Comparing Sentinel Lymph Node (SLN) Biopsy With Standard Neck Dissection for Patients With Early-Stage Oral Cavity Cancer

Inclusion Criteria:

* PRIOR TO STEP 1 REGISTRATION INCLUSION:
* Pathologically (histologically or cytologically) proven diagnosis of squamous cell carcinoma (SCC) of the oral cavity, including the oral (mobile) tongue, floor of mouth (FOM), mucosal lip, buccal mucosa, lower alveolar ridge, upper alveolar ridge, retromolar gingiva (retromolar trigone; RMT), or hard palate prior to registration
* Appropriate stage for study entry (T1-2N0M0; American Joint Committee on Cancer \[AJCC\] 8th edition \[ed.\]) based on the following diagnostic workup:

  * History/physical examination within 42 days prior to registration
  * Imaging of head and neck within 42 days prior to registration

    * PET/CT scan or contrast neck CT scan, or gadolinium-enhanced neck magnetic resonance imaging (MRI) or lateral and central neck ultrasound; diagnostic quality CT is preferred and highly recommended as part of the PET/CT when possible
  * Imaging of chest within 42 days prior to registration

    * Chest x-ray, CT chest scan (with or without contrast), or PET/CT (with or without contrast)
* Surgical assessment within 42 days prior to registration. Patient must be a candidate for surgical intervention with sentinel lymph node (SLN) biopsy and potential completion neck dissection (CND) or elective neck dissection (END)

  * Surgical resection of the primary tumor will occur through a transoral approach with anticipation of resection free margins
* Age \>= 18
* Zubrod performance status 0-2 within 42 days prior to registration
* For women of child-bearing potential, negative serum or urine pregnancy test within 42 days prior to registration
* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
* Only patients who are able to read and understand English or French are eligible to participate as the mandatory patient reported NDII tool is only available in these languages
* PRIOR TO STEP 2 RANDOMIZATION:
* FDG PET/CT required prior to step 2. Note: FDG PET/CT done prior to step 1 can be submitted for central review

  * PET/CT node negative patients, determined by central read, will proceed to randomization. PET/CT node positive patients will go off study, but will be entered in a registry and data will be collected to record the pathological outcome of neck nodes for diagnostic imaging assessment and future clinical trial development

    * NOTE: All FDG PET/CT scans must be performed on an American College of Radiology (ACR) accredited scanner (or similar accrediting organization)
* The patient must complete NDII prior to step 2 registration

Exclusion Criteria:

* PRIOR TO STEP 1 REGISTRATION EXCLUSION:
* Definitive clinical or radiologic evidence of regional (cervical) and/or distant metastatic disease
* Prior non-head and neck invasive malignancy (except non-melanomatous skin cancer, including effectively treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or cervix) unless disease free for ≥ 2 years
* Diagnosis of head and neck SCC in the oropharynx, nasopharynx, hypopharynx, and larynx
* Unable or unwilling to complete NDII (baseline only)
* Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for different cancer(s) is allowable
* Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
* Severe, active co-morbidity that would preclude an elective or completion neck dissection
* Pregnancy and breast-feeding mothers
* Incomplete resection of oral cavity lesion with a positive margin; however, an excisional biopsy is permitted
* Prior surgery involving the lateral neck, including neck dissection or gross injury to the neck that would preclude surgical dissection for this trial. Prior thyroid and central neck surgery is permissible; biopsy is permitted. Note: Borderline suspicious nodes that are \>= 1 cm with radiographic finding suggestive of NOT malignant should be biopsied using ultrasound (U/S)-guided fine-needle aspiration (FNA) biopsy
* Underlying or documented history of hematologic malignancy (e.g., chronic lymphocytic leukemia \[CLL\]) or other active disease capable of causing lymphadenopathy (e.g., sarcoidosis or untreated mycobacterial infection)
* Actively receiving systemic cytotoxic chemotherapy, immunosuppressive, anti-monocyte or immunomodulatory therapy
* Currently participating in another investigational therapeutic trial