Characterization of the humoral immune response to genital papillomaviruses.

Abstract

Human papillomaviruses (HPVs) have been detected in a wide range of proliferative lesions of squamous epithelium. A number of HPV types are associated with lesions of the genital tract. Some types (HPV types 6 and 11) are detected frequently in benign genital warts (condylomata acuminata); other types (HPV types 31, 33, 42 and others) are associated with dysplastic lesions of the uterine cervix; and certain HPV types (HPV types 16 and 18) are found in a high proportion of squamous cell carcinomas of the cervix and vulva. However, all of these HPV types have been detected also in normal epithelium. To date, investigators have relied primarily upon the detection of viral DNAs in clinical specimens as evidence of HPV infections. Such assays cannot determine whether past infections with HPVs have occurred which have subsequently resolved. Latent infections and current infections might also evade detection because of sampling errors or because of suboptimal sensitivity of DNA detection methods. Efforts to develop HPV serological assays have been hampered by the lack of appropriate viral antigens, since HPVs cannot be propagated in tissue culture and virions are not abundant in infected human tissues. Using HPV-encoded proteins expressed in Escherichia coli, we developed assays to measure human antibodies that react with HPV proteins. Human antibodies to late gene products (L1 and L2) of genital-type HPVs were more prevalent than antibodies to early gene products. However, approximately 15% of sera contained antibodies that reacted with the HPV16 E7-encoded protein, a gene product that has been implicated in HPV16-mediated cellular transformation. The human antibodies appeared to be type or "serotype" specific, because the antibodies did not cross-react with homologous proteins encoded by other HPV types. Antibodies to proteins encoded by HPV types 6 or 11 were detected in approximately 70% of adults, while antibodies to proteins encoded by HPV type 16 were found in approximately 50% of adults. Antibody prevalence was not associated with measures of sexual activity. There was also no significant difference between the prevalence of antibodies to HPV types 6 or 16 proteins in children when compared to the antibody prevalence in sexually active adults. These results suggest that infections by genital HPV types are widespread and frequently cause clinically inapparent infections. The viruses have a broad tropism for mucosal epithelium and are likely to be acquired by other modes, as well as by sexual transmission.