Seroprevalence of Human Papillomavirus Type 16 Infection in the United States
At least 30 genital human papillomavirus types infect the genital area, and persistent infection with high-risk HPV types is the strongest risk factor for cervical cancer. High-risk HPV types, including 16, 18, 31, 33 and 35, are found in up to 93 percent of cervical cancers worldwide, and HPV-16 accounts for 50 percent. In the current study, investigators report the results of a national seroepidemiologic survey of HPV-16 infection performed on surplus serum samples from the second phase of the third National Health and Nutritional Examination Survey. NHANES was conducted from 1991-1994 by the National Center for Health Statistics and CDC using a complex, stratified, multistage probability cluster design to select a representative sample of the U.S. population.
NHANES III oversampled children under age 5, persons age 60 and above, Mexican Americans, and blacks. Prevalence estimates were weighted to represent total U.S. population and accounted for oversampling and nonresponse to household interview and physical examination.
Of the 9,629 subjects selected to participate in the survey in the 12-59 age group, 7,476 (77.6 percent) agreed to examination; from them, 7,218 serum samples were available for testing. HPV-16-specific IgG antibody was detected by use of an HPV-16 virus-like particle ELISA.
Overall, 13 percent of study participants had antibodies to HPV-16. Seroprevalence was significantly higher in women (17.9 percent) than in men (7.9 percent), yielding a female:male prevalence ratio of 2.3. Seroprevalence was 12.5 percent among whites, 19.1 percent among blacks, and 8.9 percent among Mexican Americans. With increasing age, HPV-16 seroprevalence increased in women to 24.7 percent at ages 20-29 years and then declined to 11 percent after age 49 years. In men, seroprevalence peaked later, at ages 30-39 years (11.5 percent) and was sustained throughout older age groups.
In women, HPV-16 seropositivity was significantly associated with several variables, including age, race/ethnicity, education, alcohol use, marijuana use (ever), cocaine use (ever), ever having sexual intercourse, early age at first intercourse, number of lifetime partners, number of sex partners during the last year, HSV-2 seropositivity, and oral contraceptive use (ever). In the logistic model, age, race/ethnicity, marijuana smoking (ever), and age at first sexual intercourse were significantly associated with HPV-16 seropositivity before adding number of lifetime sexual partners into the model. However, after including number of lifetime partners in the model, marijuana smoking (ever) and age at first sexual intercourse were no longer statistically significant and were dropped from the model.
In men, HPV-16 seropositivity was significantly associated with several variables, including age, race/ethnicity, marital status, poverty index, urban residence, age at first intercourse, years of sexual activity, number of lifetime sex partners, number of sex partners during the last year, and having sex with a man. In the logistic model, variables that remained statistically significant were age, urban residence, race/ethnicity, age at first intercourse, years of sexual activity, and having sex with men. No other variables appeared to be confounders. Although age was no longer statistically significant, it appeared to be confounded with years of sexual activity.
The most likely explanation for higher HPV-16 seropositivity in women is that women and men have fundamental differences in immune response after exposure. In men, HPV infections may be more transient, and infection often involves keratinized epithelium that may be less likely than mucosal epithelium to induce humoral immune response. Anorectal mucosal exposure may be more likely to produce a detectable immune response and could contribute to the high seropositivity in MSM. The strong association between HPV-16 seropositivity and number of lifetime sex partners and no association with number of recent partners suggest seropositivity is a measure of lifetime rather than recent exposure.
"Our national data on seroepidemiology of naturally occurring HPV-16 infection," researchers concluded, "is useful to establish baseline HPV-16 seroprevalence in demographic groups, to highlight differences in humoral immune responses between men and women, and to document a high burden of infection with this single HPV type. Moreover, a system for monitoring seroprevalence over time will be valuable to assess effectiveness of vaccine programs."