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A cohort study of cervical screening using partial HPV typing and cytology triage. Int J Cancer 2016 Dec 01;139(11):2606-15

Date

08/11/2016

Pubmed ID

27509172

DOI

10.1002/ijc.30375

Scopus ID

2-s2.0-84988038853 (requires institutional sign-in at Scopus site)   67 Citations

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.

Author List

Schiffman M, Hyun N, Raine-Bennett TR, Katki H, Fetterman B, Gage JC, Cheung LC, Befano B, Poitras N, Lorey T, Castle PE, Wentzensen N



MESH terms used to index this publication - Major topics in bold

Adult
Aged
Cohort Studies
Female
Human papillomavirus 16
Humans
Middle Aged
Papillomaviridae
Papillomavirus Infections
Triage
Uterine Cervical Dysplasia
Uterine Cervical Neoplasms
Vaginal Smears