Comparison between prototype Hybrid Capture 3 and Hybrid Capture 2 human papillomavirus DNA assays for detection of high-grade cervical intraepithelial neoplasia and cancer

Philip E. Castle, Attila T. Lorincz, David R. Scott, Mark E. Sherman, Andrew G. Glass, Brenda B. Rush, Sholom Wacholder, Robert D. Burk, M. Michele Manos, John E. Schussler, Paul Macomber, Mark Schiffman

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49 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4022-4030
Number of pages9
JournalJournal of clinical microbiology
Volume41
Issue number9
DOIs
StatePublished - Sep 1 2003

ASJC Scopus subject areas

  • Microbiology (medical)

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    Castle, P. E., Lorincz, A. T., Scott, D. R., Sherman, M. E., Glass, A. G., Rush, B. B., Wacholder, S., Burk, R. D., Manos, M. M., Schussler, J. E., Macomber, P., & Schiffman, M. (2003). Comparison between prototype Hybrid Capture 3 and Hybrid Capture 2 human papillomavirus DNA assays for detection of high-grade cervical intraepithelial neoplasia and cancer. Journal of clinical microbiology, 41(9), 4022-4030. https://doi.org/10.1128/JCM.41.9.4022-4030.2003