Human papillomavirus (HPV) seroprevalence and determinants of seropositivity were assessed in a 10 049-woman population-based cohort in Guanacaste, Costa Rica. Serologic responses based on VLP-based ELISA were obtained from the plasma collected at study enrollment in 1993/1994 for HPV-16 (n ¼ 9949), HPV-18 (n ¼ 9928), HPV-31 (n ¼ 9932), and HPV-45 (n ¼ 3019). Seropositivity was defined as five standard deviations above the mean optical density obtained for studied virgins (n ¼ 573). 15, 16, and 11%, respectively. Of women DNA-positive for , seropositivity was 45, 34, 51, and 28%, respectively. Peak HPV seroprevalence occurred a decade after DNA prevalence; lifetime number of sexual partners was the key determinant of seropositivity independent of DNA status and age. DNA-and sero-positive women showed the highest risk for concurrent CIN3/cancer, followed by DNA-positive, sero-negative women. British Journal of Cancer (2003) (Ho et al, 1995). The prevalence of HPV DNA therefore underestimates the cumulative incidence of infection in a population, particularly where the majority of women will not develop persistent infection or cervical neoplasia. Measurement of serum antibody to HPV capsids (or virus-like particles (VLPs)) has been demonstrated as a useful although imperfect marker of past and cumulative HPV exposure, thus complementing the assessment of HPV DNA (Kirnbauer et al, 1994;Wideroff et al, 1995Wideroff et al, , 1999Carter et al, 1996;Sasagawa et al, 1998;Touze et al, 2001).As part of a large population-based study of the natural history of HPV infection and cervical neoplasia in Guanacaste, Costa Rica, we report here the population-based seroprevalence in Guanacaste women of four oncogenic HPV types found in the majority of cervical cancers worldwide Munoz et al, 2003). The data presented document the baseline burden of HPV exposure in Guanacaste, Costa Rica. As a major objective, we determined the association of risk for concurrent diagnosis of CIN3/cancer with HPV assessed jointly by serology and PCR-based DNA testing. As only about half of all HPV-DNA-positive women are seropositive using available VLP assays (Kirnbauer et al, 1994;Le Cann et al, 1995), we also investigated determinants of seropositivity in our population. METHODS Study populationThis study was conducted in an on-going population-based cohort study of 10 049 women in Guanacaste, Costa Rica (Herrero et al, 1997;Hildesheim et al, 2001) who were enrolled in 1993 -1994 with the approval of the National Cancer Institute (NCI) and local institutional review boards; all participants provided written informed consent. Briefly, the cohort was a representative sample of the adult population based on selection by cluster sampling, with oversampling for cancer. Participation among eligible women exceeded 90%, and participants completed a risk factor questionnaire that addressed demographic, behavioural, and sexual practices. Women were screened using three cytologic and one visual test at enrollment; colposcopy referral with biopsy was perform...

Enzyme immunoassays (EIAs) for detection of serum antibodies to simian virus 40 (SV40), BK virus (BKV), and JC virus (JCV) were developed by using virus-like-particles (VLPs) produced in insect cells from recombinant baculoviruses expressing the VP1 protein of the respective virus. Rhesus macaque sera with neutralizing antibodies to SV40 showed a high level of reactivity in the SV40 VLP-based EIA, and these sera also showed lower levels of reactivity in the BKV and JCV VLP-based EIAs. Rhesus macaque sera negative for neutralizing antibodies to SV40 were negative in all three EIAs. Competitive binding assays showed that SV40 VLPs inhibited BKV reactivity. In rhesus macaque sera, high optical density (OD) values for antibodies to SV40 VLPs were correlated with high OD values for antibodies to BKV but not with high OD values for antibodies to JCV VLPs. Human sera with neutralizing antibodies to SV40 were more reactive to SV40 VLPs than human sera without neutralizing antibodies to SV40. The greater SV40 reactivities of human sera were correlated with greater reactivities to BKV VLPs but not JCV VLPs. These data suggest that cross-reactivity with BKV antibodies may account for part of the low-level SV40 reactivity seen in human sera. With their greater versatility and their suitability for large-scale testing, the VLP-based EIAs for SV40, BKV, and JCV are likely to contribute to a better understanding of the biology of these viruses.