1887

Abstract

T-helper (Th) cell-dependent IL-2 production and plasma IgG responses to virus-like particles consisting of the human papillomavirus type 16 (HPV-16) major capsid protein L1 (L1-VLP) were determined in patients with cytological evidence of cervical intraepithelial neoplasia (CIN) participating in a non-intervention prospective cohort study. IgG responses were associated with HPV-16 persistence and high-grade CIN lesions, while high frequencies of Th responses were observed in patients with both virus clearance and virus persistence, irrespective of CIN grade. The IgG response was found in conjunction with an IL-2 response to L1-VLP in 87% of the patients. Recognition of the HPV-16 L1 Th epitope (amino acids 311-335) was found to be more closely associated than recognition of L1-VLP as a whole to HPV exposure and CIN development. Among the HPV-16+ patients included in this study, those showing a Th response to amino acids 311-335 were more likely to carry the HLA DRB1*11/DQB1*0301 haplotype, while those showing an IgG response to L1-VLP were more likely to carry DRB1*0101/DQB1*0501. However, neither cell-mediated nor humoral immune responses against HPV-16 L1 appear to be sufficient for the natural control of HPV infection and CIN development.

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1999-02-01
2021-09-24
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References

  1. Bontkes H. J., de Gruijl T. D., Walboomers J. M. M., Schiller J. T., Dillner J., Helmerhorst T. J. M., Verheijen R. H. M., Scheper R. J., Meijer M. C. J. L. 1999; Immune responses against human papillomavirus (HPV) type 16 virus-like particles in a cohort study of women with cervical intraepithelial neoplasia. II. Systemic but not local IgA responses correlate with clearance of HPV-16. Journal of General Virology 80:409–417
    [Google Scholar]
  2. Borysiewicz L. K., Fiander A., Nimako M., Man S., Wilkinson G. W. G., Westmoreland D., Evans A. S., Adams M., Stacey S. N., Boursnell M. E. G., Rutherford E., Hickling J. K., Inglis S. C. 1996; A recombinant vaccinia virus encoding human papillomavirus types 16 and 18, E6 and E7 proteins as immunotherapy for cervical cancer. Lancet 347:1523–1527
    [Google Scholar]
  3. Breitburd F., Kirnbauer R., Hubbert N. L., Nonnenmacher B., TrinDinh-Desmarquet C., Orth C., Schiller J. T., Lowy D. R. 1995; Immunization with viruslike particles from cottontail rabbit papillomavirus (CRPV) can protect against experimental CRPV infection. Journal of Virology 69:3959–3963
    [Google Scholar]
  4. Carter J. J., Koutsky L. A., Wipf G. C., Christensen N. D., Lee S.-K., Kuypers J., Kiviat N., Galloway D. A. 1996; The natural history of human papillomavirus type 16 capsid antibodies among a cohort of university women. Journal of Infectious Diseases 174:927–936
    [Google Scholar]
  5. Chaturvedi P., Yu Q., Southwood S., Sette A., Singh B. 1995; Peptide analogs with different affinities for MHC alter the cytokine profile of helper T cells. International Immunology 8:745–755
    [Google Scholar]
  6. Chua K. L., Wiklund L., Lenner P., Angstrom T., Hallmans G., Bergman F., Sapp M., Schiller J., Wadell G., Hjerpe A., Dillner J. 1996; A prospective study on the risk of cervical intra-epithelial neoplasia among healthy subjects with serum antibodies to HPV compared with HPV DNA in cervical smears. International Journal of Cancer 68:54–59
    [Google Scholar]
  7. de Gruijl T. D., Bontkes H. J., Stukart M. J., Walboomers J. M. M., Remmink A. J., Verheijen R. H. M., Helmerhorst T. J. M., Meijer C. J. L. M., Scheper R. J. 1996; T cell proliferative responses against human papillomavirus type 16 E7 oncoprotein are most prominent in cervical intraepithelial neoplasia patients with a persistent viral infection. Journal of General Virology 77:2183–2191
    [Google Scholar]
