Background: Only clinically validated HPV assays can be accepted in cervical cancer screening. Objectives: To update the list of high-risk HPV assays that fulfil the 2009 international validation criteria (Meijer-2009). Data Sources: PubMed/Medline, Embase, Scopus, references from selected studies; published in January 2014 to August 2020. Study eligibility criteria: HPV test validation studies and primary screening studies, involving testing with an index HPV test and a comparator HPV test with reporting of disease outcome (occurrence of histologically confirmed cervical precancer; CIN2þ). Participants: Women participating in cervical cancer screening. Interventions: Testing with an index and a comparator HPV test of clinician-collected cervical specimens and assessment of disease outcome (

Objective Thirteen human papillomavirus (HPV) genotypes are associated with the highest risk of cervical disease/cancer; however, the risk of disease progression and cancer is genotype dependent. The objective of this systematic review was to examine evidence for high-grade cervical intraepithelial neoplasia (≥CIN 3) risk discrimination using HPV genotyping. Materials and Methods A systematic review of English and non-English articles through MEDLINE, Cochrane, clinicaltrials.gov, and abstracts presented at relevant professional society conferences were searched from 2000 to 2019. Search terms included: cervical cancer screening, HPV genotyping, CIN, HPV persistence, humans, and colposcopy; prospective, controlled trials, observational studies, and retrospective studies of residual specimens; evidence included HPV genotyping (beyond genotypes 16/18/45) results. Data were obtained independently by authors using predefined fields. Risk of bias was evaluated with a modified Newcastle-Ottawa Scale. The Grading of Recommendations, Assessment, Development and Evaluation methodology facilitated overall quality of evidence evaluation for risk estimation. The study protocol was registered with the PROSPERO International Prospective Register of Systematic Reviews (CRD42018091093). The primary outcome was CIN 3 or worse risk both at baseline and at different follow-up periods. Results Of 236 identified sources, 60 full texts were retrieved and 16 articles/sources were included. Risk of bias was deemed low; the overall quality of evidence for CIN 3 or worse risk with negative for intraepithelial lesions or malignancies or low-grade squamous intraepithelial cytology was assessed as moderate; that with atypical squamous cells-undetermined significance and “all cytology” was assessed as high. Clinical and methodological heterogeneity precluded meta-analysis. Human papillomavirus genotyping discriminated risk of CIN 3 or worse to a clinically significant degree, regardless of cytology result. Conclusions The evidence supports a clinical utility for HPV genotyping in risk discrimination during cervical cancer screening.

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BackgroundHPV‐based cervical screening detects women at an increased risk of cervical cancer and precancer. To differentiate among HPV‐positive women those with (pre)cancer, triage testing is necessary. The detection of cancer‐associated host‐cell DNA methylation (FAM19A4 and hsa‐mir124‐2) in cervical samples has shown valuable as triage test. This multicenter study from 6 collaborating European laboratories and one reference laboratory was set out to determine the intra‐ and inter‐laboratory agreement of FAM19A4/mir124‐2 DNA methylation analysis utilizing the QIAsure Methylation Test.MethodsAgreement analysis for the QIAsure Methylation Test was assessed on high‐risk HPV‐positive cervical specimens (n = 1680) both at the level of the assay and at the full workflow, including bisulfite conversion.ResultsIntra‐ and inter‐laboratory assay agreement were 91.4% (534/584; 95% CI 88.9‐93.5; κ = 0.82) and 92.5% (369/399; 95% CI 90.0‐94.7; κ = 0.83), respectively. The inter‐laboratory workflow (bisulfite conversion and assay combined) agreement was 90.0% (627/697; 95% CI 87.5%‐92.0%; κ = 0.76).ConclusionThese data show that the QIAsure Methylation Test performs robust and reproducible in different laboratory contexts. These results support the use of the QIAsure Methylation Test for full molecular screening for cervical cancer, including primary HPV testing and triage testing by methylation analysis.