Association between postoperative radiotherapy for young-onset head and neck cancer and long-term risk of second primary malignancy: a population-based study

BACKGROUND: Second primary malignancy (SPM) represents the leading long-term cause of death among patients with index head and neck squamous cell carcinoma (HNSCC). We aimed to quantify the association between postoperative radiotherapy (PORT) and the risk of SPM development for index HNSCC among adolescent and young patients, who are particularly vulnerable to radiation-associated impacts due to their increased tissue susceptibilities and longer life expectancies. METHODS: This study was conducted using the Surveillance, Epidemiology, and End Results (SEER) database to collect the data of 5 year survivors of index young-onset HNSCC from 1975 to 2011. The outcome of interest was SPM, a new, metachronous malignancy after the index HNSCC. Standardized incidence ratios (SIRs) and excess absolute risks (EARs) were used to quantify the PORT-associated risks externally, and relative risks (RRs) were estimated by the multivariate Poisson regression analysis to quantify the PORT-associated risks internally. RESULTS: Of the included 2771 5 year survivors with index young-onset HNSCCs, the receipt of PORT (37.6%) was associated with higher risk of SPMs (RR, 1.23; 95% CI 1.07 to 1.43). PORT-associated risks were elevated for the majority of sites, including head and neck (RR, 1.19; 95% CI 0.95 to 1.50) and lung (RR, 1.67; 95% CI 1.18 to 2.34). With regarding to the subsites of head and neck, RRs were above unity in oral cavity squamous cell carcinoma (SCC) (RR, 1.68; 95% CI 1.39 to 2.03) and laryngeal SCC (RR, 1.02; 95% CI 0.73 to 1.43). A relatively greater RR was observed for patients younger than 35 years (RR, 1.44, 95% CI 0.37 to 5.57) and those diagnosed with localized diseases (RR, 1.16, 95% CI 0.9 to 1.5). PORT-associated risks were increased remarkably after 15 years of follow-up (RR, 1.24; 95% CI 0.97 to 1.58). CONCLUSIONS: An association was discovered between PORT treatment and increased long-term risk of SPM among patients with index young-onset HNSCC. The findings suggest long-term follow-up surveillance for these patients, particularly those with oral cavity SCC or laryngeal SCC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-022-03544-y.