Predictive Methods Determining Tumour Hypoxia in Head and Neck Cancer Patients - a Prospective Project

The incidence of head and neck squamous cell cancer (HNSCC) is around 600 000 cases per year worldwide. The main sites for HNSCC are the larynx, the pharynx and the oral cavity. Head and neck cancers, however, also include salivary gland tumours, as well as nasopharyngeal cancer and paranasal and nasal sinus cancer but these are rare. The major risk factors are smoking, alcohol abuse and Human Papillomavirus (HPV) infection. In spite of radical surgical treatment and aggressive neo-adjuvant and adjuvant therapies, the prognosis of head and neck cancer is very poor due to the fact that the tumours are often hypoxic.

Tumour hypoxia is heterogenous and results from an imbalance between oxygen supply and oxygen consumption. Acute hypoxia is caused by abnormal structure and function of the microvasculature supplying the tumour. Chronic hypoxia is caused by the increased distance through which the oxygen has to diffuse to get from the blood vessels to the tumour cells and by the reduced oxygen caused by the anaemia which can be treatment or disease-related. These hypoxic regions have been shown to affect the metabolism of the cells, making them more aggressive with increased risk of metastasis and a worse prognosis. Also, because radiotherapy relies on oxygen to cause maximal cytotoxicity, a lack of oxygen to the cells or even a lack of oxygen consumption by the cells would cause a decrease in the effectiveness of the radiotherapy and the cytotoxicity. Hypoxic cells have an acidic environment which affects drug delivery and drug activity, so chemotherapy is compromised.

In order to predict outcome and identify patients with a worse prognosis or patients that would benefit from appropriate treatments, in vivo measurement of tumour hypoxia is required. Numerous methods have been explored but there is no accepted gold standard. Imaging and biomarker analysis have been shown to have potential but the data are insufficient. In this project the investigators would prospectively use existing imaging techniques and analysis of various bodily fluids to predict outcome. This is a collaboration between 5 different departments so that as much information as possible can be analysed and used to come to a possible solution.