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Ann Intern Med. 2017 Jan 17;166(2):118-127. doi: 10.7326/M15-2735. Epub 2016 Nov 15.

Genotyping for Human Papillomavirus Types 16 and 18 in Women With Minor Cervical Lesions: A Systematic Review and Meta-analysis.

Author information

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.



High-risk human papillomavirus (hrHPV) testing to triage women with minor cervical lesions generates many referrals.


To 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 Sources:

Searches of 4 bibliographic databases, without language restrictions, from 1 January 1999 to 1 February 2016.

Study Selection:

Studies 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 Extraction:

Independent study selection, extraction of data, and quality assessment by 2 reviewers.

Data Synthesis:

Twenty-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.


Methodological and technical heterogeneity among studies; insufficient data to assess accuracy of separate assays.


Testing 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 Source:

7th Framework Programme of the European Commission.

[Indexed for MEDLINE]

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