Epidemiology & Natural History       of HPV Infection and its            Causal Relationship with        Invasive Cervical...
Outline<br /><ul><li>HPV prevalence in women & men
Risk factors for acquiring HPV
Age & HPV
Limitations of HPV serologic testing & current understanding of immunity
HPV detection
HPV persistence, clearance & reactivation
High-risk HPV & invasive cervical cancer (ICC)
Prevalence of disease & type-specific HPV
ICC natural history: SIL & CIN
ICC screening: PAP vs. HPV (measurement error)</li></li></ul><li>Human Papillomavirus (HPV)<br /><ul><li> A DNA Virus
Preferentially infects squamous epithelial cells</li></li></ul><li>Median Age of Sexual Debut for Girls is 17.6 years<br /...
Winer, et al. 2003<br />
Non-penetrative transmission has been documented, but is less likely<br />(e.g., HIV)<br />HPV in HIV+ women (pre-and post...
HPV Prevalence in Women Varies Markedly in-and-between Populations<br />Possibly<br />an artifact of different assays (“ho...
Methodological Issues to Consider <br />with HPV Prevalence  in Men<br />
in<br />
HPV Prevalence is Similar Among                    U.S. Racial/Ethnic Groups<br />CDC 2008<br />
HPV Prevalence by Age<br />CDC 2008<br />
Why Does HPV Prevalence in Women Differ by Age & their Country of Origin?<br />
High Risk HPV Prevalence Differ <br />by Age in Women, but not Men<br />
CDC 2008<br />
     HPV Detection<br /><ul><li>With an HPV DNA test
(Hybrid Capture II (The only FDA-approved HPV Test)
Can analyze residual fluid of a liquid-based cytology specimen from a Pap smear
Detects only “high risk” (hr)HPV types, but does not identify the individual type. Only research assays (“home brewed”) of...
Would be useful for determining vaccine effectiveness in the community?
Indications for use</li></ul>Routine adjunct to Pap in women 30 and over<br />Management of ASCUS (atypical squamous cells...
Collection of HPV for DNA Amplification<br />X<br />
Hybrid Capture II<br />
What Dose HPV Persistence,             Clearance & Reactivation Mean???<br />
Persistence of hrHPV Type is a Strong Risk Factor for Precancerous Lesions<br />Ho, et al. NEJM 1998<br />
Why Should We Care About HPV Infection?<br />
From 1000 Cases of Cervical Cancer, HPV DNA was Found in 99.7%<br />
CDC 2008<br />
Cervical Cancer is the 3rd Leading Cancer in Women<br />WHO IARC, 2006<br />
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Michael Marco ID Epi class slides on HPV Natural History

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Michael Marco ID Epi class slides on HPV Natural History

