Deciphering the role of HPV-mediated metabolic regulation in shaping the tumor microenvironment and its implications for immunotherapy in HNSCC.

Head and neck squamous cell carcinoma (HNSCC), as a complex and variable malignancy, poses a significant threat to human health. Since the intricate association between HPV and HNSCC emerged, its role within the TME has garnered extensive attention. HPV+HNSCC exhibits distinct immunological characteristics within the TME, intricately intertwined with mechanisms of immune evasion. HPV employs multifaceted pathways to intervene in metabolic regulation within the TME, exerting influence over immune cell functionality and neoplastic cell genesis. Furthermore, the heightened immune reactivity exhibited by HPV+HNSCC within the TME augments responses to immune interventions such as immune checkpoint inhibitors. Therefore, amidst the current limitations of therapeutic approaches, immunotherapy stands as a promising strategy to overcome the conventional confines of treating HNSCC. This article comprehensively outlines the impact of HPV on the inception and progression of HNSCC while discussing the amalgamation of metabolic regulation within the TME and immunotherapeutic strategies. By intervening in the reciprocal interactions between HPV and HNSCC within the TME, the potential to modulate the efficacy of immune-based treatments becomes evident. Concurrently, a synthesis of pertinent biomarker development is summarized. Such endeavors hold paramount significance for personalized therapeutic approaches and the more effective management of HNSCC patients.