title: Restricted cross-reactivity of hybrid capture 2 with nononcogenic human papillomavirus types.
abstract: Hybrid Capture 2 Test using probe B (HC2-B) is a clinical test for the detection of 13 human papillomavirus (HPV) types associated with cervical cancer (oncogenic types), but the potential clinical significance of HC2-B cross-reactivity with untargeted (nononcogenic) HPV types has not been fully evaluated. Thus, HC2-B test results on 954 clinical cervical specimens from a population-based natural history study of HPV in Costa Rica were compared with the data from testing of the same specimens twice by HPV type-specific MY09/MY11 L1 consensus primer PCR. Specimens positive by PCR for single HPV types not targeted by HC2-B were used for determining type-specific cross-reactivity. Effects of cross-reactivity on clinical performance were estimated by calculating sensitivity and specificity with and without cross-reactivity for the detection of high-grade cervical lesions. HC2-B tested positive for single infections by untargeted (cross-reactive) types 11, 53, 61, 66, 67, 70, 71, and 81. Cross-reactivity was strongly associated with PCR signal strength (P(Trend) = 0.0001) and cervical abnormalities (P = 0.0002, Pearson chi(2)). We estimated that HC2-B cross-reactivity resulted in minor changes in screening performance. Clinical sensitivity increased from 84.3% to 87.9%, clinical specificity decreased from 89.6% to 88.1%, and referral rates increased from 11.7% to 13.2% for detection of >or=cervical intraepithelial neoplasia grade 2. The clinical effect of cross-reactivity varied by cytologic interpretation. Among women with normal cytologic interpretations, cross-reactivity significantly improved the accuracy of identifying cytologically nonevident histology of >or=cervical intraepithelial neoplasia grade 2 because of increased sensitivity with maintained specificity. However, among women with equivocal or mildly abnormal cytologic interpretations, cross-reactivity decreased the accuracy of HPV testing because of substantial decreases in specificity. In summary, cross-reactivity with nononcogenic HPV types had little effect on the overall clinical performance of HC2-B as a general screening test, but reduction of cross-reactivity might improve the performance of HPV testing for triage of equivocal or mildly abnormal cytologic interpretations.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA. pc95p@nih.gov
authors.forename: Philip E
authors.initials: PE
authors.lastname: Castle
authors.forename: Mark
authors.initials: M
authors.lastname: Schiffman
authors.forename: Robert D
authors.initials: RD
authors.lastname: Burk
authors.forename: Sholom
authors.initials: S
authors.lastname: Wacholder
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
authors.forename: Rolando
authors.initials: R
authors.lastname: Herrero
authors.forename: M Concepcion
authors.initials: MC
authors.lastname: Bratti
authors.forename: Mark E
authors.initials: ME
authors.lastname: Sherman
authors.forename: Attila
authors.initials: A
authors.lastname: Lorincz
mesh_terms: D000328:Adult; D000367:Age Factors; D015331:Cohort Studies; D003364:Costa Rica / Q000453:epidemiology; D003429:Cross Reactions / Q000502:physiology*; D004279:DNA, Viral / Q000302:isolation & purification; D019317:Evidence-Based Medicine; D005260:Female; D006801:Humans; D009693:Nucleic Acid Hybridization; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000175:diagnosis / Q000453:epidemiology / Q000821:virology; D016133:Polymerase Chain Reaction; D015995:Prevalence; D016032:Randomized Controlled Trials as Topic; D012680:Sensitivity and Specificity; D014412:Tumor Virus Infections / Q000175:diagnosis / Q000453:epidemiology / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000821:virology; D016387:Women's Health
chemical_list: D004279:DNA, Viral