Additionally, we identified genes with early mutations that likely play roles in HPV– tumor initiation (FBXW7, NOTCH1, CASP8, FAT1, NSD1, HRAS, EP300, CREBBP and KMT2D), with over 60% of HPV– HNSCCs having a mutation in at least one of these genes. This evidence concerns the gene CASP8 and neoplasm.