Abstract
Viral infections such as human papillomavirus (HPV) and Epstein-Barr virus (EBV) play a critical role in the onset of oropharyngeal (OPC) and nasopharyngeal cancer (NPC), respectively. Despite advancements in targeted therapies and immunotherapies, in the recurrent/metastatic setting, these tumors remain incurable diseases with poor prognosis. The development of therapeutic tumor vaccines, utilizing either neoantigens or oncoviral antigens, represents a promising addition to the cancer immunotherapy arsenal. Research on vaccine-based immunotherapy for OPC and NPC focuses on targeting viral antigens, particularly HPV E6/E7 and EBV EBNA1/LMP2. The potential for vaccine platforms, including peptide-based, DNA, RNA, and viral vector-based vaccines, to induce durable immune responses against viral antigens is reported. The early-phase clinical trials evaluating vaccine-based therapies for HPV-related OPC and EBV-related NPC revealed safety and preliminary signs of efficacy; however, further clinical trials are crucial for validation. This review provides an overview of the current landscape of vaccine-based strategies for HPV-related OPC and EBV-related NPC, discussing their biological mechanisms and immune processes involved in anti-HPV and anti-EBV vaccine treatments, with a particular focus on the immune factors that influence these therapies.