title: Evaluation of any or type-specific persistence of high-risk human papillomavirus for detecting cervical precancer.
abstract: High-risk human papillomavirus (HR-HPV) testing is increasingly important. We therefore examined the impact on accuracy of repeated versus one-time testing, type-specific versus pooled detection, and assay analytic sensitivity. By using a nested case-control design from the ASCUS-LSIL Triage Study, we selected women with incident cervical intraepithelial neoplasia grade 2 or grade 3 (CIN2/3; n = 325) and a random sample of women with <CIN2 as controls (n = 401). HPV DNA status was assessed using hybrid capture 2 (HC2), a pooled test for 13 HR-HPV types, and the linear array (LA) and the line blot assay (LBA), two PCR-based HPV genotyping assays, at enrollment and the 6-month follow-up visit. The relative sensitivity and specificity for different permutations of multiple measurements were compared to a single measurement using marginal regression models. We found that repeat detection of any HR-HPV (by HC2, LA, or LBA) and of type-specific persistence (by LA or LBA) were significantly more specific but less sensitive than use of a single time point measurement of any HR-HPV. Sensitivity decreased and specificity increased further when testing intervals were increased from 12 to 24 months. Including detection of borderline carcinogenic/noncarcinogenic HPV types with HR-HPV types decreased specificity for repeat measures of HPV with no impact on sensitivity. Similar patterns were observed when we used a CIN3 end point. We conclude that assay performance for detecting incident CIN2/3 was affected by which types were included, the analytic sensitivity of the assay, and the testing interval. These trade-offs need to be considered when assessing the potential overall clinical utility of repeated testing for HR-HPV DNA to identify women at risk for CIN2/3.
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: Morgan A
authors.initials: MA
authors.lastname: Marks
authors.forename: Philip E
authors.initials: PE
authors.lastname: Castle
authors.forename: Mark
authors.initials: M
authors.lastname: Schiffman
authors.forename: Patti E
authors.initials: PE
authors.lastname: Gravitt
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D006801:Humans; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D027383:Papillomaviridae / Q000145:classification / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000150:complications / Q000175:diagnosis* / Q000821:virology*; D016032:Randomized Controlled Trials as Topic; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control* / Q000821:virology