Management of high-risk HPV-positive women for detection of cervical (pre)cancer

Expert Rev Mol Diagn. 2016 Sep;16(9):961-74. doi: 10.1080/14737159.2016.1217157. Epub 2016 Aug 5.


Introduction: Primary HPV-testing has been shown to provide a superior detection of women at risk of cervical (pre)cancer compared to cytology-based screening. However, as most high-risk HPV infections are harmless, additional triage testing of HPV-positive women is necessary to identify those with cervical (pre)cancer. In this paper, we compare the performance, advantages and limitations of clinically relevant available triage strategies for HPV-positive women.

Areas covered: Many different colposcopy triage strategies, comprising both microscopy-based and molecular (virus/host-related) markers, have been suggested: Pap cytology, p16/Ki-67 dual-stained cytology, HPV16/18 genotyping, viral DNA methylation and host cell DNA methylation. Literature search was limited to triage strategies that have achieved at least phase 2 of the five-phase framework for biomarker development and studies including large cohorts (≥100 hrHPV-positive women). Triage markers were stratified by sample type (cervical scrape, self-collected sample) and by study population (screening, non-attendee, referral). Expert commentary: At present, repeat Pap cytology and Pap cytology combined with HPV16/18 genotyping are the only triage strategies that have been robustly shown to be ready for implementation. Other strategies such as p16/Ki-67 dual-stained cytology and host cell DNA methylation analysis, with or without additional HPV16/18 genotyping, are attractive options for the near future.

Keywords: DNA methylation; Human papillomavirus; biomarker; cervical cancer; cervical intraepithelial neoplasia (CIN); cytology; genotyping; p16/Ki-67 dual-stained cytology; screening; triage.

Publication types

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

MeSH terms

  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • DNA Methylation / genetics
  • DNA, Viral / genetics
  • DNA, Viral / metabolism
  • Female
  • Genotyping Techniques / methods
  • Human papillomavirus 16* / genetics
  • Human papillomavirus 16* / metabolism
  • Human papillomavirus 18* / genetics
  • Human papillomavirus 18* / metabolism
  • Humans
  • Ki-67 Antigen / genetics
  • Ki-67 Antigen / metabolism
  • Papanicolaou Test / methods
  • Papillomavirus Infections* / diagnosis
  • Papillomavirus Infections* / genetics
  • Papillomavirus Infections* / metabolism
  • Precancerous Conditions* / diagnosis
  • Precancerous Conditions* / genetics
  • Precancerous Conditions* / metabolism
  • Precancerous Conditions* / virology
  • Triage / methods
  • Uterine Cervical Neoplasms* / diagnosis
  • Uterine Cervical Neoplasms* / genetics
  • Uterine Cervical Neoplasms* / metabolism
  • Uterine Cervical Neoplasms* / virology


  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Viral
  • Ki-67 Antigen