Several countries are in the process of switching to 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 of the candidate test compared to HC2 or GP5+/6+ PCR-EIA. Results of recent test validations according to the VALGENT-2 protocol (1) were added. A first review published in 2015 (2) was updated.
The cobas 4800 HPV Test, Abbott RealTime High Risk HPV, BD Onclarity and the PapilloCheck HPV test were each consistently validated in two or three studies, whereas the HPV Risk Assay was validated in one study. Other tests which partially fulfil the 2009-guidelines are: Cervista HPV HR Test, GP5+/6+ PCR-LMNX, an in-house E6/E7 RT qPCR, 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.
The updated review (March 2016) revealed two new studies evaluating Anyplex II HPV HR (Seegene, Seoul, Korea) and Xpert HPV (Cepheid, Sunnyvale, USA), respectively. Both assays showed non-inferior sensitivity and specificity for high-grade cervical intraepithelial neoplasia, compared to HC2 or GP5+/6+ PCR-EIA and demonstrated excellent reproducibility.
Only a limited number of existing HPV assays are clinically validated. VALGENT is an international comprehensive framework for HPV test comparison which allows verification of the clinical accuracy criteria for use in cervical cancer screening. Validation protocols may suffer from selection and ascertainment biases. Continuous monitoring of test performance, updating of the list of validated tests and further international consolidation is needed to assure optimal safety of HPV-based screening programmes. Only clinically validated assays should be used. Two new high-risk HPV assays can be added to the list of tests validated for primary cervical cancer screening.
1. Arbyn M, Depuydt C, Benoy I, et al. VALGENT: a protocol for clinical validation of human papillomavirus assays. J Clin Virol 2016;76: S14-S21.
2. Arbyn M, Snijders PJ, Meijer CJ, et al. Which high-risk HPV assays fulfil criteria for use in primary cervical cancer screening? Clin Microbiol Infect 2015;21: 817-26.