Epstein–Barr Virus Infection Is Associated with an Elevated Tumor–Stroma Ratio and Older Age in Oral Squamous Cell Carcinoma

Epstein-Barr virus (EBV) is an oncogenic virus implicated in several epithelial malignancies; however, its role in the tumor microenvironment of oral squamous cell carcinoma (OSCC) remains unclear. This study investigated the association between EBV infection and clinicopathological and microenvironmental features of OSCC. A cross-sectional analysis was conducted on 62 archived OSCC biopsy specimens. EBV was detected using polymerase chain reaction (PCR), and clinical data were obtained from medical records. Tumor-stroma ratio (TSR), perineural invasion (PNI), lymphovascular invasion (LVI), and histological differentiation were assessed microscopically, while tumor-infiltrating lymphocytes (TILs) were quantified using ImageJ software version 1.54j (National Institutes of Health, Bethesda, MD, USA). EBV DNA was identified in 43.5% of cases. EBV positivity was significantly associated with older age (<i>p</i> = 0.046), especially among patients aged 60 years or older. All EBV-positive tumors exhibited a high tumor-stroma ratio, which was significantly associated with EBV status (<i>p</i> = 0.031). No significant associations were observed between EBV status and sex, tumor site, clinical stage, TILs, PNI, LVI, or histological differentiation. These findings indicate that EBV-positive OSCC is characterized by distinct microenvironmental features, particularly an elevated tumor-stroma ratio, and suggest a potential role for EBV status in microenvironmental profiling and prognostic stratification.