title: Triage of ASC-H: A meta-analysis of the accuracy of high-risk HPV testing and other markers to detect cervical precancer.
abstract: BACKGROUND
  Women with a cytological diagnosis of atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) are usually immediately referred for colposcopy. However, triage may reduce the burden of the diagnostic workup and prevent overtreatment.
  
  
  METHODS
  A meta-analysis was conducted to assess the accuracy of high-risk human papillomavirus (hrHPV) testing and testing for other molecular markers for the detection of grade 2 cervical intraepithelial neoplasia or worse (CIN2+) or grade 3 cervical intraepithelial neoplasia or worse (CIN3+) in women with ASC-H. An additional question that was assessed was whether triage would be useful in light of the relatively high pretriage probability of underlying precancer.
  
  
  RESULTS
  The pooled absolute sensitivity and specificity of the Hybrid Capture 2 (HC2) assay for CIN2 + (derived from 19 studies) were 93% (95% confidence interval [CI], 89%-95%) and 45% (95% CI, 41%-50%), respectively. p16(INK4a) staining (only 3 studies) had similar sensitivity (93%; 95% CI, 75%-100%) but superior specificity (specificity ratio, 1.69) to HC2 for CIN2+. Testing for paired box 1 gene methylation (only 1 study) showed a superior specificity of 95% (specificity ratio, 2.08). The average pretest risk was 34% for CIN2 + and 20% for CIN3+. A negative HC2 result decreased this to 8% and 5%, respectively, whereas a positive result upgraded the risk to 47% and 28%, respectively.
  
  
  CONCLUSIONS
  Because of the high probability of precancer with a diagnosis of ASC-H, the utility of triage is limited. The usual recommendation for referring women with ASC-H for colposcopy is not altered by a positive triage test, whatever test is used. A negative hrHPV DNA or p16(INK4a) test may allow repeat testing, but this recommendation will depend on local decision thresholds for referral.
authors.affiliation: Belgian Cancer Center/Unit of Cancer Epidemiology, Scientific Institute of Public Health, Brussels, Belgium.
authors.forename: Lan
authors.initials: L
authors.lastname: Xu
authors.affiliation: Belgian Cancer Center/Unit of Cancer Epidemiology, Scientific Institute of Public Health, Brussels, Belgium.|Unit of Virus, Lifestyle, and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
authors.forename: Freija
authors.initials: F
authors.lastname: Verdoodt
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wentzensen
authors.affiliation: Laboratoire Cerba, Cergy-Pontoise, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Bergeron
authors.affiliation: Belgian Cancer Center/Unit of Cancer Epidemiology, Scientific Institute of Public Health, Brussels, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Arbyn
mesh_terms: D065309:Atypical Squamous Cells of the Cervix / Q000473:pathology; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D061809:Human Papillomavirus DNA Tests; D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging / Q000379:methods; D030361:Papillomavirus Infections / Q000175:diagnosis / Q000473:pathology*; D011230:Precancerous Conditions / Q000473:pathology*; D012680:Sensitivity and Specificity; D065310:Squamous Intraepithelial Lesions of the Cervix / Q000473:pathology* / Q000821:virology*; D014218:Triage; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000821:virology; D014626:Vaginal Smears
keywords: atypical squamous cells; cannot exclude high-grade squamous intraepithelial lesion (ASC-H); cervical cancer; cervical intraepithelial neoplasia; diagnostic test accuracy; human papillomavirus (HPV); meta-analysis; triage