Grant: Doctoral Research Award: Canada Graduate Scholarships

High-risk human papillomaviruses (HPVs) are major risk factors for the development of cervical cancer, as well as a subset of head and neck cancers. Cervical cancer is currently the fourth most deadly cancer in women globally and the prevalence of cervical cancer remains high in areas with low HPV vaccination rates. Additionally, current trends indicate that the number of individuals with head and neck cancer associated with HPV is rising in many high-income countries, including Canada, such that there are now more men living with HPV+ throat cancer (one type of head and neck cancer) in the United States than women living with cervical cancer. There are many molecular (e.g. genetic) and clinical differences between HPV+ and HPV- head and neck cancers. For example, HPV presence is associated with improved survival. Yet, rates of treatment-associated side effects remain high for both HPV+ and HPV- head and neck cancers, indicating the need for both more personalised treatments and the introduction of new therapies. In other cancer types, circular DNA elements called extrachromosomal DNAs (ecDNAs) are known contributors to the formation and progression of tumours. Although ecDNAs have been detected in HPV+ cancers, including cervical cancer and head and neck cancers, a comparison of ecDNA structure and function between HPV+ and HPV- subtypes has not been performed. Also, little is known about how ecDNAs are regulated in HPV+ cancers. Therefore, I propose to study a cohort of individuals with cervical cancer and head and neck cancer and compare results between HPV+ and HPV- cancers. For example, I will compare characteristics of ecDNAs, such as the number of these elements present within individual tumours and their organisation, between HPV+ and HPV- cancers. Such a comparison will teach us more about the unique biologies of HPV+ and HPV- cancers and may uncover new therapeutic targets worthy of further investigation.