The genes most commonly altered in HPV-negative HNSCC include TP53, CDKN2A, and CCDN1. In contrast, HPV-positive HNSCC demonstrates a low rate of TP53 and CDKN2A mutations, while PIK3CA mutations, TRAF3 loss, and E2F1 amplifications are relatively common [11]. This evidence concerns the gene E2F1 and head and neck squamous cell carcinoma.