Cervical Cancer Screening… An Overview

2. Cervical Cancer Screening…An Overview AMR NADIM, MD Professor of Obstetrics & Gynecology Ain Shams Faculty Of Medicine

3. 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%.

4. Why… Source: American Cancer Society, 2000 Incidence And Mortality For Cervical Cancer Vs Breast Cancer, [United States, 2000]

5. HPV infection • Condyloma Accuminata • Exophytic • Frond like surface • Lesion may be single or multiple • Located within or outside the transformation zone

6. HPV infection • Subclinical HPV • Flat lesions undetectable naked eye • Best assessed after acetic acid application • Shinny, snow-white lesions • Irregular outline • Satellite lesions beyond the transformation zone • Strong or partial uptake of Lugol’s iodine

7. What Makes the Cervix Vulnerable?

8. 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.

9. E7 E6 P53 RTS Immortality

10. Global distribution of HPV types in cervical cancer

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

12. Screening…? • Organized identification • High coverage of a target population • Continuous quality assessment. • Feasibility of treatment & follow up • Of a pre - clinical disease state by a test that is repeated at a given interval

13. Recommended Screening Cervical Carcinoma Breast Carcinoma Colorectal Carcinoma Not yet , for… Ovarian Cancer Bronchogenic Carcinoma Skin cancer Oral Cancer Prostate Cancer To screen or To screen not ? Cervical Cancer Screening by The Pap Smear Is one of the very few cost effective interventions to prevent cancer.

14. 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

15. 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

16. 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.

17. Cancer Cervix : A Screenable Preventable Disease • Cancer cervix still represents a problem in the developing counties: Less than 5% of the population is screened. • Its natural history is well-known. • Definitive pre-cancerous lesions are identified and treatment will eradicate the disease. • Screening tools available for more than 60 years and are subjected to continuous innovations to increase specificity and sensitivity

18. Cervical Cancer Is Preventable • Primary prevention • Education to reduce high-risk sexual behavior • Risk assessment • Secondary prevention • Identify and treat precancerous lesions before they progress to cervical cancer

19. Number per 100,000 Women Incidence Mortality Year Incidence and mortality for cervical cancer, United States, 1973–1997 (SEER) Rate is age-adjusted to 1970 U.S. population Source: Cancer Statistics Review, 1973–1997

20. 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

21. The Papanicolaou Test Nicknamed … Pap Smear

22. Cytopathology: • Cytopathology is diagnosis of disease in cells. • Exfoliative & Non-Exfoliative - cytology. • Exfoliative: Cell samples are collected from normally shedding tissues like epithelium. spatula or brush to enhances collection. • Non-Exfoliative: Cells samples collected by needles with suction pressure. (FNAC) • Cytology specimen is fixed, stained and studied under microscope.

23. What is a Pap Smear? • Screening test for cervical cancer. It is a type of exfoliative cytology test. • Simple, safe, non-invasive method • Developed by “George Papanicolaou” • Exfoliated cells from cervix are collected usually enhanced by using a variety of spatulas or brushes. • The specimen is processed and studied for morphology.

24. Who should have PAP test.. • Every woman should have an annual Pap examination when she becomes sexually active or turns 18 years old [ whichever comes first]. • Defining the target population is important in any screening program.

25. What is the best time for PAP: • The best time for a Pap examination is during the two weeks following the end of menstrual flow. (Proliferative phase). • Why…? • If menopause, Pap examination can be scheduled anytime

26. Take Care... • Use a good sampling device • Do Not use Lubricants while taking the smear. • Do Not be too slow in plating the slide • Sample the endocervical canal and the whole transformation zone . • Do Not insert the sampling device too deep in the endocervical canal: • This invites bleeding • It might draw cells different to interpret.

29. Who are at increased risk of Cervical Cancer? • Any woman can develop cancer cervix. • Multiple sex partners or a partner who has had multiple female partners. • Have had genital warts. • Sexual relations before the age of 18. • Previous abnormal pap examination. • Rare in virgins and with use of condoms.

