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Instituto Nacional de Salud Pública

2003, Number 5

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salud publica mex 2003; 45 (5)

Association between anti-Ras and anti-HPV16 E4/E7 antibodies with cervical intraepithelial lesions

Vázquez-Corzo S, Trejo-Becerril C, Cruz-Valdez A, Hernández-Nevarez P, Esquivel-Guadarrama FR, Gutiérrez-Xicotencatl ML

Language: Spanish
References: 78
Page: 335-345
PDF size: 131.56 Kb.


ABSTRACT

Objective. To evaluate whether serum antibodies anti-E4, E7 and Ras could be used as markers for early cervical lesions associated with HPV (human papillomavirus). Material and Methods. A seroepidemiological case-control study was conducted between March 1999 and April 2000 at the dysplasia clinic of Hospital General Doctor Gea Gonzalez, in Mexico City, to evaluate the presence of antibodies anti- E4, E7, and Ras through a sandwich ELISA. Analysis was done using odds ratios and 95% confidence intervals. Results. Anti-E7 antibodies were associated to women with CIN III lesions, while anti-E4 and Ras antibodies were strongly associated with CIN I-II lesions. The antibody profile of women with different cervical lesion showed that: a) the presence of antibodies against two proteins predicts the presence of CIN I-II lesions, and b) the presence of three antibodies predicts a CIN III lesion. Conclusions. The presence of serum antibodies against E4, E7 and Ras, together with other diagnostic techniques, could be useful for the timely detection of early uterine cervical lesions associated to HPV in women at risk of developing cancer.


REFERENCES

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  2. Lazcano-Ponce E, Hernández AM, López CL. Factores de riesgo reproductivo e historia de vida sexual asociados a cáncer cervical en una muestra de mujeres de la Cd. de México. Rev Invest Clin 1995;47:377-382,

  3. Muñoz N. Human papillomavirus and cancer:The epidemiological evidence. J Clin Virol 2000;1:1-5.

  4. FarthingAJ,Vousden KH. Functions of human papillomavirus E6 and E7 oncoproteins.Trends Microbiol 1994;2;170-174.

  5. 5, Matlashewski G, Schneider J, Banks L Jones N, Morray A, Crawford L. Human papillomavirus type 16 DNA cooperates with activated ras in transforming primary cells. EMBO J 1987;6:1741-1746.

  6. Ostrow RS, Liv Z, Schneider JF, McGlennen RC, Forslund K, Faras AJ. The products of the E5, E6 or E7 open reading frames of RHPVI can individually transform NIH 3T3 cells or in co-transfection with activated ras can transform primary epitelial cells.Virology 1993;196:861-867.

  7. Doorbar J, Stherlin J, Mclean L, Crawford L. Specific interaction between HPV-16, El-E4 and cytokeratins results in collapse of the epithelial cell intermediate filament network. Nature 1991;352:824-827.

  8. Doorbar J, Foo CH, Coleman N, Medcalf L, Hartley O, Prospero T et al. Characterization of events during the late stages of HPV-16 infection in vivo using high-affinity synthetic Fabs to E4.Virol 1997;238:40-52. 9.Jochmus-Kudielka I, Schneider A, Braun R, Kimming R, Koldovsky U, Schneweis KE et al. Antibodies against the human papillomavirus type 16 early proteins in human sera: Correlation of anti-E7 reactivity with cervical cancer.) Na Cancer inst 1989;81:1698-1704.

  9. Fujii T, Matsushima Y,Yajima M, Sugimura T,Terada M. Serum antibody against un-fused recombinant E7 protein of human papillomavirus type 16 in cervical cancer patients. Jpn J Cancer Res 1995;86:28-34.

  10. Gosh AK, Smith NK, Stancey SN, Glew SS, Connor ME,Arrand JR et al. Serological responses to HPV-16 in cervical displasia and neoplasia correlation of antibodies to E6 with cervical cancer. Int J Cancer 1993;53:591-596.

  11. Kanda T, OndaT, Zanma S,Yasugi T, Furund A,Watanabe S et al. Independent association of antibodies against human papillomavirus type 16 El, E4 and E7 proteins with cervical cancer.Virology 1992;190:7224-732.

  12. Kirnbauer R, Hubbert LN, Colette MW, Becker MT, Lowy RD, Schiller TJ.A virus-like particle enzyme-linked immunosorbent assay detects serum antibodies in a majority of women infected with human papillomavirus type 16.J Nat Cancer Inst 1994;86:494-498.

  13. Doherty PC,Ahmed R. Immune responses to viral infection. En: Natanson N,Ahmed R, Ed. Viral Pathogenesis and Immunity. Philadelphia (PA): Lip. Publishers, 1997:143-161.

