title: Antibodies to the E4, E6, and E7 proteins of human papillomavirus (HPV) type 16 in patients with HPV-associated diseases and in the normal population.
abstract: In a cross-sectional study, titers of antibodies to the E4 and E7 proteins of human papillomavirus (HPV) type 16 were measured by peptide-based enzyme-linked immunosorbent assay in 1707 sera. Sera were obtained from healthy individuals (ages 1 to 95 years), from patients with HPV-associated infection (cervical intraepithelial neoplasia and cervical cancer), and from patients who were at high risk for HPV infection (attending a sexually transmitted disease clinic or referred to a colposcopist because of an abnormal Papanicolaou smear). The prevalence of anti-E7 antibodies increased with age, although the overall prevalence in the adult population was low (10.36%) compared to the frequent detection of HPV 16 DNA in the population. This suggests that only a fraction of patients infected with HPV 16 develop an anti-E7 response. The age distribution of anti-E4 antibodies showed a different pattern, i.e., the prevalence was low in the adult population (1.14%) but exceeded 20% in children and teenagers. As the specificity of the anti-E4 reaction was supported by a highly significant association with anti-E6 positivity in children's sera (p = 0.002), it was assumed that infection with HPV 16 can occur frequently early in life. As compared to healthy controls, patients at high risk for HPV infection had a significantly higher frequency (p < 0.001) of antibodies to the HPV 16 E4 protein (but not to the E6 or the E7 protein) in their sera. Therefore, we conclude that in adults E4-specific antibodies may be a marker for virus replication.
authors.affiliation: Department of Obstetrics and Gynecology, Loyola University Medical Center, Maywood, IL 60153.
authors.forename: M
authors.initials: M
authors.lastname: Müller
authors.forename: R P
authors.initials: RP
authors.lastname: Viscidi
authors.forename: V
authors.initials: V
authors.lastname: Ulken
authors.forename: J N
authors.initials: JN
authors.lastname: Bavinck
authors.forename: P M
authors.initials: PM
authors.lastname: Hill
authors.forename: S G
authors.initials: SG
authors.lastname: Fisher
authors.forename: R
authors.initials: R
authors.lastname: Reid
authors.forename: N
authors.initials: N
authors.lastname: Munoz
authors.forename: A
authors.initials: A
authors.lastname: Schneider
authors.forename: K V
authors.initials: KV
authors.lastname: Shah
mesh_terms: D017504:Adenovirus E4 Proteins / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000914:Antibodies, Viral / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology*; D030361:Papillomavirus Infections / Q000097:blood*; D014412:Tumor Virus Infections / Q000097:blood*; D002583:Uterine Cervical Neoplasms / Q000097:blood; D002578:Uterine Cervical Dysplasia / Q000097:blood
chemical_list: D017504:Adenovirus E4 Proteins; D000914:Antibodies, Viral; D009856:Oncogene Proteins, Viral