Skip to main content
SpringerLink
Log in

Immunological Aspects of the E6 and E7 Oncogenes: Tools for Diagnosis and Therapeutic Intervention

  • Chapter
Papillomaviruses in Human Cancer

  • 50 Accesses

Abstract

The antibody response against structural HPV proteins that was shown to develop during the natural course of HPV infections is likely the consequence of “mucosal immunization” (i.e., uptake and presentation by M cells), or depends on “secondary infection” through small wounds resulting in the exposure of these proteins to antigen presenting cells (APC) such as macrophages or dendritic cells. There is good evidence that antibodies against HPV capsid proteins are relevant in controlling HPV infections.1

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Kirnbauer R. Papillomavirus-like particles for serology and vaccine development. Intervirology 1996; 39: 54–61.

    PubMed  CAS  Google Scholar 

  2. Stanley MA, Coleman N, Chambers M. The host response to lesions induced by human papillomavirus. In: Mindel A, ed. Genital Warts and Human Papillomavirus Infection. London: Edward Arnold, 1994: 21–44.

    Google Scholar 

  3. Benton C, Shahidulah H, Hunter JAA. Human papillomavirus in the imunosuppressed. Papillomavirus Rep 1992; 3: 23–26.

    Google Scholar 

  4. Fisher SG, Gissmann L. Convergent infections: human papillomavirus and human immunodeficiency virus. In: Advanced Technologies in Research, Diagnosis and Treatment of AIDS and in Oncology. Antibiot Chemother, Basel: Antibiot Chemother, 1994; 46: 134–149.

    Google Scholar 

  5. Stockfleth E, Gissmann L. Human papillomavirus and immunosuppression. In: Shiokawa Y, Kitamura T, eds. Global Challenge of AIDS. 1995: 113–122.

    Google Scholar 

  6. Altmann A, Gissmann L, Jochmus I. Towards HPV vaccination. In: Minson A, Neil J, McCrae M, eds. Viruses and Cancer. Cambridge University Press, 1994: 71–80.

    Google Scholar 

  7. Campo MS. Vaccination against papillomavirus in cattle. In: zur Hausen H, ed. Human Pathogenic Papillomaviruses. Current Topics Microbiol Immunol, Berlin: Springer Verlag, 1994: 255–266.

    Chapter  Google Scholar 

  8. Nindl I, Gissmann L, Fisher SG et al. The E7 protein of the human papillomavirus (HPV) type 16 expressed by recombinant vaccinia virus can be used for the detection of antibodies in sera from cervical cancer patients. J Virol Methods 1996; 62: 81–85.

    Article  PubMed  CAS  Google Scholar 

  9. Meschede et al. (submitted).

    Google Scholar 

  10. Müller M, Viscidi RP, Sun Y et al. Antibodies to HPV16 E6 and E7 proteins as markers for HPV16-associated invasive cervical cancer. Virology 1992; 187: 508–514.

    Article  PubMed  Google Scholar 

  11. Jochmus-Kudielka I, Schneider A et al. Antibodies against the human papillomavirus type 16 early proteins in human sera: Correlation of anti-E7 reactivity and cervical cancer. J Natl Cancer Inst 1989; 81: 1698–1704.

    Article  PubMed  CAS  Google Scholar 

  12. Viscidi R, Shah KV. Immune response to infections with human papillomaviruses. In: Quinn TC, Gallin JI, Fauci AS, eds. Advances in Host Defense Mechanisms. Vol. 8. New York: Raven Press, 1992.

    Google Scholar 

  13. Galloway DA. Serological assays for the detection of HPV antibodies. In: Munoz N, Bosch FX, Shah KV, Meheus A, eds. The Epidemiology of Cervical Cancer and Human Papillomavirus. IARC Scientific Publications, Lyon: International Agency for Research on Cancer 1992; 119: 147–161.

    Google Scholar 

  14. Gissmann L, Müller M. The current role of HPV-serology. In: Stanley M, Stern P, eds. Human Papillomaviruses and Cervical Cancer. Oxford: Oxford University Press, 1994: 133–144.

