title: High prevalence of serum antibodies to Ras and type 16 E4 proteins of human papillomavirus in patients with precancerous lesions of the uterine cervix.
abstract: Serum samples from 38 healthy women and 55 women with different types of cervical lesions were investigated for the presence of antibodies to Ras and against E4 and E7 proteins of human papillomavirus type 16 (HPV-16). Our results showed that anti-E7 antibodies were closely associated with cervical cancer (75%), as previously reported. Interestingly, E4 antibodies showed higher prevalence in condyloma lesions (79%; 11/14) than in cervical cancer (60%; 12/20). We also identified 11% (4/38) of healthy individuals as positive for E4 antibodies, which suggests an early immune recognition of this protein. Patients with condyloma and cervical intraepithelial neoplasia (CIN) also showed higher prevalences of Ras antibodies (approximately 40%) than cervical cancer patients (10%; 2/20). By sequencing part of the ras genes and using different Ras antigens, we showed that serum antibodies from patients were not directed to a Ras mutation, since wild-type cHa-Ras protein was recognized by these antibodies. In addition, patients positive for Ras antibodies (94%) were also positive for E4 antibodies, suggesting an association between these. The high prevalence of antibodies against Ras and E4 proteins in pre-malignant lesions opens the possibility of using both antibodies as early markers for potential cervical cancer patients.
authors.affiliation: Centro de Investigaciones Sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México.
authors.forename: A
authors.initials: A
authors.lastname: Pedroza-Saavedra
authors.forename: A
authors.initials: A
authors.lastname: Cruz
authors.forename: F
authors.initials: F
authors.lastname: Esquivel
authors.forename: F
authors.initials: F
authors.lastname: De La Torre
authors.forename: J
authors.initials: J
authors.lastname: Berumen
authors.forename: P
authors.initials: P
authors.lastname: Gariglio
authors.forename: L
authors.initials: L
authors.lastname: Gutiérrez
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D002584:Cervix Uteri / Q000821:virology; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D011905:Genes, ras; D006801:Humans; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology* / Q000378:metabolism; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000821:virology; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000276:immunology*; D014412:Tumor Virus Infections / Q000276:immunology / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000276:immunology*; D018631:ras Proteins / Q000276:immunology*
chemical_list: D000906:Antibodies; D000914:Antibodies, Viral; D004279:DNA, Viral; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; C069119:oncogene protein E4, Human papillomavirus type 16; C059731:oncogene protein E7, Human papillomavirus type 16; D018631:ras Proteins