Prevalence of Antibodies Against Defined HPV Epitopes Among Incident Cases of Cervical Neoplasia: Current Status and Concepts

  • Lena Dillner
  • Joakim Dillner

Abstract

Much of the recent discussion on HPV serology has focussed on the distinction between linear and conformational. epitopes, with the difference being that the conformational. epitopes are sensitive to conformational. changes, whereas the linear ones are not. In practice, this has amounted to that assays using immunoblotting or synthetic peptides are generally classified as linear epitope assays, whereas various other assays including immunofluorescence, immunoprecipitation and ELIS As using whole proteins are claimed to be conformational. epitope assays. In many respects, this distinction between linear and conformational. epitopes is misleading, since it erroneously implies that epitopes displayed in immunoblotting or in synthetic peptides are devoid of conformation and since it does not point out that assays using e.g. whole proteins will display both linear and conformational. epitopes. Furthermore, there exist no theoretical. grounds to assume that conformational. epitopes would be more specific than linear epitopes. On the contrary, conformational. epitopes are, by definition, more sensitive to conformational. change and assays based on such epitopes are therefore likely to have greater assay variability problems. Although there is convincing evidence demonstrating that intact HPV particles contain immunodominant and type-specific epitopes that are sensitive to conformational change1,2, there are no grounds for extrapolation of these findings into believing that conformational. epitopes would be more immunodominant or type-specific also in other proteins.

