Head and neck squamous cell carcinomas (HNSCCs) represent a diverse group of malignancies, both clinically and biologically, with human papillomavirus (HPV) infection playing a significant role. HPV-positive tumours generally tend to have a better prognosis and are driven by oncoproteins E6 and E7. In contrast, HPV-negative tumours typically have a worse prognosis and are often linked to mutations in tumour suppressor genes. HNSCCs exist within a complex environment known as the tumour microenvironment (TME). The TME includes tumour cells, cancer stem cells (CSCs), cancer-associated fibroblasts (CAFs), immune cells, extracellular matrix (ECM), blood vessels, and various signalling molecules. These components support tumour progression, invasion, metastasis, and resistance to treatment. Intercellular signalling within the TME-mediated by cytokines such as IL-6, TGF-b, and galectins-further promotes tumour growth and systemic effects like cachexia. Notably, the TME shares features with granulation tissue during wound healing, supporting the concept of cancer as a chronic, non-resolving wound. Effective therapy must target not only tumour cells but also the dynamic TME.

• Keywords
• CAF, IL-6, cancer, cancer-associated fibroblast, extracellular matrix, head and neck squamous cell carcinoma, immunity, stroma, therapy, tumour microenvironment,
• MeSH
• Squamous Cell Carcinoma of Head and Neck * immunology   pathology   MeSH
• Cancer-Associated Fibroblasts immunology   pathology   MeSH
• Papillomavirus Infections immunology   complications   MeSH
• Humans MeSH
• Neoplastic Stem Cells immunology   pathology   MeSH
• Tumor Microenvironment * immunology   MeSH
• Head and Neck Neoplasms * immunology   pathology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH