Critères d'inclusion : - Age ≤ 80 years
- Performance Status ECOG 0-1
- Squamous cell carcinoma, previously untreated
- Stage III, stage IVa (i.e. operable, but not operated) or IVb (non resectable)
- Oral cavity, oropharynx, hypopharynx or larynx
- Availability of pre-treatment tumour tissue sample (for p16 & PD -L1 expression, TILs and immune landscape)
- Recording of alcohol consumption and smoking history
- Determination of the patient's ability to receive cisplatin 100 mg /m2 for 3 cycles (fit / unfit)*
Criteria for determining if a patient is fit for receiving high dose cisplatin:
- Calculated creatinin clearance ≥ 60 mL/min as determined by the modified. method of Cockcroft and Gault or by the EDTA method
- Absolute neutrophil count ≥1 500/μL, platelets ≥100 000/μL, hemoglobin ≥ 10 g/dL, aspartate (AST) and alanine transaminase (ALT) less than 2 times the upper limit of the normal range (ULN), total bilirubin ≤ 1.5 mg/dL, serum albumin > 35 g/L
- Peripheral neuropathy < grade 2
- No clinical hearing loss (confirmed by audiogram)
- Cardiac function compatible with hyperhydration; Left ventricular ejection fraction within the institutional normal ranges as measured by echocardiogram
- Written informed consent
Critères de non-inclusion : - Nasopharyngeal, paranasal sinuses, nasal cavity tumors or thyroid cancers
- Squamous cell carcinoma involving cervical neck nodes with unknown primary site
- Metastatic disease (stage IVc)
- Viral infection (HIV, Hepatitis B/C)
- Autoimmune disease
- Immunodeficiency or immunosuppressive therapy
- Active CNS disease
- Interstitial lung disease
- Active infection
- Any prior or current treatment for invasive head and neck cancer. This will include but is not limited to: prior tyrosine kinase inhibitors, any monoclonal antibody, induction chemotherapy, prior surgical resection or RT, or use of any investigational agent
- Weight loss of > 10% during the last 4 weeks (except if renutrition with a feeding tube is planned before the onset of treatment or is ongoing)
- Concurrent treatment with any other systemic anti-cancer therapy that is not specified in the protocol
- Concomitant treatment with any drug on the prohibited medication list such as live vaccines
- History of other malignancy within the last 3 years (exception of in situ carcinoma and skin carcinomas)
- Significant disease which, in the judgment of the investigator, as a result of the medical interview, physical examinations, or screening investigations would make the patient inappropriate for entry into the trial
- Known hypersensitivity reaction to study drugs
- Any social, personal, medical and/or psychological factor(s) that could interfere with the observance of the patient to the protocol and/or the follow-up and/or the signature of the informed consent.