• Marc Arbyn, Lan Xu, Freija Verdoodt, Jack Cuzick, Anne Szarewski, Jerome L Belinson, Nicolas Wentzensen, Julia C Gage, and Michelle J Khan.
• From Scientific Institute of Public Health, Brussels, Belgium; Queen Mary University of London, London, United Kingdom; Cleveland Clinic, Cleveland, Ohio; National Cancer Institute, Bethesda, Maryland; and Kaiser Permanente Northern California, San Leandro, California.
• Ann. Intern. Med. 2017 Jan 17; 166 (2): 118127118-127.

BackgroundHigh-risk human papillomavirus (hrHPV) testing to triage women with minor cervical lesions generates many referrals.PurposeTo evaluate the accuracy of genotyping for HPV types 16 and 18 and its utility as a second triage step after hrHPV testing in women with minor cervical lesions.Data SourcesSearches of 4 bibliographic databases, without language restrictions, from 1 January 1999 to 1 February 2016.Study SelectionStudies involving women with atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions (LSIL) who were triaged with tests for hrHPV and HPV 16/18 to find cervical intraepithelial neoplasia (grade ≥2 [CIN2+] or grade ≥3 [CIN3+]).Data ExtractionIndependent study selection, extraction of data, and quality assessment by 2 reviewers.Data SynthesisTwenty-four moderate- to good-quality studies involving 8587 women with ASC-US and 5284 with LSIL were found. The pooled sensitivity of HPV 16/18 genotyping for CIN3+ was about 70% for women with either ASC-US or LSIL. The pooled specificity (with a threshold of grade <2 CIN) was 83% (95% CI, 80% to 86%) for women with ASC-US and 76% (CI, 74% to 79%) for those with LSIL. The average risk for CIN3+ was 17% and 19% in HPV 16/18-positive women with ASC-US and LSIL, respectively, and was 5% in hrHPV-positive but HPV 16/18-negative women with either ASC-US or LSIL.LimitationMethodological and technical heterogeneity among studies; insufficient data to assess accuracy of separate assays.ConclusionTesting for HPV 16/18 to triage women with minor abnormal cytology is poorly sensitive but may be useful as a second triage test after hrHPV testing, with direct referral if the woman is positive for HPV 16/18. Whether colposcopy or repeated testing is recommended for hrHPV-positive but HPV 16/18-negative women depends on local decision thresholds that can be derived from pretest-posttest probability plots.Primary Funding Source7th Framework Programme of the European Commission.

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