In HNSCC, the high frequencies of TP53 loss-of-function mutations and CDKN2A inactivation are observed in smoking-related HNSCCs, and PIK3CA mutations, TRAF3 deletion, and E2F1 amplification are seen in human papillomavirus (HPV)-related HNSCCs in The Cancer Genome Atlas (TCGA) network5. Here, TP53 is linked to head and neck squamous cell carcinoma.