Cervical Cancer Screening… “ Would we ever have a nation wide program?”

1. Cervical Cancer Screening…“Would we ever have a nation wide program?” Amr Nadim, MD Professor of Obstetrics & Gynecology Ain Shams Faculty of Medicine

2. Cervical Carcinoma • Second in frequency among women cancers. • It is still the most frequent cancer in the developing countries. • 400,000 new cases identified each year • 80% of new cases in developing countries • At least 200,000 women die each year • Screening programs reduced the mortality from cancer cervix in developed countries by 70%.

3. Why… Source: American Cancer Society, 2000 Incidence And Mortality For Cervical Cancer Vs Breast Cancer, [US, 2000]

4. Cancer Cervix…A Screenable Preventable Disease

5. Pre - requisites For Successful Screening • After Wilson and Jugner (1968): • The condition should be an important health problem. • There should be an accepted treatment . • Facilities for treatment and diagnosis should be available. • There should be a recognizable latent or early symptomatic stage. • There should be a suitable method of examination. • The test should be acceptable to the population. • The natural history of the disease should be adequately understood

6. Pre - requisites, cont.... • There should be an agreed policy on whom to treat as patients. • The cost should be economically balanced with the expenditure of medical care as a whole. • Case finding should be a continuing process. They apply reasonably well for screening of Cervical Carcinoma

7. The Evil The Good and

8. Molecular Biology Methods Cytological Methods • Traditional Pap smear • Thin layer prep HPV-DNA genotyping Visual Inspection Methods • Unaided Naked Eye visualization • Acetic Acid enhanced Naked eye Visualization • Cervicography • Colposcopy Screening Tools for Cancer Cervix

9. Risk Factors for Cervix Cancer • No prior smear screening • History of cervical dysplasia or genital warts • Young age at first coitus • Multiple sex partners • High-risk male partner (e.g., multiple female partners) • Sexually transmitted diseases • Increasing age Smoking - Nutritional Deficiencies - Immunosuppression

10. What Makes the Cervix Vulnerable?

11. The HPV-cervical cancer link • Human papillomavirus (HPV) is a very common infection (more than 50% of adults get it, in most it is a transitory infection). • 99.7% of cervical cancer cases are associated with HPV. • Progression from HPV infection to cancer usually takes 20-30 years.

12. E7 E6 P53 RTS Immortality

13. Global distribution of HPV types in cervical cancer

14. years 57% 11% LSIL HSIL >10% Invasive Cancer 35% 1% Natural History Of Cervical Cancer HPV Infection Source: PATH, 2001

17. The Papanicolaou Smear: False Negative Results • Precancerous cells or cancer cells do not shed in small percentage of cases. • Less predictable time course for development of serious glandular lesion. • The lesion is missed on sampling. • The cells are not transferred to the slide or from the sampled liquid media. • Human error in cytopathologic analysis. • Invasive cancer at the time of initial evaluation These lead to a false negative rate of 20% for cytology.

18. Cervix Cancer Screening:Current Controversies • How often should Pap tests be performed? • Should a woman who has had a hysterectomy continue to have periodic Pap tests? • When should the Pap test be repeated if endocervical cells are not present? • Should Pap tests be performed in patients older than age 60?

19. Advances in Cervical Cancer Screening • New American Cancer Society (ACS) guidelines • New Technologies: • Hybrid Capture II HPV test as part of primary screening and triage • Liquid based cytology • Computer assisted Pap smear interpretation

20. ACS Guidelines for Screening • When to Start Screening • Initiate cervical cancer screening about 3 years after the onset of vaginal intercourse. • Screening should begin no later than 21 years of age. • The need for cervical cancer screening should not be the basis for the onset of gynecologic care. • (CA: A Cancer Journal for Clinicians 53(1):27-43, 2003)

21. ACS Guidelines for Screening • When to Stop Screening: • Women aged >70 years with an intact cervix with >3 documented, consecutive, technically satisfactory/normal/negative cervical cytology tests and no abnormal/positive cytology tests within the 10 years prior to age 70 may stop cervical cancer screening. • Screening is recommended for 70+ year old women not previously screened and for whom information about previously screening is unavailable and for whom past screening is unlikely. • CA: A Cancer Journal for Clinicians 53(1):27-43, 2003)

22. ACS Guidelines for Screening • Screening After Hysterectomy • Vaginal cytology screening tests are not indicated after total hysterectomy for benign gynecologic disease. • Hysterectomy for CIN2 or greater is not considered benign. • CA: A Cancer Journal for Clinicians 53(1):27-43, 2003)

23. ACS Guidelines for Screening • Screening Interval: • After initiation of cervical screening, perform annually with conventional cervical cytology smears or every 2 years using liquid-based cytology. • Women >30 years of age with 3 consecutive, technically satisfactory normal/negative cytology results may be screened every 2 to 3 years unless they have a history of in utero DES exposure, HIV+, or are immunocompromised. • CA: A Cancer Journal for Clinicians 53(1): 27-43, 2003)

24. FDA Approval of Hybrid Capture II Test in Conjunction with Pap Test • Testing combination brings improved sensitivity to screening and has the potential to benefit the more than 30 million women age 30 and older who are screened in the U.S. each year. • Helps physicians determine which patients are at extremely low risk for cervical cancer and which patients may be monitored more closely.

