In 2015, The Cancer Genome Atlas (TCGA) used whole-exome sequencing to profile head and neck squamous cell carcinomas (HNSCC), thereby demonstrating that HPV-positive HNSCCs are characterized by PIK3CA mutations, TRAF3 loss and E2F1 gene amplification, while smoking-related HNSCCs are associated with loss-of-function TP53 mutations and CDKN2A inactivation [9]. Here, CDKN2A is linked to head and neck squamous cell carcinoma.