High-risk HPV testing in the management of atypical glandular cells: A systematic review and meta-analysis.

Whereas the utility of high-risk HPV (hrHPV) testing is widely accepted in triage of women with atypical squamous lesions, its role in managing atypical glandular cells (AGC) is not fully elucidated. A systematic review and meta-analysis were performed to evaluate the accuracy of hrHPV testing in the management of women with AGC to detect underlying high-grade intraepithelial neoplasia or worse, and adenocarcinoma in situ or worse (AIS+). Additionally, the diagnosis of extra-cervical cancer was considered as an outcome in this review. A bibliographic database search (PubMed, EMBASE, CENTRAL) identified twelve eligible studies. The occurrence of cervical intraepithelial neoplasia grade two or worse including AIS+ (CIN2+/AIS+), was 19.8% among women with AGC, and 55.7% among women with AGC and concurrent squamous lesions (atypical squamous cells of undetermined significance or worse, ASC-US+). The pooled sensitivity and specificity of hrHPV-testing with Hybrid Capture 2 (HC2) to detect CIN2+/AIS+ in women with AGC was 90.0% (95% CI = 85.1-93.4%) and 75.1% (95% CI = 64.8-83.2%), respectively. Women who were hrHPV-negative, demonstrated an increased risk for extra-cervical malignancy (endometrium, fallopian tube, ovary). In women of 50y and older, a hrHPV-negative result was linked with a 18.0% chance of extra-cervical malignancy, while the chance of cervical pre-cancer and cancer was 0.4 and 0.0%, respectively. In conclusion, given the high risk of underlying CIN2+/AIS+, women with AGC should be referred directly to colposcopy. However, hrHPV test results in combination with the age, appears to improve the diagnostic process by distinguishing the risk for cervical versus non-cervical lesions.