitions Case-finding: testing in patients at higher risk – patients seeking medical care because of a complaint – patients with familial risks / exposures / other diagnosis may be a form of secondary prevention – disease present, reduce mortality / recurrence rate diagnostic intent usually higher than average disease prevalence Operating characteristics high sensitivity low burden early detection ability to modify course of disease higher prevalence = better positive predictive value GUIDELINES ACP, USPSTF, CTF, NCI, NIH, AMA, ACC, AHA, AUA, ACOG, IOM USPSTF – evidence-based – frequent updates – factor in net benefit, quality of the evidence US Preventive Services Task Force (USPSTF) http://www.ahcpr.gov/clinic/uspstfix.htm • • • • • • • • • • • • • • • Bladder Cancer Breast Cancer / BRCA mutations Cervical Cancer Colorectal Cancer Gynecologic Cancers Lung Cancer Oral Cancer Ovarian Cancer Pancreatic Cancer Prostate Cancer Skin Cancer Testicular Cancer Thyroid Cancer Tobacco Use Vitamin Supplementation to Prevent Cancer and CHD USPSTF Ratings Strength of Recommendations – The U.S. Preventive Services Task Force (USPSTF) grades its recommendations according to one of five classifications (A, B, C, D, I) reflecting the strength of evidence and magnitude of net benefit (benefits minus harms). Quality of Evidence – The USPSTF grades the quality of the overall evidence for a service on a 3-point scale (good, fair, poor). USPSTF Ratings (Strength) Recommendation: A - routinely provide to eligible patients. The USPSTF found good evidence that [the service] improves important health outcomes and concludes that benefits substantially outweigh harms. Recommendation: B - routinely provide to eligible patients. The USPSTF found at least fair evidence that [the service] improves important health outcomes and concludes that benefits outweigh harms. USPSTF Ratings (Strength) Recommendation: C - no recommendation for or against routine provision of [the service] At least fair evidence that [the service] can improve health outcomes but concludes that the balance of the benefits and harms is too close to justify a general recommendation. Recommendation: D - recommends against routinely providing [the service] to asymptomatic patients The USPSTF found at least fair evidence that [the service] is ineffective or that harms outweigh benefits. USPSTF Ratings (Strength) Recommendation: I - evidence is insufficient to recommend for or against Evidence that [the service] is effective is lacking, of poor quality, or conflicting and the balance of benefits and harms cannot be determined. USPSTF Ratings (Quality) Good: Evidence includes consistent results from welldesigned, well-conducted studies in representative populations that directly assess effects on health outcomes. Fair: Evidence is sufficient to determine effects on health outcomes, but the strength of the evidence is limited by the number, quality, or consistency of the individual studies, generalizability to routine practice, or indirect nature of the evidence on health outcomes. Poor: Evidence is insufficient to assess the effects on health outcomes because of limited number or power of studies, important flaws in their design or conduct, gaps in the chain of evidence, or lack of information on important health outcomes. • • • • • • • • • • • • • • • D Bladder Cancer BRCA mutation Breast Cancer Cervical Cancer Colorectal Cancer I Lung Cancer I Oral Cancer D Ovarian Cancer Pancreatic Cancer D Prostate Cancer I Skin Cancer Testicular Cancer D I Thyroid Cancer Tobacco Use Vitamin Supplementation to Prevent Cancer and CHD I/D • • • • • • • • • • • • • • • D Bladder Cancer BRCA mutation Breast Cancer Cervical Cancer Colorectal Cancer I Lung Cancer I Oral Cancer D Ovarian Cancer Pancreatic Cancer D Prostate Cancer I Skin Cancer Testicular Cancer D I Thyroid Cancer Tobacco Use Vitamin Supplementation to Prevent Cancer and CHD I/D Breast Cancer North America: leading cancer in women, 2nd leading cause of cancer death 2001: 192,000 diagnoses, 40,200 deaths >50%: no known major predictors Risk increases with age, atypical hyperplasia BRCA-1 BRCA-2 BRCA-1 and -2 breast ovary colon prostate male breast? breast ovary colon? prostate? male breast pancreatic? Breast Cancer: mammography Sensitivity 56-95% – Lower