Which high-risk HPV assays fulfil criteria for use in primary cervical cancer screening?

Clin Microbiol Infect. 2015 Sep;21(9):817-26. doi: 10.1016/j.cmi.2015.04.015. Epub 2015 May 1.


Several countries are in the process of switching to high-risk human papillomavirus (hrHPV) testing for cervical cancer screening. Given the multitude of available tests, validated assays which assure high-quality screening need to be identified. A systematic review was conducted to answer the question which hrHPV tests fulfil the criteria defined by an international expert team in 2009, based on reproducibility and relative sensitivity and specificity compared to Hybrid Capture-2 or GP5+/6+ PCR-enzyme immunoassay. These latter two hrHPV DNA assays were validated in large randomized trials and cohorts with a follow-up duration of 8 years or more. Eligible studies citing the 2009 guideline were retrieved from Scopus (http://www.scopus.com) and from a meta-analysis assessing the relative accuracy of new hrHPV assays versus the standard comparator tests to detect high-grade cervical intraepithelial neoplasia or cancer in primary screening. The cobas 4800 HPV test and Abbott RealTime High Risk HPV test were consistently validated in two and three studies, respectively, whereas the PapilloCheck HPV-screening test, BD Onclarity HPV assay and the HPV-Risk assay were validated each in one study. Other tests which partially fulfil the 2009 guidelines are the following: Cervista HPV HR Test, GP5+/6+ PCR-LMNX, an in-house E6/E7 RT quantitative PCR and MALDI-TOF (matrix-assisted laser desorption-ionization time-of-flight). The APTIMA HPV assay targeting E6/E7 mRNA of hrHPV was also fully validated. However, the cross-sectional equivalency criteria of the 2009 guidelines were set up for HPV DNA assays. Demonstration of a low risk of CIN3+ after a negative APTIMA test over a longer period is awaited to inform us about its utility in cervical cancer screening at 5-year or longer intervals.

Keywords: Cervical cancer; cervical cancer screening; diagnostic test accuracy; human papillomavirus; meta-analysis; systematic review; validation of tests.

Publication types

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

MeSH terms

  • Early Detection of Cancer / methods*
  • Female
  • Genotyping Techniques / methods*
  • Humans
  • Molecular Diagnostic Techniques / methods*
  • Papillomaviridae / classification
  • Papillomaviridae / genetics
  • Papillomaviridae / isolation & purification*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Uterine Cervical Neoplasms / diagnosis*
  • Uterine Cervical Neoplasms / virology*