Tumour Microenvironment, Cancer Stem Cells and Radiation Response in Oropharyngeal Cancer

Abstract

The incidence of Human papillomavirus (HPV) induced oropharyngeal squamous cell carcinoma (OSCC) is rising. HPV-positive OSCC is associated with a favourable prognosis, the mechanism is not fully understood and could be related to intrinsic radiosensitivity of the HPV-positive OSCC. The aim of this candidature was to study the influence of tumour microenvironment on radiosensitivity by examine HIF-1α in OSCC and by using in vitro 3D tumour models. The main finding of the HIF-1α study was the HPV status remains the strongest prognostic factor in OSCC. Hypoxia might be an important factor in HPV-negative cancer. In consistent with clinical observations, in vitro studies revealed HPV-positive OSCC cells were more sensitive to radiation than were HPV-negative OSCC cells. Radiosensitivity of HPV-positive OSCC was related to G1/S cell cycle regulation, increased cyclin D1 expression and apoptosis; associated with p16/CDK/Rb pathways. HPV-negative OSCC cells displayed a radiation-induced G2 arrest indicating the activation of DNA repair mechanism. Radiation induced cyclin D1 expression indicated that responsible for HPV-positive OSCC radiosensitivity. The results from this candidature emphasize the important roles of HPV and microenvironment on cancer cell response to radiation. The results provided a biological basis for using different strategies when treating HPV-positive and HPV-negative OSCC.