The nature and pathogenesis of inverted papilloma of the nose and paranasal sinuses are debated. Evidence suggesting a viral association is controversial, and epidemiological evidence has pointed to tobacco smoking as a potential etiologic factor. A retrospective regional cohort of 197 patients with sinonasal papilloma was compared with a cohort of 1583 patients with nasal polyps showing a similar distribution by age and sex. All instances of head-and-neck carcinoma diagnosed in both cohorts during a 38-year calendar period were culled from the regional cancer registry, the incidence rate ratio was computed (papilloma:polyp, on tumors detected at the time of or prior to the index diagnosis), and the clinical details were obtained. Nine instances of oral or laryngeal squamous-cell carcinoma, all in men, were identified in the papilloma cohort, and 7 labial, oral or laryngeal carcinomas (2 in women) in patients with polyps. In addition, 5% of the papillomas progressed to sinonasal carcinoma, including 2 cases among those with other primary head-and-neck carcinomas. The incidence-rate ratio for non-sinonasal head-and-neck carcinoma was 12.8 (95% Cl, 3.7 to 50; p < 0.0001), Among the papilloma patients with oral/laryngeal carcinoma, 8 smoked tobacco. Inverted sinonasal papilloma is associated with an increase in non-sinonasal head-and-neck carcinoma, and tobacco may be a causative link. (C) 2000 Wiley-Liss, Inc.