Our results indicate a clear disproportion of CD4+ T lymphocytes between circulation and tumor tissue that suggests several issues related to HNSCC: a reduced intratumoral cooperation between CD4+ and CD8+ cells, which has sustained tumor proliferation, and a decreased migration of CD4+ lymphocytes towards the tumor site due to still unknown extracellular and/or intrinsic factors. This evidence concerns the gene CD4 and head and neck squamous cell carcinoma.