title: Five-year risk of recurrence after treatment of CIN 2, CIN 3, or AIS: performance of HPV and Pap cotesting in posttreatment management.
abstract: OBJECTIVE
  After excisional treatment, cervical intraepithelial neoplasia grade 2 or worse (CIN 2+) can recur. It is not clear how many negative posttreatment Pap or cotest results are needed to ensure adequate safety against CIN 2+ before returning to extended retesting intervals.
  
  
  METHODS
  We observed 5-year risks of CIN 2+ for 3 follow-up management strategies after treatment (Pap-alone, human papillomavirus [HPV]-alone, and HPV/Pap cotesting) for 3,273 women aged 25 years and older who were treated for CIN 2, CIN 3, or adenocarcinoma in situ (AIS) between 2003 and 2010 at Kaiser Permanente Northern California.
  
  
  RESULTS
  Five-year risks of recurrent CIN 2+ after treatment varied both by antecedent screening test result and the histology of the treated lesion. The risk ranged from 5% for CIN 2 preceded by HPV-positive/atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion to 16% for CIN 3/AIS preceded by atypical glandular cells (AGC)/atypical squamous cells cannot rule out high-grade squamous intraepithelial lesion (ASC-H)/high-grade squamous intraepithelial lesion or worse (HSIL+) (p < .0001). However, after posttreatment negative tests, risks were lowered and similar regardless of antecedent screening test and histology of treated disease. The 5-year recurrent CIN 2+ risk after a negative posttreatment cotest (2.4%) was lower than that following a negative HPV test (3.7%, p = .3) or negative Pap result (4.2%, p = .1). Two negative posttreatment tests of each kind conferred slightly lower 5-year CIN 2+ risk than one (2 negative Pap tests vs. 1, 2.7% vs 4.2%, p = .2; 2 negative HPV tests vs. 1, 2.7% vs 3.7%, p = .7; 2 negative cotests vs. 1, 1.5% vs 2.4%, p = .8). The 5-year CIN 2+ risk after 2 negative cotests of 1.5% (95% confidence interval = 0.3%-7.2%) approached the 0.68% risk after a negative Pap test during routine screening.
  
  
  CONCLUSIONS
  Women with antecedent AGC/ASC-H/HSIL+ Pap results or those treated for CIN 3/AIS had a substantial risk of developing CIN 2+ posttreatment. On the basis of the principle of "equal management of equal risks," after negative test results posttreatment, no subgroup of women achieved risk sufficiently low to return to 5-year routine screening. However, negative cotests after treatment provided more reassurance against recurrent CIN 2+ than either negative Pap tests or HPV tests alone.
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: D000230:Adenocarcinoma / Q000175:diagnosis / Q000453:epidemiology* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002140:California / Q000453:epidemiology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000175:diagnosis*; D012008:Recurrence; D018570:Risk Assessment; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000601:surgery; D014626:Vaginal Smears / Q000379:methods*; D014773:Virology / Q000379:methods*; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis / Q000453:epidemiology* / Q000601:surgery