A Retrospective Pathology Review of Atypical Glandular Cells: hrHPV Status and Glandular Neoplastic Outcomes

Objectives: To evaluate the relationship between high-risk human papillomavirus (hrHPV) status and glandular neoplastic outcomes in women with atypical glandular cells (AGC) and to characterize the clinicopathologic features of hrHPV-negative AGC. Methods: We evaluated 230,780 cervical cytology results collected from January 1, 2005 to June 1, 2017, identifying 698 (0.3%) AGC cases. Demographics, age at AGC diagnosis, Pap and reflex hrHPV results, and final AGC-related pathology were recorded. Associations between hrHPV status and glandular neoplastic outcomes were evaluated using the χ 2 test. Results: Among 698 women with AGC, 315 (45.1%) had hrHPV data, including 130 (41.3%) hrHPV-positive and 185 (58.7%) hrHPV-negative. The remaining 383 (54.9%) had no reflex hrHPV performed because of no squamous abnormalities. Of the 463 with pathology results, 49 (10.6%) had endometrial or endocervical cancer, including adenocarcinoma in situ. Of the 49, 8 (16.3%) were hrHPV-positive, 11 (22.4%) were hrHPV-negative, and 30 (61.3%) had unknown hrHPV. Of the 240 with hrHPV and pathology available, the incidence of glandular neoplastic lesions did not differ between hrHPV-negative and hrHPV-positive women (7.8% vs 8.1%; relative risk=1.04, 95% CI=0.43–2.48; p =.94). Women with glandular neoplastic lesions were significantly older at AGC diagnosis than those without neoplasia [mean (SD) age: 55.5 (16.1) vs 44.8 (11.6); p <.001]. Conclusions: AGC is associated with a significant risk of glandular neoplastic lesions, particularly among older women. hrHPV-negative AGC does not exclude clinically significant glandular neoplasia, supporting the diagnostic value of cervical cytology in AGC evaluation. These findings should be interpreted in the context of a historical, preprimary hrHPV screening practice.