title: Comparison between prototype hybrid capture 3 and hybrid capture 2 human papillomavirus DNA assays for detection of high-grade cervical intraepithelial neoplasia and cancer.
abstract: We compared the performance of a prototype version of the Hybrid Capture 3 (HC3) human papillomavirus (HPV) DNA assay to the current generation Hybrid Capture 2 (HC2) assay, both of which target 13 oncogenic HPV types, for the detection of cervical intraepithelial neoplasia grade 3 and cancer (CIN3+) with cervicovaginal lavage specimens collected at enrollment into a 10-year cohort study at Kaiser Permanente (Portland, Oreg.). HC3 results for a risk-stratified sample (n = 4,364) were compared to HC2 results for the entire cohort (n = 20,810) with receiver operating characteristics curves, and the optimal cut points for both tests (relative light units [RLU]/positive control [PC]) for the detection of CIN3+ were determined. Specimens were also tested for HPV16 and HPV18 with separate HC3 type-specific probes. The optimal cut point for detecting CIN3+ was 1.0 RLU/PC for HC2, as previously shown, and was 0.6 RLU/PC for HC3. At the optimal cut points, HC3 and HC2 had similar screening performance characteristics for CIN3+ diagnosed at the enrollment visit. In analyses that included cases CIN3+ at enrollment and those diagnosed during early follow-up, HC3 had nonsignificantly higher sensitivity and equal specificity for the detection of CIN3+ compared to HC2; this increase in sensitivity was primarily the result of increased detection of CIN3+ in women who were 30 years of age or older and were cytologically negative (P = 0.006). We also compared the performance of the hybrid capture tests to MY09/11 L1 consensus primer PCR results (n = 1,247). HC3 was less likely than HC2 to test positive for specimens that tested positive by PCR for any untargeted types (P < 0.001). HC3 was less likely than HC2 to test positive for untargeted PCR-detected single infections with HPV53 (P = 0.001) and HPV66 (P = 0.01). There was good agreement between test positivity by PCR and by single type-specific HC3 probes for HPV16 (kappa = 0.76; 95% confidence interval [CI] = 0.71 to 0.82) and for HPV18 (kappa = 0.73; 95% CI = 0.68 to 0.79). In conclusion, we suggest that HC3 (>/=0.6 RLU/PC) may be slightly more sensitive than and equally specific test as HC2 (>/=1.0 RLU/PC) for the detection of CIN3+ over the duration of typical screening intervals.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Philip E
authors.initials: PE
authors.lastname: Castle
authors.forename: Attila T
authors.initials: AT
authors.lastname: Lorincz
authors.forename: David R
authors.initials: DR
authors.lastname: Scott
authors.forename: Mark E
authors.initials: ME
authors.lastname: Sherman
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Glass
authors.forename: Brenda B
authors.initials: BB
authors.lastname: Rush
authors.forename: Sholom
authors.initials: S
authors.lastname: Wacholder
authors.forename: Robert D
authors.initials: RD
authors.lastname: Burk
authors.forename: M Michele
authors.initials: MM
authors.lastname: Manos
authors.forename: John E
authors.initials: JE
authors.lastname: Schussler
authors.forename: Paul
authors.initials: P
authors.lastname: Macomber
authors.forename: Mark
authors.initials: M
authors.lastname: Schiffman
mesh_terms: D003429:Cross Reactions; D004279:DNA, Viral / Q000032:analysis*; D005260:Female; D006801:Humans; D027383:Papillomaviridae / Q000145:classification / Q000302:isolation & purification*; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000821:virology
chemical_list: D004279:DNA, Viral