Pathologic complete response to neoadjuvant immunochemotherapy in locally advanced head and neck squamous cell carcinoma: Characteristics of 20 responders.

e18011 Background: The use of neoadjuvant immunochemotherapy for locally advanced head and neck squamous cell carcinoma (HNSCC) is increasing. However, the characteristics of patients who achieve a pathologic complete response (pCR) remain poorly defined. This study aims to describe the clinical and pathological features of this deep-responding population. Methods: We retrospectively included patients with locally advanced oropharyngeal or hypopharyngeal carcinoma who were assessed as having a partial response (PR) after two cycles of neoadjuvant immunochemotherapy (between March 2023 and May 2025) and whose postoperative pathology confirmed pCR. Data collected included clinicopathological characteristics, p16 status for all oropharyngeal cancer patients, PD-L1 expression (TPS and CPS), and survival outcomes. The primary endpoint was to describe the characteristics of the pCR population. The secondary endpoint was event-free survival (EFS). Results: A total of 20 patients with pCR were included. There were 12 (60%) oropharyngeal and 8 (40%) hypopharyngeal carcinomas. All patients with oropharyngeal cancer were p16-positive. Among the 14 patients with known PD-L1 status, TPS was <1% in 4 (29%), 1-49% in 7 (50%), and ≥50% in 3 (21%). CPS was <1 in 4 patients (29%), 1-20 in 3 (21%), and ≥20 in 7 (50%). Three patients experienced grade 3 or higher adverse events, all of which were myelosuppression. No patient deaths occurred. All patients, after providing informed consent, opted for postoperative maintenance immunotherapy. Conclusions: Neoadjuvant immunochemotherapy can lead to pCR in a subset of patients with locally advanced HNSCC, and this population demonstrates favorable early outcomes. In this pCR cohort, all oropharyngeal cancer patients were p16-positive, and half of those with known PD-L1 status had a CPS ≥20. Although limited by sample size and short follow-up, these findings suggest that p16 positivity and high PD-L1 expression may be features associated with achieving deep pathological response, warranting further validation in prospective studies.