| Summary: | Background: Somatic <i>TP53</i> mutations are frequent in head and neck squamous cell carcinoma (HNSCC) and are important pathogenic factors. Objective: To study <i>TP53</i> mutations relative to the presence of human papillomavirus (HPV) in tumors in HNSCC patients. Methods: Using a custom-made next-generation sequencing (NGS) panel on formalin-fixed, paraffin-embedded tumor tissue, we analyzed somatic <i>TP53</i> mutations and the <i>TP53</i> single-nucleotide polymorphism (SNP) codon 72 (P72R; rs1042522) (proline → arginine) from 104 patients with HNSCC. Results: Only 2 of 44 patients with HPV-positive (HPV(+)) HNSCC had a <i>TP53</i> somatic mutation, as opposed to 42/60 HPV-negative (HPV(−)) HNSCC patients (<i>p</i> < 0.001). Forty-five different <i>TP53</i> somatic mutations were detected. Furthermore, in HPV(−) patients, we determined an 80% prevalence of somatic <i>TP53</i> mutations in the <i>TP53</i> R72 polymorphism cohort versus 40% in the <i>TP53</i> P72 cohort (<i>p</i> = 0.001). A higher percentage of patients with oral cavity SCC had <i>TP53</i> mutations than HPV(−) oropharyngeal (OP) SCC patients (<i>p</i> = 0.012). Furthermore, 39/44 HPV(+) tumor patients harbored the <i>TP53</i> R72 polymorphism in contrast to 42/60 patients in the HPV(−) group (<i>p</i> = 0.024). Conclusions: Our observations show that <i>TP53</i> R72 polymorphism is associated with a tumor being HPV(+). We also report a higher percentage of somatic <i>TP53</i> mutations with R72 than P72 in HPV(−) HNSCC patients.
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