OBJECTIVES: The incidence of oral and oropharyngeal cancer is continually rising and affects increasingly younger patients. Consequently, many studies focus on early diagnosis using appropriate biomarkers. Neopterin and interleukin-6 (IL-6) are promising predictive and prognostic markers of immune response activation, both systemic and local, due to the anatomical proximity of malignancies to the salivary glands. MATERIAL AND METHODS: We collected oral fluid samples from 50 patients before and after the surgical resection of squamous cell carcinoma of the oral cavity and oropharynx. Additionally, blood samples were withdrawn from 20 of these patients and levels of neopterin and IL-6 were estimated using ELISA commercial kits. All gathered data were subsequently statistically analyzed for evaluation and compared to values from a control group of healthy individuals. RESULTS: In patients with oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC), there was a significant decrease in neopterin and IL-6 levels in saliva following the surgical removal of the malignancy. These postoperative levels approached those of the control group. There was no significant decrease in neopterin and IL-6 levels in plasma. CONCLUSION: Detection of neopterin and IL-6 in saliva is a reliable diagnostic method for early detection of OSCC and its recurrence, as well as for monitoring therapeutic success, compared to plasma. Neopterin and IL-6 appear to be promising prognostic and predictive markers of the disease.

• Keywords
• interleukin‐6, neopterin, squamous cell carcinoma of head and neck,
• MeSH
• Adult MeSH
• Interleukin-6 * blood   analysis   metabolism   MeSH
• Middle Aged MeSH
• Humans MeSH
• Biomarkers, Tumor * blood   analysis   metabolism   MeSH
• Oropharyngeal Neoplasms * blood   metabolism   surgery   diagnosis   MeSH
• Mouth Neoplasms * blood   metabolism   surgery   diagnosis   MeSH
• Neopterin * blood   analysis   metabolism   MeSH
• Prospective Studies MeSH
• Aged MeSH
• Saliva * chemistry   metabolism   MeSH
• Carcinoma, Squamous Cell * blood   surgery   metabolism   diagnosis   MeSH
• Case-Control Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• IL6 protein, human MeSH Browser
• Interleukin-6 * MeSH
• Biomarkers, Tumor * MeSH
• Neopterin * MeSH

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

Wound healing represents a complex and evolutionarily conserved process across vertebrates, encompassing a series of life-rescuing events. The healing process runs in three main phases: inflammation, proliferation, and maturation/remodelling. While acute inflammation is indispensable for cleansing the wound, removing infection, and eliminating dead tissue characterised by the prevalence of neutrophils, the proliferation phase is characterised by transition into the inflammatory cell profile, shifting towards the prevalence of macrophages. The proliferation phase involves development of granulation tissue, comprising fibroblasts, activated myofibroblasts, and inflammatory and endothelial cells. Communication among these cellular components occurs through intercellular contacts, extracellular matrix secretion, as well as paracrine production of bioactive factors and proteolytic enzymes. The proliferation phase of healing is intricately regulated by inflammation, particularly interleukin-6. Prolonged inflammation results in dysregulations during the granulation tissue formation and may lead to the development of chronic wounds or hypertrophic/keloid scars. Notably, pathological processes such as autoimmune chronic inflammation, organ fibrosis, the tumour microenvironment, and impaired repair following viral infections notably share morphological and functional similarities with granulation tissue. Consequently, wound healing emerges as a prototype for understanding these diverse pathological processes. The prospect of gaining a comprehensive understanding of wound healing holds the potential to furnish fundamental insights into modulation of the intricate dialogue between cancer cells and non-cancer cells within the cancer ecosystem. This knowledge may pave the way for innovative approaches to cancer diagnostics, disease monitoring, and anticancer therapy.

• Keywords
• IL-6, cancer-associated fibroblasts, granulation tissue, myofibroblasts, wound healing,
• MeSH
• Autoimmunity * MeSH
• Wound Healing * immunology   MeSH
• Interleukin-6 * metabolism   immunology   MeSH
• Humans MeSH
• Tumor Microenvironment * immunology   MeSH
• Neoplasms * immunology   metabolism   pathology   MeSH
• Aging * immunology   MeSH
• Inflammation * immunology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Interleukin-6 * MeSH