Antibodies to HPV-16 E6 and E7 proteins as markers for HPV-16-associated invasive cervical cancer

Möller, Martin; Viscidi, Raphael P.; Sun, Yeping; Guerrero, E; Hill, Peter; Shah, Farida; Bosch, F. Xavier; Muñóz, Núbia; Gissmann, Lutz; Shah, Keerti V.

doi:10.1016/0042-6822(92)90453-v

Cited by 146 publications

(80 citation statements)

References 16 publications

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“…Viral proteins may be accumulated sufficiently around the infected cells during this period. According to some clinical studies, the most consistent findings have been that the presence of serum Abs to the transforming E6 and E7 proteins of the virus is associated with invasive cancer compared with the sera of controls (51,52). These reports suggested the presence of circulating E6 and E7 proteins in cervical cancer patients.…”

Section: Discussionmentioning

confidence: 61%

Both E6 and E7 Oncoproteins of Human Papillomavirus 16 Inhibit IL-18-Induced IFN-γ Production in Human Peripheral Blood Mononuclear and NK Cells

Lee

Cho

et al. 2001

The Journal of Immunology

108

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Cervical carcinoma is the predominant cancer among malignancies in women throughout the world, and human papillomavirus (HPV) 16 is the most common agent linked to human cervical carcinoma. The present study was performed to investigate the mechanisms of immune escape in HPV-induced cervical cancer cells. The presence of HPV oncoproteins E6 and E7 in the extracellular fluids of HPV-containing cervical cancer cell lines SiHa and CaSki was demonstrated by ELISA. The effect of HPV 16 oncoproteins E6 and E7 on the production of IFN-γ by IL-18 was assessed. E6 and E7 proteins reduced IL-18-induced IFN-γ production in both primary PBMCs and the NK0 cell line. FACS analysis revealed that the viral oncoproteins reduced the binding of IL-18 to its cellular surface receptors on NK0 cells, whereas there was no effect of oncoproteins on IL-1 binding to its surface IL-1 receptors on D10S, a subclone of the murine Th cell D10.G4.1. In vitro pull-down assays also revealed that the viral oncoproteins and IL-18 bound to IL-18R α-chain competitively. These results suggest that the extracellular HPV 16 E6 and E7 proteins may inhibit IL-18-induced IFN-γ production locally in HPV lesions through inhibition of IL-18 binding to its α-chain receptor. Down-modulation of IL-18-induced immune responses by HPV oncoproteins may contribute to viral pathogenesis or carcinogenesis.

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Section: Discussionmentioning

confidence: 61%

Both E6 and E7 Oncoproteins of Human Papillomavirus 16 Inhibit IL-18-Induced IFN-γ Production in Human Peripheral Blood Mononuclear and NK Cells

Lee

Cho

et al. 2001

The Journal of Immunology

108

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“…Consequently, anti-E6 and anti-E7 antibodies have been associated with malignant progression of the disease, and their detection is optimum in patients with cancer of the cervix. [9][10][11] These results have been confirmed using synthetic peptides, and proteins translated in vitro or proteins produced from a baculovirus/insect cell system. [11][12][13][14][15][16][17] The studies using recombinant proteins for antigen have shown that anti-E6 and E7 antibodies are detected in 50% to 60% of patients with cervical uterine cancer.…”

Section: Antibodies Directed Against Non-structural Proteinsmentioning

confidence: 56%

Serology for human papillomavirus

Coursaget

2003

Salud pública Méx

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ResumenLas limitaciones para la utilización de la serología para el estudio del virus del papiloma humano con fines clínicos están asociadas con la gran variedad de subtipos humanos, con las reacciones cruzadas que existen entre diversos genotipos, la diversidad de lesiones precursoras de cáncer y con los sitios blancos de infección. Asimismo, la expresión del virus del papiloma humano en las capas superficiales del epitelio dan origen a una débil presentación de células inmunocompetentes de antígenos virales, lo cual origina una elevación de la respuesta serológica. Distintos esfuerzos se han realizado en décadas previas para desarrollar ensayos serológicos más específicos y sensibles. En muchas investigaciones se ha utilizado una fusión de proteínas y péptidos sintéticos que tienen como principal limitación su escasa sensibilidad y especificidad. Sólo en los últimos años, y principalmente debido al arribo de partículas parecidas a este virus, tenemos disponibles ensayos más sensibles y específicos, ampliamente descritos en este artículo. Este artículo también está disponible en: http://www.insp.mx/ salud/index.html Palabras clave: cáncer cervical; VLP; virus de papiloma humano; serología This paper is available too at: http://www.insp.mx/salud/index.html Abstract Difficulties with serology for papillomavirus are associated with the large number of human papillomavirus, crossreactions between papillomavirus, and to the diversity of lesions and target sites for infection. In addition, the expression of the papillomavirus in the superficial layers of the epithelium gives rise to the weak presentation to immunocompetent cells of viral antigens, which in turn gives rise to a weak serological response. Distinct efforts have been made in previous decades to develop more specific and sensitive serological assays. These former studies use fusion proteins and synthetic peptides, although they remain on the whole uninteresting, due to their lack of sensitivity and specificity. Only in the last few years, and principally due to the advent of various virus-like particles (VLP), have more sensitive and specific assays become available. This paper is available too at:

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“…ELISA values were used to calculate a cut-off value for IgA seropositivity based on the mean of the NHS control group plus two standard deviations using the method described in Muller et al (1992). As shown in Figure 4B, the highest frequency of seropositivity was found in the COL group (53%) compared with the NHS control group (18%).…”

Section: Discussionmentioning

confidence: 99%

“…Cut-off values were subsequently assigned using the method described in Muller et al (1992) using the mean of the NHS group ELISA values plus two standard deviations as the cut-off. Chisquared analysis was used to compare seropositive and seronegative frequencies between groups.…”

Section: Discussionmentioning

confidence: 99%

Differences in serological IgA responses to recombinant baculovirus-derived human papillomavirus E2 protein in the natural history of cervical neoplasia

Rocha‐Zavaleta

Jordan²,

Pepper³

et al. 1997

Br J Cancer

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Summary Infection with certain types of human papillomavirus (HPV) presents a high risk for the subsequent development of cervical intraepithelial neoplasia (CIN) and cervical carcinoma. Immunological mechanisms are likely to play a role in control of cervical HPV lesions.The HPV E2 protein has roles in virus replication and transcription, and loss of E2 functions may be associated with progression of cervical neoplasia. Accordingly, it is of interest to monitor immune responses to the E2 protein, and previous studies have reported associations between serological reactivity to E2 peptide antigens and cervical neoplasia. In order to investigate serological responses to native, full-length E2 protein, we expressed HPV-1 6 E2 proteins with and without an N-terminal polyhistidine tag using the baculovirus system. Purified HPV-1 6 E2 protein was used to develop enzyme-linked immunosorbent assays to detect serological IgG and IgA responses in cervical neoplasia patients and controls. We found that serum IgA levels against the E2 protein were elevated in CIN patients relative to normal control subjects but were not elevated in cervical cancer patients. Moreover, there appeared to be a gradient of response within cervical neoplasia such that the highest antibody levels were seen in lower grades of neoplasia up to CIN 2, whereas lower levels were observed in CIN 3 and still lower levels in cervical carcinoma. These findings suggest that the IgA antiboay response to E2 may associate with stage and progression in cervical neoplasia.Keywords: human papillomavirus; serology; E2 protein; cervical neoplasia; baculovirus Human papillomaviruses comprise a large group of DNA viruses that exclusively infect epithelium. Certain types of HPV are capable of infecting genital mucosal epithelium, which can result in cervical intraepithelial neoplasia (CIN). CIN is classified by histopathology into stages 1, 2 and 3, which are thought to represent progressively advanced precursor lesions of cervical carcinoma (CaCx). HPV infection is a prerequisite for the genesis of almost all CIN and cervical carcinomas Schiffman et al, 1993). Most CIN contains detectable HPV DNA. HPV-16, -18 and related types have been classed as 'high-risk' genital HPV types because of their associations with high-grade CIN and CaCx (reviewed in Walboomers et al, 1994).Genital-type HPV genomes are approximately 8 kbp in length and comprise six open reading frames (ORFs) encoding early functions (E1-E7) and two late ORFs encoding the capsid proteins. The E2 ORF encodes an approximately 45-kDa nuclear phosphoprotein that binds to specific sequence elements within the HPV long control region (LCR). Binding of the E2 protein to these elements functions in regulation of HPV transcription and replication. Binding of E2 to sites near the constitutive early promoter of HPV-16 or -18 can negatively regulate expression of the two major

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Antibodies to HPV-16 E6 and E7 proteins as markers for HPV-16-associated invasive cervical cancer

Cited by 146 publications

References 16 publications

Both E6 and E7 Oncoproteins of Human Papillomavirus 16 Inhibit IL-18-Induced IFN-γ Production in Human Peripheral Blood Mononuclear and NK Cells

Both E6 and E7 Oncoproteins of Human Papillomavirus 16 Inhibit IL-18-Induced IFN-γ Production in Human Peripheral Blood Mononuclear and NK Cells

Serology for human papillomavirus

Differences in serological IgA responses to recombinant baculovirus-derived human papillomavirus E2 protein in the natural history of cervical neoplasia

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