Another important signaling pathway in cancer, including HNSCC, is the PI3K–PTEN–AKT pathway; the class Ia PI3Ks, which are most frequently associated with cancer, are heterodimers coupled to receptor tyrosine kinases such as EGFR or adaptor molecules that may become active after receptor phosphorylation [23]. This evidence concerns the gene PIK3CA and head and neck squamous cell carcinoma.