Background A vaccine is available to prevent human papillomavirus (HPV) 6, 11, 16 and 18; in the prevaccine era, seropositivity to vaccine types is a measure of natural exposure.

Methods We describe HPV seropositivity in the USA among 14–59-year-olds using the 2003–2006 National Health and Nutrition Examination Surveys.

Results Seropositivity to HPV 6, 11, 16 and 18 was 17.5%, 6.8%, 15.1% and 5.9%, respectively, among women, and 7.0%, 2.4%, 5.2% and 1.5%, respectively, among men. Overall in both sexes, seropositivity was 22.5% for any vaccine type (31.8% in women and 12.9% in men), but substantially lower for three or more types (1.7% overall, 2.8% in women and 0.6% in men).

Conclusions Almost a quarter of the participants were seropositive to any HPV vaccine type but few were seropositive to at least three vaccine HPV types in the prevaccine era. Further study is needed to assess if seropositivity would be useful as a biological marker of vaccination.