The goal of this M-cubed grant will be to perform the first steps required to define a subset of HPV-positive head and neck cancer (HNC) patients who would benefit from de-escalated or escalated therapy to improve outcomes. Although HPV-positive patients have much better prognosis than their HPV-negative counterparts, there remains a significant percent that do not survive or survivors have significant treatment-related toxicities. The most recent clinical trial for treatment de-escalation of HPV-positive patients failed, and we believe this is due to the failure to recognize patient-specific characteristics.
Previously, looking at high versus low-risk HPV-positive HNC patients, we took a targeted gene approach based on public cancer data (TCGA) but found no differences. Additionally, research by Sartor and colleagues revealed that HPV-positive HNC patients whose tumors do not have any identified HPV integration into the host genome have significantly better survival than patients whose tumors do. High-throughput genomic analysis of these two groups suggested that tumor immune response and/or cell motility/invasion play a role, but functional studies are required. Our long-term goal is to both identify the patient subgroups most likely to benefit from de-escalated or escalated therapy and use mechanistic studies to propose a patient-specific, less toxic alternative therapy based on the tumor differentiation and immune signatures. Findings from this M-Cubed project will be used as preliminary data for an R01 proposal.