1. Genital Cancer Screening Evidence based guidelines Dr Adity Bhattacharyya, MD, FAAFP.

2. Genital Cancer Screening Breast Cancer Ovarian Cancer Prostate Cancer Cervical cancer Testicular Cancer Endometrial Cancer Vulvovaginal Cancer Penile Cancer

3. Genital Cancer screening BREAST CANCER: Most common non-skin malignancy in the US. Second most common cause of cancer related deaths. 192,200 new cases diagnosed in 2002. 40,200 patients died of the disease in 2002. Probability of developing breast cancer increases with age & as the population ages. American Cancer society. Cancer facts & figures. 2001-2002. Atlanta, Georgia: Available at http://www.cancer.org.

4. Genital Cancer Screening CASE 1: Mrs. P is a 43 year old female patient comes to your office for her annual check up. She is new to your practice. She states she has no medical problems & is on no medications. Recently her friend was diagnosed with Breast cancer & she asks you if she should be tested. She states she has no family history of cancer & she has never had any breast problems

5. Genital Cancer screening Risk factors for Breast Cancer 1.Family history 2.Personal history of breast cancer. 3.Biopsy confirmed atypical hyperplasia. 4.First child after age 30 yrs. 5.Racial predilection. National Cancer Institute surveillance, Epidemiology and end results program. 1995-1997. Available at http://www.nci.nih.gov. Accesses February 18,2002. http://www.nci.nih.gov

6. Genital Cancer Screening Screening tests available for breast Cancer: 1.MAMMOGRAPHY 2.CLINICAL BREAST EXAMINATION (CBE) 3.SELF BREAST EXAMINATION (SBE) 4.MRI of the breast Humphrey LL, Helfand M, Chan BKS. Breast cancer screening: a summary of evidence for the U.S. Preventative Services Task force. Ann Intern Med 2002;137:347-60. Bobo JK, Lee NC, Thames SF. Findings from 752081 clinical breast examinations reported to a national screening program from 1995 to 1998. J Natl Cancer Inst 2000;92(12):971-6. Harvey BJ, Miller AB, Baines CJ. Effect of self breast examination techniques on the risk of death from breast cancer. CAMJ 1997;157(9):1205-12.

7. Genital Cancer Screening: Breast Cancer When do we start screening? SCREENING RECOMMENDATIONS: USPSTF recommends screening mammograms with or without CBE every 1-2 years after age 40. RATING: B recommendation USPSTF concludes that evidence is insufficient to recommend for or against CBE alone or SBE for screening against breast cancer. RATING: I recommendation for both Nystrom L, AndersonI et al. Long term effects of mammography screening: Updated overview of the swedish randomized trials. Lancet 2002;359(9310):909-19 Shapiro S. Periodic screening for breast cancer: The HIP randomized control trial Health Insurance plan. J Natl Cancer Inst Monogr 1997; 22:27-30. Nystrom L, Rutqvist LE,et al. Breast cancer screening with mammography: overview of Swedish randomized trials. Lancet 1993:341(8851):973-8.

8. Genital Cancer screening recommendations from other agencies. AMA, ACOG, ACS & ACR support starting screening mammography at age 40 yrs for women at average risk. AAFP & CTFPHC recommend starting mammography screening at age 50 yrs though AAFP recommends screening high risk women at age 40.

9. Genital Cancer Screening Breast Cancer Screening interval: USPTF recommends screening every 1 to 2 yrs. ACS, AMA, ACOG & ACR recommend annual screening. Many experts at USPSTF feel that since breast cancer is more aggressive & mammography less sensitive in women between 40 to 49 yrs the screening interval should be shorter.

10. Genital Cancer screening Breast Cancer When do we stop screening? No agency gives a precise age when to stop screening. No studies have included women over age 74. You should screen as long as the patient has no other co-morbid condition to limit benefit from screening Anderson I, Janson L. Reduced breast cancer mortality in women under age 50: Updated results from the Malmo Mammographic screening program. J Natl Cancer Inst Monogr1997; 22:63-7 Tabar L, VitakB,et al. The Swedish Two-County trial twenty years later: updated mortality results and new insights from long term follow up. Radiol Clin North Am 2000;38(4):625-51.

