Can we predict histological outcome of distinctive cohorts of patients with glandular cell abnormalities on ThinPrep Papanicolaou testing based on human papillomavirus status, age, and associated squamous abnormalities?

Background: The cytology diagnosis of glandular cell abnormalities (GCAs) is diagnostically challenging, causing inadequate reproducibility. Histological outcome of GCA on cytology varies from benign to malignant diseases. The goal of this study is to evaluate histological outcome and identify distinctive cohorts of patients with GCA based on human papillomavirus (HPV) status, age, and associated squamous abnormality to stratify the patient into high risk for squamous/glandular lesions. Methods: From 2012 to 2017, out of 162 088 ThinPrep Papanicolaou tests performed, 998 (0.61%) were reported as GCAs. Histologic follow-up was available in 638 cases and 429 had concurrent HPV results. Results: The overall rate of high-risk human papillomavirus (hrHPV)-positivity (hrHPV+) was 33.6% (144/429 cases). Among the hrHPV+ cases, 18.1% had cervical intraepithelial neoplasia 2/3 (CIN2/3), 3.5% squamous cell carcinoma (SCC), 3.5% cervical adenocarcinoma in situ (AIS)/adenocarcinoma (ADC), and 2.8% endometrial carcinoma. Among hrHPV- cases, 1.4% had CIN2/3, 1.1% AIS/ADC, and 17.5% endometrial carcinoma. The high-grade cervical lesions (CIN2/3/AIS/ADC) were significantly higher in women with hrHPV+ and associated squamous abnormalities compared to hrHPV- and no squamous abnormality in all age groups except patients >65 years. Endometrial carcinoma was most commonly present in women >65 years especially with HPV- and no associated squamous abnormalities. Conclusions: HPV testing is useful for predicting the risk of high-grade cervical neoplasia in women with GCA especially with associated squamous abnormalities on cytology. The endometrial carcinoma is more frequent in hrHPV- older women. The combination of cytology with knowledge of associated squamous abnormality, hrHPV status, and age can significantly aid in stratifying the patient into high risk for glandular/squamous lesions which facilitates appropriate management of these patients.