TRAF3 and CYLD gene deletions or disruptive mutations were identified in 28% of HPV-positive specimens in the initial TCGA HNSCC cohort and it correlated to the absence of HPV gene integration and decreased tobacco exposure [59], leading to the consideration that both DNA damage and the presence of reactive oxygen species (induced by tobacco mutagens) may favor HPV integration. This evidence concerns the gene TRAF3 and head and neck squamous cell carcinoma.