Recent advances in next-generation sequencing (NGS) of head and neck squamous cell carcinoma (HNSCC) samples of different etiologies have revealed that HNSCC development is mainly driven by loss-of-function alterations, including gene mutations in TP53, CDKN2A, HRAS, PIK3CA, BRAF, CASP8, and NOTCH1 [5,6,7,8,9]. This evidence concerns the gene CDKN2A and head and neck squamous cell carcinoma.