  8. de Gruijl T. D., Bontkes H. J., Walboomers J. M. M., Schiller J. T., Stukart M. J., Groot B. S., Chabaud M. M. R., Remmink A. J., Verheijen R. H. M., Helmerhorst Th. J. M., Meijer C. J. L. M., Scheper R. J. 1997; Immunoglobulin G responses against human papillomavirus type 16 virus-like particles in a prospective nonintervention cohort study of women with cervical intraepithelial neoplasia. Journal of the National Cancer Institute 89:630–638
    [Google Scholar]
  9. de Gruijl T. D., Bontkes H. J., Walboomers J. M. M., Stukart M. J., Doekhie F. S., Remmink A. J., Helmerhorst Th. J. M., Verheijen R. H. M., Duggan-Keen M. F., Stern P. L., Meijer C. J. L. M., Scheper R. J. 1998; Differential T helper cell responses to human papillomavirus type 16 E7 related to viral clearance or persistence in patients with cervical neoplasia: a longitudinal study. Cancer Research 58:1700–1706
    [Google Scholar]
  10. de Roda Husman A. M., Walboomers J. M. M., Meijer C. J. L. M., Risse E. K. J., Schipper M. E. I., Helmerhorst T. J. M., Bleker O. P., Delius H., van den Brule A. J. C., Snijders P. J. F. 1994; Analysis of cytomorphologically abnormal cervical scrapes for the presence of 27 mucosotropic human papillomavirus genotypes, using polymerase chain reaction. International Journal of Cancer 56:802–806
    [Google Scholar]
  11. de Roda Husman A.-M., Walboomers J. M. M., van den Brule A. J. C., Meijer C. J. L. M., Snijders P. J. F. 1995; The use of general primers GP5 and GP6 elongated at their 3′ ends with adjacent highly conserved sequences improves human papillomavirus detection by PCR. Journal of General Virology 76:1057–1062
    [Google Scholar]
  12. Duggan-Keen M. F., Keating P. J., Stevens F. R. A., Sinnott P., Snijders P. J. F., Walboomers J. M. M., Davidson S., Hunter R. D., Dyer P. A., Stern P. L. 1996; Immunogenetic factors in HPV-associated cervical cancer: influence on disease progression. European Journal of Immunogenetics 23:275–284
    [Google Scholar]
  13. Dupuy C., Buzoni-Gatel D., Touze A., Le Cann P., Bout D., Coursaget P. 1997; Cell mediated immunity induced in mice by HPV-16 L1 virus-like particles. Microbial Pathogenesis 22:219–225
    [Google Scholar]
  14. Ertl H. C. J., Dietzschold B., Gore M., Otvos L., Larson J. K., Wunner W. H., Koprowski H. 1989; Induction of rabies virus-specific T-helper cells by synthetic peptides that carry dominant T-helper cell epitopes of the viral ribonucleoprotein. Journal of Virology 63:2885–2892
    [Google Scholar]
  15. Frazer I. H. 1996; Immunology of papillomavirus infection. Current Opinions in Immunology 8:484–491
    [Google Scholar]
  16. Höpfl R., Sandbichler M., Sepp N., Heim K., Müller-Holzner E., Wartusch B., Dapunt O., Jochmus-Kudielka I., ter Meulen J., Gissmann L., Fritsch P. 1991; Skin test for HPV type 16 proteins in cervical intraepithelial neoplasia. Lancet i:373–374
    [Google Scholar]
  17. IARC 1995 Monographs on the Evaluation of the Carcinogenic Risks to Humans vol 64 The Human Papillomavirus, Lyon; International Agency for Research on Cancer:
    [Google Scholar]
  18. Jacobs M. V., de Roda Husman A. M., van den Brule A. J. C., Snijders P. J. F., Meijer C. J. L. M., Walboomers J. M. M. 1995; Group-specific differentiation between high- and low-risk human papillomavirus genotypes by using the general primer-mediated PCR and two cocktails of oligonucleotide probes. Journal of Clinical Microbiology 33:901–905
    [Google Scholar]
  19. Kirnbauer R., Taub J., Greenstone H., Roden R., Durst M., Gissmann L., Lowy D. R., Schiller J. T. 1993; Efficient self-assembly of human papillomavirus type 16 L1 and L1–L2 into virus-like particles. Journal of Virology 67:6929–6936
    [Google Scholar]
