Specifically, the most frequently identified alterations in HNSCC participate in biologic processes regulated by the TP53 (71% mutated), FAT1 (23% mutated and 5% deleted), NOTCH1 (9% mutated and 66% signaling pathway alterations), CASP8 (10% mutated), CDKN2A (22% mutated and 60% gene copy loss) genes, and PIK3CA (~20% mutated and 30% signaling pathway alterations) [3]. The gene discussed is PIK3CA; the disease is head and neck squamous cell carcinoma.