<h4>Objective</h4>This study evaluated the clinical relevance of EBI3 polymorphisms, along with tumor Epstein-Barr virus (EBV) and Human Cytomegalovirus (HCMV) status, in prognostically adverse HPV-negative OSCCs.<h4>Methodology</h4>EBI3 (rs4740, rs4905, rs428253) genotyping was performed by qPCR in 95 HPV-negative OSCC patients and 108 age- and sex-matched controls. The gene discussed is EBI3; the disease is neoplasm.