  14. Dinner L, Fredricksson A, Persson E, Forslund O, Hansson BG, Dillner ).Antibodies against papillomavirus antigens in cervical secretions from condyloma patients. J Clin Microbiol 1993;31:192-197.

  15. Suchánková A, Krchnak V,Vanger J, Hamsikova E, Krcmar M, Ritterova

  16. L et al, Epitope mapping of the human papillomavirus type 16 E4 protein by means of synthetic peptides.) Gen Virol 1992;73:429-432. 17.Pedroza-Saavedra A, Cruz A, Esquivel F, De La Torre F, Berumen J, Gariglio P et al. High prevalence of sera antibodies to Ras and to human papillomavirus type 16 E4 proteins in patients with pre-cancerous lesions from the uterine cervix.ArchVirol 2000;145:603-623.

  17. Schiffman MH, Brinton LA.The epidemiology of cervical carcinogenesis. Cancer 1995;75:1988-1901.

  18. Riou GF. Proto-oncogenes and prognosis in early carcinoma of uterine cervix. Cancer surveys 1988;7:441-455.

  19. Parker MF,Arroyo GF, Geradts J. Molecular characterization of adenocarcinoma of the cervix. Gynecol. Oncol 1997;64:242-251. 21.Ishiji T. Molecular mechanism of carcinogenesis by human papillomavirus-16.J Dermatol 2000;27:73-86.

  20. Gravitt PE, Peyton CL,Apple RJ,Wheeler CM. Genotyping of 27 human papillomavirus types by using LI consensus PCR products by a single-hybridization reverse line blot detection method,) Clin Microbiol 1998;36:3020-3027.

  21. Hall S, Lorincz A, Shah F, Sherman ME,Abbas F, Pauli G et al. Human papillomavirus DNA detection in cervical specimens by hybrid capture: Correlation with cytologic and histologic diagnoses of squamous intraepithelial lesions of the cervix. Gynecol Oncol 1996;62:353-359.

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  24. Lazcano-Ponce E, Herrero R, Muñoz N, Cruz A, Shah KV,Alonso P et al. Epidemiology of HPV infection among Mexican women with normal cervical cytology. Inc J Cancer 2001;91:412-420.

  25. 27.Manos MM,TingY,Wright DK, LewisAJ, Broker TR,Wolinsky SM. The use of polymerase chain reaction amplification for the detection of genital HPV. Cancer Cells 1989;7:209-214.

  26. 28.Lautenberger JA, Court D, Papas TS. High level expression in E. coli of the carboxy-terminal sequences of the avian myelocytomatosis virus (MC29) v-myc protein. Gene 1983;23:75-84.

  27. Meschede W, Zumbach K, Braspenning J, Scheffner M, Benitez-BL, Luande J et al. Antibodies against early proteins of human papillomaviruses as diagnostic markers for invasive cervical cancer.J Clin Microbiol 1998;36:475-480.

  28. Palefsky JM,Winkler B, Rabanus JP, Clark C, Chan S, NizetV et al . Characterization of in vivo expression of the human papillomavirus type 16 E4 protein in cervical biopsy tissues.J Clin Invest 1991;87(6): 2132-2141.

  29. 31.Hashido M, Kanda T, Zanma S,Watanabe S, Komiyama N,Yoshikawa H et al. Detection of human antibody against the HPV type 16 E7 protein. Jpn J Cancer Res 1991;82:1406-1412.

  30. 32.Jha PK, Beral V, Peto J, Hack S, Hermon C, Deacon J et al.Antibodies to human papillomavirus and to other genital infectious agents and invasive cervical cancer risk. Lancet 1993;341:1 1 16-I 118.

  31. Dillner J, Leaner M, Eklund C, Heino P,Wiklund F, Hallmans G et al.A population-based sero-epidemiological study of cervical cancer. Cancer Res 1994;54:134-141.

  32. Ho GYF, Bierman R, Beardsley L, Chang ChJ, Burk RD. Natural history of cervicovaginal papillomavirus infection in young women. N Eng, J Med 1998;338:423-428.

  33. 35.Takahashi M, Chen W, Byrd DR, Disis ML, Huseby ES, Qin H et al. Antibody to ras proteins in patients with colon cancer. Clin Cancer Res 199510:1071-1077.

  34. Canevari S, Pupa SM, Ménard S. Revised anti-cancer serological response: Biological significance and clinical implications 1975-1995.Ann Oncol 1996;7:227-232.

  35. Soussi TThe humoral response to the tumor-suppressor gene-product p53 in human cancer: implications for diagnosis and therapy. Immunol Today 1996;17:354-356.

  36. Harnsikova E, Ludvikova V, Smahel M, Sapp M,Vonka V. Prevalence of antibodies to human papillomaviruses in the general population of the Czech Republic. Int./ Cancer 1998;77(5):689-694.