    Google Scholar 

  15. Gissmann L. The current role of HPV serology. In: von Krogh G, Gross G, eds. Human Papillomavirus Infections in Dermatovenereology. Boca Raton: CRC Press, 1996: 365–374.

    Google Scholar 

  16. Viscidi RP, Sun Y, Tsuzali B et al. Serologic response in human papillomavirus-associated invasive cervical cancer. Int J Cancer 1993; 55: 780–784.

    Article  PubMed  CAS  Google Scholar 

  17. Sun Y, Eluf-Neto J, Bosch FX et al. Human papillomavirus-related serological markers of invasive cervical carcinoma in Brazil. Cancer Epidemiol Biomarkers Prevention 1994; 3: 341–347.

    CAS  Google Scholar 

  18. Nindl I, Benitez-Bribiesca L, Berumen J et al. Antibodies against linear and conformational epitopes of the human papillomavirus (HPV) type 16 E6 and E7 oncoproteins in sera of cervical cancer patients. Arch Virol 1994; 137: 341–353.

    Article  PubMed  CAS  Google Scholar 

  19. Baay MF, Duk MP, Walboomers JMM et al. Antibodies to human papillomavirus type 16 E7 related to clinicopathological data in patients with cervical carcinoma. J Clin Pathol 1995; 48: 410–414.

    Article  PubMed  CAS  Google Scholar 

  20. Baay MF, Duk JM, Burger MP et al. Follow-up of antibody responses to human papillomavirus type 16 E7 in patients treated for cervical carcinoma. J Med Virol 1995; 45: 342–78.

    Article  PubMed  CAS  Google Scholar 

  21. Suchankova A, Ritterova L, Krcmar M et al. Comparison of ELISA and Western Blotting for HPV16 E7 antibody determination. J Gen Virol 1991; 72: 2577–2581.

    Article  PubMed  CAS  Google Scholar 

  22. Köchel HG, Monazahian M, Sievert K et al. Occurrence of antibodies to L1, L2, E4 and E7 gene products of human papillomavirus types 6b, 16 and 18 among cervical cancer patients and controls. Int J Cancer 1991; 48: 682–688.

    Article  PubMed  Google Scholar 

  23. Mandelson MT, Jenison SA, Sherman KJ et al. The association of human papillomavirus antibodies with cervical cancer risk. Cancer Epidemiol Biomarkers Prevention 1992; 1: 281–286.

    CAS  Google Scholar 

  24. Kanda T, Onda T, Zanma S et al. Independent association of antibodies against human papillomavirus type 16 E1/E4 and E7 proteins with cervical cancer. Virology 1992; 190: 724–732.

    Article  PubMed  CAS  Google Scholar 

  25. Onda T, Kanda T, Zanma S et al. Association of the antibodies against human papillomavirus 16 E4 and E7 proteins with cervical cancer positive for human papillomavirus DNA. Int J Cancer 1993; 54: 624–628.

    Article  PubMed  CAS  Google Scholar 

  26. Paez CG, Yaegashi N, Sato S et al. Prevalence of serum IgG antibodies for the E7 and L2 proteins of human papillomavirus type 16 in cervical cancer patients and controls. Tohoku J Exp Med 1993; 170: 113–121.

    Article  PubMed  CAS  Google Scholar 

  27. Mann VM, Loo de Lao S, Brenes M et al. Occurrence of IgA and IgG antibodies to select peptides representing human papillomavirus type 16 among cervical cancer cases and controls. Cancer Res 1990; 50: 7815–7819.

    PubMed  CAS  Google Scholar 

  28. Bleui C, Müller M, Frank R et al. Human papillomavirus type 18 E6 and E7 antibodies in human sera: Increased anti-E7 prevalence in cervical cancer patients. J Clin Microbiol 1991; 29: 1579–1588.

    Google Scholar 

  29. Krchnak V, Pistek T, Vagner J et al. Identification of seroreactive epitopes of human papillomavirus type 18 E7 protein by synthetic peptides. Acta Virol 1993; 37: 395–402.

