Pathogenesis of Head and Neck squamous cell carcinoma: From Mechanisms to Translational Insights

Head and neck cancers comprise a biologically and clinically heterogeneous group of malignancies arising across anatomically distinct sites, including the oral cavity, oropharynx, nasopharynx, sinonasal tract and larynx. Collectively, these cancers represent a substantial global health burden, with marked geographic variation in incidence, anatomical distribution, and underlying aetiological factors. Head and neck squamous cell carcinoma (HNSCC) accounts for the majority of cases, although the biological characteristics of individual tumour sites differ considerably These cancers are characterised by diverse aetiologies, cellular origins, histopathological features, genomic profiles, and tumour microenvironments. Oral cavity and laryngeal cancers are predominantly associated with tobacco and alcohol exposure, whereas oropharyngeal carcinomas are increasingly linked to human papillomavirus (HPV) infection. Nasopharyngeal carcinoma (NPC), in contrast, has a strong association with Epstein–Barr virus (EBV), particularly in populations from China and Southeast Asia. Thus, despite their anatomical proximity, these malignancies represent distinct biological entities with substantially different molecular and pathological characteristics.

Elucidating the complex pathogenesis of head and neck malignancies requires an integrated approach that combines established pathological principles with contemporary molecular and cellular biology. A detailed understanding of the molecular pathology of these cancers—from early viral oncogenesis and cellular reprogramming to the complex interplay between malignant cells and the tumour microenvironment—is essential for uncovering novel biological vulnerabilities and informing the development of more precise diagnostic and therapeutic strategies.

This special issue focuses on the fundamental science and translational frontiers of HNSCC. It aims to bring together high-quality research that advances understanding of tumour biology, and identifies robust biomarkers and potential therapeutic targets. By emphasising fundamental discovery through preclinical investigation, the issue seeks to present a focused body of research for understanding these diverse malignancies and to support the development of the next generation of precision diagnostics and targeted interventions.

Contributors are invited to submit Original Research Articles, Review Articles, Methods Articles, Perspectives, and Opinion Articles that provide novel insights into the aetiology, histopathology, molecular pathology, biology, and translational potential of head and neck malignancies, including but not limited to the following themes

• Epidemiology and aetiological determinants of head and neck cancers
• Genetic risk factors in head and neck carcinogenesis
• Histopathological features and pathological classification of head and neck malignancies
• Histopathological assessment of HNSCCs
• Molecular and cellular mechanisms of head and neck carcinogenesis
• HPV-associated oropharyngeal cancer biology and viral oncogenesis
• EBV-associated nasopharyngeal carcinoma and mechanisms of viral carcinogenesis
• Genomic, epigenomic, transcriptomic, and proteomic alterations in head and neck cancers
• Tumour microenvironment, immune regulation, and immune evasion
• Cancer stem cells, epithelial–mesenchymal transition, and tumour initiation
• Spatial biology, single-cell technologies, and digital pathology
• Molecular pathology and emerging approaches to tumour classification
• Biomarker discovery and validation for diagnosis, prognosis, and treatment selection
• Mechanisms of metastasis and therapeutic resistance
• Identification and validation of novel therapeutic targets
• Functional genomics and preclinical models of head and neck cancer
• Artificial intelligence, computational pathology, and bioinformatics approaches
• Novel approaches to diagnostics
• Personalized therapeutic strategies
• Laboratory quality improvement and widening accessibility (relating to Head and Neck cancer)


Clinical trials and case reports/series will be outside the scope of this special issue.

Article types and fees

This Special Issue accepts the following article types, unless otherwise specified in the Special Issue description:

• Biomedical Science in Brief
• Case Report
• Editorial
• Letter to the Editor
• Opinion
• Original Research
• Review

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Special Issue accepts the following article types, unless otherwise specified in the Special Issue description:

• Biomedical Science in Brief
• Case Report
• Editorial
• Letter to the Editor
• Opinion
• Original Research
• Review

Keywords: Head and neck cancer, head and neck squamous cell carcinoma, oral cancer, oropharyngeal cancer, nasopharyngeal carcinoma, HPV, EBV, molecular pathology, cancer genomics, tumour microenvironment, tumour heterogeneity, spatial transcriptomics, biomarkers, therapeutic resistance, precision oncology