in younger, dense breasts, HRT Specificity 94-97% – More false positives (less specific) in younger women Abnormal mammogram & chance of cancer: – 40-49: 2-4% PPV – 50-59: 5-9% – 60+: 7-19% Breast Cancer: Clinical Breast Exam Sensitivity 40-69% Specificity 86-99% 4% of patients with abnormal CBE diagnosed with cancer in a large community trial These trials compared CBE with mammography, mortality trials use both CBE & mammogram Breast Cancer: age considerations Most screening trials 50-69 40-49: weaker evidence, delay in benefit (lower prevalence in younger women) – Interval for screening is unknown Over 70: – evidence generalized unless comorbid conditions reduce life expectancy – Higher absolute risk of cancer Mammography benefits (absolute) increase with age Mammography risks (RELATIVE) diminish with age Breast Cancer The (USPSTF) recommends screening mammography, with or without clinical breast examination (CBE), every 1-2 years for women aged 40 and older. B recommendation Breast Cancer: CBE The USPSTF concludes that the evidence is insufficient to recommend for or against routine CBE alone to screen for breast cancer. I recommendation Breast Cancer: Self Breast Exam Sensitivity 26-41% Specificity unknown No known mortality difference Risks of abnormal self exam – Anxiety – False positive results – Unnecessary biopsies Breast Cancer: self-exam The USPSTF concludes that the evidence is insufficient to recommend for or against teaching or performing routine breast selfexamination (BSE). I recommendation Breast Cancer: other considerations Patient preferences, clinical judgment Family history BRCA Other organizations have varying recommendations: – – – – Yearly after age 40: AMA, ACOG, ACS, ACR Yearly after 50: CTF, AAFP, ACPM Interval varies (q1, q2 between 40-49) BSE: ACOG, ACS, AMA, AAFP favor teaching Chemoprophylaxis for Breast Cancer tamoxifen and raloxifene may prevent some breast cancers in women at low or average risk for breast cancer tamoxifen can significantly reduce the risk for invasive ER-positive breast cancer in women at high risk for breast cancer and that the likelihood of benefit increases as the risk for breast cancer increases raloxifene – consistent evidence (fewer studies) Chemoprophylaxis – side effects VTE Symptomatic side effects (hot flashes) Endometrial cancer (tamoxifen only) Need to balance harms vs benefits Variable Age 45 Age 55 Age 65 Age 75 No Family history 0.7 1.1 1.5 1.6 Family history 1.6 2.3 3.2 3.4 3-4 5-6 7-8 8 8 11-12 16 17 No Family history 1-2 2 2-3 2-3 Family history 2-3 3-4 4-5 5-6 <1 3 5 15 1-2 12 21 "22" 1 3 9 20 Pulmonary emboli caused, n 1-2 4-5 9 18 Cases of DVT caused, n 1-2 1-2 3 4 5-year risk of breast cancer, % Based upon Gail model Benefits per 1,000 women of 5 y of tamoxifen Cases of invasive breast cancer avoided, n No Family history Family history Cases of noninvasive breast cancer avoided, n Hip fractures avoided, n Harms per 1000 women of 5 y of tamoxifen Cases of endometrial cancer caused, n Strokes caused, n Chemoprophylaxis for Breast Cancer The U.S. Preventive Services Task Force (USPSTF) recommends against the routine use of tamoxifen or raloxifene for the primary prevention of breast cancer in women at low or average risk for breast cancer. D recommendation Chemoprophylaxis for Breast Cancer The USPSTF recommends that clinicians discuss chemoprevention with women at high risk for breast cancer and at low risk for adverse effects of chemoprevention. Clinicians should inform patients of the potential benefits and harms of chemoprevention. B recommendation Cervical Cancer 13,000 cases yearly 4,100 deaths (2002) Risks: – – – – early intercourse increased # of sexual partners smoking HPV (95-100% of squamous cell CA of cervix) Cervical Cancer Natural history of HPV – slow transition to cancer – – “orderly fashion from less severe to more severe dysplasia” Not faster in HIV+ women (prevalence higher) – – Every 6-12 months Younger women: HPV may be transient Older women: higher chance of progression to cancer PAP smear: 60-80% sensitive New technologies (“ThinPrep”): no good data yet Cervical Cancer - timing Interval: every 3 years after 2-3 normals – – – Sensitivity 60-80% for high grade lesions for a single PAP test ACS: wait until age 30 to extend screening interval