Next-Generation Paradigms in Head and Neck Oncology: From Precision Diagnostics and Targeted Platforms to Immunotherapy

Immunotherapy has fundamentally rewritten the therapeutic paradigm for head and neck cancers, shifting the clinical standard of care from an exclusive reliance on aggressive local modalities to targeted immune restoration. While immune checkpoint inhibitors targeting the PD-1/PD-L1 axis have offered durable survival benefits for a subset of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), a substantial proportion of patients still experience primary or acquired resistance. The highly heterogeneous nature of head and neck tumors, coupled with a notoriously immunosuppressive, "cold" tumor immune microenvironment (TIME), presents a profound barrier to long-term clinical efficacy.To break through these therapeutic ceilings, the next generation of head and neck oncology must look beyond standard monotherapies toward integrated, multi-disciplinary frameworks. Emerging cellular effector platforms (such as CAR-T/CAR-NK), antibody-drug conjugates (ADCs), and targeted small-molecule inhibitors offer powerful mechanisms to bypass standard resistance pathways. Concurrently, the clinical deployment of these advanced therapeutics relies heavily on breakthroughs in precision diagnostics—including Next-Generation Sequencing (NGS), liquid biopsies, and artificial intelligence (AI)-driven radiomics—to accurately map tumor evolution, predict patient response, and monitor minimal residual disease (MRD).Furthermore, as these potent systemic therapies move into earlier, perioperative windows, balancing high curative intent with the mitigation of severe functional and structural toxicities remains a paramount challenge. A deeper mechanistic understanding of how advanced molecular diagnostics, targeted platforms, and multi-modal treatments intersect is essential for designing safer, more durable, and personalized therapeutic paradigms.This Research Topic aims to bring together basic, translational, and clinical studies that dissect the modern landscape of head and neck cancer management. We seek to highlight high-impact research bridging molecular discovery, innovative diagnostic tracking, targeted small-molecule intervention, and immune modulation to fundamentally improve patient survival and quality of life.Scope and Suggested Sub-themesWe welcome submissions of original research, reviews, mini-reviews, perspectives, and clinical studies that focus on, but are not limited to, the following themes in head and neck cancers:• Advanced Diagnostics & Precision Medicine• Next-Generation Sequencing (NGS) & Molecular Profiling: Clinical utility of NGS in characterizing aggressive head and neck variants, tracking tumor heterogeneity, and driving targeted therapies.• Liquid Biopsies and Biomarkers: Utilizing circulating tumor DNA (ctDNA), saliva biomarkers, or circulating HPV-DNA for early recurrence detection, treatment monitoring, and tracking MRD post-resection.• Multi-Omics & Spatial Transcriptomics: Applying single-cell sequencing and spatial mapping to dissect the cellular architecture and evolutionary pathways of head and neck tumors.• Next-Generation Immunotherapy & Effector Platforms• Perioperative Immunotherapy Sequencing: Preclinical rationale and clinical outcomes of neoadjuvant and adjuvant immunotherapy in locally advanced disease.• Cellular and Targeted Therapeutics: Development, optimization, and microenvironmental interactions of CAR-T, CAR-NK, bispecific antibodies, and antibody-drug conjugates (ADCs) in solid head and neck tumors.• Novel Checkpoints & Vaccines: Investigation of emerging targets (e.g., LAG-3, TIGIT) and therapeutic cancer vaccines to reverse immune evasion. Topic editors: Yasmine Ghantous, Imad Abu El-naaj Source: https://www.frontiersin.org/research-topics/83049/next-generation-paradigms-in-head-and-neck-oncology-from-precision-diagnostics-and-targeted-platforms-to-immunotherapy