HPV-associated head and neck cancers, particularly oropharyngeal carcinoma, provide a unique model for the interaction between the virus, tumor cells and the microenvironment. This session provides a comprehensive overview of recent advances, ranging from the classification of HPV-associated cancers and the role of the tumor microenvironment to virocellular signatures that distinguish HPV-positive oropharyngeal cancers from other anatomical sites. Systemic serological approaches will provide insight into host immune responses and their potential diagnostic and prognostic value. Particular attention will be given to metabolic reprogramming in oropharyngeal cancer, highlighting virus-induced vulnerabilities that could be exploited for therapeutic purposes. Finally, the development of therapeutic vaccines targeting HPV-induced malignant tumors will be discussed, including the validation of target epitopes, the use of orthotopic tumor models and the induction of mucosal antitumor immunity. Overall, this session emphasizes a strongly translational perspective at the crossroads of virology, immunology and innovative cancer therapies.