Annual screening: cervical neoplasia, HPV, other STDs, high risk sexual behavior Cessation of screening – – Low predictive value for women over 65 (ACS: 70), no abnormal PAP in past 10 years Hysterectomy for benign disease (only cancer in 1995 study of 10,000 PAP smears was vaginal squamous cell CA) Cervical Cancer – HPV testing Sensitivity 82% Specificity 78% Benefits untested 8 ongoing studies Cervical Cancer The USPSTF strongly recommends screening for cervical cancer in women who have been sexually active and have a cervix. A recommendation Cervical Cancer The USPSTF recommends against routinely screening women older than age 65 for cervical cancer if they have had adequate recent screening with normal Pap smears and are not otherwise at high risk for cervical cancer . D recommendation Cervical Cancer The USPSTF recommends against routine Pap smear screening in women who have had a total hysterectomy for benign disease. D recommendation Cervical Cancer The USPSTF concludes that the evidence is insufficient to recommend for or against the routine use of new technologies to screen for cervical cancer. I recommendation The USPSTF concludes that the evidence is insufficient to recommend for or against the routine use of human papillomavirus (HPV) testing as a primary screening test for cervical cancer. I recommendation ASC-H = atypical squamous cells suspicious for HSIL Colorectal Cancer 4th most common cancer in US 2nd leading cause of cancer death At age 50, 5% risk of being diagnosed with colon cancer Adenomatous polyps – precursor Hereditary polyposis syndromes (FAP, HNPCC) – 6% of all colon cancers Colorectal Cancer - DRE Little evidence Sensitivity much less than multiple test cards False negatives – no stool in vault False positives – rectal trauma Therefore, not recommended as a tool for colorectal cancer screening Colorectal Cancer - FOBT sensitivity 26 - 92%, specificity 90-99% 3 samples, rehydrated cards improve sensitivity (diminishes specificity) Annual screening has detected 49% of incident cancers FOBT: 33% reduction in mortality over controls inexpensive Colorectal Cancer sigmoidoscopy Alone: – detects approximately 7 cancers and 60 large polyps/1000 exams – estimated detection of significant colonic lesions of 80% Sigmoid abnormalities often trigger colonoscopy Combination with FOBT: – detects 65-75% of polyps and 40-65% of cancers – reduces mortality by 60% – detects an additional 7 cancers over FOBT alone Colorectal Cancer - DCBE Limited studies: sensitivity 86-90% for cancer / polyps Only 48% sensitive for polyps > 1cm in National Polyp Study Specificity 85% No outcome data Colorectal Cancer colonoscopy Sensitivity 90% for large polyps, 75% for small polyps Specificity difficult to define Minority of patients who have polypectomy would have developed cancer PROS: view entire colon, ability to biopsy/treat during procedure CONS: cost, complications, prep/discomfort Colorectal Cancer colonoscopy The effectiveness of colonoscopy to prevent colorectal cancer or mortality has not been tested in a randomized clinical trial.1 Comparisons with historical controls: estimates 76-90% reduction in cancers. 1USPSTF website: http://www.ahcpr.gov/clinic/3rduspstf/colorectal/colorr.htm Colorectal Cancer - costs Costs for screening, 2002 – Stool hemoccult – Flexible sigmoidoscopy – Colonoscopy $7-10 $176-299 $670-981 excluding facility fee Among 6 high-quality cost-effectiveness analyses examining only direct costs, the average cost-effectiveness ratio values for screening adults older than 50 with each of the major strategies were under $30,000 per life-year saved (Year 2000 dollars). Studies varied as to which strategy was most cost-effective, however. (USPSTF) Colorectal Cancer The USPSTF strongly recommends that clinicians screen men and women 50 years of age or older for colorectal cancer. A recommendation Colorectal Cancer Other considerations: – – – Family history of colon cancer <60: test earlier “The choice of screening strategy should be based on patient preferences, medical contraindications, patient adherence, and resources for testing and followup.” (USPSTF) Timing (American Cancer Society) FOBT: yearly Sigmoid: every 5 years DCBE: every 5 years Colonoscopy: every 10 years (One-in-a-lifetime after age 55) Prostate