The mutational landscape of the 42 HNSCC cell lines, all of which were HPV-negative [7], demonstrated similarities with primary tumor samples from HPV-negative patients; including frequent mutations in tumor suppressor genes TP53 (74% of cell-lines [9]; 62% of tumors [10]) and CDKN2A, and less frequent ones in PTEN, SMAD4, NOTCH1 and NOTCH2 (Figures 1 and 2). This evidence concerns the gene SMAD4 and head and neck squamous cell carcinoma.