    PubMed  CAS  Google Scholar 

  30. Jha P, Beral V, Peto J et al. Antibodies to human papillomavirus and to other genital infections and their relation to invasive cervical cancer risk. The Lancet 1993; 341: 1116–1118.

    Article  CAS  Google Scholar 

  31. Dinner J, Lenner P, Lehtinen M et al. A population-based seroepidemiological study of cervical cancer. Cancer Res 1994; 54: 134–141.

    Google Scholar 

  32. Sasagawa T, Inoue, M, Tanizawa O et al. Identification of antibodies against human papillomavirus type 16 E6 and E7 proteins in sera of patients with cervical neoplasia. Jap J Cancer Res 1992; 83: 705–713.

    Article  CAS  Google Scholar 

  33. Fisher SG, Benitez-Bribiesca L, Nindl I et al. The association of human papillomavirus type 16 E6 and E7 antibodies with stage of cervical cancer. Gynecol Oncol 1996; 61: 73–78.

    Article  PubMed  CAS  Google Scholar 

  34. Eschle D, Durst M, ter Meulen J et al. Geographic dependence of sequence variations in the E7 gene of human papillomavirus type 16. J Gen Virol 1992; 73: 1829–1832.

    Article  PubMed  CAS  Google Scholar 

  35. ter Meulen J, Schweigler AC, Eberhardt HC et al. Sequence variation in the E7 gene of human papillomavirus type 18 in tumor and nontumor patients and antibody response to a conserved seroreactive epitope. Int J Cancer 1993; 53: 257–259.

    Article  PubMed  Google Scholar 

  36. Wank R, Schendel DJ, Thomssen C. HLA antigens and cervical carcinoma. Nature 1992; 356: 22–23.

    Article  PubMed  CAS  Google Scholar 

  37. Helland A, Borresen AL, Kristensen G et al. DQA1 and DQB1 genes in patients with squamous cell carcinoma of the cervix: relationship to human papillomavirus infection and prognosis. Cancer Epidemiol Biomarkers Prey 1994; 3: 479–486.

    CAS  Google Scholar 

  38. Gregoire L, Lawrence WD, Kukuruga D et al. Association between HLA-DQB1 alleles and risk for cervical cancer in African-American women. Int J Cancer 1994; 57: 504–537.

    Article  PubMed  CAS  Google Scholar 

  39. Apple RJ, Erlich HA, Klitz W et al. HLA DR-DQ associations with cervical carcinoma show papillomavirus-type specificity. Nat Genet 1994; 6: 157–162.

    Article  PubMed  CAS  Google Scholar 

  40. Apple RJ, Becker TM, Wheeler CM et al. Comparison of human leukocyte antigen DR-DQ disease associations found with cervical dysplasia and invasive cervical carcinoma. J Natl Cancer Inst 1995; 87: 427–436.

    Article  PubMed  CAS  Google Scholar 

  41. Nawa A, Nishiyama Y, Kobayashi T et al. Association of human leukocyte antigen-B1*03 with cervical cancer in Japanese women aged 35 years and younger. Cancer 1995; 75: 518–521.

    Article  PubMed  CAS  Google Scholar 

  42. Jenison SA, Yu XP, Valentine JM et al. Evidence of prevalent genital-type human papillomavirus infections in adults and children. J Inf Dis 1990; 162: 60–69.

    Article  CAS  Google Scholar 

  43. Kaye JN, Starkey WG, Kell B et al. Human papillomavirus type 16 in infants: use of DNA sequence analyzes to determine the source of infection. J Gen Virol 1996; 77: 1139–1143.

    Article  PubMed  CAS  Google Scholar 

  44. Shah KV, Howley PH. Papillomaviruses. In: Fields BN et al. Virology. Philadelphia: Virology. 1996; 2: 2077–2109.

    Google Scholar 

  45. Chambers MA, Stacey SN, Arrand JR et al. Delayed-type hypersensitivity response to human papillomaviruses type 16 E6 protein in a mouse model. J Gen Virol 1994; 75: 165–169.

