Clinical characteristics of non-HPV infection-associated gastric-type endocervical adenocarcinoma

Gastric-type endocervical adenocarcinoma (GAS) is a special type of cervical adenocarcinoma that is not associated with high-risk human papilloma virus (HPV) infection, making early diagnosis challenging. This study aims to investigate the clinical characteristics, diagnosis, treatment, and prognosis of non-HPV infection-associated GAS, summarize relevant experiences, and improve the ability to recognize early lesions.

A total of 21 patients with GAS treated at the Department of Gynecology, Third Xiangya Hospital of Central South University, from April 2016 to February 2023, were included. Clinical data, including age, clinical manifestations, HPV/thin-prep cytology test (TCT) results, tumor markers, imaging examinations, diagnostic methods, Federation International of Gynecology and Obstetrics (FIGO) (2018) staging, pathological results, immunohistochemistry findings, treatment, and follow-up outcomes were collected and analyzed. Kaplan-Meier method was used to calculate survival rates, log-rank test was used to calculate survival rates, log-rank test was used to compare survival differences, and Cox regression method was used to analyze prognostic factors.

The patients' ages ranged from 18 to 67 years [(48.4±12.0) years]. The most common initial symptom was noticeable vaginal discharge in 13 cases, followed by purulent vaginal discharge in 1 case, postmenopausal vaginal bleeding in 3 cases, bleeding during intercourse in 2 cases, prolonged menstruation in 1 case, and lower abdominal distension in 1 case. Except for 2 patients without sexual experience, the remaining patients underwent TCT and HPV testing, with 17 HPV-negative cases and 2 HPV-positive cases (1 for type 16 and 1 unclassified); TCT results were negative in 13 cases, with 2 cases of atypical squamous cells of undetermined significance (ASC-US), 1 case of atypical glandular cells-not otherwise specified (AGC-NOS), 1 case of atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (ASC-H), and 2 cases of atypical glandular cells (AGC). Preoperative tumor markers were elevated in 6 of 12 cases for CA199, 4 of 21 cases for CA125, 3 of 13 cases for human epididymal protein 4 (HE4), and 1 of 19 cases for squamous cell carcinoma antigen (SCC). Among the 21 patients who underwent preoperative ultrasound, 9 cases were suspected to have cervical malignancy, and 1 case of endometrial malignancy was identified. In the 17 patients who underwent pelvic MRI, 9 cases were suspected of having cervical malignancy, along with 2 cases of endometrial malignancy. In the 9 patients who underwent pelvic CT, 7 cases were suspected of cervical malignancy. For preoperative pathology, 9 patients had a single biopsy with a confirmation rate of 33.3% (3/9), 7 patients had 2 biopsies with a confirmation rate of 71.4% (5/7), and 5 patients had 3 biopsies with a confirmation rate of 100% (5/5), leading to an overall confirmation rate of 61.9% (13/21). All patients underwent surgical treatment, with postoperative pathological staging: 3 cases at stage ⅠB1, 1 case at stage ⅠB2, 2 cases at stage ⅠB3, 1 case at stage ⅡA1, 1 case at stage ⅡA2, 2 cases at stage ⅡB, 7 cases at stage ⅢC1p, and 4 cases at stage ⅢC2p. Para-cervical infiltration was observed in 7 cases, with residual cancer at the vaginal stump in 2 cases, deep stromal infiltration (depth ≥1/2) in 19 cases, lymphovascular space invasion in 15 cases, neural invasion in 9 cases, pelvic lymph node metastasis in 11 cases, and para-aortic lymph node metastasis in 4 cases. The follow-up time ranged from 3.5 to 28.0 months (median: 13.5 months), with 13 cases not experiencing recurrence, 7 cases relapsing (6 deceased, 1 alive with tumor), and 1 case lost to follow-up. The overall survival (OS) ranged from 3.5 to 28.0 months [(22.7±1.8) months], and disease-free survival (DFS) ranged from 3.5 to 28.0 months [(20.4±2.3) months]. OS showed no correlation with age, tumor stage, tumor size, depth of stromal infiltration, lymphovascular space invasion, lymph node metastasis, or treatment method (all P>0.05). Cox regression analysis indicated that age, pathological stage, tumor size, depth of stromal infiltration, lymphovascular space invasion, neural invasion, and lymph node metastasis were not associated with DFS or OS (all P>0.05).

GAS is rare in clinical practice, prone to missed or misdiagnosis, with a low early diagnosis rate, strong invasiveness, high recurrence and metastasis rates, and poor prognosis. Clinicians should be vigilant for this disease in HPV-negative patients with significant vaginal discharge and consider performing multiple deep tissue biopsies in conjunction with imaging examinations for early diagnosis.