Within the different HNSCC variants, HNSCC HPV-negative is the most frequent, with mutations at TP53, cyclin-dependent kinase inhibitor 2A (CDKN2A), phosphatidylinositol-4,5-bisphospate 3-kinase catalytic subunit alpha (PIK3CA), FAT atypical cadherin 1 (FAT1), and NOTCH receptors (NOTCH) due to tobacco and alcohol consumption [15]. The gene discussed is PIK3CA; the disease is head and neck squamous cell carcinoma.