The chemotherapeutic use of afatinib as a first-line treatment for advance or metastatic EGFR-positive-mutation (EFGRm+) NSCLC has been approved [14,15,16], while the efficacy of afatinib in treating recurrent/metastatic HNSCC has not been yet approved since activating EGFRm+ in HNSCC has not been found, despite its overexpression in 90% of HNSCCs, and a minority of patients with HNSCC and NSCLC respond to EGFR-directed inhibition [17,18,19,20]. This evidence concerns the gene EGFR and head and neck squamous cell carcinoma.