title: The low risk of precancer after a screening result of human papillomavirus-negative/atypical squamous cells of undetermined significance papanicolaou and implications for clinical management.
abstract: BACKGROUND
  Different US practice guidelines have conflicting recommendations for when women should return after a screening result of human papillomavirus (HPV)-negative with an equivocal Papanicolaou (Pap) result of atypical squamous cells of undetermined significance (ASC-US) (ie, return in either 3 or 5 years). One way to determine management is to compare the risk of precancer/cancer after an HPV-negative/ASC-US result with the risks after other negative screening results. For example, if the risk after an HPV-negative/ASC-US result was similar to the risk after a negative Pap test, a 3-year return would be preferred because guidelines agree that women with negative Pap test results should return in 3 years. Alternatively, if the risk after an HPV-negative/ASC-US result is similar to that after a cotest-negative result (HPV negative/Pap test negative), a 5-year return would be preferred because guidelines agree that women testing cotest negative should return in 5 years.
  
  
  METHODS
  The authors compared risks of cervical intraepithelial neoplasia of grade 3 or higher (CIN3+) and cervical cancer among women aged 30 years to 64 years at Kaiser Permanente Northern California with the following test results from 2003 through 2012: 17,191 women testing HPV negative/ASC-US; 980,268 women testing Pap test negative (regardless of HPV result); and 892,882 women testing cotest negative.
  
  
  RESULTS
  The 5-year CIN3+ and cancer risks after an HPV-negative/ASC-US result were closer to the risks after a negative Pap test result (CIN3+: 0.48% vs 0.31% [P =.0019]; and cancer: 0.043% vs 0.031% [P =.4]) than after a negative cotest (CIN3+: 0.48% vs 0.11% [P<.0001]; and cancer: 0.043% vs 0.014% [P =.016]).
  
  
  CONCLUSIONS
  Women testing HPV negative/ASC-US were found to have precancer/cancer risks that were more closely aligned with women with negative Pap test results, suggesting that women testing HPV negative/ASC-US should be managed similarly to women testing negative on Pap tests with a 3-year return for screening.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland.
authors.forename: Julia C
authors.initials: JC
authors.lastname: Gage
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: Catherine
authors.initials: C
authors.lastname: Behrens
authors.forename: Abha
authors.initials: A
authors.lastname: Sharma
authors.forename: Fang-Hui
authors.initials: FH
authors.lastname: Zhao
authors.forename: Jack
authors.initials: J
authors.lastname: Cuzick
authors.forename: Zi Hua
authors.initials: ZH
authors.lastname: Yang
authors.forename: Walter K
authors.initials: WK
authors.lastname: Kinney
mesh_terms: D000328:Adult; D065309:Atypical Squamous Cells of the Cervix; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D006801:Humans; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D065006:Papanicolaou Test; D017410:Practice Guidelines as Topic; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000628:therapy; D018570:Risk Assessment / Q000379:methods / Q000706:statistics & numerical data; D012307:Risk Factors; D013997:Time Factors; D014481:United States; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis
keywords: atypical squamous cells of undetermined significance (ASC-US); cervical intraepithelial neoplasia (CIN); cytology; human papillomavirus (HPV)