A cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) 2009–2010 estimated the prevalence of oral human papillomavirus (HPV) infection in the U.S. population aged 14–69 years. The overall prevalence was 6.9% (95% CI, 5.7%–8.3%), with 1.0% of cases being HPV type 16. The prevalence of oral HPV infection showed a bimodal pattern with peaks in individuals aged 30–34 years (7.3%) and 60–64 years (11.4%). Men had a significantly higher prevalence than women (10.1% vs 3.6%, P<.001). Oral HPV infection was more common among individuals with a history of sexual contact (7.5% vs 0.9%, P<.001) and increased with the number of sexual partners and daily cigarette smoking. In multivariable models, age, sex, number of sexual partners, and current smoking intensity were independently associated with oral HPV infection. The study found that oral HPV infection is predominantly sexually transmitted, with higher prevalence among sexually experienced individuals and those with more sexual partners. The prevalence of oral HPV infection was higher among men than women, consistent with higher rates of HPV-positive oropharyngeal squamous cell carcinomas (OSCC) in men. The bimodal age pattern was most evident for high-risk HPV infections, suggesting an association with persistence. The study also noted that the prevalence of oral HPV infection was higher among current smokers and heavy alcohol drinkers, and that smoking was more strongly associated with oral HPV infection in women than in men. The study highlights the importance of understanding the epidemiology of oral HPV infection, as it is a significant cause of oropharyngeal cancer. The findings suggest that modifiable risk factors such as smoking and sexual behavior play a key role in the transmission and persistence of oral HPV infection. The study also notes that the prevalence of oral HPV infection is lower than that of genital HPV infection, and that the incidence of HPV-positive OSCC has increased significantly in the U.S. over the past three decades, particularly among men. The study recommends further research to understand the natural history of oral HPV infection and to develop effective prevention strategies, including HPV vaccination. The study also emphasizes the need for targeted secondary prevention strategies given the rising incidence of HPV-positive OSCC.A cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) 2009–2010 estimated the prevalence of oral human papillomavirus (HPV) infection in the U.S. population aged 14–69 years. The overall prevalence was 6.9% (95% CI, 5.7%–8.3%), with 1.0% of cases being HPV type 16. The prevalence of oral HPV infection showed a bimodal pattern with peaks in individuals aged 30–34 years (7.3%) and 60–64 years (11.4%). Men had a significantly higher prevalence than women (10.1% vs 3.6%, P<.001). Oral HPV infection was more common among individuals with a history of sexual contact (7.5% vs 0.9%, P<.001) and increased with the number of sexual partners and daily cigarette smoking. In multivariable models, age, sex, number of sexual partners, and current smoking intensity were independently associated with oral HPV infection. The study found that oral HPV infection is predominantly sexually transmitted, with higher prevalence among sexually experienced individuals and those with more sexual partners. The prevalence of oral HPV infection was higher among men than women, consistent with higher rates of HPV-positive oropharyngeal squamous cell carcinomas (OSCC) in men. The bimodal age pattern was most evident for high-risk HPV infections, suggesting an association with persistence. The study also noted that the prevalence of oral HPV infection was higher among current smokers and heavy alcohol drinkers, and that smoking was more strongly associated with oral HPV infection in women than in men. The study highlights the importance of understanding the epidemiology of oral HPV infection, as it is a significant cause of oropharyngeal cancer. The findings suggest that modifiable risk factors such as smoking and sexual behavior play a key role in the transmission and persistence of oral HPV infection. The study also notes that the prevalence of oral HPV infection is lower than that of genital HPV infection, and that the incidence of HPV-positive OSCC has increased significantly in the U.S. over the past three decades, particularly among men. The study recommends further research to understand the natural history of oral HPV infection and to develop effective prevention strategies, including HPV vaccination. The study also emphasizes the need for targeted secondary prevention strategies given the rising incidence of HPV-positive OSCC.