The field of head and neck oncology is confronted by the challenge of accurately predicting disease trajectory and tailoring treatment approaches for a highly heterogeneous group of malignancies, primarily squamous cell carcinomas. While traditional prognostication and staging systems, grounded primarily in anatomical and clinical parameters, have provided a foundational framework for care, they are increasingly recognized as inadequate for capturing the biological diversity inherent to these tumors. Recent years have ushered in a wave of molecular research, revealing critical insights into the genomic, epigenetic, and immunologic underpinnings of head and neck cancers. Landmark discoveries, such as the impact of HPV infection on prognosis and molecular differences between anatomical subsites, suggest that a one-size-fits-all approach can no longer suffice. Despite promising advances in other cancer types, the adoption of molecular diagnostics for head and neck cancer has lagged, leaving significant gaps in personalized risk prediction and therapeutic guidance.

Molecular testing is emerging as a powerful adjunct to existing clinical practice, underpinning the development of novel biomarkers and multi-omics approaches that have the potential to refine both diagnosis and prognostication. This includes the use of immunohistochemistry, next-generation sequencing, epigenetic profiling, and spatial transcriptomics, which can capture tumor complexity and identify actionable alterations. Yet, the translation of these molecular insights into clinical algorithms for staging, risk stratification, and therapy selection remains a work in progress, necessitating continued investigation and robust validation.

This Research Topic aims to spotlight cutting-edge advances in molecular diagnostics and biomarker science that are redefining our understanding of head and neck cancer behavior. We seek to highlight research that evaluates the translational value of novel prognostic tools, explores the integration of genomic and molecular profiling into staging, and demonstrates how molecular data may enhance decision-making for individualized patient care.

Submissions may explore a broad spectrum of molecular innovation within head and neck cancer, with a focus on expanding the current boundaries of risk stratification and therapy guidance. We welcome original research and comprehensive review articles that address, but are not limited to, the following themes:

Novel biomarkers with prognostic or predictive value
Genomic and molecular assessment technologies for clinical application
Applications and challenges of next-generation sequencing and spatial transcriptomics
Integrative analytics linking molecular features to clinical outcomes
Translational research bridging laboratory findings with precision oncology
Strategies for biomarker discovery and validation in multicenter cohorts
Articles may be original research or comprehensive reviews and should emphasize translational implications and the advancement toward personalized care in head and neck cancer.

Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.

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Molecular Testing and Prognostication in Head and Neck Cancer