  20. Kirnbauer R., Chandrachud L. M., O’Neil B. W., Wagner E. R., Grindlay G. J., Armstrong A., McGarvie G. M., Schiller J. T., Lowy D. R., Campo M. S. 1996; Virus-like particles of bovine papillomavirus type 4 in prophylactic and therapeutic immunization. Virology 219:37–44
    [Google Scholar]
  21. Le Cann P., Coursaget P., Iochmann S., Touze A. 1994; Selfassembly of human papillomavirus type 16 capsids by expression of the L1 protein in insect cells. FEMS Microbiology Letters 117:269–274
    [Google Scholar]
  22. Lehtinen M., Dillner J., Knekt P., Luostarinen T., Aromaa A., Kirnbauer R., Koskela P., Paavonen J., Peto R., Schiller J. T., Hakama M. 1996; Serologically diagnosed infection with human papillomavirus type 16 and risk for subsequent development of cervical carcinoma: nested case-control study. British Medical Journal 312:537–539
    [Google Scholar]
  23. Luxton J. C., Rose R. C., Coletart T., Wilson P., Shepherd P. S. 1997; Serological and T-helper cell responses to human papillomavirus type 16 L1 in women with cervical dysplasia or cervical carcinoma and in healthy controls. Journal of General Virology 78:917–923
    [Google Scholar]
  24. Nonnenmacher B., Hubbert N. L., Kirnbauer R., Shah K. V., Munoz N., Bosch F. X., Desanjose S., Viscidi R., Lowy D. R., Schiller J. T. 1995; Serologic response to human papillomavirus type 16 (HPV-16) virus-like particles in HPV-16 DNA-positive invasive cervical cancer and cervical intraepithelial neoplasia grade III patients and controls from Colombia and Spain. Journal of Infectious Diseases 172:19–24
    [Google Scholar]
  25. Remmink A. J., Walboomers J. M. M., Helmerhorst T. J. M., Voorhorst F. J., Rozendaal L., Risse E. K. J., Meijer C. J. L. M., Kenemans P. 1995; The presence of persistent high-risk HPV genotypes in dysplastic cervical lesions is associated with progressive disease: natural history up to 36 months. International Journal of Cancer 61:306–311
    [Google Scholar]
  26. Schiller J. T., Roden R. B. S. 1995; Papillomavirus-like particles. Papillomavirus Report 6:121–128
    [Google Scholar]
  27. Shepherd P. S., Rowe A. J., Cridland J. C., Coletart T., Wilson P., Luxton J. C. 1997; Proliferative T cell responses to human papillomavirus type 16 L1 peptides in patients with cervical dysplasia. Journal of General Virology 77:593–602
    [Google Scholar]
  28. Suzich J. A., Ghim S.-J., Palmer-Hill F. J., White W. I., Tamura J. K., Bell J. A., Newsome J. A., Jenson A. B., Schlegel R. 1995; Systemic immunization with papillomavirus L1 protein completely prevents the development of viral mucosal papillomas. Proceedings of the National Academy of Sciences, USA 92:11553–11557
    [Google Scholar]
  29. Tindle R. W. 1996; Human papillomavirus vaccines for cervical cancer. Current Opinions in Immunology 8:643–650
    [Google Scholar]
  30. Tsukui T., Hildesheim A., Schiffman M. H., Luci J. III, Contois D., Lawler P., Rush B. B., Lorincz A. T., Corrigan A., Burk R. D., Qu W., Marshall M. A., Mann D., Carrington M., Clerici M., Shearer G. M., Carbone D. P., Scott D. R., Houghten R. A., Berzofsky J. A. 1996; Interleukin 2 production in vitro by peripheral lymphocytes in response to human papillomavirus-derived peptides: correlation with cervical pathology. Cancer Research 56:3967–3974
    [Google Scholar]
  31. Wang Z., Hansson B. G., Forslund O., Dillner L., Sapp M., Schiller J. T., Bjerre B., Dillner J. 1996; Cervical mucus antibodies against human papillomavirus type 16, 18, and 33 capsids in relation to presence of viral DNA. Journal of Clinical Microbiology 34:3056–3062
    [Google Scholar]
  32. Wikström A., van Doornum G. J. J., Quint W. G. V., Schiller J. T., Dillner J. 1995; Identification of human papillomavirus sero-conversions. Journal of General Virology 76:529–539
    [Google Scholar]
  33. Zinkernagel R. M. 1996; Immunology taught by viruses. Science 271:173–178
    [Google Scholar]
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