Objective:
To update the list of HPV assays fulfilling international validation criteria for primary cervical cancer screening. 
 
Methods:
A recent systematic review targeted published studies regarding new assays that show non-inferior sensitivity and specificity to detect cervical intraepithelial neoplasia of grade-2 or worse (CIN2+) and demonstrated sufficient intra- and inter-laboratory reproducibility according to quantified thresholds (margins for relative sensitivity and specificity of new versus comparator tests at 0.90 and 0.98, respectively; left 95% CI bound around reproducibility ≥87% and kappa ≥0.5).  In addition, the more stringent WHO TPP criterion for reproducibility ≥94% was verified. Finally, the list of second generation standard comparator HPV tests was updated.
 
Results:
One  HPV mRNA and 19 DNA assays fulfilled the three international criteria: A) (two initial standard comparator tests validated through randomized trials demonstrating lower cervical cancer incidence compared to cytology (Hybrid Capture-2 HPV DNA Test and GP5+/6+ PCR-EIA); B) nine HPV DNA tests that were validated consistently in ≥2 studies against a first generation standard comparator (Alinity m HR HPV Assay, Anyplex II HPV HR Detection, Cobas 4800 HPV Test, HPV-Risk Assay, NeuMoDX HPV assay, Onclarity HPV Assay, PapilloCheck HPV-Screening Test, RealTime High Risk HPV Test, Xpert HPV); C) six assays evaluated in only one study against HC2/GP5+6+PCR (CLART HPV4S, OncoPredict HPV Screening, OncoPredict HPV QT, REALQUALITY RQ-HPV Screen, RIATOL HPV genotyping qPCR, and Vitro HPV Screening Assay); D) one assay evaluated in three studies against a second generation standard comparator (Cobas-6800) and another assay evaluated in three studies against first and second generation comparators (Allplex HPV HR Detection assay); and E) one mRNA assay validated consistently for the cross-sectional validation criteria against HC2/GP5+/6+ PCR which also demonstrated longitudinal safety (APTIMA HPV Assay).  
Six assays satisfied the criteria for second generation standard comparator testing and can replace the initial comparator assays (Anyplex II HPV HR Detection, Allplex HPV HR Detection assay, Cobas 4800 HPV Test and Cobas test run on the 6800 platform, Onclarity HPV Assay,  RealTime High Risk HPV Test).
Six of the 19 validated HPV DNA assays are not anymore or are not yet available on the market. Three assays do not provide any genotyping; eight tests allow limited genotyping (separate detection of HPV16/18 and 10-12 other types in bulk); three assays offer extended genotyping; and six assays can identify all targeted types separately.
 
Conclusion:
Fourteen HPV assays are fully validated against the current Meijer/VAGENT criteria and are accessible on the market. Only the assays with full genotyping capacity can distinguish the four carcinogenic groups and can be used for fine-tuned risk-based triage. Validation guidelines need urgent updating to accommodate continuously new developments in assay manufacturing and screening approaches (genotyping, viral load assessment, specimen adequacy, testing on self-samples, point-of care testing, tests with restricted HPV valency, …).