PhD ceremony Mr. L.J. Melchers: New molecular biomarker discovery for diagnosis and prognosis in oral and oropharyngeal cancer

PhD ceremony: Mr. L.J. Melchers

Dissertation: New molecular biomarker discovery for diagnosis and prognosis in oral and oropharyngeal cancer

Promotor(s): prof. J.L.N. Roodenburg, prof. E. Schuuring

Faculty: Medical Sciences

Squamous cell carcinoma of the oral cavity and oropharynx (OOSCC) affects 400,000 persons worldwide every year. The most important factor in treatment decision is the presence of metastases in the regional lymph nodes in the neck, which should be treated by surgical removal of the lymph nodes by neck dissection. However, current imaging techniques to detect metastases are suboptimal, resulting in significant over- and undertreatment of patients with OOSCC, unnecessary morbidity and healthcare costs.

Goal of this thesis was to identify and evaluate new biological and clinical biomarkers in the primary tumour that aid the clinician to more accurately predict the presence of lymph node metastases and prognosis for OOSCC patients.

Infiltration depth of the tumour in the surrounding tissue can be easily assessed during routine histopathological examination of the tumour. Our research showed that tumours with an infiltration depth ≥4 mm have a significantly increased risk for metastasis and these patients should be treated by a neck dissection. We also tested various molecular biomarkers for their ability to predict the presence of lymph node metastases compared to clinical predictors. This resulted in the identification of expression of claudin-7, presence of high-risk human papilloma virus, and hypermethylation of DAPK1 and MGMT as predictive biomarkers. These markers might improve decision making by predicting which patients should undergo a neck dissection.