Advances in HPV-Driven Head and Neck Cancer: Pathogenesis, Treatment, and Prevention

Dear Colleagues,

Human papillomavirus (HPV)-driven head and neck squamous cell carcinoma (HNSCC) has emerged as a biologically and clinically distinct disease entity whose incidence continues to rise, particularly among younger patients. Despite its generally favorable prognosis relative to HPV-negative disease, critical challenges remain: identifying which patients can safely undergo treatment de-escalation without compromising oncological control, understanding the mechanisms driving resistance in the subset with poor outcomes, and translating molecular insights into actionable clinical tools.

This Topic collection brings together basic, translational, and clinical research to address these challenges across the full disease spectrum. We welcome contributions examining viral oncogenesis and virus–host interactions, including the molecular consequences of HPV integration, E6/E7-driven oncogenic reprogramming, and epigenetic remodeling of the host genome. Studies addressing tumor heterogeneity, cancer stem cell biology, and immune evasion mechanisms are particularly encouraged, as are investigations into the determinants of response and resistance to immunotherapy and targeted agents. A central focus of this collection will be the development and validation of biomarkers capable of guiding patient stratification—from circulating tumor HPV DNA and liquid biopsy-based multi-omics platforms to novel tissue and immune signatures. Contributions proposing or evaluating de-escalation strategies, whether in the context of radiotherapy, chemotherapy, or combined modality treatment, are equally welcome, provided they engage rigorously with the tension between toxicity reduction and disease control. By integrating molecular pathogenesis with therapeutic innovation, this collection aims to define the research priorities that will shape the next generation of HPV-associated HNSCC management.

Dr. Shilpi Gupta
Prof. Dr. Bhudev Chandra Das
Dr. Prabhat Kumar
Topic Editors