Defining Optimal Triage Strategies for hrHPV Screen-Positive Women-An Evaluation of HPV 16/18 Genotyping, Cytology, and p16/Ki-67 Cytoimmunochemistry

Abstract

Background: Several options for the triage of high-risk HPV screen-positive (hrHPV⁺) women were assessed.Methods: This study incorporated CIN2⁺ cases and controls, all of whom tested hrHPV⁺ and whose results of liquid-based cytology (LBC), HPV16/18 genotyping, and p16/Ki67 cytoimmunochemistry were available. Sensitivity and specificity for the CIN2⁺ of these triage tests were evaluated.Results: Absolute sensitivities of HPV 16/18 typing, LBC, and p16/Ki-67 cytoimmunochemistry for CIN2⁺ detection were 61.7%, 68.3%, and 85.0% for women with hrHPV⁺ clinician-taken samples. Respective specificities were 70.5%, 89.1%, and 76.7%. The absolute accuracy of the triage tests was similar for women with a hrHPV⁺ self-sample. P16/Ki-67 cyto-immunochemistry was significantly more sensitive than LBC although significantly less specific.Conclusions: All three single-test triage options, if positive, exceed the threshold of 20% risk at which colposcopy would be indicated. However, none of them conferred a post-test probability of CIN2⁺ <2%; which would permit routine recall. P16/Ki-67 cytoimmunochemistry on HPV16/18 negative women had a post-test probability of CIN2⁺ of 1.7% and 0.6% if also LBC negative.Impact: This is one of the few studies to directly compare the performance of triage strategies of hrHPV⁺ women, in isolation and combinations. It is the only study assessing triage strategies in women who test hrHPV⁺ in self-taken vaginal samples. A combined triage option that incorporated HPV 16/18 typing prior to p16/ki-67 cytoimmunochemistry in HPV 16/18-negative women yielded a post-test probability of CIN2⁺ of >20%, whereas women who tested negative had a probability of CIN2⁺ of <2%. Cancer Epidemiol Biomarkers Prev; 26(11); 1629-35. ©2017 AACR.