Induction PD-1 Inhibitor and Chemotherapy Followed by Chemoradiotherapy in Unresectable or Inoperable HPV-negative LA-HNSCC

Inclusion Criteria:

* Pathologically confirmed HPV-negative head and neck squamous cell carcinoma (including laryngeal, hypopharyngeal, or oropharyngeal cancer).
* Loco-regionally advanced (Stage III-IVB) disease according to the 8th edition clinical staging system of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC).
* Confirmed by a multidisciplinary team (MDT) as not amenable to curative surgery and deemed suitable for definitive concurrent chemoradiotherapy.

"Not amenable to curative surgery" includes unresectable disease (anatomic impossibility of resection) or inoperable disease (patient medically unable to tolerate or declining surgical resection).

* ECOG performance status of 0-1.
* Pre-treatment neutrophils ≥ 1.5 × 10⁹/L, hemoglobin ≥ 90 g/L, platelets ≥ 100 × 10⁹/L; total bilirubin ≤ 1.5 × upper limit of normal (ULN), ALT ≤ 1.5 × ULN, AST ≤ 1.5 × ULN, ALP ≤ 2.5 × ULN; creatinine ≤ 1.5 × ULN.
* Activated partial thromboplastin time (APTT) and international normalized ratio (INR) ≤ 1.5 × ULN (patients on a stable dose of anticoagulant therapy, such as low molecular weight heparin or warfarin, with an INR within the therapeutic range for the anticoagulant, are eligible for screening).
* Normal pulmonary and cardiac function.
* Normal myocardial enzyme profile.
* No prior radiotherapy, chemotherapy, immunotherapy, or biological targeted therapy, or any other antitumor treatment for the current tumor lesion(s).
* Women of childbearing potential must have a negative pregnancy test (serum) within 7 days before enrollment and must voluntarily use appropriate contraception during the observation period and for 8 weeks after the last treatment; for men, they must be surgically sterile or agree to use appropriate contraception during the observation period and for 8 weeks after the last treatment.
* Participants must sign informed consent and be willing and able to comply with the requirements of visits, treatment, laboratory tests and other research requirements stipulated in the research schedule.

Exclusion Criteria:

* Has a history or presence of other malignancies, except for those that have been cured and with no evidence of disease for over 5 years (such as basal cell carcinoma of the skin, carcinoma in situ of the cervix, and papillary thyroid carcinoma, etc.).
* Has active autoimmune diseases or a history of autoimmune diseases (e.g., interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes); excluding autoimmune-mediated hypothyroidism stabilized with thyroid hormone replacement therapy; type I diabetes mellitus stabilized on insulin regimen; vitiligo or childhood asthma/allergies that have resolved and require no intervention in adulthood.
* Has uncontrolled cardiac clinical symptoms or diseases, such as: (a) NYHA Class II or above heart failure; (b) unstable angina; (c) myocardial infarction within the past year; (d) clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention.
* Has severe infection (CTCAE \> Grade 2) within 4 weeks prior to the first dose of the study drug, active infection during screening, or unexplained fever \> 38.5°C before administration (tumor-related fever may be considered for inclusion).
* Has a history of allergy to any component of anti-PD-1 antibodies, paclitaxel-based drugs, or cisplatin.
* Prior radiotherapy, chemotherapy, immunotherapy (including PD-1, anti-PD-L1 antibodies, anti-CTLA-4 antibodies, cancer vaccines, etc.), or biological targeted therapy for the current hypopharyngeal/laryngeal/oropharyngeal cancer.
* Concurrent participation in another clinical study, unless it is an observational (non-interventional) study or the follow-up phase of an interventional study.
* Requirement for systemic treatment with corticosteroids (prednisone equivalent dose \> 10 mg/day) or other immunosuppressive agents within 2 weeks prior to the first dose of the study drug, except for topical use to manage local inflammation, prevent allergies, or manage nausea and vomiting. Other special cases should be discussed with the investigator. Inhaled or topical steroids and physiological doses of corticosteroid replacement for adrenal insufficiency (≤ 10 mg/day prednisone equivalent) are permitted in the absence of active autoimmune disease.
* Major surgery or severe trauma within 4 weeks prior to the first dose of the study drug.
* Has a history of immunodeficiency, including positive HIV test, other acquired or congenital immunodeficiency diseases, or history of organ transplantation or allogeneic bone marrow transplantation.
* Has a history of interstitial lung disease (excluding radiation pneumonitis not treated with steroids) or non-infectious pneumonitis.
* Has a history or CT evidence of active tuberculosis infection, or history of active tuberculosis infection within 1 year prior to enrollment, or history of active tuberculosis infection more than 1 year ago without formal treatment.
* Active hepatitis B (HBV DNA ≥ 2000 IU/mL or 10⁴ copies/mL) or hepatitis C (positive HCV antibody with HCV-RNA above the lower limit of detection of the assay).
* Known history of drug abuse, alcohol abuse, or substance addiction
* Pregnant or lactating women.
* Other factors considered by the investigator that may lead to premature termination of the study, such as other severe diseases (including psychiatric disorders) requiring combined treatment, severely abnormal laboratory test values, family or social factors, or any other circumstances that may compromise subject safety or integrity of the study data.