title: Optimal threshold for a positive hybrid capture 2 test for detection of human papillomavirus: data from the ARTISTIC trial.
abstract: We present data on the use of the Hybrid Capture 2 (HC2) test for the detection of high-risk human papillomavirus (HR HPV) with different thresholds for positivity within a primary screening setting and as a method of triage for low-grade cytology. In the ARTISTIC population-based trial, 18,386 women were screened by cytology and for HPV. Cervical intraepithelial neoplasia lesions of grade two and higher (CIN2+ lesions) were identified for 453 women within 30 months of an abnormal baseline sample. When a relative light unit/cutoff (RLU/Co) ratio of > or = 1 was used as the threshold for considering an HC2 result positive, 15.6% of results were positive, and the proportion of CIN2+ lesions in this group was 14.7%. The relative sensitivity for CIN2+ lesion detection was 93.4%. When an RLU/Co ratio of > or = 2 was used as the threshold, there was a 2.5% reduction in positivity, with an increase in the proportion of CIN2+ lesions detected. The relative sensitivity decreased slightly, to 90.3%. Among women with low-grade cytology, HPV prevalences were 43.7% and 40.3% at RLU/Co ratios of > or = 1 and > or = 2, respectively. The proportions of CIN2+ lesions detected were 17.3% and 18.0%, with relative sensitivities of 87.7% at an RLU/Co ratio of > or = 1 and 84.2% at an RLU/Co ratio of > or = 2. At an RLU/Co ratio of > or = 1, 68.3% of HC2-positive results were confirmed by the Roche line blot assay, compared to 77.2% of those at an RLU/Co ratio of > or = 2. Fewer HC2-positive results were confirmed for 35- to 64-year-olds (50.3% at an RLU/Co ratio of > or = 1 and 63.2% at an RLU/Co ratio of > 2) than for 20- to 34-year-olds (78.7% at an RLU/Co ratio of > or = 1 and 83.7% at an RLU/Co ratio of > 2). If the HC2 test is used for routine screening as an initial test or as a method of triage for low-grade cytology, we would suggest increasing the threshold for positivity from the RLU/Co ratio of > or = 1, recommended by the manufacturer, to an RLU/Co ratio of > or = 2, since this study has shown that a beneficial balance between relative sensitivity and the proportion of CIN2+ lesions detected is achieved at this threshold.
authors.affiliation: Manchester Clinical Virology, Central Manchester University Hospitals NHS Foundation Trust, Manchester M13 9WL, United Kingdom. alex.sargent@cmft.nhs.uk
authors.forename: A
authors.initials: A
authors.lastname: Sargent
authors.forename: A
authors.initials: A
authors.lastname: Bailey
authors.forename: A
authors.initials: A
authors.lastname: Turner
authors.forename: M
authors.initials: M
authors.lastname: Almonte
authors.forename: C
authors.initials: C
authors.lastname: Gilham
authors.forename: H
authors.initials: H
authors.lastname: Baysson
authors.forename: J
authors.initials: J
authors.lastname: Peto
authors.forename: C
authors.initials: C
authors.lastname: Roberts
authors.forename: C
authors.initials: C
authors.lastname: Thomson
authors.forename: M
authors.initials: M
authors.lastname: Desai
authors.forename: J
authors.initials: J
authors.lastname: Mather
authors.forename: H
authors.initials: H
authors.lastname: Kitchener
mesh_terms: D000328:Adult; D019411:Clinical Laboratory Techniques / Q000379:methods*; D005260:Female; D006801:Humans; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D009693:Nucleic Acid Hybridization; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000473:pathology / Q000821:virology; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000821:virology*; D055815:Young Adult