The Sinai Robotic Surgery Trial in HPV-related Oropharyngeal Squamous Cell Carcinoma (SIRS 2.0 Trial)

Inclusion Criteria: * Patients must have histologically or cytologically confirmed and identified resectable primary OPSCC with positive p16 immunohistochemistry, defined as strong and diffuse nuclear and cytoplasmic staining in \> 70% of tumor cells. Immunohistochemistry must be performed or reviewed at the central laboratory. P16 status may be determined prior to consent and must be confirmed by surgical specimen if a biopsy is unavailable. HR-HPV status and postoperative cfHPVDNA testing must be performed and resulted prior to treatment assignment. Tissue from the primary site must be available for biomarker studies after surgery. * Patients enrolled in the trial must have pre-surgery baseline cfHPVDNA using the NavDX assay (Naveris, Cambridge, MA). Detectable baseline cfHPVDNA copy number is defined as ≥ 10 fragments/mL and is required for inclusion in the trial. * Undetectable cfHPVDNA after surgery. All patients should have a repeat cfHPVDNA test within 1 to 5 weeks post-operatively and prior to treatment assignment. Undetectable cfHPVDNA is defined as \< 5 fragments/mL. * AJCC 7th edition early and intermediate stage (T1N0-2B, T2N0-2B) (non-matted) disease without evidence of distant metastases or gross extranodal extension. * Age ≥ 18 years at screening * No previous surgery, radiation therapy, or chemotherapy for head and neck cancer (other than excision/incisional biopsy of the primary site, excisional/incisional nodal biopsy, or tonsillectomy) is allowed at time o…