Abstract B027: Early-Onset Head and Neck Cancer: Implications for Risk Stratification and Survival

Abstract Introduction: Head and neck cancers (HNC) represent nearly 4% of all cancers in the U. S. , with established risk factors including tobacco, alcohol, and human papillomavirus (HPV) infection. While the mean age at diagnosis is 64 years, ∼20% of cases occur in adults 55, and 4–6% in those 40. Reports suggest rising incidence of early-onset HNC. A subset of younger patients without previously established risk factors indicates alternative etiologies. We aimed to describe demographic determinants of early-onset HNC and evaluate survival differences by age of onset. Methods: We analyzed data from the National Cancer Database (NCDB) from 2004–2022, including adults with HNC diagnosis codes (n=816, 747). The NCDB is a clinical registry with data abstracted from patient records at Commission on Cancer–accredited facilities. Multivariable logistic regression estimated adjusted odds ratios (aORs) for early-onset HNC (50 years) vs. traditional onset (≥50 years), adjusting for sex, race, ethnicity, Great Circle distance, Charlson-Deyo comorbidity (CDCC) score, and HPV-tumor status. Distance was analyzed in quartiles. Cox proportional hazards models estimated adjusted hazard ratios (aHRs) by age of onset, adjusting for the same variables plus tumor stage. Results: In adjusted models, several demographics were significantly associated with early-onset HNC. Males were linked to slightly lower odds than females (aOR: 0. 92, 95% CI: 0. 86–0. 99). White adults had reduced odds compared to Black adults (aOR: 0. 52, 95% CI: 0. 48–0. 57), as did Non-Hispanic vs. Hispanic adults (aOR: 0. 56, 95% CI: 0. 51–0. 63). Greater distance from reporting facility showed a dose-response association, with higher quartiles linked to increased odds (Quartile 4 vs. 1 aOR: 1. 25, 95% CI: 1. 15–1. 35). Higher comorbidity burden was associated with lower odds (CDCC 1 aOR: 0. 54, 95% CI: 0. 49–0. 59; CDCC 2 aOR: 0. 28, 95% CI: 0. 23–0. 34; CDCC 3 aOR: 0. 29, 95% CI: 0. 23–0. 35). HPV-positive tumors were more common in early-onset cases (aOR: 1. 25, 95% CI: 1. 17–1. 33). In survival analyses, adults aged 40–49 had improved survival vs. those ≥50 (aHR: 0. 89, 95% CI: 0. 82–0. 97), while survival among those 18–39 was similar (aHR: 0. 96, 95% CI: 0. 78–1. 19). Male sex (aHR: 0. 95, 95% CI: 0. 91–0. 99) and White race (aHR: 0. 94, 95% CI: 0. 89–0. 99) were associated with modest survival benefits. Increasing comorbidity burden was linked to worse survival (CDCC 1 vs. 0 aHR: 1. 09, 95% CI: 1. 04–1. 14; CDCC 2 vs. 0 aHR: 1. 19, 95% CI: 1. 11–1. 27; CDCC 3 vs. 0 aHR: 1. 24, 95% CI: 1. 16–1. 33), as was advanced stage. HPV-positive tumors were associated with improved survival (aHR: 0. 87, 95% CI: 0. 84–0. 91). Conclusions: These findings underscore the need to investigate non-traditional risk factors and biological mechanisms underlying early-onset HNC, especially in subgroups not explained by conventional exposures. Citation Format: Morgan C. Byrd, Joab O. Odera, Trisha Kibugi, Rong Jiang, Tammara Watts, Nosayaba Osazuwa-Peters. Early-Onset Head and Neck Cancer: Implications for Risk Stratification and Survival abstract. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31 (23Suppl): Abstract nr B027.