FBXW7 and head and neck squamous cell carcinoma: Interestingly, one of the most strongly selected variants among HPV− HNSCC (and the strongest selected variant in HPV+ HNSCCs) is characterized by a low expected mutation frequency and a low prevalence of oncogenic substitution, occurring in the E3 ubiquitin ligase-encoding gene FBXW7, a known tumor suppressor which has been molecularly characterized as a regulator of common HNSCC oncogenes [44, 45].