  1. 1. Epidemiology & Natural History of HPV Infection and its Causal Relationship with Invasive Cervical Cancer<br />Michael Marco, M.Phil., MPH, <br />ID/Epi Pre-doctoral Training Fellow, CIDER, ICAP<br />Infectious Disease Epidemiology - P8406<br />15 April 2010<br />
  2. 2. Outline<br /><ul><li>HPV prevalence in women & men
  3. 3. Risk factors for acquiring HPV
  4. 4. Age & HPV
  5. 5. Limitations of HPV serologic testing & current understanding of immunity
  6. 6. HPV detection
  7. 7. HPV persistence, clearance & reactivation
  8. 8. High-risk HPV & invasive cervical cancer (ICC)
  9. 9. Prevalence of disease & type-specific HPV
  10. 10. ICC natural history: SIL & CIN
  11. 11. ICC screening: PAP vs. HPV (measurement error)</li></li></ul><li>Human Papillomavirus (HPV)<br /><ul><li> A DNA Virus
  12. 12. Preferentially infects squamous epithelial cells</li></li></ul><li>Median Age of Sexual Debut for Girls is 17.6 years<br />CDC 2008<br />
  13. 13. Winer, et al. 2003<br />
  14. 14. Non-penetrative transmission has been documented, but is less likely<br />(e.g., HIV)<br />HPV in HIV+ women (pre-and post-HAART) is worthy a separate lecture. See Steben & Franco-Duarte review<br />(Debatable; more for progression to cancer)<br />CDC 2008<br />
  15. 15.
  16. 16.
  17. 17. HPV Prevalence in Women Varies Markedly in-and-between Populations<br />Possibly<br />an artifact of different assays (“home brewed”) used to measure HPV?<br />
  18. 18.
  19. 19. Methodological Issues to Consider <br />with HPV Prevalence in Men<br />
  20. 20. in<br />
  21. 21. HPV Prevalence is Similar Among U.S. Racial/Ethnic Groups<br />CDC 2008<br />
  22. 22. HPV Prevalence by Age<br />CDC 2008<br />
  23. 23. Why Does HPV Prevalence in Women Differ by Age & their Country of Origin?<br />
  24. 24. High Risk HPV Prevalence Differ <br />by Age in Women, but not Men<br />
  25. 25. CDC 2008<br />
  26. 26.
  27. 27. HPV Detection<br /><ul><li>With an HPV DNA test
  28. 28. (Hybrid Capture II (The only FDA-approved HPV Test)
  29. 29. Can analyze residual fluid of a liquid-based cytology specimen from a Pap smear
  30. 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. 31. Would be useful for determining vaccine effectiveness in the community?
  32. 32. Indications for use</li></ul>Routine adjunct to Pap in women 30 and over<br />Management of ASCUS (atypical squamous cells of undetermined significance) <br />
  33. 33. Collection of HPV for DNA Amplification<br />X<br />
  34. 34. Hybrid Capture II<br />
  35. 35. What Dose HPV Persistence, Clearance & Reactivation Mean???<br />
  36. 36. Persistence of hrHPV Type is a Strong Risk Factor for Precancerous Lesions<br />Ho, et al. NEJM 1998<br />
  37. 37.
  38. 38. Why Should We Care About HPV Infection?<br />
  39. 39. From 1000 Cases of Cervical Cancer, HPV DNA was Found in 99.7%<br />
  40. 40. CDC 2008<br />
  41. 41. Cervical Cancer is the 3rd Leading Cancer in Women<br />WHO IARC, 2006<br />
  42. 42.
  43. 43.
  44. 44. Natural History of HPV Infection and Cervical Cancer<br />
  45. 45. Natural History of HPV Infection and Cervical Cancer<br />
  46. 46. SIL: cytological (cells from Pap smear)<br />CIN: histological (tissue from colposcopy)<br />
  47. 47.
  48. 48.
  49. 49. Colposcopy +/- Biopsy are Warranted after an Abnormal Pap or Repeat hrHPV Detection<br />
  50. 50. Measurement Error is Common in the Reading of Colposcopic Biopsies<br />Shiffman, et al. 2007<br />
  51. 51. CIN can Clear Spontaneously or Regress<br /><ul><li>CIN 1 lesions spontaneously clear in 60% of the cases and rarely progresses to cancer (1%)
  52. 52. CIN 2 & CIN 3 lesions spontaneously clear in 30-40% of cases, however a higher percentage progress to cancer >12% if untreated
  53. 53. Cannot tell by the “look” of the lesions which ones will progress
  54. 54. CIN 2 is defined as an “intermediate diagnosis,” but is treated for safety as if it was CIN 3
  55. 55. Development of CIN 2 or CIN 3 are most often used as “surrogate endpoints” for invasive cervical cancer in prospective cohort studies
  56. 56. An immediate vs. differed treatment study for CIN 2 lesions would be beneficial, however, no IRB would approve it. </li></ul>Moskowitz 2007; Woodman 2007, Wacholder 2003<br />
  57. 57.
  58. 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. <br />
  59. 59. Shiffman & Wacholder 2009<br />
  60. 60. With HPV Testing, is it Now Time to Retire the Pap?<br />
  61. 61. What about HPV & the Need for Vaccination in Animals?<br />Dad, I am nearing my sexual debut. Can I be the first puppy to get the HPV vaccine?<br />

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