title: Genotyping for Human Papillomavirus Types 16 and 18 in Women With Minor Cervical Lesions: A Systematic Review and Meta-analysis.
abstract: BACKGROUND
  High-risk human papillomavirus (hrHPV) testing to triage women with minor cervical lesions generates many referrals.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  Searches of 4 bibliographic databases, without language restrictions, from 1 January 1999 to 1 February 2016.
  
  
  METHODS
  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+]).
  
  
  METHODS
  Independent study selection, extraction of data, and quality assessment by 2 reviewers.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Methodological and technical heterogeneity among studies; insufficient data to assess accuracy of separate assays.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  7th Framework Programme of the European Commission.
authors.affiliation: 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.
authors.forename: Marc
authors.initials: M
authors.lastname: Arbyn
authors.affiliation: 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.
authors.forename: Lan
authors.initials: L
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Freija
authors.initials: F
authors.lastname: Verdoodt
authors.affiliation: 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.
authors.forename: Jack
authors.initials: J
authors.lastname: Cuzick
authors.affiliation: 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.
authors.forename: Anne
authors.initials: A
authors.lastname: Szarewski
authors.affiliation: 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.
authors.forename: Jerome L
authors.initials: JL
authors.lastname: Belinson
authors.affiliation: 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.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wentzensen
authors.affiliation: 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.
authors.forename: Julia C
authors.initials: JC
authors.lastname: Gage
authors.affiliation: 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.
authors.forename: Michelle J
authors.initials: MJ
authors.lastname: Khan
mesh_terms: D055088:Early Detection of Cancer; D005260:Female; D005838:Genotype; D052162:Human papillomavirus 16 / Q000235:genetics*; D052161:Human papillomavirus 18 / Q000235:genetics*; D006801:Humans; D030361:Papillomavirus Infections / Q000175:diagnosis / Q000821:virology*; D011230:Precancerous Conditions / Q000175:diagnosis / Q000821:virology; D012307:Risk Factors; D012680:Sensitivity and Specificity; D014218:Triage; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000821:virology*