However, the treatment effects of CPIs rely mainly on the infiltration, reinvigoration, and activation of tumor-oriented antigen-specific T cells (Gubin et al., 2014), and HPV-infected malignant cells can change the tumor microenvironment (TME), affecting antigen presentation and immune cell infiltration (particularly the CD4+/CD8+ T-cell ratio), which have a significant impact on HNSCC immunotherapy (Lechner et al., 2022). This evidence concerns the gene CD4 and head and neck squamous cell carcinoma.