Distribution and incidence of atypical glandular lesions in cervical cytology focusing on the association with high-risk human papillomavirus subtypes

Adenocarcinoma in situ (AIS) is considered a precursor of adenocarcinoma. Cervical adenocarcinoma has been associated with human papillomavirus (HPV), while other subtypes of AIS and endocervical adenocarcinoma have no precursor lesions and are not associated with HPV. Cervical cytology and HPV genotyping are important in the detection of these different subtypes. Notably, endometrial lesions and infiltration with secondary adenocarcinoma may lead to misdiagnosis of endocervical lesions. The aim of the present study was to avoid misdiagnosis of squamous cell changes and endometrial lesions as endocervical lesions in cervical screening. A total of 210,510 female cytological samples were analyzed between the beginning of January 2020 and the beginning of January 2021. The samples were processed for conventional cytological techniques, and for molecular detection and subtyping of high-risk HPV (HPV-HR) according to the advice and measurements of BD Biosciences (117,765 samples) and the PapilloCheck(®) HPV test (5,579 samples). The present study was carried out in Germany using the Munich classification III. II-g (Bethesda classification: atypical glandular cells not otherwise specified) was detected in 0.12% of cases under the age of 35 years. Another peak was noticed within the 41–60-years age group (0.11%). In the 41–50-years age group, a peak for II-e (Bethesda classification: Endometrial cells) (1.5%) was identified. An association was revealed between HPV16, HPV18 and HPV45 with cervical intraepithelial neoplasia III, AIS, endocervical adenocarcinoma and squamous cell carcinoma, in addition to other HPV-HR subtypes, such as HPV33/58, as well as 52, 56/59/66 in the different age groups. In patients aged <35 years, 0.03% of cases were vaccinated cases against HPV. In the 35–40-years age group, there was only one vaccinated case (0.0045%); in the 41–50-years age group, there were 11 vaccinated cases (0.031%); and in the 51–60-years age group, there was one vaccinated case (0.002%). No patients aged >60 years were vaccinated against HPV in the analyzed cohort. In conclusion, most cases of HPV-associated glandular dysplastic changes and neoplasia occurred in sexually active women aged between 35 and 60 years. In addition, endocervical adenocarcinoma may occur at any age with or without an HPV infection.