TCGA data analysis indicated that smoking-associated HNSCC exhibited a higher frequency of TP53 and CDKN2A inactivating mutations, along with copy number amplifications in 3q26/28 and 11q13/22, whereas HPV-positive HNSCC was predominantly characterized by PIK3CA helical domain mutations.21 Here, TP53 is linked to head and neck squamous cell carcinoma.