    Article  PubMed  CAS  Google Scholar 

  46. Höpfl RM, Sandbichler M, Sepp N et al. Skin test for HPV16 proteins in cervical intraepithelial neoplasia. Lancet 1991; 337: 373–374.

    Article  PubMed  Google Scholar 

  47. Comerford SA, McCance DJ, Dougan G et al. Identification of Tand B-cell epitopes of the E7 protein of human papillomavirus type 16. J Virol 1991; 65: 4681–4690.

    PubMed  CAS  Google Scholar 

  48. Shepherd PS, Tran TTT, Rowe AJ et al. T cell responses to the human papillomavirus type 16 E7 protein in mice of different haplotypes. J Gen Virol 1992; 73: 1269–1274.

    Article  PubMed  CAS  Google Scholar 

  49. Tindle RW, Fernando GJP, Sterling JC et al. A “public” T-helper epitope of the E7 transforming protein of human papillomavirus 16 provides cognate help for several B-cell epitopes from cervical cancer-associated human papillomavirus genotypes. Proc Natl Acad Sci USA 1991; 88: 5887–5891.

    Article  PubMed  CAS  Google Scholar 

  50. Tindle RW, Herd K, Londono P et al. Chimeric Hepatitis B core antigen particles containing B- and Th-epitopes of human papillomavirus type 16 E7 protein induce specific antibody and T-helper responses in immunised mice. Virology 1994; 200: 547–557.

    Article  PubMed  CAS  Google Scholar 

  51. Tindle RW, Croft S, Herd K et al. A vaccine conjugate of ëISCARI immunocarrier and peptide epitopes of the E7 cervical cancer associated protein of human papillomavirus type 16 elicits specific Th1and Th2-type responses in immunized mice in the absence of oil-based adjuvants. Clin Exp Immunol 1995; 101: 265–271.

    PubMed  CAS  Google Scholar 

  52. Gao L, Chain B, Sinclair C, Crawford L et al. Immune response to human papillomavirus type 16 E6 in a live vaccinia vector. J Gen Virol 1994; 75: 157–164.

    Article  PubMed  CAS  Google Scholar 

  53. Cubie HA, Norval M, Crawford L et al. Lymphoproliferative response to fusion proteins of human papillomavirus in patients with cervical intraepithelial neoplasia. Epidemiol Infect 1989; 103: 625–632.

    Article  PubMed  CAS  Google Scholar 

  54. Kadish AS, Romney SL, Ledwidge R et al. Cell-mediated immune responses to E7 peptides of human papillomavirus (HPV) type 16 are dependent on the HPV type infecting the cervix whereas serological reactivity is not type-specific. J Gen Virol 1994; 75: 2277–2282.

    Article  PubMed  Google Scholar 

  55. Altmann A, Jochmus-Kudielka I, Frank R et al. Definition of immunogenic determinants of the human papillomavirus type 16 nucleoprotein E7. Eur J Cancer 1992; 28: 326–333.

    Article  PubMed  CAS  Google Scholar 

  56. de Gruijl TD, Bontkes HJ, Stukart MJ et al. T cell proliferative responses against human papillomavirus type 16 E7 oncoprotein are most prominent in cervical intraepithelial neoplasia patients with persistent viral infection. J Gen Virol 1996; 77: 2183–2191.

    Article  PubMed  Google Scholar 

  57. Strang G, Hickling JK, McIndoe GA et al. Human T cell responses to human papillomavirus 16 L1 and E6 synthetic peptides: Identification of T cell determinants, HLA-DR restriction and virus-type specificity. J Gen Virol 1990; 71: 423–431.

    Article  PubMed  CAS  Google Scholar 

  58. McLean CS, Sterling JS, Mowat J et al. Delayed-type hypersensitivity response to human papillomavirus type 16 E7 protein in a mouse model. J Gen Virol 1993; 74: 239–245.

    Article  PubMed  CAS  Google Scholar 

  59. Chambers MA, Wej Z, Coleman N et al. “Natural” presentation of human papillomavirus type-16 E7 protein to immunocompetent mice results in antigen-specific sensitization or sustained unresponsiveness. Eur J Immunol 1994; 24: 738–745.

