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

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


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

Purpose: 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.

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

Conclusion: 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.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Early Detection of Cancer
  • Female
  • Genotype
  • Human papillomavirus 16 / genetics*
  • Human papillomavirus 18 / genetics*
  • Humans
  • Papillomavirus Infections / diagnosis
  • Papillomavirus Infections / virology*
  • Precancerous Conditions / diagnosis
  • Precancerous Conditions / virology
  • Risk Factors
  • Sensitivity and Specificity
  • Triage*
  • Uterine Cervical Neoplasms / diagnosis
  • Uterine Cervical Neoplasms / virology*