The incidence of p16-positive oropharyngeal cancer (p16+0PC) is rising in certain countries, including Australia. While -15% of these patients develop recurrences, treatment-associated toxicities also remain a major concern. Using tumour cell culture models for personalizing treatment can potentially streamline therapy for these patients. I have developed a workflow to culture circulating tumour cells (:TCs) from p16+0PC patients with unparalleled efficiency. The proposed study explores the utility of these cultures for personalizing therapy. The project involves 100 p16+0PC patients with sample collection at diagnosis, and, 13th week and 1 year post-treatment. CTCs will be isolated and cultured according to the developed protocol. These cultures will be characterized for molecular markers and will be tested for their sensitivity to a panel of commonly used chemotherapeutic agents for p16+OPC. To evaluate the drug efficacy in a more physiologically relevant environment, this study will also develop protocols to culture CTCs as 30 models and in-vivo transplants. Further, this study will investigate the utility of CTC cultures for disease monitoring and secondary treatment selection.