11. Genital cancer screening Breast cancer ROLE OF CBE & SBE? USPSTF finds no evidence of mortality benefit for CBE or SBE vs. Mammography alone. ACS recommends that CBE should be part of the physical exam every 2 to 3 yrs from age 20 to 40 yrs & annually there after.( expert opinion). ACOG has similar recommendations though it acknowledges that there is no data to prove mortality benefit

12. Genital cancer screening Ovarian cancer Ovarian cancer is the 5 th leading cause of cancer death in the US. There were 25,400 new cases & 14,300 deaths from Ovarian cancer in 2003. Age adjusted prevalence is 17/100,000 women. Most women are diagnosed in Stage III. Stage I ovarian cancer is mostly curable. American Cancer Society facts & figures2003. Available at WWW.cancer.org/downloads/STT/?CAFF2003PWSecured.pdf WWW.cancer.org/downloads/STT/?CAFF2003PWSecured.pdf SatoS, YokoyamaY et al. Usefulness of mass screening for ovarian cancer using transvaginal ultrasonography. Cancer 2000;89(3)582-8. Van Nagell Jr et al. the efficacy of transvaginal sonographic screening for ovarian cancer. Gynecol Oncol 2000;77(3):350-6

13. Genital Cancer Screening CASE 2: Mrs. S is a 36 yr old female patient who comes to your office complaining of a dull left lower quadrant abdominal pain for the past month. The pain is non specific & the patient cannot relate it to food, bowels, menstruation, sex or movement. She is G2P2 with regular periods. She has no known medical problems & the only medication she is taking is Ortho-Tricyclen Lo which she has been taking since the birth of her last child 6 years ago. She has no urinary or bowel complains. She is a little anxious as her mother was diagnosed with ovarian cancer 6 months ago at age 62. Mrs. S wants to know if she can be screened for ovarian cancer. Her aunt (mother’s sister) was diagnosed with breast last year at age 70.

14. Genital Cancer Screening Ovarian Cancer RISK FOR OVARIAN CANCER: Family History. Genetic predisposition. Risk is decreased by pregnancy & Oral Contraceptive use. Whittemore As, Harris R et al. Characteristics related to ovarian cancer risk: Collaborative analysis of 12 US case- controlled studies. II. Invasive epithelial ovarian cancers in white women. Collaborative Ovarian Cancer Group. Am J Epidemiol 1992;136(10)1184-1203

15. Genital cancer Screening Ovarian cancer Screening tests available: Ca 125 Threshold of 30-35U/ml Transvaginal ultrasound Jacobs I, Davies AP et al. Prevalence screening for ovarian cancer in post-menopausal women by CA125 measurement & ultrasonography. BMJ1993;306(6884):1030-4.

16. Genital cancer screening Ovarian cancer USPSTF recommends against routine screening for ovarian cancer in women with average risk. ACS also does not recommend screening women at average risk, only women with a strong family history. ACOG suggests the generalist be vigilant to the early signs of ovarian cancer & evaluate women with these symptoms using Ca 125 & TVUS.

17. Genital cancer screening Role of genetic testing Breast & Ovarian cancer Specific families have mutations in the tumor suppressor genes BRCA1 & BRCA2 genes. These genetic mutations increase the chance of developing breast & ovarian cancer & possibly other cancers. Only 2% of the general population are at risk for these mutations. Both maternal & paternal history is important. Miki Y, Swenson J, et al. A strong candidate for the Breast & Ovarian cancer susceptibility gene BRCA1. Science 1994;266:66-71. Wooster R, Bignel G, Lancaster J, et al Identification o the Breast cancer susceptibility gene BRCA2. Nature 1995;378:789-92.

18. Genital cancer screening Genetic testing. Breast & Ovarian Ca How do we identify patients at risk? 1.Two 1 st degree relatives with breast cancer, one diagnosed before 50. 2.A combination of 3 or more 1 st or 2 nd degree relatives with breast cancer, regardless of age. 3.Combination of breast & ovarian cancer in 1 st & 2 nd degree relatives. 4.1 st degree relative with bilateral breast cancer 5.Breast cancer in a male relative. 6.2 or more relatives with ovarian cancer. 7.One relative with breast & ovarian cancer at any age.

19. Genital Cancer screening Genetic testing. Breast & Ovarian Ca TESTING IN SPECIAL GENETIC GROUPS: Ashkenazi Jews, Clusters in Netherlands, Iceland & Sweden 1.Any 1 st degree relative with breast or ovarian cancer. 2.Two 2 nd degree relatives on the same side of the family with breast or ovarian cancer.

