Behavioral characteristics significantly associated with HPV-11 seropositivity included age at first sexual intercourse, lifetime number of sexual partners, and ever use of cocaine and marijuana (Table 2). Five male and 10 female respondents with no reported history of sexual intercourse were found to be HPV-11 seropositive. Almost all (n = 14) of these 15 individuals were also seropositive for another sexually transmitted infection, herpes simplex virus 2 (HSV-2). One female was of missing HSV-2 status and could not be evaluated. The seroepidemiology of HSV-2 in this population has been described in detail elsewhere.41
In the multiple logistic regression model, statistically significant predictors of HPV-11 infection included female gender, African American race, increasing number of lifetime sexual partners, less than high school education, and HPV-16 coinfection (Table 3). Urban residence and drug use did not remain significant in the final model. Socioeconomic status as measured by living below or above the poverty level marginally confounded the association between HPV-11 and race, but the difference was not statistically significant and did not affect any of the estimates. Therefore, poverty level was not included in the model. We found no other confounding or effect modification, and thus no other variables were included in the model.
This study is the first to describe the seroprevalence and distribution of HPV-11 infection in the United States. Our results indicate that the odds of HPV-11 seropositivity were over 2 times higher among females compared to males. This observed sex difference is not surprising given inherent immunologic and anatomical differences between males and females that are well known to result in differential susceptibility to most sexually transmitted infections.42 Results of a study of genital warts among NHANES participants from 1999 to 2004 by Dinh et al. indicate that “women were three times more likely to report having a history of genital warts than men,” supporting our findings.43 Moreover, seroprevalences of other genital HPVs have also been reported to be significantly higher in females compared to males.9,44 In contrast to our findings, anogenital warts24,26 have been reported to have similar sex distributions. However, the results from this study are not directly comparable to the reported prevalence of anogenital warts, particularly data derived from genital warts claims submitted by privately insured patients who may not be representative of the general US population. Our results indicate that HPV-11 seroprevalence is much higher in both male and female non-Hispanic African Americans, a racial category that is likely underrepresented in the insurance claim data.
Although our data suggest that the prevalence of HPV-11 is only slightly lower among people who reported never having sex compared to those who reported ever having sex (4.4% vs. 5.5%, respectively), these results must be interpreted with caution. Only 15 respondents seropositive for HPV-11 reported never having had sex. This small number leads to an unstable and therefore uninterpretable estimate. Moreover, upon closer examination of the 15 respondents, we found that at least 14 were herpes simplex virus type 2 seropositive. Presence of 2 different sexually transmitted infections in this group may be an indication that the respondents either did not understand the sexual history questions or did not feel comfortable answering questions related to sexual history.
There was a significant trend for increasing HPV-11 seroprevalence up to 39 years of age in females and 49 years in males. Thereafter, HPV-11 appeared to decline although the downward trend was not found to be significant. This observed pattern suggests that the risk of HPV-11 infection begins as a person becomes sexually active and increases through the third decade in females and the fourth decade in males, after which it appears to gradually decline. Although we did not find significant decreases in seroprevalence in either males or females, the observed decrease may either represent a cohort effect such that older persons may have been less likely to be exposed to HPV-11 or a loss of antibodies to the virus over time.
As expected, we found the overall prevalence of HPV-11 (4.7%) to be lower than that previously reported for HPV-16 in the same population (13%).9 However, results of this study suggest that HPV-11 is a common sexually transmitted infection.
Other factors that were found to be independently associated with HPV-11 in the current study include nonwhite race (especially non-Hispanic African American race) and number of lifetime sex partners. About the latter, the data indicate that HPV-11 seroprevalence increases commensurate with increasing number of lifetime sex partners.
This study has some limitations. First, sexual behavior and other risk factors are self-reported and thus subject to reporting bias, including underreporting of risk factors. Second, use of serologic testing may underestimate infection with HPV-11 given the low rate of seroconversion after natural infection. In addition, while type-specific VLPs were used in the ELISA, cross-reactivity between closely related types, particularly HPV-6, cannot be excluded. Despite limitations, however, serology is currently the best approach to ascertaining exposure in the population. Finally, due to lack of HPV-6 VLPs required for testing specimens, we were unable to evaluate the seroprevalence of HPV-6 in this population.
The results of this study represent the most comprehensive picture of HPV-11 infection in the United States to date. Importantly, this study provides baseline data on the prevalence of HPV-11 before availability of a prophylactic vaccine against HPV 6, 11, 16, and 18, thereby allowing better assessment and evaluation of the impact of this vaccine on this common infection.
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