Approximately 80% of HPV- HNSCC have muted tumor protein p53 (TP53), resulting in gene dysfunction.138,153,154 Exon 4 or intron 6 is the location of TP53 mutations that occur early in the progression of HNSCC, especially OSCC.155 Consistently, p53 mutation is commonly observed in HPV- OSCC, as the HPV E6 oncoprotein degrades p53.156 In both subtypes, mutations in p53 are correlated with a lower overall survival rate, treatment resistance, and an increased risk of relapse.138 In early OSCC, TP53 expression is also associated with tumor stage and grade, as well as surgical margin dysplasia. The gene discussed is TP53; the disease is neoplasm.