In patients with p16-negative LA-HNSCC, adding an EGFR inhibitor to conventional treatments showed significantly worse PFS (HR = 1.75 [95% CI: 1.09–2.81], P = 0.02) and OS (HR = 2.03 [95% CI: 1.11–3.74], P = 0.02) outcomes. This evidence concerns the gene EGFR and head and neck squamous cell carcinoma.