Anogenital Dysplasia Research Articles

Induction of an HPV 6bL1-specific mucosal IgA response by DNA immunization

Human papillomavirus (HPV) plays a crucial role in the development of human anogenital dysplasia. To prevent infection, it is important to induce an HPV-specific mucosal immune response. We investigated whether DNA vaccination would induce an intravaginal mucosal antibody response against HPV 6bL1. New Zealand White rabbits were immunized with an HPV 6bL1 DNA vaccine by one of the three routes: muscular, vaginal, or rectal. We found that vaginal immunization of rabbits with HPV 6bL1 DNA induced 6bL1 virus-like particle-specific lgA antibodies in vaginal secretions. They were detectable until at least 14 weeks after the first immunization. The antibodies also showed neutralizing activity in a hemagglutination inhibition assay. No mucosal immune response was detected in vaginal secretions of rabbits immunized intramuscularly or intrarectally. Our data suggest that vaginal immunization with HPV 6bL1 DNA induces long-lasting IgA responses with neutralizing activity in vaginal secretions of rabbits.

Human papillomavirus infection with particular reference to genital disease.

HPV is the commonest sexually transmitted viral infection in the United Kingdom and as such poses a major public health problem. In addition to the potential physical morbidity associated with...

Condylomata acuminata of the penis progressing rapidly to invasive squamous cell carcinoma.

Introduction Condylomata acuminata are caused by human papilloma virus (HPV) infections and epidemiological and molecular-biological evidence points to an association between HPV infection and anogenital dysplasia.' Human immunodeficiency virus (HIV)...

A two-site enzyme immunoassay for quantitation of human papillomavirus type 16 particles.

A group of human papillomaviruses (HPV), in particular HPV type 16, are the major cause of anogenital dysplasias, which are precursors of anogenital cancer. The mode of transmission, extent of infectivity and natural history of infection are incompletely understood because methods to quantify shedding of viral particles have not been available. A two-site ELISA was developed to detect and quantify HPV-16 particles. Rabbits and guinea pigs were immunized with a series of peptides from the L1 and L2 capsid proteins of HPV-16. Among rabbit antipeptide sera tested for use as capture antibodies, only sera against one peptide bound detectable amounts of virus. Guinea pig antisera against several peptides were used as reporter antibodies to detect bound virus particles. If antisera against the same peptide were used both as capture antibody and reporter antibody, only intact particles were detected. Disrupted particles were quantified using antibodies against one L1 peptide as capture antibody and antibodies against other L1 peptides as reporter antibody. The lowest detectable amount of virus was 3 ng (0.06 micrograms/ml). There was no detectable cross-reaction with HPV type 6 or 11. The assay could be used both with cervical swabs in several common sample collection buffers and with surgical material solubilized in NP40-containing extraction buffers. Among 15 surgically removed condyloma acuminata, only 1 specimen was found to contain HPV-16 particles, at a concentration of 375 ng/ml (1.1 micrograms/specimen). Among 29 cervical swab samples from patients with koilocytotic atypia, 9 samples were found to contain virus. The results indicate that this assay is useful for large-scale studies on shedding of HPV particles.

Identification of B epitopes in human papillomavirus type 16 E7 open reading frame protein

Human papillomavirus (HPV) type 16 is implicated in the aetiology of anogenital dysplasia which may progress to malignancy. HPV-16 DNA is actively transcribed in cervical carcinomas, the most abundant transcripts being from the E6 and E7 early open reading frames. The E7 protein has been shown to have transforming activity in vitro. In this report we define four immunodominant B epitopes within the protein corresponding to the E7 gene, using a panel of murine monoclonal antibodies. Three epitopes are linear and lie within the N-terminal region of the molecule, and are unique to the HPV-16 E7 protein. One epitope is non-linear and presumed to be conformational. At least three of the four epitopes of the E7 protein are detectable by immunoprecipitation from an HPV-16-infected cervical carcinoma cell line. The demonstrated immunogenicity of the E7 protein allows us to deduce that this molecule may be a potential candidate for incorporation in a vaccine against cervical cancer.

Condyloma and intraepithelial neoplasia of the uterine cervix: a case-control study.

Cervical condyloma and cervical intraepithelial neoplasia are related to human papillomavirus infections, some of which may be involved in the etiology of cancer of the uterine cervix. This case-control study was designed to assess the relation of age at first sexual intercourse, number of sexual partners, and cigarette smoking to the risk of cervical condyloma and cervical intraepithelial neoplasia. Cases and controls were premenopausal women under age 50 years who had been referred for examination at the Colposcopy Clinic of Saint-Sacrement Hospital in Quebec from 1982 to 1985. These were 136 cases of histologically confirmed cervical condyloma and 247 cases of cervical intraepithelial neoplasia. The 137 controls were women without anogenital condyloma, dysplasia, or carcinoma. Information on personal characteristics and exposures of subjects was obtained by interview. Associations observed with age at first intercourse were different for condyloma and cervical intraepithelial neoplasia. Relative risk of condyloma varied little with age at first intercourse. In contrast, relative risk of cervical intraepithelial neoplasia increased as age at first intercourse decreased. For the two types of lesions, relative risk was elevated among women with more than one sexual partner and increased steadily with increasing number of cigarettes smoked per day. The association with cigarette smoking was, however, somewhat stronger for cervical intraepithelial neoplasia.