Closing the Gap: HPV Vaccination and Head and Neck Cancer Prevention.

PURPOSE OF REVIEW: The association between Human Papillomavirus (HPV) infection and Head and Neck Squamous Cell Carcinoma (HNSCC), particularly Oropharyngeal SCC (OPSCC), represents a growing public health concern due to the rising incidence and the lack of effective screening programs. This review synthesizes current clinical evidence supporting prophylactic HPV vaccination as a primary prevention strategy against HNSCC and highlights emerging innovative management strategies. RECENT FINDINGS: Multiple randomized controlled trials and meta-analyses confirm the high efficacy of available HPV vaccines in preventing oral high-risk HPV infection, which serves as a validated surrogate endpoint for OPSCC prevention. Despite strong evidence and accelerated FDA approval for HNSCC prevention, global vaccination coverage remains suboptimal, especially among males, who are disproportionately affected by the rising incidence of HPV-related OPSCC. Furthermore, a persistent lack of awareness regarding the HPV–HNSCC link prevails among both the general population and healthcare providers, representing a major barrier to uptake. Emerging data also suggest promising roles for therapeutic vaccines and the use of circulating tumor DNA (ctDNA) for monitoring residual disease and early recurrence. HPV vaccination is a safe and highly effective tool for the primary prevention of HNSCC. However, realizing its full potential requires urgent, targeted global efforts focused on improving gender-neutral vaccination uptake, strengthening provider recommendations, and bridging the knowledge gap. Future strategies should integrate these preventive measures with innovative monitoring tools to optimize patient outcomes.