Preoperative Immune Checkpoint Inhibitor for Patients With Primary Untreated or Recurrent/Metastatic SCCHN

Inclusion: Cohort 1: Subjects must have histologically confirmed previously untreated squamous cell carcinoma of the head and neck which is amenable to surgical resection as part of standard of care. Cohort 2: Subjects must have histologically confirmed recurrent squamous cell carcinoma of head and neck, which is amenable for salvage surgery. Sites of recurrence may either be locoregional or distant if resection can be done ideally in one surgical field. * The primary site should be a head and neck squamous cell carcinoma (including, but not limited to oral cavity, oropharynx, hypopharynx, or larynx, paranasal sinuses, nasal cavity). Squamous cell carcinoma of unknown primary, diagnosed in lymph nodes in neck, can be included but should be tested for p16 and confirmed specific assay. * Subjects with oropharyngeal primary tumors must have confirmation of human papillomavirus (HPV) tumor status per clinical standards, although not necessary at enrollment. * Subjects must have been determined to be candidates for surgical resection by a multidisciplinary team including a surgeon, a medical oncologist and a radiation oncologist. * Subjects must have at least one lesion that can be biopsied at baseline. * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1. * Age \>18 years. * Life expectancy of greater than 6 months. * Patients must have normal organ and marrow function as defined below: * leukocytes ≥ 1,500/ microliter (mcL) * absolute neutrophil count ≥ 1,000/mcL * platelets ≥ 100,000/mcL * total bilirubin ≤ 1.5 X institutional upper limit of normal (except subjects with Gilbert syndrome, who can have total bilirubin \< 3.0 mg/dL) * aspartate aminotransferase (AST) (SGOT) / alanine aminotransferase (ALT) (SGPT) ≤ 3 X institutional upper limit of normal * Creatinine OR creatinine clearance within normal institutional limits OR ≥ 40 mL/min (using modified Cockcroft-Gault formula) for patients with creatinine levels above institutional normal. * Resting and walking O2 saturation must remain above 90% at the time of screening * Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study treatment. * Women must not be breastfeeding * Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception for the duration of treatment with study treatment and for 5 months post-treatment completion. Women should use an adequate method(s) of contraception (Refer to nivolumab Investigator's Brochure (IB) for WOCBP and methods of contraception to be provided) * Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception (Refer to protocol appendix E) for the duration of treatment with study treatment(s) and 7 months post-treatment completion. In addition, male participants must be willing to refrain from sperm donation during this time. Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception * Patient understands the study regimen, its requirements, risks and discomforts and is able and willing to sign the informed consent form. Voluntary signed and dated Institutional Review Board (IRB) / Independent Ethics Committee (IEC) approved written informed consent form in accordance with regulatory and institutional guidelines must be obtained before the performance of any protocol related procedures that are not part of normal patient care. Subjects must be competent to report adverse events (AEs), understand the drug dosing schedule and use of medications to control AEs. * Measurable disease - either radiologically (per RECIST) or clinically measurable on exam in order to assess treatment response. Exclusion Criteria * Any active history of a known autoimmune disease. Subjects with vitiligo, type 1 diabetes mellitus, residual hypothyroidism requiring hormone replacement, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. * Patients who have had prior chemotherapy for newly diagnosed (cohort 1) or recurrent (cohort 2) head and neck cancer. In cohort 2 only, previous perioperative chemotherapy or chemoradiation for the management of localized or locally advanced disease permitted. * Patients who had prior surgical resection of distant metastasis (metastasectomy) within 3 months of enrollment. * Patients who received prior therapy with anti-programmed death (PD) 1 (anti-PD-1), anti-PD-L1, anti-PD-L2, cluster of differentiation (CD)137 (CD137), anti-cytotoxic T-lymphocyte associated (CTLA) protein 4 (anti-CTLA-4) (cytotoxic T-lymphocyte associated protein 4) antibody therapies, any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. Any live / attenuated vaccine (eg varicella, zoster, yellow fever, rotavirus, oral polio and measles, mumps, rubella (MMR)) during treatment and until 100 days post last dose. * Patients with uncontrolled brain metastases * Patients with brain metastases must have stable neurologic status following local therapy (surgery or radiation) for at least 2 weeks without the use of steroids or on stable or decreasing dose of \< 10mg daily prednisone (or equivalent), and must be without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with a history of carcinomatous meningitis are not eligible. * Patients who have an active concurrent malignancy that is not controlled/cured and could impact life expectancy within the next 3 years. E.g. patients with localized cutaneous squamous cell carcinoma or basal cell carcinoma or treated prostate cancer with no evidence of disease progression may be allowed to enroll after review by the study team. * Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, administration of live vaccination in the prior 3 months, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, myocardial infarction or new onset angina within six months of enrollment, or psychiatric illness/social situations that would limit compliance with study requirements. * Women who are pregnant or nursing. * Men with female partners who are not willing to use contraception. * Active infection with hepatitis B or hepatitis C. * Patients with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids and adrenal replacement steroid doses \< 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. * Patients Epstein-Barr virus + (EBV+) with nasopharynx carcinoma * Patient with HIV are excluded given the unknown risk of interaction with HAART and the unknown benefit of immunotherapy in this population. * Participants who have received a live / attenuated vaccine within 30 days of first treatment.