High‐Risk HPV Oncoproteins and PD‐1/PD‐L1 Interplay

ABSTRACT Human papillomavirus (HPV) related cancers often arise from a background of chronic inflammation. Systemic treatment for advanced HPV‐related cancers has been disappointing due to their strong resistance to chemotherapy and even to tyrosine kinase inhibitors (TKIs). Recently, the use of immune checkpoint inhibitor (ICI) therapy has revolutionized the systemic treatment of advanced HPV‐related cancers. For the first time, clinical trials testing ICIs, anti‐CTLA‐4, and anti‐PD1/PDL1 reported a survival benefit in patients with sorafenib resistance. However, it took a long time to find the right combination regimen to use ICIs in combination with the antiangiogenic agent bevacizumab to substantially prolong overall survival (OS) of patients with advanced HPV‐related cancer after sorafenib. This review provides a comprehensive history of ICI therapy in HPV‐related cancer, up‐to‐date information on the latest ICI clinical trials, and discusses the recent development of novel ICIs that would potentially lead to a new checkpoint blockade therapy for advanced HPV‐related cancer.