# Oncological Outcomes and Genomic Features of Gastric-Type Endocervical Adenocarcinoma, the Most Aggressive and Common HPV-Independent Cervical Cancer

## TL;DR

This study explores gastric-type endocervical adenocarcinoma, a rare and aggressive cervical cancer not caused by HPV, focusing on its genomic features and clinical outcomes to improve diagnosis and treatment.

## Contribution

The study provides new insights into the genomic alterations and clinical behavior of gastric-type endocervical adenocarcinoma, highlighting potential targets for treatment.

## Key findings

- GEA has a high rate of lymph node metastasis and poor 5-year survival compared to other cervical cancers.
- Ovary metastasis is a strong indicator of poor prognosis in GEA patients.
- Genomic alterations like TP53 mutation, PTEN deletion, and STK11 mutation are prevalent in GEA.

## Abstract

As the most common HPV-independent cervical cancer, gastric-type endocervical adenocarcinoma is more aggressive than HPV-associated squamous or adenocarcinoma and thus may constitute the last phase in the WHO’s effort to eliminate the disease. However, its genomic and clinicopathological information are limited compared with that for HPV-associated cervical cancer. This study contributes valuable data on treatment regimen, oncological outcomes, prognosis analysis, and genomic alterations. The prognostic value of ovary metastasis provided in this study affords clinicians detailed information on GEA with which to better diagnose and treat this disease. Moreover, the genomic information provided herein serves as evidence for the benefits of targeted therapy, which will be valuable for future practice and research in the field of GEA.

Background/Objectives: In order to develop a comprehensive understanding of gastric-type endocervical adenocarcinoma (GEA), an increasingly prevalent HPV-independent cervical cancer, we summarized clinicopathological information and performed prognostic analysis. Methods: A total of 182 patients diagnosed with GEA at our center during the period 2014–2025 were included in this study. Nineteen GEA cases, 6 HPV-independent non-GEA cases, 59 HPV-associated usual endocervical adenocarcinoma cases, and 66 squamous cell carcinoma cases from online database were also included. Results: Vaginal bleeding (39.56%) and watery discharge (35.16%) were the most common symptoms. As many as 21.43% of patients had no specific complaints, and 80% of GEA showed no distinct mass through gynecological examination. A total of 64% of GEA were stage IIB–IV at diagnosis, with a 5-year survival of 41% versus 85% for stage I–IIA (p < 0.05). The rate of lymphovascular space invasion (LVSI), lymph node metastasis, and ovarian metastasis were 49.64%, 42.00%, and 29.29%, respectively. The 5-year survival and recurrence rates after primary therapy were 57% and 23%, respectively. For GEA treatment, surgery might be associated with improved overall survival for the population at stage III–IV. Survival analysis identified deep infiltration depth (≥2/3), a maximum diameter of the tumor (MDOT) of ≥3 cm, and ovary metastasis as potential indicators of worse OS and PFS for whole patients. Additionally, ovary metastasis indicated poor PFS and OS for stage I–II. Genomic information TP53 mutation, PTEN deletion and STK11 mutation might be the most prevalent genomic alterations. Conclusions: These findings indicated GEA as an aggressive cervical cancer, with high rate of lymph node metastasis, high recurrence rate and short 5-year survival. Ovary metastasis reflected advanced disease burden and surgery might be associated with improved survival in advanced stage. For genomic information, GEA showed genetic heterogeneity and a low level of genomic instability.