Keywords

Adenocarcinoma Polypeptide Carboxy Papilloma Sera 

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References

  1. 1.
    N.D. Christensen and J.W. Kreider, Antibody-mediated neutralization in vivo of infectious papillomavi-ruses, J Virol. 64:3151 (1990).PubMedGoogle Scholar
  2. 2.
    J. Dillner. Immunobiology of papillomavirus. Prospects for vaccination, Cancer J. 5:181 (1992).Google Scholar
  3. 3.
    D.A. Galloway and S.A. Jenison, Characterization of the humoral. immune response to genital. papillomaviruses, Mol Biol Med. 7:59 (1990).PubMedGoogle Scholar
  4. 4.
    S.A. Jenison, X.P. Yu, J.M. Valentine, A. Koutsky, A.E. Christiansen, A.M. Beckmann, and D.A. Galloway, Evidence of prevalent genital-type human papillomavirus infections in adults and children, J Infect Dis. 162:60 (1990).PubMedCrossRefGoogle Scholar
  5. 5.
    H. zur Hausen, Viruses in human cancers, Science 254:1167 (1991).PubMedCrossRefGoogle Scholar
  6. 6.
    M.H. Schiffman, Recent progress in defining the epidemiology of human papillomavirus infection and cervical neoplasia, J Natl Cancer Inst. 84:394 (1992).PubMedCrossRefGoogle Scholar
  7. 7.
    L. Dillner, P. Heino, J. Moreno-Lopez, and J. Dillner, Antigenic and immunogenic epitopes shared by human papillomavirus type 16 and bovine, canine, and avian papillomaviruses, J Virol. 65:6862 (1991).PubMedGoogle Scholar
  8. 8.
    S.A. Jenison, X.P. Yu, J.M. Valentine, and D.A. Galloway, Characterization of human antibody-reactive epitopes encoded by human papillomavirus types 16 and 18, J Virol. 65:1208 (1991).PubMedGoogle Scholar
  9. 9.
    G. Orth, F. Breitburd, and M. Favre, Evidence for antigenic determinants shared by the structural. polypeptides of (Shope) rabbit papillomavirus and human papillomavirus type 1. Virology 91:243 (1978).PubMedCrossRefGoogle Scholar
  10. 10.
    S.A. Jenison, X.P. Yu, J.A. Valentine, and D.A. Galloway, Human antibodies react with an epitope of the human papillomavirus type 6b LI open reading frame which is distinct from the type-common epitope, J Virol. 63:809 (1989).PubMedGoogle Scholar
  11. 11.
    J. Dillner, P. Lenner, M. Lehtinen, C. Eklund, P. Heino, F. Wiklund, G. Hallmans and U. Stendahl, A population-based seropeidemiological. study of cervical. cancer, Cancer Res. In press 1994.Google Scholar
  12. 12.
    L. Dillner, P. Heino, E. Åvail, A. Zellbi, C. Pettersson, O. Forslund, B.G. Hansson, M. Grandien, P. Bistoletti and J. Dillner, Analysis of the presence of antibodies against defined HPV epitopes and HPV DNA status among incident cases of cervical. cancer, In preparation.Google Scholar
  13. 13.
    L. Dillner, Z. Bekassy, N. Jonsson, J. Moreno-Lopez, and J. Blomberg, Detection of IgA antibodies against human papillomavirus in cervical. secretions from patients with cervical. intraepithelial. neoplasia, Int J Cancer 43:36 (1989).PubMedCrossRefGoogle Scholar
  14. 14.
    L. Dillner, J. Moreno-Lopez, and J. Dillner, Serological. responses to papillomavirus group-specific antigens in women with neoplasia of the cervix uteri, J Clin Microbiol. 28:624 (1990).PubMedGoogle Scholar
  15. 15.
    P.J. Baird, Serological. evidence for the association of papillomavirus and cervical. neoplasia, Lancet ii:17 (1983).CrossRefGoogle Scholar
  16. 16.
    N.D. Christensen, J.W. Kreider, K.V. Shah, and R.F. Rando, Detection of human serum antibodies that neutralize infectious human papillomavirus type 11 virions, J Gen Virol. 73:1261 (1992).PubMedCrossRefGoogle Scholar
  17. 17.
    I. Jochmus-Kudielka, A. Schneider, R. Braun, R. Kimmig, U. Koldovsky, K. E. Schneweis, K. Seedorf, and L. Gissman, Antibodies against the human papillomavirus type 16 early proteins in human sera: Correlation of anti-E7 reactivity with cervical. cancer, J Nat Cancer Inst. 81:1698 (1989).PubMedCrossRefGoogle Scholar
  18. 18.
    Muller, M., R. P. Viscidi, Y. Sun, E. Guerrero, P. M. Hill, F. Shah, F. X. Bosch, N. Munoz, L. Gissmann, and K. V. Ghah. 1992. Antibodies to HPV-16 E6 and E7 proteins as markers for HPV-16 associated invasive cervical. carcinoma. Virology 187:508–514.PubMedCrossRefGoogle Scholar
  19. 19.
    V.M. Mann, S. Loo de Lao, M. Brenes, L.A. Brinton, J.A. Rawls, M. Green, W.C. Reeves, and W.E. Rawls, Occurrence of IgA and IgG antibodies to select peptides representing human papillomavirus type 16 among cervical. cancer cases and controls, Cancer Res. 50:7815 (1990).PubMedGoogle Scholar
