Serological responses to HPV 16 in cervical dysplasia and neoplasia: Correlation of antibodies to E6 with cervical cancer

Abstract

Sera from patients with cervical cancer, cervical intraepithelial neoplasia (CIN) and non-genital cancers, and from healthy individuals, were investigated for antibodies to human papilloma virus (HPV) early proteins E4, E6 and E7 and the major capsid protein LI by Western blot analysis of recombinant HPV proteins. There was a significantly higher prevalence of sera with antibodies to E6 in cervical cancer patients than in healthy individuals or in CIN or non-genital-cancer patients. Antibodies to E7 were detected in 25% of cervical-cancer patients, which is significantly higher than in HPV-associated cervical lesions or in control populations, but not significantly different from the incidence in patients with non-genital cancers. Antibodies to LI were found more frequently in CIN, while antibodies to E4 had a similar prevalence in cervical-cancer, cervical-dysplasia and non-genital-cancer groups, with 24% in the controls. The inability to detect antibodies to E6 and E7 in the majority of cervical-cancer patients limits the application of this methodology to the monitoring of HPV infection and the development of cervical cancer. However, the latter approach may be useful in combination with other assay systems which allow detection of different, including conformational, epitopes of HPV E6 and/or E7 recombinant proteins.

Antibodies against linear and conformational epitopes of the human papillomavirus (HPV) type 16 E6 and E7 oncoproteins in sera of cervical cancer patients

“…With the exception of the E6-specific peptide ELISA, by all assays the antibody-positivity rate was shown to be higher within the sera of the HPV 16 DNA positive patients as compared to the negatives. In all instances, however, there is a substantial number of positive sera also within the group of HPV 16 negative patients (see Table 1) as also reported by others [6,12]. It is not clear whether the presence of cross-reacting antibodies directed against the E6 or E7 proteins of other HPV types accounts for the low type-specificity of the serological assays which were used in this study.…”

Serological and molecular evidence of rhesus papillomavirus type 1 infections in tissues from geographically distinct institutions

“…Fax + 1 612 626 7031. e-mail ron@molbio.cbs.umn.edu These studies have involvedproducing various gene products of papillomaviruses in bacterial expression vectors for use in Western blot assays of humoral antibodies (Barber et al, 1992;Ghosh et al, 1993;Jenison et al, 1990Jenison et al, , 1991Jochmus-Kudielka et al, 1992;Kochel et al, 1991). The genes useful in such studies include E7, which is known to interact with the retinoblastoma gene product, a cellular tumour suppressor gene (Gage et al, 1990); E2, which is a transactivating protein important for control of early gene expression (Guido et al, 1992); E4, which, although its function has not been delineated, is usually a fairly abundant protein in productively infected cells Jochmus-Kudielka et al, 1992;Onda et al, 1993); and L2 and L1, which are structural proteins (Kirnbauer et al, 1992).…”

“…The genes useful in such studies include E7, which is known to interact with the retinoblastoma gene product, a cellular tumour suppressor gene (Gage et al, 1990); E2, which is a transactivating protein important for control of early gene expression (Guido et al, 1992); E4, which, although its function has not been delineated, is usually a fairly abundant protein in productively infected cells Jochmus-Kudielka et al, 1992;Onda et al, 1993); and L2 and L1, which are structural proteins (Kirnbauer et al, 1992). Using either Western blot or ELISA techniques, significant correlations have been demonstrated between antibodies to HPV-16 E7 and cervical cancer compared to controls (Ghosh et al, 1993 ;Jochmus-Kudielka et al, 1992;Kochel et al, 1991;Such~inkov~i et al, 1991Such~inkov~i et al, , 1992. In some studies, antibodies to HPV-16 E4 have shown positive correlations in cancer patients compared to controls (Jochmus-Kudielka et al, 1992;Kochel et al, 1991) and in studies on patients with premalignant disease, levels of both E4 and L2 antibodies were found to be higher when compared to controls (Barber et al, 1992)…”

Fowlpox virus recombinants expressing HPV-16 E6 and E7 oncogenes for the therapy of cervical carcinoma elicit humoral and cell-mediated responses in rabbits

“…The use of viral vectors in a prime-boost regimen has already been shown to enhance the effectiveness of vaccination and a high antibody level was seen to be inversely correlated with disease progression [53,54]. In this study, the antibody response detectable when either the E6 or E7 proteins were plated was very low and did not increase overtime, especially during priming.…”