Primary Objective: To assess the 2-year progression-free survival of de-intensified post-operative chemoradiation based on post-operative circulating tumor HPV-DNA in patients with HPV-associated oropharyngeal cancer. Secondary Objectives: To determine relevant oncologic outcomes, including the overall survival, locoregional control, distant control, cause-specific survival of de-intensified post-operative chemoradiation in patients with HPV-associated oropharyngeal cancer. To assess quality of life changes before, during and after treatment via a multi-dimensional assessment, including Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), Hearing Handicap Inventory for Adults (HHIA-S), EORTC QLQ-C30, the University of Michigan Xerostomia-Related Quality of Life Scale (XeQoLS), and the 5-level version of the EuroQol five dimensional instrument EQ-5D-5L. To assess dysphagia before, during, and after treatment with the MD Anderson Dysphagia Inventory (MDADI) tool and modified barium swallow test. To assess the 2-year PFS in the high-risk (positive margins, extranodal extension, ?5 positive lymph nodes) and intermediate-risk (all others) subgroups. We also plan to combine patients from this protocol with our prior deintensification protocol (NCT04502407) to perform a combined analysis of outcomes cross both trials. We also plan to compare outcomes on this protocol to outcomes on our prior deintensification protocol.

• CS Cancer Tarzana
• CS Cancer at Beverly Hills
• CS Cancer at Cedars-Sinai Medical Center
• CS Cancer at The Angeles Clinic and Research Institute
• Hunt Cancer Institute, an Affiliate of Cedars-Sinai Cancer