Indeed, in HNSCC, in addition to the tumor suppressor genes that are downregulated due to cancer-specific methylation of their promoter, such as PAX1 and PAX5, tumor suppressor genes that are inactivated by both promoter methylation and somatic mutations (GABRB3, HOXC12, PARP15, SLCO4C1, CDKN2A, PAX1, PIK3AP1, HOXC6, PLCB1, and ZIC4) have also been recognized [18]. This evidence concerns the gene CDKN2A and cancer.