Feasibility and Tolerance of Nivolumab Neoadjuvant Immunotherapy in High Risk HPV Driven Oropharynx Cancer

Inclusion Criteria: 1. Age ≥18 years old 2. Histologically confirmed HPV-positive Oropharyngeal squamous cell carcinoma (OPSCC) amenable to curative treatment with RT-CT (HPV status is defined on the basis of the combination of 2 assays: p16 protein overexpression assessed by immunohistochemistry (IHC) and high-risk HPV DNA identification by in-situ Hybridization (ISH) or PCR. An HPV-driven OPSCC is defined as a tumor that is positive for both p16 IHC and HPV-DNA ISH or PCR) 3. According to the 8th TNM edition, eligible stages are as follow: * Irrespective of tobacco consumption: Stage T4 (any N), N2 or N3 (any T) * Only if tobacco consumption ≥10 pack- years: T1-3N1 and T3N0 (T1N0 and T2N0 irrespective of tobacco consumption are not eligible for the study) 4. Planned date of chemoradiation allowing 2 treatment infusions, 2 weeks apart 5. Eastern Cooperative Oncology Group (ECOG) performance status ≤1 6. Screening laboratory values must meet the following criteria (using CTCAE v5.0) and should be obtained within 7 days prior to the randomisation: 1. Polynuclear neutrophils ≥1.5 x 10⁹/L 2. Platelets ≥100 x 10⁹/L 3. Hemoglobin ≥9.0 g/dL 4. Alanine aminotransferase (ALAT)/aspartate transaminase (ASAT) ≤2.5 x upper limit of normal (ULN) 5. Total Bilirubin ≤1.5 x ULN (except Gilbert Syndrome : \<3.0 mg/dL) 6. Creatinine clearance ≥60 mL/min (measured or calculated by Cockcroft and Gault formula) 7. Potentially reproductive patients must agree to use a highly effective contraceptive method while on treatment and up to 6 months after the end of chemoradiation 8. Women of childbearing potential must have a negative serum or urine pregnancy test done within 72 hours before randomisation 9. Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures (including mandatory study-specific biopsies) 10. Subjects must have at least one lesion amenable to biopsy 11. Subjects must have at least one measurable lesion (different from the lesion amenable to biopsy) as per RECIST v1.1 to assess efficacy 12. Consent to provide archived tumour tissue sample, if available 13. Patients must be affiliated to a Social Security System 14. Patient information and written informed consent form signed Exclusion Criteria: 1. Prior treatment for OPSCC 2. Prior treatment with anti PD-1/PD-L1 and CTLA-4 3. Distant metastases 4. Tumour embolization within 28 days prior to the first dose of study drug. 5. Contra-indication(s) to receive high-dose cisplatin as listed in the most updated Summary of Product Characteristics (including creatinine clearance \<60 mL/min, pre-existing hearing loss or neurological disorder) 6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, or psychiatric illness and social situations that would limit compliance with study requirement or compromise the ability of the subject to give written informed consent 7. Current or prior use of immunosuppressive medication within 14 days before the first dose, including intranasal and inhaled corticosteroids or systemic corticosteroids 8. Active or prior documented autoimmune or inflammatory disease within the 2 years prior to start of treatment (including inflammatory bowel disease \[e.g., ulcerative colitis, Crohn's disease\], celiac disease, irritable bowel disease, or other serious chronic gastrointestinal conditions associated with diarrhea; systemic lupus erythematosus; Wegener syndrome \[granulomatosis with polyangiitis\]; myasthenia gravis; Graves' disease; rheumatoid arthritis; hypophysitis, uveitis, etc.) The following are exceptions to these criteria:a) Subjects with vitiligo or alopecia, b) Subjects with hypothyroidism (e.g.,Hashimoto syndrome) stable on hormone replacement and c) Subjects with psoriasis not requiring systemic treatment (within the past 2 years) 9. History of primary immunodeficiency or organ transplant requiring immunosuppressive drugs 10. Patients with a known HIV, active hepatitis B or C infection 11. Other invasive malignancy within 3 years except for noninvasive malignancies such as cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that has/have been surgically cured 12. Pregnant women or women who are breast-feeding 13. Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the study 14. Individuals deprived of liberty or placed under the authority of a tutor 15. Severe infection requiring parenteral antibiotics treatment 16. Known history or active symptomatic interstitial lung disease 17. Patients with major surgery within 28 days, or open biopsy within 7 days, prior to randomisation. Patients must have recovered from major side effects of the surgery before randomisation