20. Genital cancer screening Genetic testing: Breast & Ovarian Ca USPSTF recommends against routine referral for genetic counseling or testing for women at average risk for breast or ovarian cancer RATING: D recommendation USPSTF recommends that women whose family history suggests a risk of genetic mutation be referred for genetic counseling & evaluation for BRCA testing RATING: B recommendation

21. Genital cancer screening Genetic testing : Breast & Ovarian Ca RECOMMENDATION BY OTHER AGENCIES: ACMG recommends risk assessment & genetic counseling before genetic testing ACOG recommends risk assessment & referral for genetic testing in high risk families

22. Genital cancer screening Genetic testing: Breast & Ovarian Ca What do we do if a genetic mutation is noted? 1.Role of tamoxifen. 2.Role of intensive monitoring. 3.Role of prophylactic surgery. 4.Role of Oral Contraceptive pill for ovarian cancer. Warner E, Plewes DB, Hill KA, et al. Surveillance of BRCA1 & BRCA2 mutation carriers with MRI, ultrasound, mammography, & Clinical breast examination. JAMA 2004;292:1317-25. Kauff ND, Satagopan JM, et al. Risk reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med 2002;346:1607-15.

23. Genital cancer screening Prostate cancer Second most common cause of cancer related deaths in the US in men. In 2002, 189,000 men were diagnosed & 30,200 died of prostate cancer. Risk factors are Age, Ethnicity & Family history. Jemal A, Thomas A, Murray T. Cancer statistics, 2002, CA Cancer J Clin 2002;52:23-47.

24. Genital Cancer screening: CASE 3: Mr. J is a 45 year old African American Male patient in your office who comes for his 6 monthly check up for his Hypertension & elevated Cholesterol, both of which are controlled with medications. He tells you that he recently read an article in “Newsweek” magazine about prostate cancer & wants to know if he should be screened. He has no urinary symptoms and has no family history of cancer.

25. Genital cancer screening Prostate cancer SCREENING TESTS AVAILABLE. PSA : Cut off of 4.0ng/ml.(standard cut off) Age specific PSA cut off. PSA cut off of 2.6ng/ml. Percentage of free PSA PSA Velocity. Digital rectal examination (DRE) Richert-Boe KE, Humphrey LL, et al. Screening Digital Rectal examination & Prostate cancer mortality: A care control study. J Med Screen 1998;52:172-79. Catalona WJ, Southwick PC, et al. Comparison of percent free PSA, PSA density, and age specific PSA cut-offs for prostate cancer detection & staging. Urology 2000;56:255-60. Finne P, Zhang WM, et al. Use of the complex between prostate specific antigen & alpha 1 protease inhibitor for screening prostate cancer. J Urol 2000;164:1956-1960. Smith DS, Catalona WJ. Rate of change in prostate specific antigen levels as a method for prostate cancer detection. J Urol 1994;152:1163-1167.

26. Genital Cancer screening Prostate cancer SCREENING RECOMMENDATIONS: USPSTF concludes that the evidence is insufficient to recommend for or against routine screening for prostate cancer. RATING I recommendation ACS does nor recommend routine screening for patients at average risk but recommends offering PSA testing & DRE annually beginning at age 50 for men with average risk & at age 45 for men with a family history or of American African descent. If there is a very high risk testing could begin at 40. It is not appropriate to discourage testing.

27. Genital cancer screening Cervical cancer Second most common cancer in women world wide. About 4000 women in America die annually from cervical cancer, most of them have never been screened or are under screened. Highest incidence in Vietnamese women, highest mortality in black women. This cancer has a prolonged precancerous phase in which if detected can be totally curable. Hartman KE, Hall HA, Nanda K, et al, Screening for cervical cancer. Systematic evidence based review. No 25. (Prepared by the research triangle institute) : Agency for Health care research & quality. January 2002.

28. Genital Cancer screening Cervical cancer Cause: Almost all cases of Cervical cancer is caused by Oncogenic HPV. COFACTORS : 1.Tobacco use. 2.History of STD 3.HIV disease 4.Multiple sexual partners 5.Early age at first intercourse.

29. Genital cancer screening Cervical cancer CURRENT RECOMMENDATIONS: USPSTF/ ACS/ ACOG 1.Start screening 3 yrs after initiating vaginal intercourse or age 21 whichever is first, Continue annually till age 29. 2.At age 30, you may increase the screening interval to every 2 to 3 yrs if previous PAPS have been normal. 3.Patients who have had a hysterectomy for a benign cause do not need further screening. 4.Women older than 70 who have normal PAP smears in the past 10 years may stop screening at the discretion of their Physician. Smith RA, Cokkinedes V. American Cancer society guidelines for early detection of cervical neoplasia,and cancer. CA Cancer J Clin 2002;52(1):8-22. American College of Obstetricians & Gynecologists. Guidelines for Women's health care. 2 nd ed. Washington, DC:ACOG 2002: 121-134, 140-141.

