# Risk Assessment of Precancers and Cancers in Women with Atypical Glandular Cells of Endocervical, Endometrial, and Unknown Origin

## TL;DR

This study examines the risk of precancers and cancers in women with abnormal cervical cell findings, showing how age and HPV status influence different types of lesions.

## Contribution

The study identifies distinct age and HPV-related risk profiles for different atypical glandular cell subtypes, guiding targeted evaluation strategies.

## Key findings

- AGC-EC and AGC-NOS in HPV-positive women show higher risk of cervical neoplasia.
- AGC-EM is more associated with endometrial pathologies in women aged ≥ 50.
- Age and HPV status significantly influence the risk profiles of different AGC subtypes.

## Abstract

Objective: To assess the risk of precancers [high-grade squamous intraepithelial lesions (HSIL), adenocarcinoma in situ (AIS) and atypical endometrial hyperplasia (AEH)] and cancers [squamous cell carcinoma (SCC) and adenocarcinoma (ADC)] in women with atypical glandular cells (AGC) cytology.

Methods: A total of 1,028 women diagnosed with abnormal cervical glandular cytology from January 2019 and December 2023 were enrolled. Of these, 670 underwent both HPV genotyping and cervical biopsy.

Results: Participants were classified into three groups: AGC-EC (endocervical), AGC-EM (endometrial), and AGC-NOS (unknown origin). AGC-EC was more prevalent than AGC-EM and AGC-NOS among younger women (cutoffs at 40 and 50; P < 0.0001 and < 0.0001) and in the HPV-positive group (P = 0.001). In the HPV-positive group, AGC-EC and AGC-NOS lesions were primarily endocervical, with significantly higher incidences of HSIL+, SCC, and AIS+ compared to the HPV-negative group (P = 0.00021, 0.047, < 0.0001 for AGC-EC; P ≤ 0.0001, = 0.004, < 0.0001 for AGC-NOS). However, hrHPV status did not significantly affect the incidence of endometrial and extrauterine lesions. Stratified by age, AGC-NOS's ECA and EUC were more common after age 65 (P = 0.028 and 0.001), and AGC-EM's AEH+ and EMC also increased significantly after 65 (P = 0.001, 0.000401). Moreover, for AGC-EM, older women (≥ 50) had significantly higher rates of AEH+ and EMC compared to younger groups (P < 0.05).

Conclusion: Distinct cytological categories of AGC exhibit differential age and HPV-related risk profiles. AGC-EC and AGC-NOS in HPV-positive women indicate a higher risk of cervical neoplasia, highlighting the importance of HPV testing in triaging these cases. In contrast, AGC-EM is predominantly linked to endometrial pathologies in older women, especially those aged ≥ 50. These findings underscore the necessity of age- and subtype-specific evaluation strategies to optimize early detection of glandular and extrauterine malignancies in AGC patients.