Time‐varying association of second primary malignancy and long‐term survival outcomes in patients with head and neck cancer

A high risk of developing second primary malignancy (SPM) has been reported among head and neck cancer patients. Here, we aimed to statistically quantify the impact of SPM development on the survival of head and neck cancer patients. Our study was conducted using the Surveillance, Epidemiology and End Results database to collect the data of 48 316 patients who received curative surgical resection for initial primary head and neck squamous cell carcinoma (IP‐HNSCC) in 1975 to 2019. SPM diagnosis was treated as a time‐varying covariate and multivariable Cox regression analysis was conducted to estimate the association between SPM development and survival, overall or by the subsite of IP‐HNSCC. Of the included patients, 11 238 patients (23.3%) developed SPM during the follow‐up period. A significant reduction in survival was observed among patients with SPM (hazard ratio [HR] for overall survival, 3.30; 95% confidence interval [CI]: 3.20‐3.41). The impact of SPM development on reduced survival was more significant in patients with localized IP‐HNSCC vs regional IP‐HNSCC (HROS, 3.41; 95% CI: 3.24‐3.6 vs HROS, 3.18; 95% CI: 3.05‐3.31; P for interaction