Association Between Epstein-Barr Virus Infection and PD-L1 Expression in Gastric Cancer: Prevalence, Clinicopathological Features, and Prognostic Implications.

Background: Epstein-Barr virus-associated gastric cancer (EBVaGC) represents a distinct molecular subgroup with potential responsiveness to immunotherapy approved for programmed death-ligand 1 (PD-L1)-positive gastric cancer. This retrospective study aimed to assess the prevalence and association between EBVaGC and PD-L1 positivity among patients with gastric adenocarcinoma treated at a university hospital in Southern Thailand from January 2017 to October 2023.

Methods: The EBV status of the patients and PD-L1 expression were determined using in situ hybridization and immunohistochemistry, respectively.

Results: The prevalence of EBVaGC was 4.5% among 132 patients, whereas 9.1% of patients exhibited a PD-L1 combined positive score (CPS) of ≥1, with no significant association observed between them. EBVaGC was more prevalent in males, non-antral tumors, diffuse/mixed histologic subtypes, and poorly differentiated tumors. Median overall survival for patients with EBVaGC and PD-L1 CPS ≥ 1 was 9.48 and 14.19 months, respectively, compared with 10.32 and 9.79 months for those with non-EBVaGC (hazard ratio: 1.24; 95% CI: 0.50-3.04; p = 0.645) and PD-L1 CPS < 1 (hazard ratio: 0.82; 95% CI: 0.40-1.69; p = 0.590), respectively.

Conclusions: Our findings revealed a low prevalence of EBVaGC and PD-L1 positivity in Thailand, with no significant association or survival impact observed. These findings highlight the regional variation in these biomarkers and support EBV as an independent biomarker from PD-L1. However, further research, particularly studies evaluating immunotherapy outcomes, is warranted to clarify the predictive and clinical significance of EBV in gastric cancer.