This phase I, open-label, single-arm trial uses a "3+3" dose-escalation design to evaluate the safety, tolerability, and preliminary efffcacy of intranasal WSK-IM05 vaccine combined with tislelizumab as neoadjuvant therapy in patients with resectable HPV-positive oropharyngeal squamous cell carcinoma. Participants receive two cycles of WSK-IM05 (intranasal) and tislelizumab (200 mg IV) on day 1 of each 3-week cycle, followed by surgery. After surgery, patients receive standard of care (chemoradiotherapy or radiotherapy as indicated) plus 15 cycles of adjuvant tislelizumab. The main outcomes include dose-limiting toxicities and treatment-related adverse events.

Inclusion Criteria:

1. Age ≥ 18 years, male or female.2. Histologically confirmed oropharyngeal squamous cell carcinoma meeting all of the following criteria: Newly diagnosed, HPV-positive, without distant metastases; Confirmed p16 positive by immunohistochemistry (defined as ≥70% moderate to strong nuclear and cytoplasmic staining of tumor cells)；Assessed by head and neck surgery as resectable; Willing to undergo surgical treatment.3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.4. Adequate organ and bone marrow function, defined as:Hematology: neutrophil count (NEUT) ≥ 1.5×10⁹/L; platelet count (PLT) ≥ 80×10⁹/L; hemoglobin ≥ 8 g/dL; Liver function: AST, ALT, ALP ≤ 2.5×upper limit of normal (ULN); total bilirubin (TBIL) ≤ 1.5×ULN; Albumin ≥ 2.8 g/dL.Renal function: serum creatinine (Cr) ≤ 1.5×ULN or creatinine clearance (CCr) > 60 mL/min; Coagulation: international normalized ratio (INR) ≤ 1.5; activated partial thromboplastin time (APTT) ≤ 1.5×ULN; Adenovirus type 5(Ad5) neutralizing antibody titer ≤ 1:200.5. Willing to voluntarily sign the informed consent form and able to comply with protocol-required visits and procedures.

Exclusion Criteria:

1. History of other malignancies (except for adequately treated and with no recurrence within 5 years:basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer,cervical carcinoma in situ, intramucosal gastrointestinal carcinoma, or other malignancies deemed eligible by the investigator).2. Any active autoimmune disease or history of autoimmune disease,including but not limited to immune-related neurological disorders, multiple sclerosis, autoimmune(demyelinating) neuropathy, Guillain-Barré syndrome, myasthenia gravis, systemic lupus erythematosus(SLE), connective tissue disease, scleroderma, inflammatory bowel disease (including Crohn's disease and ulcerative colitis), autoimmune hepatitis, toxic epidermal necrolysis (TEN), or Stevens-Johnson syndrome (excluding type I diabetes mellitus managed with stable insulin doses).3. History of allergic disease, severe drug allergy, or known allergy to any component of large molecule protein preparations,PD-1 monoclonal antibody injections, or the intranasal recombinant adenovirus vaccine (note: severe allergy is defined as requiring hospitalization).4. Prior receipt of any of the following treatments:a. Prior use of PD-1 antibody, PD-L1 antibody, PD-L2 antibody, CTLA-4 antibody, EGFR antibody, or EGFR-TKI.b. Prior receipt of an antitumor vaccine.c. Use of any active vaccine against infectious diseases (e.g.,inffuenza vaccine, varicella vaccine) within 4 weeks before first dose or planned during the study period.d. Major surgery or severe trauma within 4 weeks before first dose.e. Prior antitumor toxicity not recovered to ≤ CTCAE v5.0 grade 1 (excluding alopecia or sequelae of prior platinum-related neuropathy) or to the levels specified in inclusion/exclusion criteria.5. Presence of severe medical conditions, such as: Cardiac dysfunction grade II or higher (NYHA criteria), ischemic heart disease (e.g., myocardial infarction or angina), clinically significant supraventricular or ventricular arrhythmias; Poorly controlled diabetes (fasting blood glucose ≥ 10 mmol/L); Poorly controlled hypertension (systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg); Echocardiography showing ejection fraction < 50%; QTc interval: > 450 msec in males, > 470 msec in females; Any ECG abnormality that, in the investigator's opinion, poses additional risk for the study drug.6. History of interstitial lung disease, non-infectious pneumonitis, or high suspicion of interstitial lung disease; or conditions that might interfere with detection or management of suspected drug-related pulmonary toxicity. Patients with a prior history of drug-induced or radiation-induced non-infectious pneumonitis who are asymptomatic may be enrolled. Active tuberculosis or past tuberculosis that remains uncontrolled after treatment.7. Patients with hyperthyroidism or organic thyroid disease. Hypothyroidism managed with a stable dose of thyroid replacement hormone may be enrolled (as conffrmed by the investigator and/or endocrinologist).8. Active infection, or unexplained fever within 48 hours before first dose, or use of systemic antibiotics within 1 week before signing informed consent.9. Active hepatitis B (HBV DNA ≥ 2000 IU/mL or 10⁴ copies/mL) or active hepatitis C (positive HCV antibody with HCV RNA above the lower limit of detection), or known positive HIV test or known acquired immunodeffciency syndrome (AIDS).10. Clear history of neurological or psychiatric disorders, such as epilepsy or dementia.11. Clear history of drug abuse or alcohol abuse within 3 months.12. Pregnant or breast feeding women; participants (and their partners) who plan to conceive within 3 months after the study period, have unprotected sexual intercourse, or are unwilling to use adequate contraceptive measures (e.g., condom,intrauterine device, or partner sterilization).13. Receipt of any investigational drug within 4 weeks before first dose, or concurrent enrollment in another clinical study, unless it is an observational (non-interventional) study or the follow-up phase of an interventional study.14. Any other condition that,in the investigator's judgment, might interfere with the study, including inability to complete study treatment and follow-up.