  37. 39.Hildesheim A, Herrero R, Castle PE,Wacholder S, Bratti MC, Sherman ME, et al. HPV co-factors related to the development of cervical cancer: Results from a population-based study in Costa Rica. Br J Cancer 2001;84(9):1219-1226.

  38. Moscicki AB, Hills N, Shiboski S, Powell K, Jay N, Hanson E et al. Risks for incident human papillomavirus infection and low-grade squamous intraepithelial lesion development in young females. JAMA 2001;285(23):2995-3002.

  39. Zur Hausen H. Papillomavirus infection: A cause of human cancers. Biochim Biophys Acta 1996;1288:F55-F78.

  40. Lazcano-Ponce E, Hernández AM, López CL. Factores de riesgo reproductivo e historia de vida sexual asociados a cáncer cervical en una muestra de mujeres de la Cd. de México. Rev Invest Clin 1995;47:377-382,

  41. Muñoz N. Human papillomavirus and cancer: The epidemiological evidence. J Clin Virol 2000;1:1-5.

  42. Farthing AJ,Vousden KH. Functions of human papillomavirus E6 and E7 oncoproteins. Trends Microbiol 1994;2;170-174.

  43. Matlashewski G, Schneider J, Banks L, Jones N, Morray A, Crawford L. Human papillomavirus type 16 DNA cooperates with activated ras in transforming primary cells. EMBO J 1987;6:1741-1746.

  44. Ostrow RS, Liv Z, Schneider JF, McGlennen RC, Forslund K, Faras AJ. The products of the E5, E6 or E7 open reading frames of RHPVI can individually transform NIH 3T3 cells or in co-transfection with activated ras can transform primary epitelial cells. Virology 1993;196:861-867.

  45. Doorbar J, Stherlin J, Mclean L, Crawford L. Specific interaction between HPV-16, El-E4 and cytokeratins results in collapse of the epithelial cell intermediate filament network. Nature 1991;352:824-827.

  46. Doorbar J, Foo CH, Coleman N, Medcalf L, Hartley O, Prospero T et al. Characterization of events during the late stages of HPV-16 infection in vivo using high-affinity synthetic Fabs to E4. Virol 1997;238:40-52.

  47. Jochmus-Kudielka I, Schneider A, Braun R, Kimming R, Koldovsky U, Schneweis KE et al. Antibodies against the human papillomavirus type 16 early proteins in human sera: Correlation of anti-E7 reactivity with cervical cancer.) Na Cancer inst 1989;81:1698-1704.

  48. Fujii T, Matsushima Y, Yajima M, Sugimura T, Terada M. Serum antibody against un-fused recombinant E7 protein of human papillomavirus type 16 in cervical cancer patients. Jpn J Cancer Res 1995;86:28-34.

  49. Gosh AK, Smith NK, Stancey SN, Glew SS, Connor ME, Arrand JR et al. Serological responses to HPV-16 in cervical displasia and neoplasia correlation of antibodies to E6 with cervical cancer. Int J Cancer 1993;53:591-596.

  50. Kanda T, OndaT, Zanma S, Yasugi T, Furund A, Watanabe S et al. Independent association of antibodies against human papillomavirus type 16 El, E4 and E7 proteins with cervical cancer. Virology 1992;190:7224-732.

  51. Kirnbauer R, Hubbert LN, Colette MW, Becker MT, Lowy RD, Schiller TJ. A virus-like particle enzyme-linked immunosorbent assay detects serum antibodies in a majority of women infected with human papillomavirus type 16. J Nat Cancer Inst 1994;86:494-498.

  52. Doherty PC, Ahmed R. Immune responses to viral infection. En: Natanson N, Ahmed R, Ed. Viral Pathogenesis and Immunity. Philadelphia (PA): Lip. Publishers, 1997:143-161.

  53. Dinner L, Fredricksson A, Persson E, Forslund O, Hansson BG, Dillner). Antibodies against papillomavirus antigens in cervical secretions from condyloma patients. J Clin Microbiol 1993;31:192-197.

  54. Suchánková A, Krchnak V, Vanger J, Hamsikova E, Krcmar M, Ritterova L et al, Epitope mapping of the human papillomavirus type 16 E4 protein by means of synthetic peptides.) Gen Virol 1992;73:429-432.

  55. Pedroza-Saavedra A, Cruz A, Esquivel F, De La Torre F, Berumen J, Gariglio P et al. High prevalence of sera antibodies to Ras and to human papillomavirus type 16 E4 proteins in patients with pre-cancerous lesions from the uterine cervix. Arch Virol 2000;145:603-623.

