1. HPV AND WOMEN’S CANCER A.C. Evans. M.D., Ph.D.

2. HPV and Women’s Cancer I have no relevant financial relationships with the manufacturer(s) of any commercial product(s) and/or provider(s) of commercial services discussed in this CME activity. I do not intend to discuss an unapproved/investigative use of a commercial product/device in my presentation DISCLOSURES

3. HPV and Women’s Cancer  Cervical Cancer  Squamous Carcinoma  Adenocarcinoma  Virtually all are HPV-related  Vulvar Cancer  Squamous Carcinoma  About 40% are HPV-related  Vaginal Cancer  Squamous Carcinoma  Over 80% are HPV-related HPV-ASSOCIATED GYNECOLOGIC CANCERS

4. HPV and Women’s Cancer  Virtually all cases of cervical cancer are attributable to HPV  About 100 subtypes of HPV  Approximately 15 types are related to anogenital cancer risk  HPV 16 accounts for about 50% of cases  Most of the rest are caused by types 18, 45, 31, 33, 35, 52, 58  Cervical infection is COMMON; cancer is RARE  Other co-factors include  Cigarette smoking  High parity  OCP use  Co-infection CERVICAL NEOPLASIA AND HPV

5. HPV and Women’s Cancer  HPV is a small double-stranded DNA virus, nonenveloped with a 72-sided icosahedral protein capsid  The HPV genome is maintained in the host cell nucleus  HPV associated proteins (E6 and E7) are partially responsible for the transformation of normal cells to cancer  Other cellular DNA mutations must also be present to give rise to cancer.  3 main phases of cancer development  HPV exposure/acquisition  HPV infection/persistence  Development of invasion BIOLOGIC ELEMENTS

6. HPV and Women’s Cancer  Transmission is primarily sexual  Multiple viral types can be transmitted concurrently  Age of acquisition is similar to other sexually-transmissible infections  Most infections clear within 6 to 24 months  Immune response is important for clearance vs. persistence  Cell-mediated responses are most important  Specific immunological markers are not well characterized  Virtually all HPV infections become undetectable within 2 years  Persistence of carcinogenic types is important for development of precancers  Different viral types have different propensities to persist  Time to precancer is approximately 5 to 10 years  Time to cancer development is about 15 to 20 years HPV NATURAL HISTORY

7. HPV and Women’s Cancer  Host genetic factors  Socioeconomic status  Condoms  Tobacco use  Pregnancy/multiparity  Hormone use  Immunosuppression  Endogenous  Exogenous  Nutrients  Coinfection COFACTORS IN HPV PROGRESSION

8. HPV and Women’s Cancer  Cervical anatomy  CIN1  CIN2  CIN3 CERVICAL INTRAEPITHELIAL NEOPLASIA

9. HPV and Women’s Cancer  Demographics  Staging  Treatment CERVICAL CANCER

10. HPV and Women’s Cancer  HPV association  Preinvasive  Staging  Treatment VAGINAL CANCER

11. HPV and Women’s Cancer  HPV association  Pre-invasive disease  Staging  Treatment VULVAR CANCER

12. HPV and Women’s Cancer  Vaccine types  Efficacy in prevention of dysplasia  Efficacy in prevention of cancer HPV VACCINES

13. HPV and Women’s Cancer  Vaccine safety  Vaccine deployment HPV VACCINES

14. HPV and Women’s Cancer  Pap test  HPV co-testing  HPV testing after treatment HPV TESTING IN SCREENING

15. HPV and Women’s Cancer  Cytologic screening  Molecular testing  Stand-alone HPV testing PRIMARY HPV CERVICAL SCREENING

16. HPV and Women’s Cancer  Cost-effectiveness  Frequency VACCINATION EFFECT ON SCREENING

17. HPV and Women’s Cancer  HPV and lower genital tract cancer in women. SUMMARY