Lymphoscintigraphy Directed Elective Neck Radiation for p16+ Favorable Risk Oropharynx Cancer

Inclusion Criteria: Pathologically confirmed squamous cell carcinoma of the oropharynx Patients to be treated with bilateral neck radiation per current guidelines must have either present (see below): Nodal status (based on staging manual, AJCC (American Joint Committee on Cancer) 8th ed.): N0 (provided the tumor is within 1cm of midline) N1> 1 lymph nodes (on the same side of the neck as the primary cancer) or cN3 (cranial nerve III) with no contralateral neck adenopathy Tumor stage T1-2 that approaches within 1 cm but does not cross midline as appreciated radiographically and/or by the treating radiation oncologist or a head and neck surgeon CT with contrast and/or MRI with contrast performed within 56 days prior to registration that does not demonstrate bilateral neck adenopathy. In the setting of medical contraindication to both CT and MRI contrast please contact the study PI PET/CT performed with 28 days prior to registration that does not demonstrate bilateral neck adenopathy. Immunohistochemical staining for p16 that demonstrates moderate to severe staining in at least 70% of cells. Patients must provide their smoking history prior to registration. Number of pack-years = [Frequency of smoking (number of cigarettes per day) x duration of cigarette smoking (years)]/20 Patients must have clinically and/or radiographically evident disease that can be accurately measured in accordance with RECIST criteria v. 1.1. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1 within 56 days prior to registration Age ≥ 18 years. Adequate hematologic function within 14 days prior to registration Adequate renal function within 14 days prior to registration Adequate hepatic function within 14 days prior to registration Exclusion Criteria: Tumors that cross midline, regardless of T stage N2 adenopathy (bilateral neck adenopathy) Gross total excision of the primary site in a diagnostic procedure prior to either imaging and/or physical examination by registering physician. p16-negative squamous cell carcinoma Definitive clinical or radiologic evidence of metastatic disease or adenopathy below the clavicles Prior systemic therapy for the study cancer Prior head and neck cancer surgery that involved the neck (includes excisional biopsy) Prior radiation therapy to the head and neck that would result in overlap of treated fields History of allergic reaction attributed to Technetium-99m-tilmanocept used in lymphoscintigraphy Uncontrolled intercurrent illness including, but not limited to, any other malignancy, other ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Pregnant or breast feeding