Single center, non-randomized Phase II study enrolling Stage I-II p16+ oropharyngeal cancer patients to one of two de-escalation treatment paradigms: (1) receive surgery followed by observation or risk-adjusted adjuvant radiation (+/-chemo), or (2) individualized adaptive definitive chemoradiation (CRT).
Patients must have FDG-avid (maximum SUV ≥ 4.0) (from PET scan of any date, any scanner) and histologically or cytologically proven squamous cell carcinoma of the oropharynx (tonsil, base of tongue, oropharyngeal wall, soft palate) or unknown primary that is p16 positive by immunohistochemistry or HPV positive by in situ hybridization
Clinical stage: Stage I-II AJCC 8th edition staging
History/physical examination, including documentation of weight within 4 weeks prior to registration;
For Cohort B, FDG-PET/CT scan for staging within 6 weeks prior to registration. For Cohort A, acceptable imaging for staging can include diagnostic CT neck/chest or PET-CT within 6 weeks prior to registration
cT4, cN3, or cM1 disease (also explained as AJCC 8th edition clinical staging,)
Patients with radiographic ECE or matted lymph nodes, defined as three nodes abutting one another with loss of intervening fat plane that is a replaced with radiologic evidence of extracapsular spread.
Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (For example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible);
Any prior therapy for the study cancer; note that prior chemotherapy for a different cancer is allowable if >3 years prior to study;