OBJECTIVES: We quantified the excess risk of synchronous second primary cancers (SPC) versus metachronous SPCs among patients with an index head and neck squamous cell carcinoma (HNSCC).

METHODS: This was a population-based cohort study of 109,512 patients with HNSCC in the Surveillance, Epidemiology, and End Results registry (2000-2014). Synchronous SPCs were defined as distinct, solid cancers diagnosed ≤6 months; and metachronous SPCs as distinct, solid cancers diagnosed >6 months of the index HNSCC. SPC risk was quantified by using standardized incidence ratios (SIRs), and excess absolute risk (EAR) per 10,000 person-years at risk (PYR).

RESULTS: Among the 109,512 patients with an index HNSCC, 3,151 synchronous SPCs were observed, leading to a relative risk of SIR=4.64 (95% CI: 4.48–4.80) and excess risk (EAR of 468.01 excess cases per 10,000 PYR). On the other hand, 11,637 metachronous SPCs were observed, leading to a relative risk of SIR=2.17 (95% CI: 2.14–2.21) and excess risk (EAR of 160.51 excess cases per 10,000 PYR). The highest relative risk of synchronous SPCs was observed for gum (SIR=58.48; 95% CI: 49.55–68.55); hypopharynx (SIR=58.15; 95% CI: 46.82–71.40); and floor of mouth (SIR=46.03; 95% CI: 34.86–59.64). The excess burden of disease was highest for lung (EAR=171), thyroid (EAR=50), and tonsil (EAR=35), excess cases per 10,000 PYR. The highest relative risk of metachronous SPCs was observed for gum (SIR=29.68; 95% CI: 27.37–32.13); floor of mouth (SIR=26.34; 95% CI: 23.11–29.89); and tongue (SIR=17.47; 95% CI: 16.34–18.65). The excess burden of disease was highest for lung (EAR=72), tongue (EAR=22), gum (EAR=15), and esophagus (EAR=10) excess cases per 10,000 PYR.

CONCLUSIONS: Both synchronous and metachronous SPC risks were in the head and neck, lung and esophagus even though the risks were higher for synchronous SPCs. The findings from the current study may inform care strategies among HNSCC cancer survivors.