Grant: Project Grant

Human papillomaviruses (HPV) infect undifferentiated stem cells of our skin. While our immune system clears most of these infections, the persistence of HPV can lead to the development of cervical cancer as well as head and neck cancer such as oropharyngeal cancer (OPC). Over the last decade, the number of Canadian suffering from HPV-induced oropharyngeal cancers has drastically increased (27% in men and 14% in women). Although patients suffering from HPV-induced OPCs generally have a good response to chemoradiation therapy, a significant proportion still exhibit poor prognosis. Thus, other biological elements must dictate how HPV-induced OPCs respond to treatments. To survive chemoradiation, cells rely on a sophisticated response to detect and repair the DNA damages induced by the treatment. Others and I have shown that HPV disrupts this response in OPCs but it remains largely unclear how the virus controls this phenomenon. Thus, our first goal is to elucidate how HPV manipulates genomic integrity in HPV+ OPC and to determine how it affects their resistance to chemoradiation treatment. To understand how different cellular backgrounds impact the response of HPV+ OPCs to anti-cancer treatment, we aim to identify the landscape of genes that promote resistance in these cancer cells by using a CRISPR/Cas9 genome editing approach. Finally, as different types of viral genome integration are detected in OPCs, we also plan to investigate how they affect the response of OPCs to treatments. Globally, our findings will define how the virus impacts the biology of OPCs and how it is affecting their response to chemoradiation treatments. Furthermore, our unbiased approach to identify genes that promote resistance to treatment is likely to provide therapeutic targets that can be exploited to treat HPV+ OPC patients that resist current therapies. Finally, our project has the potential to reveal new biomarkers to measure the responsiveness of HPV+ OPCs to treatments.