    Article  PubMed  CAS  Google Scholar 

  60. Stauss HJ, Davies H, Sadovnikova E et al. Induction of cytotoxic T lymphocytes with peptides in vitro: Identification of candidate T-cell epitopes in human papilloma virus. Proc Natl Acad Sci USA 1992; 89: 7871–7875.

    Article  PubMed  CAS  Google Scholar 

  61. Feltkamp MCW, Smits HL, Vierboom MPM et al. Vaccination with cytotoxic T lymphocyte epitope-containing peptide protects against a tumor induced by human papillomavirus type 16-transformed cells. Eur J Immunol 1993; 23: 2242–2249.

    Article  PubMed  CAS  Google Scholar 

  62. Feltkamp MCW, Vreugdenhil GR, Vierboom MPM et al. Cytotoxic T lymphocytes raised against a subdominant epitope offered as a synthetic peptide eradicate human papillomavirus type 16-induced tumors. Eur J Immunol 1995; 25: 2638–2642.

    Article  PubMed  CAS  Google Scholar 

  63. Sadovnikova E, Zhu X, Collins SM, Zhou J et al. Limitations of predictive motifs revealed by cytotoxic T lymphocyte epitope mapping of the human papilloma virus E7 protein. International Immunol 1994; 6: 289–296.

    Article  CAS  Google Scholar 

  64. Ossevoort MA, Feltkamp MCW, van Veen KJH et al. Dendritic cells as carriers for a catotoxic T-lymphocyte epitope-based peptide vaccine in protection against a human papillomavirus type 16-induced tumor. J Immunother 1995; 18: 86–94.

    Article  CAS  Google Scholar 

  65. Zhu X, Tommasino M, Vousden K et al. Both immunization with protein and recombinant vaccinia virus can stimulate CTL specific

    Google Scholar 

  66. Chen L, Thomas EK, Hu S-L et al. Human papillomavirus type 16 nucleoprotein E7 is a tumor rejection antigen. Proc Natl Acad Sci USA 1991; 88: 110–114.

    Article  PubMed  CAS  Google Scholar 

  67. Chen L, Mizuno MT, Singhal MC et al. Induction of cytotoxic T lymphocytes specific for a syngeneic tumor expressing the E6 oncoprotein of human papillomavirus type 16. J Immunol 1992; 148: 2617–2621.

    PubMed  CAS  Google Scholar 

  68. Chen L, Ashe S, Brady WA et al. Costimulation of antitumor immunity by the B7 counterreceptor for the T lymphocyte molecules CD28 and CTLA-4. Cell 1992; 71: 1093–1102.

    Article  PubMed  CAS  Google Scholar 

  69. Meneguzzi G, Cerni C, Kieny MP et al. Immunization against human papillomavirus type 16 tumor cells with recombinant vaccinia viruses expressing E6 and E7. Virology 1991; 181: 62–69.

    Article  PubMed  CAS  Google Scholar 

  70. Gao L, Walter J, Travers P et al. Tumor-associated E6 protein of human papillomavirus type 16 contains an unusual H-2Kb-restricted cytotoxic T cell epitope. J Immunol 1995; 155: 5519–5526.

    PubMed  CAS  Google Scholar 

  71. Kast WM, Brandt RMP, Sidney J et al. Role of HLA-A motifs in identification of potential CTL epitopes in human papillomavirus type 16 E6 and E7 proteins. J Immunol 1994; 152: 3904–3912.

    PubMed  CAS  Google Scholar 

  72. Ressing ME, Sette A, Brandt RMP et al. Human CTL epitopes encoded by human papillomavirus type 16 E6 and E7 identified through in vivo and in vitro immunogenicity studies of HLA-A*0201-binding peptides. J Immunol 1995; 154: 5934–5943.

    PubMed  CAS  Google Scholar 

  73. Jochmus I, Osen W, Altmann A, Buck G, Hofmann B, Schneider A, Gissmann L, Rammensee H-G. Specificity of human cytotoxic T lymphocytes induced by a human papillomavirus type A6 E7-derived peptide. J Gen Virol 1997; 78:in press.

