title: A cohort study of cervical screening using partial HPV typing and cytology triage.
abstract: HPV testing is more sensitive than cytology for cervical screening. However, to incorporate HPV tests into screening, risk-stratification ("triage") of HPV-positive women is needed to avoid excessive colposcopy and overtreatment. We prospectively evaluated combinations of partial HPV typing (Onclarity, BD) and cytology triage, and explored whether management could be simplified, based on grouping combinations yielding similar 3-year or 18-month CIN3+ risks. We typed ∼9,000 archived specimens, taken at enrollment (2007-2011) into the NCI-Kaiser Permanente Northern California (KPNC) HPV Persistence and Progression (PaP) cohort. Stratified sampling, with reweighting in the statistical analysis, permitted risk estimation of HPV/cytology combinations for the 700,000+-woman KPNC screening population. Based on 3-year CIN3+ risks, Onclarity results could be combined into five groups (HPV16, else HPV18/45, else HPV31/33/58/52, else HPV51/35/39/68/56/66/68, else HPV negative); cytology results fell into three risk groups ("high-grade," ASC-US/LSIL, NILM). For the resultant 15 HPV group-cytology combinations, 3-year CIN3+ risks ranged 1,000-fold from 60.6% to 0.06%. To guide management, we compared the risks to established "benchmark" risk/management thresholds in this same population (e.g., LSIL predicted 3-year CIN3+ risk of 5.8% in the screening population, providing the benchmark for colposcopic referral). By benchmarking to 3-year risk thresholds (supplemented by 18-month estimates), the widely varying risk strata could be condensed into four action bands (very high risk of CIN3+ mandating consideration of cone biopsy if colposcopy did not find precancer; moderate risk justifying colposcopy; low risk managed by intensified follow-up to permit HPV "clearance"; and very low risk permitting routine screening.) Overall, the results support primary HPV testing, with management of HPV-positive women using partial HPV typing and cytology.
authors: National Cancer Institute Division of Cancer Epidemiology and Genetics, Rockville, MD. schiffmm@exchange.nih.gov.
authors: Mark
authors: M
authors: Schiffman
authors: National Cancer Institute Division of Cancer Epidemiology and Genetics, Rockville, MD.
authors: Noorie
authors: N
authors: Hyun
authors: Kaiser Permanente Northern California Division of Research, Oakland, CA.
authors: Tina R
authors: TR
authors: Raine-Bennett
authors: National Cancer Institute Division of Cancer Epidemiology and Genetics, Rockville, MD.
authors: Hormuzd
authors: H
authors: Katki
authors: Kaiser Permanente Northern California Regional Laboratory, Berkeley, CA.
authors: Barbara
authors: B
authors: Fetterman
authors: National Cancer Institute Division of Cancer Epidemiology and Genetics, Rockville, MD.
authors: Julia C
authors: JC
authors: Gage
authors: Information Management Services, Calverton, MD.
authors: Li C
authors: LC
authors: Cheung
authors: Information Management Services, Calverton, MD.
authors: Brian
authors: B
authors: Befano
authors: Kaiser Permanente Northern California Regional Laboratory, Berkeley, CA.
authors: Nancy
authors: N
authors: Poitras
authors: Kaiser Permanente Northern California Regional Laboratory, Berkeley, CA.
authors: Thomas
authors: T
authors: Lorey
authors: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.
authors: Philip E
authors: PE
authors: Castle
authors: National Cancer Institute Division of Cancer Epidemiology and Genetics, Rockville, MD.
authors: Nicolas
authors: N
authors: Wentzensen
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D052162:Human papillomavirus 16 / Q000145:classification / Q000302:isolation & purification; D006801:Humans; D008875:Middle Aged; D027383:Papillomaviridae / Q000145:classification / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000473:pathology* / Q000821:virology*; D014218:Triage / Q000379:methods; D002583:Uterine Cervical Neoplasms / Q000473:pathology* / Q000821:virology*; D014626:Vaginal Smears / Q000379:methods; D002578:Uterine Cervical Dysplasia / Q000473:pathology* / Q000821:virology*
keywords: HPV; cancer; cervix; cytology; screening