Background: Patients with head and neck squamous cell carcinoma (HNSCC) are at significantly elevated risk of second primary malignancies (SPM), most commonly within the head and neck, lung, and esophagus (HNLE). Our objectives were to quantify the excess risk of SPM across all anatomic sites in which SPM risk is meaningfully elevated, including non-HNLE sites, in a large cohort of US patients.
Methods: Population-based analysis of 75,087 patients with HNSCC in the SEER program, quantifying excess SPM risk by integrating relative (standardized incidence ratio; SIR) and absolute (excess absolute risk per 10,000 person-years at risk; EAR) statistics.
Results: In HNSCC patients, the SIR of a second primary solid cancer was 2.2 (95% CI 2.1-2.2), corresponding to EAR of 167.7 additional cases per 10,000 person-years at risk. Over 1 year, 60 patients would need to be followed to observe one excess SPM. Lung cancer burden was most markedly elevated in absolute terms (EAR = 75.2), followed by HN (EAR = 59.8), esophageal (EAR = 14.2), and colorectal (EAR = 4.3) cancers. Lesser but significant excess risks were also observed for cancers of the bladder, liver, stomach, pancreas, kidney, salivary glands, nasopharynx, uterine cervix, and lymphoma.
Conclusions: Data from a large population-based US cohort reveals that HNSCC patients experience markedly excess risk of SPM, predominantly in the HNLE sites. Furthermore, the risk of SPM is also meaningfully elevated, although to a lesser degree, in multiple other tobacco-associated sites.