The distinctive pattern of APOBEC-signature mutations in exon 9 of the PIK3CA proto-oncogene in HPV-positive HNSCC and in other cancer types displaying the APOBEC mutational signature implicates APOBEC activity in the generation of oncogenic driver events [143,214], findings that were confirmed by analysis of TCGA HPV-positive HNSCC cohorts [215,216]. Here, PIK3CA is linked to cancer.