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.