    Google Scholar 

  74. Ressing ME, van Driel WJ, Celis E et al. Occasional memory cytotoxic T-cell responses of patients with human papillomavirus type 16-positive cervical lesions against a human leukocyte antigen -A*0201-restricted E7-encoded epitope. Cancer Res 1996; 56: 582–588.

    PubMed  CAS  Google Scholar 

  75. Bartholomew JS, Stacey SN, Coles B et al. Identification of a naturally processed HLA A0201-restricted viral peptide from cells expressing human papillomavirus type 16 E6 oncoprotein. Eur J Immunol 1994; 24: 3175–3179.

    Article  PubMed  CAS  Google Scholar 

  76. Tarpey I, Stacey S, Hickling J et al. Human cytotoxic T lymphocytes stimulated by endogenously processed human papillomavirus type 11 E7 recignize a peptide containing a HLA-A2 (A*0201) motif. Immunology 1994; 81: 222–227.

    PubMed  CAS  Google Scholar 

  77. Gissmann L. Human papillomaviruses and genital cancer. Semin Cancer Biol 1992; 3 /5: 253–261.

    PubMed  CAS  Google Scholar 

  78. Cromme FV, Meijer CJLM, Snijders PJF et al. Analysis of MHC class I and II expression in relation to presence of HPV genotypes in premalignant and malignant cervical lesions. Br J Cancer 1993; 67: 1372–1380.

    Article  PubMed  CAS  Google Scholar 

  79. Wu T-C, Guarnieri FG, Staveley-OíCarroll KF et al. Engineering an intracellular pathway for major histocompatibility complex class II presentation of antigens. Proc Natl Acad Sci USA 1995; 92: 11671–11675.

    Article  PubMed  CAS  Google Scholar 

  80. Lin K-Y, Guarnieri FG, Staveley-OlCarroll KF et al. Treatment of established tumors with a novel vaccine that enhances major histocompatibility class II presentation of tumor antigen. Cancer Res 1996; 56: 21–26.

    PubMed  CAS  Google Scholar 

  81. Boursnell MEG, Rutherford E, Hickling JK et al. Construction and characterization of a recombinant vaccinia virus expressing human papillomavirus proteins for immunotherapy of cervical cancer. Vaccine 1996; 14: 1485–1494.

    Article  PubMed  CAS  Google Scholar 

  82. Borysiewicz LK, Fiander A, Nimako M et al. A recombinant vaccinia vii us encoding human papillomavirus types 16 and 18, E6 and E7 proteins as immunotherapy for cervical cancer. Lancet 1996; 347: 1523–1527.

    Article  PubMed  CAS  Google Scholar 

  83. Tindle RW. Human papillomavirus vaccines for cervical cancer. Curr Opin Immunol 1996; 8: 643–650.

    Article  PubMed  CAS  Google Scholar 

  84. Thomson SA, Khanna R, Gardner J et al. Minimal epitopes expressed in a recombinant polyepitope protein are processed and presented to CD8+ cytotoxic T-cells. Proc Natl Acad Sci USA 1995; 13: 5845–5849.

    Article  Google Scholar 

  85. Pozzi G, Contorni M, Oggioni MR et al. Delivery and expression of a heterologous antigen on the surface of streptococci. Infect Immunity 1992; 60: 1902–1907.

    CAS  Google Scholar 

  86. Oggioni MR, Manganelli R, Contorni M et al. Immunization of mice by oral colonization with live recombinant commensal streptococci. Vaccine 1995; 13: 775–779.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Ingrid Jochmus
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lutz Gissmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Jochmus, I., Gissmann, L. (1997). Immunological Aspects of the E6 and E7 Oncogenes: Tools for Diagnosis and Therapeutic Intervention. In: Papillomaviruses in Human Cancer. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-6127-6_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-6127-6_5

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-6129-0

  • Online ISBN: 978-1-4757-6127-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation