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. Here, USP22 is linked to head and neck squamous cell carcinoma.