Role of High-Risk HPV Testing in Papanicolaou Tests With Atypical Glandular Cells With and Without Concurrent Squamous Cell Abnormalities

Objectives Data on Papanicolaou (Pap) tests with atypical glandular cells (AGCs) with concurrent squamous cell abnormalities (AGC + Sq) are limited. We evaluated histologic outcomes and the role of high-risk human papillomavirus (HR-HPV) testing in this setting compared with AGCs without concurrent squamous cell abnormalities (AGC-alone). Methods This study used a retrospective cohort of patients with Pap test diagnoses of AGC + Sq and AGC-alone between October 2013 and August 2021. Results We included 287 Pap tests from 278 patients. The HR-HPV test was positive in 55% of AGC + Sq cases and 14% of AGC-alone cases (P < .0001). Most AGC + Sq cases displayed squamous lesions (41.5%) or were benign (41.5%) on histology, whereas AGC-alone cases were predominantly benign (72%) or extracervical neoplasms (18%). AGC + Sq cases showed higher rates of significant histologic lesions (P = .0001), which were associated with positive HR-HPV status (P = .0012). In AGC-alone cases, HR-HPV status was associated with significant histology only in patients 50 years of age or younger. In both groups, 20% or more of HR-HPV–negative patients harbored significant lesions. Conclusions AGC + Sq represents a distinct group of patients. HR-HPV testing and patient age provide useful information in the evaluation of AGC, but triage based on HR-HPV testing is not recommended because of the potential for missing significant lesions.