Pembrolizumab in Combination With Low-dose PFas Neoadjuvant Treatment for Locally Advanced HNSCC

Inclusion Criteria: 1. Age ≥ 18 years old, ≤ 85 years old 2. Histologically or cytologically proven squamous cell carcinoma of the head and neck; Patients diagnosed with head and neck squamous cell carcinoma with stage III and IV A without distant metastasis according to AJCC staging (8th editon), including squamous cell carcinoma of oropharyngeal (P16-), oral cavity, hypopharyngeal and larynx 3. Measurable primary lesions per RECIST 1.1 criteria 4. Treatment-naive patients without any previous disease-related therapy (except for diagnostic biopsies on primary lesions) 5. ECOG performance status of 0 or 1 6. Selective standard surgery+ standard adjuvant chemo-radiotherapy/radiotherapy as judged by the investigator 7. No active autoimmune disease 8. No concurrent malignancy 9. Life expectancy is estimated to be over 3 months 10. Have sufficient tumour tissue samples available for CPS PD-L1 immunohistochemical examination (22C3 DAKO) 11. No abvious signs of hematological disorders, ANC≥1.5×109 /L, platelets ≥100×109 /L, Hb≥ 90 g/L,WBC ≥3.0×109 /L before enrollment, no blood transfusion and bleeding tendency within 7 days 12. ALT,AST and ALP ≤ 2.5 × upper limit of normal (ULN); Serum bilirubin ≤ 1.5 × ULN, for patients with known Gilbert disease, serum bilirubin ≤ 3 x ULN 13. Serum creatinine ≤1.5 or creatinine clearance\>50 mL/min 14. HPV status determined by p16 IHC, in situ hybridization, or by polymerase chain reaction-based assays 15. Able to understand this study, patient and (or) legal representative voluntarily agree to participate in this trial and sign informed consent Exclusion Criteria: 1. Multiple organs failure 2. HPV p16 positive oropharyngeal cancer 3. Patients with local advanced head and neck squamous cell carcinoma stage T4B and/or N3 4. Patients with distant metastasis 5. Uncontrolled serious diseases that, as assessed by investigator, may affect the subject's treatment with the study protocol, such as serious heart disease, cerebrovascular disease, uncontrolled diabetes mellitus, uncontrolled hypertension, uncontrolled infection, active peptic ulcer, etc. 6. Diagnosis of dementia, altered mental status or any mental illness that would prevent subjects understanding or giving informed consent or completing questionnaires 7. Subjects with ≥ Grade 2 peripheral neuropathy according to CTCAE V5.0 8. Subjects with ≥ Grade 2 hearing impairment according to CTCAE V5.0 9. History of allergy or hypersensitivity to any of the therapeutic ingredients 10. Diagnosis of malignancy within 5 years prior to screening, including HNSCC (other than current HNSCC) and other malignancies; Eligibility is achieved if all of the following criteria are met: malignancies received curative therapy, such as adequately treated cervical carcinoma in situ, non-melanoma cutaneum carcinoma, localized prostate cancer after radical operation, breast ductal carcinoma in situ after radical operation; There was also no evidence of recurrence or metastasis based on imaging and tumor markers 11. Known history of human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) 12. Patients diagnosed with nasopharyngeal carcinoma or squamous cell carcinoma whose lesions are located in parts other than the oral cavity, oropharynx, larynx and hypopharynx (such as sinuses, paranasal sinuses and unknown primary site) 13. Participated in other clinical intervention trials or received other investigational therapies within 30 days prior to screening 14. Patients received systemic corticosteroids (prednisone equivalent dose\>10mg/day) or other immunosuppressive drugs within 14 days prior to randomization. If there is no active autoimmune disease, inhaled or topical steroid hormones and adrenal hormone replacement therapy with prednisone equivalent doses\>10mg per day are permitted 15. Pregnant or breastfeeding; Subjects of childbearing age refuse to accept contraceptive measures 16. Patients unfit for study as assessed by the investigator 17. Received systemic antibiotics within 1 weeks prior to first dose of study therapy or active infection requiring treatment 18. Known history of HBV infection (defined as HBsAg positive) or active HCV infection (defined as HCV RNA detected) 19. Has received live vaccine during study or within 30 days prior to first dose of study therapy