title: A study of HPV typing for the management of HPV-positive ASC-US cervical cytologic results.
abstract: BACKGROUND
  In US cervical screening, immediate colposcopy is recommended for women with HPV-positive ASC-US (equivocal) cytology. We evaluated whether partial typing by Onclarity™ (BD) might identify HPV-positive women with low enough CIN3+ risk to permit 1-year follow-up instead.
  
  
  METHODS
  The NCI-Kaiser Permanente Northern California Persistence and Progression cohort includes a subset of 13,890 women aged 21+ with HC2 (Qiagen)-positive ASC-US at enrollment; current median follow-up is 3.0years. Using stratified random sampling, we typed 2079 archived enrollment specimens including 329 women subsequently diagnosed with CIN3+, 563 with CIN2, and 1187 with <CIN2. Adjusting for sampling, we computed 3-year cumulative CIN3+ risks for each Onclarity typing channel, using Kaplan-Meier methods.
  
  
  RESULTS
  The 3-year CIN3+ risk for all HC2-positive women with ASC-US was 5.2%; this establishes the "benchmark" risk for colposcopic referral. Hierarchically, 3-year cumulative risks for each typing channel were 16.0% for HPV16, 7.4% for HPV18, 7.0% for HPV31, 7.1% for grouped HPV33/58, 4.3% for HPV52, 3.9% for HPV45, 2.7% for HPV51, 1.6% for HPV39/68/35, and 1.3% for HPV59/56/66.
  
  
  CONCLUSIONS
  ASC-US linked to HPV16, HPV18, HPV31, or HPV33/58 warrants immediate colposcopy. Optimal management of women with HPV52 or HPV45 is uncertain. Risk of women with only HPV51, HPV39/68/35, or HPV59/56/66 might be low enough to recommend 1-year retesting permitting viral clearance. This strategy would defer colposcopy for 40% of women with HPV-positive ASC-US, half of whom would be cotest-negative at 1-year return. Approximately 10% of those with CIN3 diagnosable at enrollment would be delayed 1year instead. Cost-effectiveness analyses are needed.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA. Electronic address: schiffmm@mail.nih.gov.
authors.forename: Mark
authors.initials: M
authors.lastname: Schiffman
authors.affiliation: BD Diagnostics, Sparks, MD, USA.
authors.forename: Laurence M
authors.initials: LM
authors.lastname: Vaughan
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
authors.forename: Tina R
authors.initials: TR
authors.lastname: Raine-Bennett
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, The Bronx, NY, USA.
authors.forename: Philip E
authors.initials: PE
authors.lastname: Castle
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA.
authors.forename: Hormuzd A
authors.initials: HA
authors.lastname: Katki
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA.
authors.forename: Julia C
authors.initials: JC
authors.lastname: Gage
authors.affiliation: Kaiser Regional Laboratory, Berkeley, CA, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Fetterman
authors.affiliation: Information Management Systems, Inc., Calverton, MD, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Befano
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wentzensen
mesh_terms: D000328:Adult; D065309:Atypical Squamous Cells of the Cervix / Q000473:pathology / Q000821:virology*; D005260:Female; D005838:Genotype; D006801:Humans; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections / Q000821:virology*; D065310:Squamous Intraepithelial Lesions of the Cervix / Q000473:pathology / Q000821:virology*; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000821:virology*; D014626:Vaginal Smears / Q000379:methods; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000821:virology*
keywords: ASC-US; Cervical screening; HPV testing; Triage