Factors affecting outcomes in early-onset vs average-onset head and neck cancers: A multicenter retrospective database study.

Abstract

e18108 Background: The incidence of early-onset (EO) head and neck squamous cell carcinoma (HNSCC) is increasing and appears to be associated with improved survival compared with average-onset (AO) disease, suggesting potential biological differences. However, data are limited. We compared demographics, primary tumor sites, metastatic patterns, and outcomes between EO and AO HNSCC. Methods: We performed a multicenter retrospective study using the TriNetX federated, de-identified electronic medical record network. Patients with HNSCC were identified with diagnosis as the index event. EO was defined as diagnosis before age 50 and AO as age ≥51. Primary and metastatic sites were identified using ICD-O and ICD-10 codes. Propensity score matching (1:1 greedy nearest-neighbor, caliper 0.1) was performed for sex, race, primary site, HPV status, and comorbidities. Kaplan–Meier survival analysis and comparative statistics were performed within TriNetX. Results: Among 468,496 patients, 41,596 (8.9%) had EO HNSCC. EO patients were more often female (43.1% vs 29.6%), Asian (12.2% vs 7.2%), and African American (8.2% vs 7.1%), and less often White (40.4% vs 61.7%) (all p<0.0001). Primary tumors were more frequently nasopharyngeal (15.0% vs 4.8%) and parotid (7.7% vs 5.3%), and less frequently tonsillar (5.3% vs 7.6%), oropharyngeal (4.6% vs 6.2%), and base of tongue (2.0% vs 5.7%) (all p<0.0001). After matching, each cohort included 39,535 patients. Median overall survival was not reached in the EO cohort (3,450 deaths, 8.7%) and was 6,011 days in the AO cohort (7,823 deaths, 19.8%) (HR 0.49, 95% CI 0.47–0.51; p<0.0001). Stage IV disease developed less frequently in EO patients (12.6% vs 16.5%, p<0.0001). EO patients had fewer lung (3.1% vs 4.0%), lymph node (11.4% vs 13.5%), liver (1.6% vs 2.1%) all p<0.0001, and bone metastases (3.5% vs 3.7%, p=0.03), with no difference in brain metastases. There was no difference in receiving radiation treatment and those that received surgery within 6 months of diagnosis. Conclusions: EO HNSCC differs significantly from AO disease in demographics, tumor site distribution, metastatic patterns, and survival. EO disease is associated with fewer metastases and superior overall survival, suggesting distinct tumor biology and supporting the need for further mechanistic studies.