Identification of the genetic and the epigenetic profile of the Oral Leukoplakia for diagnostic and prognostic purposes

The Oral Squamous Cell Carcinoma (OSCC) stands as the most prevalent malignancy within the head and neck region. OSCC is acknowledged for its unfavourable prognosis, but mortality is closely linked to the stage at diagnosis. Early diagnosis of OSCC is achieved in only about half of all cases. Diagnostic delays necessitate highly invasive therapies, which, in turn, adversely impact the residual quality of life. This PhD thesis is structured around two main projects that evaluate the clinical and economic aspects of OSCC diagnosis, treatment, and prognosis, with a particular focus on patients at high risk for OSCC development. The first project was to assess the financial burden of OSCC on healthcare systems and explore how education and training can improve the diagnostic skills of dental students and practitioners. To achieve this, a retrospective observational study was conducted, analysing the costs associated with patients diagnosed with OSCC who underwent surgical treatment. Additionally, a survey-based study was conducted. Dentistry students and practitioners with varying levels of clinical experience participated in the survey, which involved evaluating 40 clinical images of benign and malignant oral lesions. The second project investigates the molecular and epigenetic mechanisms underlying OSCC with an emphasis on the predictive and diagnostic capabilities of DNA methylation analysis from oral brushing samples as a non-invasive method to identify patients at high risk of developing OSCC. A case report was described, demonstrating how methylation analysis successfully predicted the malignant transformation of an apparently low-risk Oral Leukoplakia and identified the occurrence of a second carcinoma in the same patient. Then, two prospective studies with larger populations were conducted applying the DNA methylation analysis from oral brushing samples to patients who had undergone surgical treatment for OSCC and those with OPMDs. This PhD thesis is based on a combination of published paper and unpublished data.