Beyond Viral Infections: The Multifaceted Roles of Human Papillomavirus and Epstein-Barr Virus in Shaping the Tumor Microenvironment

The tumor microenvironment (TME) exerts a profound influence on the oncogenesis and progression of various cancers, notably those instigated by the human papillomavirus (HPV) and the Epstein-Barr virus (EBV). The etiology of HPV and EBV-associated malignancies is rooted in intricate interactions that intertwine viral infections, genetic predispositions, and distinct TME dynamics. These interactions foster a milieu that can either support or hinder tumorigenic progression. Gaining in-depth knowledge of the TME's unique features, including its cellular composition, cytokine profiles, and metabolic alterations specific to HPV and EBV-associated cancers, is fundamental to innovating more efficacious therapeutic strategies. This review delineates the intricate roles of HPV and EBV in shaping the TME and expounds upon the unique TME characteristics specific to HPV and EBV-driven cancers. Additionally, we spotlight innovative approaches to remodel the TME, aiming to augment therapeutic efficacy in combatting HPV and EBV-associated neoplasms.