Sex-dependent different clinicopathological characterization of Epstein–Barr virus-associated gastric carcinoma: a large-scale study

Background Epstein–Barr virus (EBV)-associated gastric cancer (EBVaGC) has been reported to account for approximately 5–16% of all GCs with good prognosis compared to EBV-negative GC. We evaluated the clinicopathological characteristics of EBVaGC including survival rate in South Korea. Methods A total of 4,587 patients with GC who underwent EBV in situ hybridization (EBV–ISH) were prospectively enrolled at the Seoul National University Bundang Hospital from 2003 to 2021. Age, sex, smoking status, cancer type and stage, tumor size and location, histological type, molecular features and survival information were analyzed. Results A total of 456 patients with GC (9.9%) were positive for EBV. The EBVaGC group displayed a higher proportion of males ( P < 0.001), a predominant presence in the proximal stomach ( P < 0.001), a higher proportion of undifferentiated cancer ( P < 0.001), and a lower cancer stage ( P = 0.004) than the EBV-negative group. Cox multivariate analyses revealed age (hazard ratio [HR] = 1.025, P < 0.001), tumor size (HR = 1.109, P < 0.001), and cancer stage (stage2 HR = 4.761, P < 0.001; stage3 HR = 13.286, P < 0.001; stage4 HR = 42.528, P < 0.001) as significant risk factors for GC-specific mortality, whereas EBV positivity was inversely correlated (HR = 0.620, P = 0.022). Furthermore, the EBVaGC group displayed statistically significant survival advantages over the EBV-negative cancer group in terms of both overall ( P = 0.021) and GC-specific survival ( P = 0.007) on the Kaplan–Meier survival curve. However, this effect was evident only in males. Conclusions EBVaGC patients showed better prognoses despite their association with proximal location and poorly differentiated histology in male, probably due to the difference in immunity between males and females.