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

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. Cancer Cytopathol 2016;124:261-72. (c) 2015 American Cancer Society. Because of the high probability of precancer in patients with a diagnosis of atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H), the utility of triage is limited. The usual recommendation of referring women with ASC-H to colposcopy is not altered by a positive triage test, whatever test is used. A negative high-risk human papillomavirus DNA or p16(INK4a) test may allow repeat testing, but this recommendation will depend on local decision thresholds for referral.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. Cancer Cytopathol 2016;124:261-72. (c) 2015 American Cancer Society. Because of the high probability of precancer in patients with a diagnosis of atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H), the utility of triage is limited. The usual recommendation of referring women with ASC-H to colposcopy is not altered by a positive triage test, whatever test is used. A negative high-risk human papillomavirus DNA or p16(INK4a) test may allow repeat testing, but this recommendation will depend on local decision thresholds for referral.A