30. Genital cancer screening cervical cancer Role of new liquid based technology. Role of HPV testing. The HPV vaccine.

31. Genital Cancer Screening Testicular cancer Testicular cancer is a rare cancer Lifetime risk is about 1 in 300. Lifetime risk of dying from this disease is 1 in 5000. Occurs between ages of 10 & 35 years. Testicular cancer is one of the most curable form of cancer. US Preventative Service Task Force; Guide to Clinical Preventative Services. 2 nd ed. Washington DC: Office of disease prevention & health promotion.;1996.

32. Genital cancer screening Testicular cancer Risks: 1.Undescended testes. 2.Testicular atrophy. 3.Ambiguous genitalia. 4.Testicular trauma. 5.Family history. 6.HIV infection. Harland SJ, Cook PA, et al. Intratubular Germ cell neoplasia of the contra lateral testes in testicular cancer: defining a high risk group.

33. Genital Cancer screening Testicular cancer. SCREENING RECOMMENDATIONS: USPSTF does not recommend routine self testicular examinations to screen for testicular cancer. ACS advises testicular examination as a part of a general physical examination. Patient with risk factors should be instructed on how to perform a self examination & encouraged to do monthly examinations.

34. Genital Cancer screening Endometrial cancer Adenocarcinoma of the uterus is the most common gynecological cancer in the US & the 4 th common overall cancer in women. Peak incidence is between 55 & 65 years. White women are twice as likely to develop endometrial cancer. Robert A Smith, Cokkinides A. American Cancer Society Guidelines for early detection of cancer. CA Cancer. J Clin 2006;56:11-25.

35. Genital cancer screening endometrial cancer SCREENING FOR WOMEN AT RISK 1.Obesity 2.Other hyper estrogenic states 3.Medications 4.Family history 5.Pelvic radiation. 6.History of other cancers. 7.Diabetes

36. Genital cancer screening endometrial cancer RECOMMENDATIONS:RECOMMENDATIONS: ACS in 2001 concluded that there is Insufficient evidence to recommend screening for women at average risk, or somewhat increased risk. They should be counseled about the risks & symptoms of endometrial cancer at the onset of menopause. Women at very high risk due toWomen at very high risk due to 1.Known hereditary non polyposis colon cancer associated mutation 2.Substantial likelihood of being a mutation carrier Should consider annual testing at age 35 yrs. SCREENING TEST: Endometrial biopsy. These are recommendations from experts with no clear evidence of mortality benefit.

37. Genital cancer screening Vulvar cancer Fourth common gynecological cancer in the US Accounts for 1% of all cancers in women. Average age 65 to 70 yrs. Slow growing cancer with potential for cure if found in the early stages.

38. Genital cancer screening Vulvar cancer. Recommendations fro ACS:Recommendations fro ACS: There are no current screening for this disease other than routine physical examination. Careful examination of the vulvar & perenial area during a pelvic exam should be done in older women & all suspicious lesions should be biopsied.There are no current screening for this disease other than routine physical examination. Careful examination of the vulvar & perenial area during a pelvic exam should be done in older women & all suspicious lesions should be biopsied.

39. Genital cancer screening Penile cancer It is a rare disease. Penile cancer occurs in 1 in 100,000 men in the US.It is a rare disease. Penile cancer occurs in 1 in 100,000 men in the US. In 2006 about 1530 cases of penile cancer will be diagnosed & 280 men will die of the disease.In 2006 about 1530 cases of penile cancer will be diagnosed & 280 men will die of the disease. It is a much more common disease in Africa & South America.It is a much more common disease in Africa & South America. Known risk factors are Poor hygiene, HPV infection, HIV infection & cigarette smokingKnown risk factors are Poor hygiene, HPV infection, HIV infection & cigarette smoking

40. Genital Cancer screening Penile cancer Screening recommendations:Screening recommendations: ACS has no clear screening recommendations for penile cancer except for a general physical examination. Any suspicious lesion should be biopsied.ACS has no clear screening recommendations for penile cancer except for a general physical examination. Any suspicious lesion should be biopsied.

41. Genital Cancer screening Thank You. QUESTIONS??