  20. 20.
    A. Suchankova, L. Ritterova, M. Krcmar, V. Krchnak, J. Vagner, I. Jochmus, L. Gissman, J. Kanka, and V. Vonka, Comparison of ELIS A and Western blotting for human papillomavirus type 16 E7 antibody determination, J Gen Virol. 72:2577 (1991).PubMedCrossRefGoogle Scholar
  21. 21.
    J. Dillner, Mapping of linear epitopes of human papillomavirus type 16: The El, E2, E4, E5, E6 and E7 open reading frames. Int J Cancer 46:703 (1990).PubMedCrossRefGoogle Scholar
  22. 22.
    J. Dillner, Disappearance of antibodies against HPV 16 E7 following treatment for cervical. cancer, Lancet 341:1594 (1993).PubMedCrossRefGoogle Scholar
  23. 23.
    J. Dillner, L. Dillner, J. Robb, J. Willems, I. Jones, W. Lancaster, R. Smith, and R. Lerner, A synthetic peptide defines a serologic IgA response to a human papillomavirus-encoded nuclear antigen expressed in virus-carrying cervical. neoplasia, Proc Natl Acad Sci. USA 86:3838 (1989).PubMedCrossRefGoogle Scholar
  24. 24.
    M. Lehtinen, P. Parkkonen, H. Luoto, A. Ylä-Outinen, U. Romppanen, I. Rantala, and J. Paavonen, Antipeptide IgA antibodies to a human papillomavirus type 16 E2 derived synthetic peptide predict the natural. history of cervical. HPV infection, Serono Symposia Publications 78:509 (1990).Google Scholar
  25. 25.
    W.C. Reeves, J.A. Rawls, M. Green, and W.E. Rawls, Antibodies to human papillomavirus type 16 in patients with cervical. neoplasia, Lancet i:551 (1990).CrossRefGoogle Scholar
  26. 26.
    H. Strickler, M.H. Schiffman, and J. Dillner, Unpublished observation.Google Scholar
  27. 27.
    M. Lehtinen, A. Leminen, T. Kuoppala, M. Tiikkainen, T. Lehtinen, P. Lehtovirta, R. Punnonen, E. Vesterinen, and J. Paavonen, Pre-and posttreatment serum antibody responses to HPV 16 E2 and HSV 2 ICP8 proteins in women with cervical. carcinoma, J Med Virol. 37:180 (1992).PubMedCrossRefGoogle Scholar
  28. 28.
    K. Elfgren, P. Bistoletti, L. Dillner, and J. Dillner, Unpublished observation.Google Scholar
  29. 29.
    M. Lehtinen, A. Leminen, J. Paavonen, P. Lehtovirta, H. Hyöty, E. Vesterinen, and J. Dillner, Predominance of serum antibodies to synthetic peptide stemming from HPV 18 open reading frame E2 in cervical. adenocarcinoma, J Clin Pathol. 45:494 (1992).PubMedCrossRefGoogle Scholar
  30. 30.
    P. Heino, S. Goldman, U. Lagerstedt, and J. Dillner, Molecular and serological. studies of human papillomavirus among patients with anal. epidermoid carcinoma, Int J Cancer 53:377 (1993).PubMedCrossRefGoogle Scholar
  31. 31.
    A. Suchankova, V. Krchnak, J. Vagner, E. Hamsikova, M. Krcmar, L. Ritterova, and V. Vonka, Epitope mapping of the human papillomavirus type 16 E4 protein by means of synthetic peptides, J Gen Virol. 73:429 (1992).PubMedCrossRefGoogle Scholar
  32. 32.
    A. Wikström, C. Eklund, G. von Krogh, P. Lidbrink, and J. Dillner, Levels of immunoglobulin G antibodies against defined epitopes of the L1 and L2 capsid proteins of human papillomavirus type 6 are elevated in men with a history of condylomata acuminata, J Clin Microbiol. 30:1795 (1992).PubMedGoogle Scholar
  33. 33.
    J. Dillner, L. Dillner, G. Utter, C. Eklund, A. Rotola, S. Costa, and D. DiLuca. 1990. Mapping of linear epitopes of human papillomavirus type 16: The L1 and L2 open reading frames. Int J Cancer. 45:529 (1990).PubMedCrossRefGoogle Scholar
  34. 34.
    M. Lehtinen, J. Niemelä, J. Dillner, P. Parkkonen, T. Nummi, E. Liski, P. Nieminen, T. Reunala, and J. Paavonen, Evaluation of serum antibody responses to a newly identified B-cell epitope in the minor nucleocapsid protein L2 of human papillomavirus type 16, Clin Diagn Virol. 1:153 (1993).PubMedCrossRefGoogle Scholar
  35. 35.
    A. Wikström. G. van Doornum, L. Pronk, and J. Dillner, Unpublished observation.Google Scholar
  36. 36.
    C. Bleul, M. Muller, R. Frank, H. Gausepohl, U. Koldovsky, H.N. Mgaya, J. Luande, M. Pawlita, J. ter Meulen, R. Viscidi, and L. Gissmann, Human papillomavirus type 18 E6 and E7 antibodies in human sera:Increased anti-E7 prevalence in cervical. cancer patients, J Clin Microbiol. 29:1579 (1991).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • Lena Dillner
    • 1
  • Joakim Dillner
    • 1
  1. 1.Department of VirologyKarolinska InstituteStockholmSweden

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