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

Cancer Epidemiol Biomarkers Prev. 2017 Nov;26(11):1629-1635. doi: 10.1158/1055-9965.EPI-17-0534. Epub 2017 Sep 8.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cervical Intraepithelial Neoplasia / diagnosis*
  • Cervical Intraepithelial Neoplasia / virology
  • Colposcopy
  • Cross-Sectional Studies
  • Cyclin-Dependent Kinase Inhibitor p16 / analysis
  • Early Detection of Cancer / methods*
  • Female
  • Genotype
  • Genotyping Techniques / methods
  • Human papillomavirus 16 / genetics*
  • Human papillomavirus 16 / isolation & purification
  • Human papillomavirus 18 / genetics*
  • Human papillomavirus 18 / isolation & purification
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / analysis
  • Liquid Biopsy
  • Middle Aged
  • Papillomavirus Infections / diagnosis*
  • Papillomavirus Infections / virology
  • Sensitivity and Specificity
  • Triage / methods*
  • Uterine Cervical Neoplasms / diagnosis*
  • Uterine Cervical Neoplasms / virology
  • Young Adult

Substances

  • Cyclin-Dependent Kinase Inhibitor p16
  • Ki-67 Antigen