Recent large scale cancer genome sequencing projects have identified spectrum of driver genomic alterations in HNSCC including CDKN2A, TP53, PIK3CA, NOTCH1, HRAS, FBXW7, PTEN, NFE2L2, FAT1, and CASP8 [2–4]. Here, CASP8 is linked to head and neck squamous cell carcinoma.