Indeed, these cells also exhibit typical HNSCC histology and mutations impacting Trp53, Fat1-4, Keap1, Notch1-3, Kmt2b-d, and others, which represent some of the most frequently altered gene pathways in HPV− human HNSCC (Fig. 1d, e, and Supplementary Data 1–4). This evidence concerns the gene KEAP1 and head and neck squamous cell carcinoma.