1. Epidemiology & Natural History of HPV Infection and its Causal Relationship with Invasive Cervical Cancer Michael Marco, M.Phil., MPH, ID/Epi Pre-doctoral Training Fellow, CIDER, ICAP Infectious Disease Epidemiology - P8406 15 April 2010

3. Risk factors for acquiring HPV

4. Age & HPV

5. Limitations of HPV serologic testing & current understanding of immunity

6. HPV detection

7. HPV persistence, clearance & reactivation

8. High-risk HPV & invasive cervical cancer (ICC)

9. Prevalence of disease & type-specific HPV

10. ICC natural history: SIL & CIN

13. Winer, et al. 2003

14. Non-penetrative transmission has been documented, but is less likely (e.g., HIV) HPV in HIV+ women (pre-and post-HAART) is worthy a separate lecture. See Steben & Franco-Duarte review (Debatable; more for progression to cancer) CDC 2008

17. HPV Prevalence in Women Varies Markedly in-and-between Populations Possibly an artifact of different assays (“home brewed”) used to measure HPV?

19. Methodological Issues to Consider with HPV Prevalence in Men

20. in

21. HPV Prevalence is Similar Among U.S. Racial/Ethnic Groups CDC 2008

22. HPV Prevalence by Age CDC 2008

23. Why Does HPV Prevalence in Women Differ by Age & their Country of Origin?

24. High Risk HPV Prevalence Differ by Age in Women, but not Men

25. CDC 2008

28. (Hybrid Capture II (The only FDA-approved HPV Test)

29. Can analyze residual fluid of a liquid-based cytology specimen from a Pap smear

30. Detects only “high risk” (hr)HPV types, but does not identify the individual type. Only research assays (“home brewed”) offer information on the specific genotype

31. Would be useful for determining vaccine effectiveness in the community?

32. Indications for useRoutine adjunct to Pap in women 30 and over Management of ASCUS (atypical squamous cells of undetermined significance)

33. Collection of HPV for DNA Amplification X

34. Hybrid Capture II

35. What Dose HPV Persistence, Clearance & Reactivation Mean???

36. Persistence of hrHPV Type is a Strong Risk Factor for Precancerous Lesions Ho, et al. NEJM 1998

38. Why Should We Care About HPV Infection?

39. From 1000 Cases of Cervical Cancer, HPV DNA was Found in 99.7%

40. CDC 2008

41. Cervical Cancer is the 3rd Leading Cancer in Women WHO IARC, 2006

44. Natural History of HPV Infection and Cervical Cancer

45. Natural History of HPV Infection and Cervical Cancer

46. SIL: cytological (cells from Pap smear) CIN: histological (tissue from colposcopy)

49. Colposcopy +/- Biopsy are Warranted after an Abnormal Pap or Repeat hrHPV Detection

50. Measurement Error is Common in the Reading of Colposcopic Biopsies Shiffman, et al. 2007

52. CIN 2 & CIN 3 lesions spontaneously clear in 30-40% of cases, however a higher percentage progress to cancer >12% if untreated

53. Cannot tell by the “look” of the lesions which ones will progress

54. CIN 2 is defined as an “intermediate diagnosis,” but is treated for safety as if it was CIN 3

55. Development of CIN 2 or CIN 3 are most often used as “surrogate endpoints” for invasive cervical cancer in prospective cohort studies

56. An immediate vs. differed treatment study for CIN 2 lesions would be beneficial, however, no IRB would approve it. Moskowitz 2007; Woodman 2007, Wacholder 2003

58. Our study found that a single round of HPV testing was associated with a significant decline in the rate of advanced cervical cancers and associated deaths, as compared with the unscreened control group. By contrast, there was no significant reduction in the rate of death in either the cytologic-testing group or the VIA group, as compared with the control group. NOTE: no cancer-related deaths were observed in any of the HPV-negative women.

59. Shiffman & Wacholder 2009

60. With HPV Testing, is it Now Time to Retire the Pap?

61. What about HPV & the Need for Vaccination in Animals? Dad, I am nearing my sexual debut. Can I be the first puppy to get the HPV vaccine?