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

## TL;DR

This study finds that Epstein-Barr virus (EBV) infection in oral cancer is linked to older age and a higher tumor-stroma ratio, suggesting a unique tumor environment.

## Contribution

The study identifies a novel association between EBV positivity and elevated tumor-stroma ratio in oral squamous cell carcinoma.

## Key findings

- EBV positivity was significantly associated with older age (p = 0.046).
- All EBV-positive tumors exhibited a high tumor–stroma ratio (p = 0.031).
- No significant associations were found between EBV status and tumor-infiltrating lymphocytes or clinical stage.

## Abstract

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 (p = 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 (p = 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.