Immune Checkpoint Inhibitors and Laryngological Outcomes in Patients with Non-Head and Neck Cancer

Objectives As immune checkpoint inhibitor (ICI) utilization increases in cancer treatment, immune-related adverse events continue to be recognized. Voice, swallowing, and oral dysfunction substantially impair quality of life and treatment tolerance in cancer patients, but the laryngological risks of ICI therapy remain unclear. We compared outcomes for these functions after ICI versus non-ICI antineoplastic therapies. Methods Using the TriNetX research network, we identified adults with non-head and neck malignancies treated with ICIs versus non-ICI systemic antineoplastics. To isolate off-target adverse events from the effects of cancer and its treatment, both cohorts excluded prior head and neck malignancy, laryngectomy or pharyngectomy, and head and neck radiotherapy. Cohorts were matched 1:1 on demographics, malignancy subtype, autoimmune conditions, and pertinent comorbidities. Incident laryngeal diagnoses were assessed at 6 months, 1 year, and 5 years after treatment initiation using hazard ratios (HR) from Cox proportional hazards regressions. Results After matching, 123,628 patients remained in each cohort with all covariates well balanced. ICI exposure showed significantly higher hazards of voice disturbance (6 months: HR 1.59, 95% CI 1.44–1.75; 1 year: 1.61, 1.48–1.74; 5 years: 1.43, 1.35–1.52), vocal fold paralysis (6 months: 1.31, 1.13–1.51; 1 year: 1.37, 1.21–1.54; 5 years: 1.44, 1.30–1.58), xerostomia (6 months: 2.52, 2.29–2.78; 1 year: 2.65, 2.45–2.87; 5 years: 2.33, 2.19–2.48), dysphagia (6 months: 1.35, 1.29–1.41; 1 year: 1.44, 1.38–1.49; 5 years: 1.47, 1.43–1.51), and oral mucositis (6 months: 1.25, 1.18–1.31; 1 year: 1.41, 1.34–1.47; 5 years: 1.52, 1.46–1.58). Laryngospasm was elevated significantly with ICI exposure at 5 years (HR 1.53, 95% CI 1.09–2.13). Acute and chronic laryngitis, laryngeal edema, and chronic pharyngitis did not differ significantly at any interval. Conclusions ICI initiation was associated with elevated hazards of voice, oral, and swallowing dysfunction across acute and long-term intervals. These adverse effects warrant consideration in pretreatment counseling and goals-of-care discussions, and clinicians should evaluate new voice, oral, or swallowing complaints promptly throughout ICI treatment.