  56. Schiffman MH, Brinton LA. The epidemiology of cervical carcinogenesis. Cancer 1995;75:1988-1901.

  57. Riou GF. Proto-oncogenes and prognosis in early carcinoma of uterine cervix. Cancer surveys 1988;7:441-455.

  58. Parker MF, Arroyo GF, Geradts J. Molecular characterization of adenocarcinoma of the cervix. Gynecol. Oncol 1997;64:242-251.

  59. Ishiji T. Molecular mechanism of carcinogenesis by human papillomavirus-16. J Dermatol 2000;27:73-86.

  60. Gravitt PE, Peyton CL, Apple RJ, Wheeler CM. Genotyping of 27 human papillomavirus types by using LI consensus PCR products by a single-hybridization reverse line blot detection method,) Clin Microbiol 1998;36:3020-3027.

  61. Hall S, Lorincz A, Shah F, Sherman ME, Abbas F, Pauli G et al. Human papillomavirus DNA detection in cervical specimens by hybrid capture: Correlation with cytologic and histologic diagnoses of squamous intraepithelial lesions of the cervix. Gynecol Oncol 1996;62:353-359.

  62. Muñoz N, Franceschi S, Bosetti C, Moreno V, Herrero R, Smith JS et al. Role of parity and human papillomavirus in cervical cancer: The IARC multicentric case-control study. Lancet 2002;359:1093-1101.

  63. Hernández AM, Lazcano PE, Berumen CJ, Cruz VA, Alonso DRP, González LG. Human papilloma virus 16-18 infection and cervical cancer in Mexico:A case-control study.Arch Med Res 1997;28:265-271.

  64. Lazcano-Ponce E, Herrero R, Muñoz N, Cruz A, Shah KV,Alonso P et al. Epidemiology of HPV infection among Mexican women with normal cervical cytology. Inc J Cancer 2001;91:412-420.

  65. Manos MM, TingY, Wright DK, Lewis AJ, Broker TR, Wolinsky SM. The use of polymerase chain reaction amplification for the detection of genital HPV. Cancer Cells 1989;7:209-214.

  66. Lautenberger JA, Court D, Papas TS. High level expression in E. coli of the carboxy-terminal sequences of the avian myelocytomatosis virus (MC29) v-myc protein. Gene 1983;23:75-84.

  67. Meschede W, Zumbach K, Braspenning J, Scheffner M, Benitez-BL, Luande J et al. Antibodies against early proteins of human papillomaviruses as diagnostic markers for invasive cervical cancer.J Clin Microbiol 1998;36:475-480.

  68. Palefsky JM, Winkler B, Rabanus JP, Clark C, Chan S, Nizet V et al. Characterization of in vivo expression of the human papillomavirus type 16 E4 protein in cervical biopsy tissues. J Clin Invest 1991;87(6): 2132-2141.

  69. Hashido M, Kanda T, Zanma S, Watanabe S, Komiyama N, Yoshikawa H et al. Detection of human antibody against the HPV type 16 E7 protein. Jpn J Cancer Res 1991;82:1406-1412.

  70. Jha PK, Beral V, Peto J, Hack S, Hermon C, Deacon J et al. Antibodies to human papillomavirus and to other genital infectious agents and invasive cervical cancer risk. Lancet 1993;341:1116-1118.

  71. Dillner J, Leaner M, Eklund C, Heino P,Wiklund F, Hallmans G et al. A population-based sero-epidemiological study of cervical cancer. Cancer Res 1994;54:134-141.

  72. Ho GYF, Bierman R, Beardsley L, Chang ChJ, Burk RD. Natural history of cervicovaginal papillomavirus infection in young women. N Eng, J Med 1998;338:423-428.

  73. Takahashi M, Chen W, Byrd DR, Disis ML, Huseby ES, Qin H et al. Antibody to ras proteins in patients with colon cancer. Clin Cancer Res 199510:1071-1077.

  74. Canevari S, Pupa SM, Ménard S. Revised anti-cancer serological response: Biological significance and clinical implications 1975-1995. Ann Oncol 1996;7:227-232.

  75. Soussi TThe humoral response to the tumor-suppressor gene-product p53 in human cancer: implications for diagnosis and therapy. Immunol Today 1996;17:354-356.

  76. Harnsikova E, Ludvikova V, Smahel M, Sapp M, Vonka V. Prevalence of antibodies to human papillomaviruses in the general population of the Czech Republic. Int./Cancer 1998;77(5):689-694.

  77. Hildesheim A, Herrero R, Castle PE, Wacholder S, Bratti MC, Sherman ME, et al. HPV co-factors related to the development of cervical cancer: Results from a population-based study in Costa Rica. Br J Cancer 2001;84(9):1219-1226.

  78. Moscicki AB, Hills N, Shiboski S, Powell K, Jay N, Hanson E et al. Risks for incident human papillomavirus infection and low-grade squamous intraepithelial lesion development in young females. JAMA 2001;285(23):2995-3002.




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