The trends in head and neck cancer incidence and smoking prevalence are reviewed, discussing where such trends parallel but also how and why they may not. In the U.S., public health efforts at tobacco control and education have successfully reduced the prevalence of cigarette smoking, resulting in a lower incidence of head and neck cancer. Vigilance at preventing tobacco use and encouraging cessation should continue, and expanded efforts should target particular ethnic and socioeconomic groups. However, an unfortunate stagnation has been observed in oropharyngeal cancer incidence and likely reflects a rising attribution of this disease to oncogenic human papillomavirus, in particular type 16 (HPV-16). For the foreseeable future, this trend in oropharyngeal cancer incidence may continue, but with time the effects of vaccination of the adolescent and young adult female population should result in a lower viral prevalence and hopefully a reduced incidence of oropharyngeal cancer. To hasten the reduction of HPV-16 prevalence in the population, widespread vaccination of adolescent and young adult males should also be considered. Cancer 2007. © 2007 American Cancer Society.