Cancer 2nd leading cause of cancer death among men in US 2002: 189,000 new cases Risk increases with age (6.5% by age 60) Ethnic differences (mortality): – – – – Asian/Pacific Islanders: Latino/Hispanic White Black 1.0 1.08 1.67 3.33 Black men have higher incidence rate Most men will not die of their disease (3% out of 15%) Prostate Cancer Considerations: – DRE, PSA accuracy – – Early detection Mortality benefit? – – DRE: <60% sensitivity, operator-dependent PSA: 60-80% sensitive using 4.0 as abnormal Scant evidence, some showing reduced deaths from prostate cancer after prostatectomy but complications not considered Complications of treatment (the “I”s) Age of patient Screening is most likely to benefit the following: – – 50-70 year old men at average risk Men over 45 with risk factors (Black men, Family hx) Prostate Cancer - USPSTF “Despite the absence of firm evidence of effectiveness, some clinicians may opt to perform prostate cancer screening for other reasons. Given the uncertainties and controversy surrounding prostate cancer screening, clinicians should not order the PSA test without first discussing with the patient the potential but uncertain benefits and the possible harms of prostate cancer screening. Men should be informed of the gaps in the evidence, and they should be assisted in considering their personal preferences and risk profile before deciding whether to be tested.” Prostate Cancer Prostate cancer guidelines – USPSTF: do not recommend screening – ACS, AUA, AAFP, AMA: consider DRE at age 40, PSA over 50 (40 for Black men) – CTF: recommend against PSA, do not recommend discontinuation of DRE – ACP: do not recommend screening – All groups advise physicians to give information to patients about screening, risk/benefit, treatment & individualize testing Prostate Cancer The U.S. Preventive Services Task Force (USPSTF) concludes that the evidence is insufficient to recommend for or against routine screening for prostate cancer using prostate specific antigen (PSA) testing or digital rectal examination (DRE). I recommendation Skin Cancer The U.S. Preventive Services Task Force concludes that the evidence is insufficient to recommend for or against routine counseling by primary care clinicians to prevent skin cancer. I recommendation [No evidence that routine counseling changes behaviors in adults – may increase use of sunscreen for children] Tobacco Cessation The USPSTF strongly recommends that clinicians screen all adults for tobacco use and provide tobacco cessation interventions for those who use tobacco products. A recommendation The USPSTF strongly recommends that clinicians screen all pregnant women for tobacco use and provide augmented pregnancy-tailored counseling to those who smoke. A recommendation The USPSTF concludes that the evidence is insufficient to recommend for or against routine screening for tobacco use or interventions to prevent and treat tobacco use and dependence among children or adolescents. I recommendation Vitamin Supplementation to Prevent Cancer The U.S. Preventive Services Task Force (USPSTF) concludes that the evidence is insufficient to recommend for or against the use of supplements of vitamins A, C, or E; multivitamins with folic acid; or antioxidant combinations for the prevention of cancer or cardiovascular disease. I recommendation The USPSTF recommends against the use of betacarotene supplements, either alone or in combination, for the prevention of cancer or cardiovascular disease. D recommendation What’s new Virtual colonoscopy (2003) Genetic testing – – Colon cancer (2004) Breast cancer (2005) Virtual colonoscopy Virtual colonoscopy 54.3 % said virtual colonoscopy was more uncomfortable 38.1 % said traditional method was more uncomfortable CT colography (“virtual colonoscopy”) Non-invasive 10-15 minutes 85-90% sensitive in research setting Prep still necessary, insufflation in some centers Limited outcome data – Does detection = reduction in mortality? New software? Genetic testing for colon cancer MTAP = multi-targeted assay panel Genetic testing for colon cancer Pros: – Non-invasive – More sensitive than FOBT Epithelial shedding is continuous, bleeding is intermittent) – Good specificity for mutations Cons: – Inconvenience – Cumbersome – Not as sensitive as colonoscopy for