HPV-positive oropharynx cancer is frequently characterized as a disease of never-smokers due to higher HPV prevalence in oropharynx tumors among never-smokers than ever-smokers. We sought to estimate the burden (incidence rates and case counts) of HPV-positive oropharynx cancers among never, former, and current smokers in the US population by combining data from several sources.

We decomposed the SEER population-level incidence of oropharynx cancers into rates among never-, former-, and current-smokers using a formula based upon rate ratios (RR) for the smoking-oropharynx cancer association (NIH-AARP cohort study) and smoking prevalence in the U.S. population (NHANES 2007/2008). These rates were multiplied by smoking strata-specific HPV prevalence in oropharynx cancer patients (RTOG0129) to estimate incidence of HPV-positive and HPV-negative oropharynx cancers, which were applied to the US population of smokers to calculate annual case counts. Analyses were conducted overall and gender-stratified.

The incidence of HPV-positive oropharynx cancers was significantly higher among ever versus never-smokers in the US population aged 20+ years during 2007/2008 (RR=1.81; 95%CI=1.32-2.47), including significantly higher incidence in current smokers (RR=2.26; 95%CI=1.60-3.21) and former smokers (RR=1.38; 95%CI=1.02-1.85). Of the estimated 6677 (5418 in men and 1259 in women) annually incident HPV-positive oropharynx cancers in the U.S during 2007/2008, 63.3% arose among ever smokers and 36.7% among never-smokers (p<0.001). In both men and women, incidence rates and annual cases of HPV-positive oropharynx cancers were higher in ever smokers versus never smokers.

The population-level burden of HPV-positive oropharynx cancers is significantly higher among ever-smokers than never-smokers in the U.S.