Antibiotic Use and Immune Checkpoint Inhibition in Head and Neck Squamous Cell Carcinoma

BACKGROUND: The clinical relevance of antibiotic exposure on immune checkpoint inhibitor (ICI) efficacy in head and neck squamous cell carcinoma (HNSCC) is not well characterized. METHODS: This retrospective study included patients with recurrent/metastatic HNSCC treated between 2015 and 2025. Cox proportional hazards and Kaplan-Meier method modeled overall survival (OS). RESULTS: Of 316 patients (median age 68 years, 70.9% male), primary tumor site was 40.5% oral cavity, 34.8% oropharynx, 14.9% sinonasal/nasopharynx, 9.8% hypopharynx/larynx. One hundred and forty-eight (46.8%) patients received antibiotics surrounding ICI. Antibiotics were associated with decreased OS (HR = 1.53, 95% CI 1.15-2.04). On multivariable analysis, while intravenous route of administration and spectrum of antibiotic activity were not risk factors, oral cavity site (HR = 1.72, 95% CI 1.07-2.76), ECOG 2-4 (HR = 2.78, 95% CI 1.70-3.67), PD-L1 CPS < 1 (HR = 3.16, 95% CI 1.79-5.04), and number of antibiotic classes (HR = 1.37, 95% CI 1.18-1.59) independently predicted decreased OS. CONCLUSIONS: Antibiotic exposure was associated with decreased survival in HNSCC treated with ICI; however, future studies are needed to evaluate potential mechanistic etiologies underlying this association.