Incidence and pattern of second primary malignancies in patients with index oropharyngeal cancers versus index nonoropharyngeal head and neck cancers

BACKGROUND A recent review of the Surveillance, Epidemiology, and End Results registry suggested that patients with index squamous cell carcinoma (SCC) of the oropharynx (SCCOP) are less likely to develop second primary malignancies (SPM) than patients with index SCC of nonoropharyngeal sites (oral cavity, larynx, hypopharynx). The objectives of this study were to determine the impact of index primary tumor site on SPM risk and to explore factors that potentially affect this risk within a large, prospectively accrued cohort of patients with index SCC of the head and neck (SCCHN). METHODS A cohort of 2230 patients with incident SCCHN was reviewed for development of SPM. Kaplan-Meier analysis, log-rank testing, and Cox proportional hazards models were used to detect the impact of various factors, including index tumor site, on SPM risk. RESULTS The SPM rate was lower for patients with index SCCOP than for patients with index nonoropharyngeal cancer (P <.001). Among patients with SCCOP, former smokers had a 50% greater risk of SPM, and current smokers had a 100% greater risk of SPM than never-smokers (P_trend =.008). Also among patients with SCCOP, those with the classic SCCHN phenotype had an SPM risk similar to that of patients with index nonoropharyngeal cancers; those with a typical human papillomavirus phenotype had a very low SPM risk. SPM most commonly occurred at nontobacco-related sites in patients with index SCCOP and at tobacco-related sites in patients with index nonoropharyngeal cancers. CONCLUSIONS In patients with SCCHN, index cancer site and smoking status affect the risk and distribution of SPM.