Our results showed the positive regulation of E2F2 and E2F8 but the negative regulation of E2F4 on B cells, CD8+ cells, and NK cells in males and this could be correlated with the suppressive function of E2F4 but improved effects of E2F2 and E2F8 on the OS of male HNSCC patients. This evidence concerns the gene E2F2 and head and neck squamous cell carcinoma.