Despite considerable development in the therapeutic repertoire for managing cancer-related malignancies, head and neck cancer mortality has not significantly improved. The burden of HNSCC fluctuates across countries and has been associated with exposure to tobacco-derived carcinogens, excessive alcohol consumption or combinations. Due to late detection, patients often present with oral pre-malignant lesions which have progressed to an advanced stage of HNSCC. In this study, the samples were from a male cohort as generally, men are at two to four-fold higher risk than women with over 90% of HNSCCs arising in the upper aerodigestive tract. Therefore, the purpose of this thesis was to identify HNSCC biomarkers in males associated within defined anatomical region (tongue) and causative agents, specific to smoking. An iTRAQ proteomic approach was used to profile protein changes in matched normal and tumour samples from male non-smoking (n=6) and smoking patients (n=6) with tongue carcinomas revealing identification of potential targets specific to cancer. Samples were subjected to liquid nitrogen cryo-pulverisation and protein determination. Protein extracts from the same category were pooled, trypsin digested and iTRAQ 4-plex labelled. Data was generated by 2D-LC/MS on an Orbitrap Fusion and significantly changed proteins (median ± SD) were subject to bioinformatics appraisal. A total of 3426 proteins were identified and quantified by proteomic analysis. Comparison of non-smoker tumour (NS:T) with smoker tumour (S:T) distinguished 64 proteins that were upregulated and 62 downregulated, S:T vs S:N categorised 349 proteins up- and 395 down-regulated respectively and NS:T vs NS:N identified 469 proteins up- and 431 down-regulated, respectively. Arginase-1 (ARG1), Keratin Type-2 Cytoskeletal 8 (KRT8), Lipocalin-1 (LCN1) and DNA replication licensing factor MCM2 (MCM2) were identified as biologically associated with smoking compared to non-smoking, providing viable targets for verification by immunochemical methods which further supported the proteomic data. Overall, the project demonstrated the importance of using matched biopsies with good clinicopathological data for experimental design and provided a set of unique targets for a more expanded verification study.

Introduction. La tomographie par cohérence optique (TCO) est une modalité d'imagerie permettant de dévoiler la microarchitecture des tissus en temps réel. Compte tenu de ses propriétés, il existe un intérêt croissant pour déterminer les applications potentielles de la TCO en chirurgie endocrinienne cervico-faciale. Méthodologie. Trente-six patients opérés pour thyroïdectomie, parathyroïdectomie et/ou évidement cervical pour un cancer bien différencié de la thyroïde (CBDT) ont été recrutés prospectivement. Les spécimens de thyroïde, glandes parathyroïdes, ganglions et tissus adipeux sains et pathologiques ont été imagés avec la TCO avant l'analyse histopathologique. Les images ont été examinées par deux évaluateurs indépendants et une équipe multidisciplinaire. Résultats. Basé sur 137 spécimens chirurgicaux, la TCO ne permettait pas de différencier les nodules thyroïdiens bénins des nodules malins et les adénomes parathyroïdiens des ganglions sains. Pour les tissus sains, la TCO permettait de distinguer chaque type de tissu avec une sensibilité et une spécificité de 100% et 99% pour la thyroïde, 93% et 100% pour les glandes parathyroïdes, 100% et 99% pour les tissus adipeux, et 98% et 99% pour les ganglions. Les coefficients kappa de Cohen pour l'accord intra- et inter-évaluateurs étaient de 0,968 et 0,951. La TCO permettait également de différencier les ganglions bénins des ganglions malins avec une sensibilité, spécificité, valeur prédictive positive et négative de 85,1%, 89,5%, 80,8% et 92,2%. La fiabilité intra- et inter-évaluateurs étaient de 0,836 et 0,792. Conclusion. La TCO pourrait servir d'outil d'appoint pour confirmer l’identification des glandes parathyroïdes et différencier les ganglions métastatiques des ganglions bénins lors de la thyroïdectomie. / Background. Optical coherence tomography (OCT) is a non-invasive imaging modality that renders real-time tissue images with resolution in the order of micrometers, allowing to unveil their microarchitecture. Given its properties, there is growing interest in determining the potential applications of OCT in thyroid and parathyroid surgery. Methodology. Thirty-six patients undergoing thyroidectomy, parathyroidectomy and/or neck dissection for well-differentiated thyroid carcinoma (WDTC) were prospectively recruited in a single tertiary center. Freshly excised specimens of healthy and pathologic thyroid, parathyroid glands, lymph nodes and adipose tissues were imaged with OCT prior to histopathological analysis. Images were reviewed by two blinded independent raters, and a multidisciplinary team. Results. Based on 137 surgical specimens, OCT could not consistently differentiate benign from malignant thyroid nodules, and parathyroid adenomas from normal lymph nodes. For healthy tissues, OCT could differentiate each tissue type with high sensitivity and specificity 100% and 99% for thyroid tissue, 93% and 100% for parathyroid glands, 100% and 99% for adipose tissue, and 98% and 99% for lymph nodes. Cohen’s kappa coefficients for intra- and inter-rater agreement were 0.968 and 0.951. OCT could also differentiate benign from malignant lymph nodes in WDTC with sensitivity, specificity, positive and negative predictive values of 85.1%, 89.5%, 80.8%, and 92.2%. Cohen’s kappa coefficients for intra- and inter-rater reliability were 0.836, and 0.792. Conclusion. Evidence suggests that OCT could serve as an adjunct tool to identify parathyroid glands during thyroidectomy and differentiate benign from metastatic lymph nodes in WDTC.