Management of women with a cytological diagnosis of atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) includes immediate referral to colposcopy because of its high associated risk of underlying high-grade cervical intraepithelial neoplasia (CIN). However, triage may reduce the burden of diagnostic workup and avoid overtreatment.
A systematic review and meta-analysis were conducted to evaluate the accuracy of hrHPV testing with Hybrid Capture-2 (HC2) or other assays, HPV16/18 genotyping and testing for other molecular markers for the detection of CIN grade two or worse (CIN2+) or CIN grade three or worse (CIN3+) in the management of women with ASC-H. The relative accuracy of the other hrHPV assays or molecular markers using HC2 as comparator was also evaluated. An additional question assessed was whether triage is useful given the relatively high pretriage probability of underlying precancer.
The pooled absolute sensitivity and specificity of hrHPV testing with HC2 to detect CIN2+ (derived from 19 studies) was 93% (95% CI: 89-95%) and 45% (95% CI: 41-50%), respectively. The p16INK4a staining (only 3 studies) has similar sensitivity (ratio=0.99, 95% CI:0.87-1.12) but superior specificity (ratio= 1.69, 95% CI: 1.39-2.06) compared to HC2 for detecting CIN2+. The average pre-test risk was 34% for CIN2+ and 20% for CIN3+. A negative HC2 result decreased this risk to 8% and 5%, whereas a positive result upgraded the risk to 47% and 28%.
A cytological result of ASC-H is associated with a high risk of cervical precancer, which justifies immediate referral for colposcopy. Results in this meta-analysis support a certain utility of hrHPV DNA testings and in particular of p16INK4a cyto-immunochemistry. A positive triage result does not alter the decision to refer, but those testing negative could be recalled for a repeat test 6-12 months later in countries with a conservative follow-up policy. Nonetheless, in countries with a low decision threshold for colposcopy referral, triage of ASC-H would be considered as not useful to orient diagnostic workup.