HPV-related HNSCC (in particular, oropharyngeal cancers) often shows the following features—P16 overexpression, low EGFR expression, wild-type TP53 and low CyclinD1 expression; in addition they show a lower TMB and an higher number of epigenetic changes, if compared with the mutagen-related counterpart [4,52,53]. This evidence concerns the gene CCND1 and oropharynx cancer.