Inclusion Criteria:
1. Pathologically diagnosed with HPV-negative head and neck squamous cell carcinoma (HNSCC), including oral, laryngeal, hypopharyngeal, and HPV-negative oropharyngeal carcinoma (with HPV testing methods for oropharyngeal carcinoma, including p16 immunohistochemistry or HPV DNA tests).
2. Patients with resectable locally advanced head and neck squamous cell carcinoma (LA-HNSCC), classified as stage III-IVB according to the 8th edition of UICC/AJCC staging.
3. Age greater than or equal to 18 and less than 75 at the time of study entry.
4. Karnofsky Performance Status (KPS) score ≥ 70 points.
5. No prior exposure to other relevant anti-tumor treatments.
6. No distant metastasis (DM).
7. Intention to undergo curative treatment.
8. Adequate bone marrow function: total white blood cell count ≥ 3.5 × 10\^9 /L, absolute lymphocyte count ≥ 0.8 × 10\^9/L, absolute neutrophil count ≥ 1.5 × 10\^9/L, platelets ≥ 100 × 10\^9 /L, hemoglobin ≥ 90g/L.
9. Adequate hepatic function: bilirubin ≤ 1.5 x ULN; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN.
10. Adequate renal function: serum creatinine ≤ 1.5 x ULN, creatinine clearance (Ccr) ≥ 60 ml/min (if using the Cockcroft-Gault formula), urinalysis indicating urinary protein less than 2+, or 24-hour urinary protein quantification \< 1g.
11. Adequate coagulation function: international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN. If the subject is currently receiving anticoagulant therapy, PT within the therapeutic range of the anticoagulant can be accepted.
12. No severe organic heart disease and arrhythmia.
13. Women of childbearing age (15-49 years) must have a negative pregnancy test within 7 days before treatment. Both men and women of reproductive age must use highly effective contraception during the study and for 3 months after treatment.
14. Willingness and ability to sign an approved Informed Consent Form.
Exclusion Criteria:
1. Previous treatment of any other form of anti-tumor therapy;
2. Patients with allergies and congenital immunodeficiency;
3. active infection;
4. Previous organ transplantation;
5. History of autoimmune diseases or other conditions requiring prolonged systemic use of corticosteroids or immunosuppressive therapy;
6. Patients with a history of use of the following drugs (CYP3A4 inhibitors: clarithromycin, indinavir, itraconazole, ketoconazole, lopinavir, ritonavir, nefazodone, nelfinavir, posaconazole, saquinavir, telaprevir, telithromycin, voriconazole and grape sleeve or grape sleeve juice, ziprasidone, lorlostazol, ticagrelor, aprepitant, netupitant, ondansetron, domperidone, etc.; CYP3A4 inducers: rifampicin, carbamazepine, enzalutamide, phenytoin, rifampicin and St. John's wort, efaviren, bosentan, modafinil, etc.);
7. Human Immunodeficiency Virus (HIV) positive;
8. Active hepatitis B or C infection (HBV DNA, HCV RNA exceeding normal upper limits);
9. Abnormal blood counts: White blood cells \<3.5×10\^9/L, absolute lymphocyte count \<0.8×10\^9/L, neutrophils \<1.5×10\^9/L, platelets \<100×10\^9/L, hemoglobin \<90g/L; elevated bilirubin \>1.5 times the upper limit of normal, transaminases (AST, ALT) \>3 times the upper limit of normal (5 times if liver metastasis), serum creatinine \>1.5 times the upper limit of normal; abnormal coagulation function, international normalized ratio (INR) or prothrombin time (PT) \>1.5 times the upper limit of normal.
10. Severe cardiovascular, respiratory, or immune system diseases, including urinary obstruction, positive cardiac stress test, myocardial infarction, arrhythmias, obstructive or restrictive lung disease, or other diseases that investigators believe may increase the risk of subjects.
11. Pregnant or lactating females;
12. Patients unwilling to use effective contraception during the treatment period and the following 3 months.
13. Simultaneous participation in other clinical studies.
14. Patients in critical condition unable to complete the investigation.
15. Patients with a history of mental illness (e.g., schizophrenia, bipolar disorder, anxiety disorders, depression, phobias, etc.) or those diagnosed with a mental disorder at the time of clinical trial enrollment or their spouses.
16. Patients or spouses experiencing communication barriers or inability to respond normally due to reasons such as confusion, aphasia, intellectual disability, etc.
17. Presence of other malignant tumor diseases.
18. Other factors deemed unsuitable or likely to affect the subject's participation or completion of the study by the investigator.
