Virus-mediated immunosuppression in head and neck cancer

Head and neck cancer is the seventh most common cancer worldwide and its development is associated with viral infection. Human papillomavirus (HPV) is the major cause of oropharyngeal cancer and encodes three known oncoproteins, E5, E6, and E7. Epstein-Barr virus (EBV), which is the causative agent of most nasopharyngeal carcinoma, also employs several immunosuppressive mechanisms that contribute to the development of the disease. In this review, we synthesize and discuss several mechanisms used by these viruses to evade and escape the host immune system. In particular, we focus on the evasive tactics of HPV E5 which, we argue, is critical to establishing persistent infection and the development and progression of carcinomas. Importantly the mechanisms by which these viruses suppress immune responses may also play a key role in resistance to checkpoint blockade immunotherapies and thus impact patient outcomes.