Therapeutic Vaccines for Head and Neck Squamous Cell Carcinoma and Nasopharyngeal Carcinoma

Background and Objectives: Recent evidence demonstrates additional survival benefit of immune checkpoint inhibitor (ICI) therapy in the treatment of head and neck squamous cell carcinoma (HNSCSC) and nasopharyngeal carcinoma (NPC). However, overall outcomes remain relatively stagnant despite this significant progress. Therapeutic vaccines are a promising adjunct to existing systemic therapy strategies in HNSCC and NPC. This review aims to summarize current evidence, review ongoing studies, and discuss areas of opportunity and potential future directions of vaccine therapy in this space. Methodology: A comprehensive review of the current literature was conducted through database searches on PubMed and ClinicalTrials.gov. Studies were stratified by tumor type, vaccine delivery platform, and early versus recurrent metastatic (RM) disease. Results: Therapeutic vaccines in combination with ICI for HPV-associated HNSCC have shown the most promise, though modest. Vaccine delivery in HPV-negative HNSCC and NPC are still in early development. Integration of therapeutic vaccines across these tumor types is challenged by immune escape mechanisms, lack of viable targets, and tumor heterogeneity. Conclusions: Early data suggest that therapeutic vaccines in combination with ICIs may offer additional benefit in the treatment of HNSCC and NPC, especially in RM HPV-associated HNSCC. Future efforts should validate these early findings through phase 3 trials. Data regarding therapeutic vaccines combined with chemotherapy or radiation is limited but may also provide additional benefit.