||3U01CA182915-05S1 Interpret this number
||University Of Michigan At Ann Arbor
||Mechanistic Modeling of Oropharyngeal Cancer Treatment and Recurrence (SUPPLEMENT)
While the incidence of HPV-related OPSCCs is increasing, these cancers usually have better prognoses and
clinical outcomes than HPV-unrelated OPSCCs, which are typically related to smoking and alcohol use. This
difference has been hypothesized to be due, at least in part, to the fact that inactivation of critical cancer
pathways in HPV-related OPSCCs is caused by the presence of viral genes rather than somatic mutations or
genetic/epigenetic inactivation of key tumor suppressor genes (as is the case for HPV-unrelated OPSCCs).
This difference suggests that some of these pathways might be partially active or recoverable, leading to better
responses to therapies that, for example, activate p53-mediated apoptosis. The exact mechanisms are still not
fully known, but clinicians are nonetheless exploring less aggressive treatment options for HPV-related cancers
as a way to minimize secondary effects and sequelae (treatment de-escalation).
Here we propose to investigate the impact of treatment de-escalation and its possible non-inferiority in
treatment trials and evaluate the impact of treatment de-escalation for HPV-related OPSCCs using data from
treatment trials and natural history models of cancer recurrence.
None. See parent grant details.