Reducing Excision Margins After Neoadjuvant Chemoimmunotherapy for HPV Negative Resectable Locally Advanced HNSCC

Inclusion Criteria: 1. Age is 18-70 years old, gender is unlimited; 2. Histological diagnosis of oral, oropharyngeal, hypopharyngeal, or laryngeal squamous cell carcinoma; preoperative evaluation can be surgical resection. 3. HPV negative evaluation criteria: P16 immunohistochemistry is negative, that is, p16 is less than 70% negative, and negative HPV FISH test shall prevail; locally advanced, defined as per the United States Joint Committee on Cancer \[AJCC\] guidelines: -HPV negative disease, III, IVa, IVb; no previous tumor treatment for head and neck squamous cell carcinoma; 4. According to the RECIST version 1.1 standard, With at least one evaluable target lesion; 5. the ECOG physical status is 0-1 points; 6. the main organ function is normal, That is, the following standards should meet: (1) routine blood inspection standards should meet: (no blood transfusion within 14 days) a. Hb 90g / L: b. ANC≥1.5x109/L; c. PLT 80x109 / L; (2) biochemical inspection should meet the following standards a.BIL \<1.25 times the upper normal value limit (ULN); b.ALT and AST\<2.5xULN; In case of liver metastases, Then, ALT and AST \<5xULN: c. Serum Cr ULN, Endophytic creatinine clearance\> 50ml / min (Cockcroft-Gaut formula); 7. Signed written informed consent prior to any test-related activity; 8. Investigators judged the ability to comply with the study protocol; 9. pregnancy test at screening (for fertile female patients) negative; 10. Fertility of male patients and female patients at risk of fertility and pregnancy must agree to the use of two contraceptive methods (at least one of which is considered efficient) throughout the study period. Unfertile women (i. e., meet one of at least the following criteria): -hysterectomy and/or bilateral oophorectomy with documented records; -medically confirmed ovarian function decline; -Postmenopausal status, defined as menopause for at least 12 consecutive months of menopause without other pathologic or physiologic reasons and confirmed by serum follicle-stimulating hormone (FSH) levels. 11. Patients who are willing and able to comply with visit schedules, treatment plans, laboratory tests, and other research procedures.12 A signed and dated informed consent indicates that the patient (or legal representative, if permitted by local guidelines/practice practices) has been informed of all relevant aspects of the study Exclusion Criteria: 1. Previous immunotherapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 or anti-CTLA-4 antibodies (including ipilimumab), or any other antibodies or drugs specifically targeted to the T cell co-stimulation or immune checkpoint pathway. 2. Major surgery for the first 4 weeks before enrollment; 3. People with a proven allergy to PD-1 antibody or its excipients; 4. Any active autoimmune disease or a history of autoimmune disease (e. g., Interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, myocarditis, nephritis, hyperthyroidism, reduced thyroid function (can be included after effective hormone replacement therapy): vitiligo or asthma in childhood, Asthmatic patients living in adults, either without any intervention and requiring medical intervention with bronchodilators, may be included); 5. Previous or concurrent cases of other malignancies (cured, Except for malignancies with cancer-free survival of more than 5 years, Such as skin basal cell carcinoma, cervical carcinoma in situ, and papillary thyroid carcinoma); 6. Heart clinical symptoms or diseases that cannot be controlled, For example: (1) heart failure of grade NYHAII or above (2) unstable heart pattern pain (3) myocardial infarction within 1 year (4) patients with clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention; 7. Within 14 days before the administration of the study drug, Subjects who require systemic treatment with corticosteroids (\> 10 mg/day, an efficacy dose of prednisone) or other immunosuppressants, In the absence of active autoimmune disease, Allow inhaled or topical use of steroids and adrenal hormone replacement with efficacy doses of prednisone\> 10 mg/day； 8. Active infection requiring treatment; 9. Having an innate or acquired immune deficiency (e. g., an HIV-infected person), active hepatitis B (HBV-DNA 104 copy number/ml or 2000IU / ml), or hepatitis C (hepatitis C antibody positive, And HCV-RNA is above the lower limit of analysis); 10. Patients have received other oncology treatments before treatment; 11. Live vaccine within 4 weeks before the start of study treatment; 12. Known history of psychotropic substance abuse, alcohol or drug use; 13. Women during pregnancy or lactation; 14. Researchers judge, Subjects had other factors that could contribute to their forced termination of the study midway, If other serious diseases (including mental illness) require combined treatment, Laboratory examination values were seriously abnormal, Family or social factors, May affect the subject safety or trial data collection; 15. Patients considered not feasible for radical resection; 16. active tuberculosis; 17. Severe infections occurring within 4 weeks prior to initiation of study treatment (including but not limited to hospitalization, due to complications of infection, bacteremia or severe pneumonia); 18. Receiving systemic immune stimulation medication within 4 weeks before initiation of study treatment (including but not limited to interferon or interleukin-2 \[IL-2\]) or remaining in 5 drug half-lives (older of both).