Identification of human papillomavirus seroconversions

Abstract

The temporal relationship between primary genital human papiUomavirus (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 ofHPV 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.

Sexual behaviour and papillomavirus exposure in cervical intraepithelial neoplasia: a population-based case-control study.

“…For HPV-16, this is in good agreement with previous studies that have mostly reported sensitivities of 50 % or greater (Kirnbauer et al, 1994 ;Chua et al, 1996 ;de Gruijl et al, 1997 ;Dillner et al, 1996 ;Wideroff et al, 1995 ;Wikstro$ m et al, 1995). For HPV-18 and -33 seropositivity, the present study provides the first large-scale evaluation of sensitivity and type-specificity, which were found to be similar to HPV-16.…”

“…Presence of cervical HPV DNA is usually transient Evander et al, 1995 ;Hildesheim et al, 1994), is correlated with recent partner change (Hildesheim et al, 1993) and shows declining prevalence with age (Melkert et al, 1993). In contrast, presence of HPV antibodies in serum is also found after clearance of viral DNA (Wikstro$ m et al, 1995 ;Carter et al, 1996), the antibody levels persist on prolonged follow-up (af Geijersstam et al, 1998) and there is no consistent association of HPV seropositivity with age (Chua et al, 1996 ;Dillner et al, 1996 ;Wikstro$ m et al, 1995 ;. Also, HPV seropositivity is not related to recent partner change, but strongly dependent on lifetime number of sexual partners (linear increase of seroprevalences with about 4 % per partner) (Dillner et al, 1996 ;Wideroff et al, 1996), arguing that seroprevalences are preferable as markers of lifetime cumulative HPV exposure (Olsen et al, 1997).…”

Determinants of human papillomavirus 16 serological conversion and persistence in a population-based cohort of 10 000 women in Costa Rica

“…Although IgG seroconversion against HPV-16 has been reported within 6 -12 months of infection (Wikstrom et al, 1995;Carter et al, 2000), the duration of serologic detection (e.g. being seropositive) remains unclear (Stone et al, 2002).…”

Serological and T-helper cell responses to human papillomavirus type 16 L1 in women with cervical dysplasia or cervical carcinoma and in healthy controls.

“…So-called ' falsepositives ' may have occurred because the PCR technique has failed to detect HPV DNA in an infected individual due to sampling error or because the individual was infected at a site other than that which was biopsied. The absence of a detectable ELISA response may be explained by the possibility that the serological response may not peak until days or weeks after infection has been established and there is some evidence that the latter is true (Wikstrom et al, 1995). Alternatively, the B cell response may be sustained after the virus infection has been cleared because antigen is retained in the regional lymph nodes, for example.…”