The finding that MAPK pathway mutations span the diversity of HNSCC subsites (including oral, oropharyngeal, laryngeal, and pharyngeal) to identify patients with good outcomes is superior to that of HPV-positivity (largely restricted to oropharyngeal subsite), and in particular, these mutations predict extraordinary patient outcomes even among TP53-mutated HNSCC patients (median OS >14 yr). The gene discussed is TP53; the disease is head and neck squamous cell carcinoma.