25. FDA Approval of Hybrid Capture II Test in Conjunction with Pap Test • Studies show the testing combination provides a very high certainty that a woman with a satisfactory and negative Pap result who is HPV-negative is at low risk for having or developing high-grade cervical disease or cancer in the near term. • Combined screening interval should be no more often than once every three years. • Screen for high risk HPV types only.

26. Abnormal PAP smear: Colposcopy

28. Cervical Cancer: Have We Decreased the Incidence? • The curve has been stable for the past decade in part because we are not reaching the unscreened population. • With the advent of the Pap smear, the incidence of cervical cancer has dramatically declined.

29. Cervical Cancer Screening: Who Is Not Getting a Pap Smear? • Uninsured or Underinsured • Low socioeconomic status • Residents in rural locations • Minorities, especially Hispanic, Asian Pacific Islander, African-American and American-Indian women • Residents in developing countries • Elderly

30. Cervical Cancer Screening: Who Is Not Getting a Pap Smear? • Reasons for Lack of Screening: • Cultural barriers • Financial barriers • Access • Poor education, myths

31. Barriers to Screening • Embarrassment, unpleasantness • Lack of knowledge of recommended screening interval • Financial barriers • Lack of knowledge concerning the importance of screening

32. IN EGYPT... • Only sporadic attempts of screening. • Lack of screening of the older women : the priority target group. • Lack of appreciation by the women of the relevance of the disease • Lack of availability of health care in the rural areas. • Fatalism • الخـــوفمنالمجـــــهــــول

33. Findings of many community based studies • Demand for cervical cancer prevention services is strong among women and communities. • Organized prevention programs are feasible and can be integrated with existing services.

34. Role of the Primary Care Physician in Preventing Cervix Cancer • Identify patients who should be screened • Educate patients regarding the importance and timing of Pap smears • Conduct Pap smears properly • Follow up abnormal Pap smear results

35. Findings The single-visit screen-and-treat approach is safe and effective in low-resource settings. This is a major paradigm shift in cervical cancer prevention. …and if it works in subsaharan Africa, it should work for us!!!

36. Treatment Modality Destructive Methods Cryotherapy Laser ablation Excision Cervical conization LEEP Cure Rate (5-year) Overall 85-95% 85-95% >90% >90% Treatment of Cervix Dysplasia

37. More Education Needed for All! • Public awareness • TV commercials • Magazines • Physician Education • Primary Care Providers • FP’s who work with adolescents • Physician to Patient

38. What kinds of Education? • Disease awareness in general for all • Link of HPV to Cervical Cancer • Perfect opportunity for physicians to combine with discussions of adolescent sexuality and risk-taking behaviors • Do we limit discussions and education to female patients only? Probably not.

39. Family Barriers • HPV is a sexually transmitted disease • Adolescents are invulnerable (so they think) • The home will protect fully

40. Cervical Cancer: How Do We Eradicate Cervical Cancer? • Optimal screening with 100% participation • Better detection of glandular precancer lesions • Early detection of invasive cancers followed by adequate evaluation and treatment • HPV vaccines

41. HPV vaccine Evolution of Molecular-based Therapies

42. Cervical Cancer: Vaccines • Prophylactic Vaccines • Vaccinate young people before exposure to HPV • Polyvalent HPV vaccines are being studied • Decreased incidence of dysplasia and cancer may not be seen for several generations • Therapeutic vaccines • Under evaluation for treatment of CIN and cancer • Many different technologies • Participants needed for clinical trials

43. HPV vaccine news headlines • “Vaccine prevents most cervical cancers.” - New York Times, October 7, 2005. • Vaccine proves 100 percent effective in preventing cervical cancer –Seattle Times, October 6, 2005. • “Promising new vaccines could wipe out cervical cancer. But they must be administered to preteens, and some groups oppose that.”–Philadelphia Inquirer, July 4, 2005. • “OK Roll up your sleeve; new vaccines are arriving but the economics are still a challenge”–Business Week, July 25, 2005.

44. HPV vaccine opportunity • 2 vaccines protecting against HPV 16 and 18 are nearing licensure. • Both have high efficacy in Phase II trials and appear very safe. • Phase III trials will involve over 50,000 women worldwide. • Both manufacturers express interest in serving developing country markets.

45. Effective Screening Program Should be tailored to suit the principles for national cancer control programs. We Should NOT copy other’s programs... Otherwise Too much money & effort will be spent with minimal impact on the incidence & mortality from the disease.

46. Coming to an end… • Cervical cancer is a preventable disease. • Cervical screening is one of the most successful public health measures ever introduced for the prevention of cancer. • Successful screening strategy should be coupled with an effective treating policy to eradicate pre-malignant lesions

47. Still, many of the world's, most vulnerable women are not being screened. • Implementation of comprehensive, organized, and quality cervical screening programs demand our energies and attention as health professionals, policymakers, governments, and citizens.

48. Thank you !!!