Triage of ASC-H: A meta-analysis of the accuracy of high-risk HPV testing and other markers to detect cervical precancer

Cancer Cytopathol. 2016 Apr;124(4):261-72. doi: 10.1002/cncy.21661. Epub 2015 Nov 30.


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.

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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Atypical Squamous Cells of the Cervix / pathology
  • Early Detection of Cancer / methods*
  • Female
  • Human Papillomavirus DNA Tests
  • Humans
  • Neoplasm Invasiveness / pathology
  • Neoplasm Staging / methods
  • Papillomavirus Infections / diagnosis
  • Papillomavirus Infections / pathology*
  • Precancerous Conditions / pathology*
  • Sensitivity and Specificity
  • Squamous Intraepithelial Lesions of the Cervix / pathology*
  • Squamous Intraepithelial Lesions of the Cervix / virology*
  • Triage
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology
  • Vaginal Smears