The temporal relationship between primary genital human papillomavirus (HPV) infections and the induction of antibodies against viral antigens has not been established. In order to address this question we studied a cohort of 110 women and 48 men with multiple heterosexual partners, who were followed for 220 person-years during which they made 583 visits to the sexually transmitted diseases clinic of the Amsterdam Public Health Service. At each visit spatula or brush samples from multiple anogenital and oral sites were collected for HPV DNA analysis by PCR. Serum samples were also collected and analysed for serological reactivity to peptides derived from the L1, L2 and E2 regions of HPV types 6, 16 and 18 as well as to bovine papillomavirus and HPV-16 virus-like particles. Seroconversions for at least three antigens were found among 16/158 patients. Of these, 10/16 were HPV-positive and in 5/16 cases seroconversions occurred concomitantly with the detection of HPV DNA. Analysis of participants who were HPV-negative at entry, but became HPV DNA-positive during follow-up revealed that antibodies against several HPV antigens were regularly induced at the time of a new HPV infection, in particular the IgG responses against HPV-16 virus-like particles and against the HPV-16 E2-derived peptide 245. Whereas the responses induced among the women with new HPV-16 infection tended to continuously increase, the responses among the men with any type of new HPV infection were mostly transient and disappeared during follow-up. In conclusion, we find that antibody responses to multiple viral antigens are often induced following the detection of genital HPV infection, that the type-specificity of the response is limited and that transient responses are common.


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