Detection of prognostic biomarkers and application in clustering patients with oral squamous cell carcinoma, according to the risk of relapse

Most head and neck cancers derive from the mucosal epithelium of the oral cavity, pharynx and larynx and are known collectively as head and neck squamous cell carcinoma (HNSCC), accounting for over 600,000 new cases diagnosed per year and of these, more than 300.000 new cases annually are reported to take origin from the surface of the oral mucosa. Current evidence supports that these subsites exhibit distinctive molecular and clinical behaviors, leading to an "anatomical bias" both for research and clinical decision-making. Oral squamous cell carcinoma (OSCC), in particular involving oral tongue (OTSCC) is the most common malignancy of the head and neck region, characterized by a high rate of local and regional recurrences, which strongly decreases patients’ survival rates. The American Joint Committee on Cancer (AJCC) staging system is the standard tool used to classify oncological patients and predict their clinical outcomes. Despite advancements in patients’ prognostic stratification, the 8th edition of AJCC fails to identify patients characterized by early relapse and poor prognosis. Currently, no prognostic biomarkers have been validated to stratify these patients and their risk of recurrence and death. This scenario calls for the investigation of biomarkers from basic research combined with bioinformatics to clinical and routine diagnostic application in a translational pathway. This project aimed to investigate prognostic biomarkers in HNSCC, OSCC and OTSCC, 4 by different approaches, such as reviews and meta-analysis, histopathology, and bioinformatics. This is to highlight possible histopathologic and genetic biomarkers to be integrated in future staging systems in a precision medicine environment. Different histopathologic features were tested, such as tumour budding, eosinophils infiltration, lymph-vascular invasion, perineural invasion, lymphocytes infiltration, and tumour-stroma ratio. This investigation led to the development of promising and easy to be assessed histopathologic biomarkers, such as immune-phenotype, thresholds, and improved staging systems. Furtherly, a new prognostic classification system was developed based on TP53 gene mutations. In conclusion, the heterogeneous background of HNSCC, including OSCC and, OTSCC emerged, and new prognostic biomarkers were proposed to be furtherly evaluated in other cohorts for routine translational application in the aim of precision medicine.