one-time screening – Cost ($400-$800) BRCA screening Who is at risk? – non-Ashkenazi Jewish women: 2 first-degree relatives with breast cancer, 1 of whom received the diagnosis at age 50 years or younger 3 or more first- or second-degree relatives with breast cancer regardless of age at diagnosis both breast and ovarian cancer among first- and second-degree relatives a first-degree relative with bilateral breast cancer 2 or more first- or second-degree relatives with ovarian cancer regardless of age at diagnosis a first- or second-degree relative with both breast and ovarian cancer at any age history of breast cancer in a male relative. BRCA screening Who is at risk? – Ashkenazi Jewish women: any first-degree relative (or 2 second-degree relatives on the same side of the family) with breast or ovarian cancer. BRCA screening “important adverse ethical, legal, social consequences of testing” “important harms of interventions such as prophylactic surgery, chemoprevention, or intensive screening” in non-high risk women “…prophylactic surgery for [high risk] women significantly decreases breast and ovarian cancer incidence. Thus, the potential benefits of referral and discussion of testing and prophylactic treatment for these women may be substantial.” BRCA screening The USPSTF recommends against routine referral for genetic counseling or routine breast cancer susceptibility gene (BRCA) testing for women whose family history is not associated with an increased risk for deleterious mutations in breast cancer susceptibility gene 1 (BRCA1) or breast cancer susceptibility gene 2 (BRCA2). D recommendation BRCA screening The USPSTF recommends that women whose family history is associated with an increased risk for deleterious mutations in BRCA1 or BRCA2 genes be referred for genetic counseling and evaluation for BRCA testing. B recommendation VACCINATIONS Td pneumovax influenza Hepatitis B Varicella Hepatitis A Meningococcus MMR Polio HPV Pneumococcal Vaccine – Contains capsular polysaccharides of 23 common strains – underused (only 45% of patients over age 65) – >65, chronic disease (CHF, COPD, liver disease, alcoholism, DM), HIV, splenectomy – Revaccinate: nephrotic syndrome, renal failure, transplant, (ab titer wanes) – maybe revaccinate elderly after 6 years – Vaccinate preganant women if high risk: after first trimester – safe Influenza vaccine Only 65% of patients over 65 receive flu shots 2 type A strains, 1 type B strain reduces illness in healthy patients (7090%) reduces mortality & hospitalizations in elderly (despite only 30-40% effectiveness) Influenza vaccine Eligible: – >50 – nursing home/long-term care facility – chronic illness (DM, renal, Hb-opathies, cardiopulmonary disease, immunosuppressed, long term ASA use) – health care / home care / day care Influenza vaccine Adverse reactions: – soreness at site – febrile illness (24-48 hours) - not influenza – immediate hypersensitivity (rare, even in egg allergic patients) – Guillain-Barre (1976 with Swine flu vaccine, 1990-91 a few cases, very rare now) Influenza vaccine Contraindications – Severe egg allergy – Active neurologic disease Hepatitis B vaccine Safe, effective (90% immunity in healthy patients less if older, obese, smokers, chronic disease – liver/renal/DM, HIV) 0,1,6 months Indications: – sexual exposure - multiple, homosexual – health care workers – IVDA – HIV (50-70% seroconversion) – infants born to HBsAg positive women post-exposure prophylaxis – depends on type of exposure, patient risk – high: HBIG + Hep B series – low: Hep B series or booster Hepatitis B vaccine Adverse reactions: local Pregnancy is not a contraindication Non-responders: – 3 additional doses, check titers (30-50% response) Revaccination or checking titers – not recommended for immunocompetent people – recommended for hemodialysis patients Td Tetanus rare, but fatality rate high (31-42%) Primary series: 3 doses at 0,1,6 months toxoid every 10 years local erythema common Arthus reaction uncommon anaphylaxis, urticaria, angioedema, neurologic complications - very rare wound prophylaxis (high risk, unvaccinated): immune globulin + Td at different sites MMR Measles (live, attenuated vaccine): – resurgence 1990 – Resurgence in inner city, college campuses – Vaccine produces noncommunicable disease – Single dose is 95% effective, life long immunity MMR all adults born after 1956 & no h/o disease – revaccinate travelers to endemic areas, high risk of natural disease Postexposure prophylaxis: vaccinate immediately (protective within 72 hours) OR immune globulin MMR fever, rash common side effects do not give 14 days before or 5 months after I.G., blood, or ab-containing blood products do not give to the following: – – – – – acute leukemia, lymphoma malignancy steroid, chemotherapy, alkylating agents HIV unless stable/well Pregnant women, considering within 3 mos. MMR Mumps: – orchitis, meningitis, nerve deafness – live, attenuated vaccine – 90% effective after single dose – all adults born after 1956 – parotitis, encaphalitis rare – same timing as measles, same contraindications – Egg/neomycin allergy Rubella – Main issue is prevention of congenital rubella – Vaccinate women of child bearing age – MMR - 95% effective – joint pains – 40%, but arthritis rare – Arthralgias may persist up to 3 weeks – Rare neurologic side effects (neuritis) – avoid in pregnancy, neomycin allergy – Same contraindications as measles Polio vaccine – (OPV), IPV - both trivalent, 95% effective – IPV preferred (higher risk of paralysis with OPV - 1/1.2 million – no longer available in U.S.) – Single booster for travelers to endemic areas who were immunized – travelers not previously immunized – complete primary series (3 doses: 0,1,6 months) – No need to vaccinate adults otherwise – IPV: hypersensitivity only – avoid in pregnancy, immunocompromised HPV – Gardasil recently FDA approved – The Advisory Committee on Immunization Practices (ACIP) recommended routine vaccination for girls 11-12 years of age. – allows for vaccination of women/girls beginning at nine years old, 13-26 years old – ACIP recommendations become CDC policy once they are accepted by director of the CDC and the Secretary of HHS and are published in CDC’s Morbidity and Mortality Weekly Report (MMWR). HPV – 0, 2, 6 month dosing – Covers 4 strains of HPV (6, 11, 16, 18) 70% of cancers, 90% of genital warts – $120 / dose Hepatitis A – Inactivated vaccine – Indications: endemic areas, homosexual men, IVDA, liver disease, occupational risk – 95% effective after 3 weeks, 99%+ after 2nd dose – immune globulin if travel within 2 weeks or if food borne outbreak/close contact (diaper/sexual contact/day care) Varicella – Live, attenuated vaccine – 85% effective in children, reduces severity of illness if contracted – well tolerated Varicella – PHN prevention Shingles is common and causes significant morbidity (PHN) in older adults. Vaccines boost both humoral and cell-mediated immunity, and may help reduce PHN (CMI effect) Herpes Zoster/Shingles Zostavax® is a lyophilized preparation of the Oka/Merck strain of live, attenuated VZV used in the prevention of herpes zoster (shingles) and post herpetic neuralagia. On October 25, 2006, the Advisory Committee on Immunization Practices (ACIP) voted to recommend ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] be given to adults 60 years of age and older to help protect against shingles and postherpetic neuralgia. The vaccine is for subcutaneous administration and is given as a single dose. A history of chickenpox or primary VZV infection is not required before administration. A history of prior shingles disease is not a contraindication. Duration of protection is at least 4 years but total duration is unknown. ZOSTAVAX® should not be administered to individuals: • with a history of anaphylactic/anaphylactoid reaction to gelatin or neomycin; • with a history of primary or acquired immunodeficiency states including leukemia; lymphomas of any type, or other malignant neoplasms affecting the bone marrow or lymphatic system; or AIDS or other clinical manifestations of infection with human immunodeficiency viruses (see WARNINGS); • on immunosuppressive therapy, including high-dose corticosteroids (> 20 mg/day for 3 months or longer); • with active untreated tuberculosis; • who are or may be pregnant. Meningococcus High risk only: – – – – household contacts >4 hours spent with patient for 5 of 7 days prior dorms, barrack roommates, day care mouth-to-mouth prophylaxis: – [rifampin (600mg q 12h x 4) – resistance] – cipro 750 mg x 1 – ceftriaxone 250 mg IM x 1