title: Five-year risks of CIN 3+ and cervical cancer among women with HPV-positive and HPV-negative high-grade Pap results.
abstract: OBJECTIVE
  High-grade Pap results (e.g., atypical glandular cells [AGC], atypical squamous cells cannot rule out HSIL [ASC-H], and high-grade squamous intraepithelial lesion [HSIL]) predict high cancer risks, resulting in referral for colposcopy without HPV triage. However, new guidelines recommending cotesting for women 30 years and older imply that clinicians will often receive the HPV test result concurrently for high-grade Pap results. We examined whether HPV testing provides useful risk stratification in this context.
  
  
  METHODS
  From a cohort of 965,360 women aged 30 to 64 years undergoing cotesting at Kaiser Permanente Northern California, we estimated 5-year risks for cervical cancer and CIN 3+ after AGC (2,074 women), ASC-H (1,647 women), and HSIL (2,019 women) according to HPV test results.
  
  
  RESULTS
  HPV positivity of AGC Pap results was 25% and decreased with age (30 to 34 vs 60 to 64 years, 44% vs 17%, p < .0001), whereas HPV positivity of ASC-H and HSIL was much higher (71% and 94%) and decreased less with age. Even for these high-grade Pap results, 5-year CIN 3+ risks differed substantially between HPV-positive and HPV-negative women (AGC, 33% vs 0.93%, p < .0001; ASC-H, 25% vs 3.5%, p < .0001; HSIL, 49% vs 30%, p = .006). However, except for AGC, cervical cancer risks differed less between HPV-positive and HPV-negative women (AGC, 9.0% vs 0.37%, p < .0001; ASC-H, 2.5% vs 2.1%, p = .8; HSIL, 6.6% vs 6.8%, p = .7).
  
  
  CONCLUSIONS
  The risks of CIN 3+ among women with HPV-negative high-grade Pap results were lower than those among women with HPV-positive high-grade Pap results, especially after AGC. However, by the principle of "equal management of equal risks," all HPV-negative high-grade Pap results had cancer risks high enough to warrant colposcopy, confirming that there is no current role for HPV triage of high-grade Pap results.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health/DHHS, Bethesda, MD 20892, USA. katkih@mail.nih.gov
authors.forename: Hormuzd A
authors.initials: HA
authors.lastname: Katki
authors.forename: Mark
authors.initials: M
authors.lastname: Schiffman
authors.forename: Philip E
authors.initials: PE
authors.lastname: Castle
authors.forename: Barbara
authors.initials: B
authors.lastname: Fetterman
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Poitras
authors.forename: Thomas
authors.initials: T
authors.lastname: Lorey
authors.forename: Li C
authors.initials: LC
authors.lastname: Cheung
authors.forename: Tina
authors.initials: T
authors.lastname: Raine-Bennett
authors.forename: Julia C
authors.initials: JC
authors.lastname: Gage
authors.forename: Walter K
authors.initials: WK
authors.lastname: Kinney
mesh_terms: D000328:Adult; D002140:California / Q000453:epidemiology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000175:diagnosis*; D018570:Risk Assessment; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000453:epidemiology*; D014626:Vaginal Smears / Q000379:methods*; D014773:Virology / Q000379:methods*; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000453:epidemiology*