In conclusion, we showed a higher prevalence of the codon 72 single-nucleotide polymorphism TP53 R72 (i.e., proline → arginine) in HPV(+) OPSCC versus HPV(−) HNSCC and reported an association of the TP53 R72 SNP with an increased prevalence of TP53 somatic mutations in HPV(−) HNSCC. Here, TP53 is linked to head and neck squamous cell carcinoma.