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

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

Author information

1
Belgian Cancer Center/Unit of Cancer Epidemiology, Scientific Institute of Public Health, Brussels, Belgium.
2
Unit of Virus, Lifestyle, and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
3
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland.
4
Laboratoire Cerba, Cergy-Pontoise, France.

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.

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

PMID:
26618614
PMCID:
PMC4833620
DOI:
10.1002/cncy.21661
[Indexed for MEDLINE]
Free PMC Article

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