To investigate the neoadjuvant chemoimmunotherapy regimen of Ivonescimab combined with chemotherapy (Paclitaxel plus Cisplatin/Carboplatin) for the treatment of locally advanced resectable oral squamous cell carcinoma and oropharyngeal squamous cell carcinoma.

Two cycles of treatment with Ivonescimab combined with chemotherapy were administered, with an interval of 3 weeks between the two cycles. Oral swab and saliva samples were collected within 3 days prior to the initiation of the first cycle of Ivonescimab plus chemotherapy, within 3 days prior to the initiation of the second cycle, and within 3 days prior to surgery. Intraoperatively, tumor tissues and paracancerous tissues were harvested. A 3 mm-thick section of the resected primary tumor lesion was obtained for pathological examination to investigate the tumor regression pattern.

Inclusion Criteria:

1. Histopathologically diagnosed as oral squamous cell carcinoma (OSCC) or oropharyngeal squamous cell carcinoma (OPSCC)
2. Patients staged according to the AJCC criteria (8th edition) as locally advanced (Stage III/IVA oral cancer, HPV-negative oropharyngeal cancer, or Stage II/III HPV-positive oropharyngeal cancer) and assessed by the investigators as resectable.
3. Age 18 to 80 years
4. Complete blood count (CBC): White blood cell (WBC) count ≥3×10⁹/L; Platelet (PLT) count ≥75×10⁹/L; Hemoglobin (Hb) concentration ≥80g/L
5. Liver function: Aspartate transaminase (AST) and Alanine transaminase (ALT) ≤2.5 times the upper limit of normal (ULN)
6. Kidney function: Estimated glomerular filtration rate (eGFR) > 50 mL/min
7. Patients must have adequate function of vital organs (including cardiac, pulmonary, thyroid, and other organs) and a general condition that allows tolerance of the treatment regimen of this study.
8. Sign the Informed Consent Form (ICF)

Exclusion Criteria:

1. Pregnancy or lactation (for female participants)
2. A history of epilepsy or mental illness that is not effectively controlled
3. Unresolved toxicities of grade > 2 per CTCAE criteria resulting from prior anticancer therapy
4. Other conditions deemed unsuitable for study participation by the investigators, including patients with autoimmune diseases or those at high risk of bleeding due to various causes

Patients were diagnosed with oral squamous cell carcinoma (OSCC) (a carcinoma arising from the oral mucosal epithelium with squamous differentiation, involving the mobile tongue, buccal mucosa, gingiva, hard palate, floor of the mouth and other oral mucosal sites) or oropharyngeal squamous cell carcinoma (OPSCC) (a carcinoma arising from the oropharyngeal mucosal epithelium with squamous differentiation, involving the base of tongue, vallecula epiglottica, lateral and posterior walls of the oropharynx, as well as the soft palate and uvula). All patients were confirmed as locally advanced diseases according to the 8th edition of the American Joint Committee on Cancer (AJCC) staging criteria: Stage III/IVA for OSCC or HPV-negative OPSCC, and Stage II/III for HPV-positive OPSCC.