Meanwhile, HPV infection has also been proven to be associated with T cell exhaustion, in which HPV-positive HNSCC expressed higher levels of multiple T cell exhaustion markers such as PD1, TIM3, LAG3, and TIGIT compared to HPV-negative HNSCC, suggesting of stronger antigen-specific T cell immunity in HPV-positive HNSCC (Gameiro et al., 2018; Kansy et al., 2017). This evidence concerns the gene PDCD1 and head and neck squamous cell carcinoma.