Point of Care Detection of Antibodies Against HPV16/18 E6 and E7 Oncoproteins in Oropharyngeal Cancer

Fast-Track proposals will be accepted. Direct-to-Phase II proposals will NOT be accepted. Number of anticipated awards: 2-4 Budget (total costs, per award): Phase I: up to $400,000 for up to 12 months Phase II: up to $2,250,000 for up to 2 years PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED. Summary The incidence of oropharyngeal cancer (OPC) is on the rise in many countries. A significant number of OPCs are caused by human papillomavirus (HPV) infections. Current prophylactic HPV vaccines can eventually prevent HPV-related cancers, as has been shown already for cervical cancer in young women. However, there are still several generations of people at risk of HPV-related OPC for whom prophylactic HPV vaccination will not be offered and would have limited or no benefit. Early detection could optimize effective intervention and treatment to reduce the deaths caused by HPV-related OPCs. Unfortunately, there is currently no recommended screening test or approach for the prevention or early detection of HPVrelated OPC. Therefore, there is a significant unmet need to improve the early detection of HPV-related OPC for optimizing intervention and treatment. HPV16 is the most important type in HPV-positive cancers, accounting for 90% of HPV-driven OPCs; HPV18 is the next most important type. HPV is a very common exposure, but most are benign and will become undetectable in a year or two. Thus, the detection of HPV DNA is sensitive, but not specific for HPV-related cancers. However, it is known that antibodies against HPV E proteins are strongly associated with and are highly specific for HPV-related OPC. Specifically, anti-HPV16 E6 and E7 antibodies can be detected years before HPV-related OPC becomes clinically detected. Detecting antibodies against HPV16 and 18 E6/E7 oncoproteins in high-risk individuals will facilitate increased surveillance, including imaging and biopsy, particularly for high-risk subjects, such as males, in regions with high cancer incidence, leading to the improvement of clinical guidelines and targeted interventions.