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

<b>Background/Objectives</b>: 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. <b>Methods</b>: 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. <b>Results</b>: 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 (<i>p</i> < 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. <b>Conclusions</b>: 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.