Introduction/Background Atypical glandular cells, favor neoplastic (AGC-FN) PAP smears are rare and might be frequently associated with cervical precancer/cancer. This study explores the value of the HPV test and methylation test as a co-test in stratifying patients with AGC-FN cytology for further management.

Methodology We have been prospectively collecting AGC-FN PAP smears (both conventional (CC) and liquid-based (LBC) signed out in Biopticka laboratory, Pilsen (BL), between 2017–2021. In the case of CC, it was supplemented by a subsequent LBC smear. Residual LBC material was used for HPV genotyping and methylation assay (QIAsure Methylation Test, QIAGEN). Patients were followed and treated according to current Guidelines. In case of surgery, histologic results were obtained.

Results AGC-FN represented 0.08% PAP smears performed at BL between 2017–2021. Seventy-three patients fulfilled the inclusion criteria of the study. All patients in HPV+/methylation+ subgroup (53 patients) presented some cervical pathology (10 [18.9%] cervical cancer, 41 [77.3%] HSIL and/or AIS, and 2 [3.8%] LSIL. HPV+/methylation- subgroup consisted of 11 patients. Six of them (54.5%) presented AIS and/or HSIL and 4 (36.4%) were without dysplasia. There were six patients in the HPV-/methylation+ subgroup. Four of them (66.7%) had an invasive disease (3 endometrial cancer, 1 gastric type of cervical adenocarcinoma). HPV-/methylation- subgroup consisted of three patients (1 with HGSC – high-grade serous carcinoma of the endometrium, 2 without dysplasia).

Conclusion AGC-FN PAP smear is frequently associated with cervical precancer/cancer and cancer of other parts of the female genital tract. We show that the HPV co-test can identify patients with a high probability of cervical pathology (HPV+). In the HPV negative subgroup we recommend an close examination of the uterine cavity and pelvic organs in addition to colposcopy/biopsy. In our experience, irrespective of HPV status, a positive methylation test predicts precancer or malignancy.

Disclosures Study was supported by grant: FNPl 00669806/Ministry of Health of the Czech Republic