Taking into account the numerous functions of deubiquitinating modification observed in human tumors, DUB enzymes are important in the development of HNSCC; for example, USP9X [30] and USP22 [31] promote HNSC cell proliferation, and CYLD1 [32] and BPLF1 [33] accelerate HNSCC development by inhibiting the immune cell escape mechanism or by promoting the spread of viral infection. This evidence concerns the gene ZUP1 and head and neck squamous cell carcinoma.