Two clinical trials uncovered that afatinib achieved better clinical improvements than erlotinib in lung squamous cell carcinoma (LUSC) [29] or methotrexate in head and neck squamous cell carcinoma (HNSCC) [30], illustrating afatinib’s outstanding clinical efficacy in tumors with wild-type EGFR. This evidence concerns the gene EGFR and head and neck squamous cell carcinoma.