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Background: Oral human papillomavirus type-16 (HPV16) infection is a risk factor for oropharyngeal cancer. We examined oral HPV infection among healthy men.Methods: Oral rinse/gargle specimens and questionnaire data were collected from 1,688 healthy men aged 18 to 74 (median ¼ 31 years), from the United States, Mexico, and Brazil. HPV16,18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59, and noncarcinogenic HPV types were detected using Roche Linear Array.Results: Oral HPV DNA was detected in 67 of 1,680 (4.0%, 95% CI ¼ 3.1%-5.0%) b-globin-positive specimens; carcinogenic HPVs were detected in 1.3% (95% CI ¼ 0.8%-2.0%; n ¼ 22) and HPV16 was the most commonly detected carcinogenic HPV type (0.6%, 95% CI ¼ 0.2%-1.1%; n ¼ 10). The prevalence of oral HPV infection was similar by country except for HPV55, which had notably higher prevalence in Mexico (3.0%) than Brazil (0%) or the United States (0.2%). Oral HPV prevalence nonsignificantly increased over increasing age categories (P trend ¼ 0.096). The strongest predictor of oral HPV was current tobacco use, which increased the odds 2.5-fold (95% CI ¼ 1.4-4.4). Oral sexual behaviors were not associated with oral HPV infection.Conclusions: Oral HPV16 infection was rare in healthy men, especially at younger ages, and was positively associated with current tobacco use.Impact: Oral HPV appears to be about 10-fold less prevalent than infection at genital sites in men (4% vs. $40%, respectively). It remains unclear whether this reflects reduced exposure or if the oral region is more resistant to HPV infection compared with anogenital sites. Cancer Epidemiol Biomarkers Prev; 20(1); 172-82. Ó2011