30. What should happen… From onset of sexual activity and throughout life. Covering all social classes. Covering urban and rural sectors. What should be avoided … Limiting screening to the CBP Limiting screening to a particular social class or a particular sector. The Target Population It is estimated that less than 5 % of women in the developing countries are screened. These are essentially women under 35.

31. Cervical Cancer Burden (more than 50% of the cases) In the States: Unequal Burden of Disease Source: Shingleton et al., 1995

32. INEGYPT... • Only sporadic attempts of screening. • No nation-wide program • Primary health care providers…? • 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 • الخـــوف من المجـــــهــــول

33. Characteristics of women never or rarely screened for cervical cancer • Older • Low SES and/or lack of insurance or ability to pay for screening • Less educated • No regular health care provider • Live in culturally-isolated urban neighborhoods or hard-to-reach rural areas

34. Pathology of Cervix: • the uterine cervix is continually being bombarded by a variety of stress including mechanical, microbiologic, chemical, and hormonal insults. • The cervix responds by • Acute or chronic inflammatory reactions • Adaptive proliferative responses like Hyperplasia, Metaplasia & Dysplasia. • Anaplasia - Benign & Malignant tumors.

35. Normal Cervix:

36. Carcinoma Cervix:

37. Normal Cervix : SUPER F INTERM BASAL

38. Chronic Cervicitis:

39. PAP Smear Normal:

40. Pathogenesis: (non-neoplastic) • Chronic cervicitis • Hyperplasia – Number • Metaplasia – Change to squamous • Dysplasia – no-maturation, disorder(CIN 1-3, CIS)

41. Pathogenesis: (Neoplastic) • Malignant (Cervical Cancer) • Invasion & Spreading.

42. Pap Smear Results:

43. Existing Screening Guidelines • WHO (1992): Annual Pap tests are often unnecessary—“it is clear that it is more cost-effective to recruit a high proportion of the population and screen them infrequently, than to recruit a low proportion and screen them often.”

44. Existing Screening Guidelines (continued) • USPSTF (1996): “There is little evidence that women who receive annual screening are at significantly lower risk for invasive cervical cancer than are women who are tested every 3–5 years.”

45. Existing Screening Guidelines (continued) • ACPM (1996): “Estimates from mathematical models indicate that regular triennial screening would achieve 91-96% of the benefit of annual screening, while greatly reducing the cost, potential harms, and inconvenience.”

46. Existing Screening Guidelines (continued) • ACOG (2000): “After a woman has had three or more consecutive, satisfactory, annual cytological examinations with normal findings, the Pap test may be performed less frequently on a low-risk woman at the discretion of her physician.” • ACS (2001): “After three or more consecutive annual exams with normal findings, the Pap test may be performed less frequently at the discretion of the physician.”

47. TheScreening Interval…A Controversy • A negative smear ensures a protective effect of 93% if repeated yearly and 91 % if repeated at 3 years interval. • At 10 years interval the protective effect drops to 64 % …still a 2/3 reduction of the risk.

48. Screening Interval…Our Policy • Annual Screening of ladies is advocated, we think it is a way of establishing a multiplicative correction effect by which the 20% false negative screening results may be reduced down to 1 % . • “Unsatisfactory smears” are repeated the following cycle. • “Satisfactory smears but limited by….” are repeated as soon as the condition is corrected. • If laser or conization were made, the smear is repeated after 3 months.

49. Pap Test as a Screening Tool • Sensitivity • Moderate: 51–88% • Specificity • High: 95–98% Given the sensitivity and specificity of the Pap test, “...the major barrier to prevention of cervical cancer is not the accuracy of the Pap test, but the failure to be screened at all.” Source: Meyers et al., 2000 Brown and Garber, 1999

50. The Fluid - Based TechnologyThe Thin - Prep • The sample is put into a liquid medium “collection vial” which is sent to the lab where it is processed as a thin layer slide. • There is no more: • Air drying artifacts. • Dirty backgrounds. • Spreading errors • Cells left entangled in the sampling device.