Immunosuppressive cytokine Interleukin-10 (IL-10) is up-regulated in high-grade CIN but not associated with high-risk human papillomavirus (HPV) at baseline, outcomes of HR-HPV infections or incident CIN in the LAMS cohort (original) (raw)

Abstract

Bypassing the local immunological defense reactions in the cervix is one of the prerequisites for human papillomaviruses (HPV) infections to progress to intraepithelial neoplasia (CIN). The role of potent immunosuppressive cytokines, e.g., interleukin-10 (IL-10), depressing these local virus-specific immunological responses is incompletely studied. To assess, whether IL-10 expression in cervical HPV lesions has any implications in the outcome of HPV infections or disease progression to CIN. Baseline cervical biopsies from 225 women of the LAMS study sub-cohort were analyzed for IL-10 expression using immunohistochemistry, to assess its associations with CIN grade, and high-risk HPV (HR-HPV) at baseline, as well as in predicting outcomes of HR-HPV infections, and development of incident CIN1+ and CIN2+ in this longitudinal setting. Expression of IL-10 in cervical lesions was up-regulated most often in high-grade CIN, and IL-10 over-expression retained its value as independent predictor of CIN2+ (odds ratio (OR) = 4.92) and CIN3+ (OR = 7.51) also in multivariate model, including HR-HPV and several known covariates of IL-10 expression. Up-regulation was not related to HR-HPV detection, and showed no relationship to HR-HPV viral loads. Using longitudinal predictive indicators (SE, SP, PPV, NPV), IL-10 expression was of no value in predicting (1) the outcomes of HR-HPV infections, or (2) the surrogate endpoints (incident CIN1+, CIN2+) of progressive disease. IL-10 over-expression (along with HR-HPV) was one of the independent covariates of CIN2/3. This immunosuppressive cytokine might play an important role in creating a microenvironment that favors progressive cervical disease and immune evasion by HR-HPV.

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Acknowledgements

This study has been supported by the European Commission, INCO-DEV Programme (Contract# ICA4-CT-2001-10013). The generous contribution of former DIGENE Inc. (USA) donating the HC2 tests at our disposal is gratefully acknowledged.

Conflict of interest statement

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Oral Pathology, Institute of Dentistry, University of Turku, Turku, Finland
    Stina Syrjänen
  2. Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil
    Paulo Naud & L. S. Hammes
  3. Universidade Estadual de Campinas, Campinas, Brazil
    Luis Sarian & Sophie Derchain
  4. Hospital Leonor M de Barros, Sao Paulo, Brazil
    Cecilia Roteli-Martins
  5. Instituto Adolfo Lutz, Sao Paulo, Brazil and University of Minho, Braga, Portugal
    Adhemar Longatto-Filho
  6. First Chair Gynecology Hospital de Clinicas, Buenos Aires, Argentina
    Silvio Tatti
  7. Unit of Cytopathology, National Centre of Epidemiology, Surveillance and Promotion of Health, National Institute of Health (ISS), Rome, Italy
    Margherita Branca
  8. SIZE Diagnostic Center, Ljubljana, Slovenia
    Mojca Eržen
  9. Department of Obstetrics and Gynecology, S.Orsola-Malpighi Hospital, Bologna, Italy
    S. Costa
  10. Department of Oncology and Radiotherapy, Turku University Hospital, Savitehtaankatu 1, FIN-20521, Turku, Finland
    Kari Syrjänen

Authors

  1. Stina Syrjänen
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  2. Paulo Naud
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  3. Luis Sarian
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  4. Sophie Derchain
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  5. Cecilia Roteli-Martins
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  6. Adhemar Longatto-Filho
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  7. Silvio Tatti
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  8. Margherita Branca
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  9. Mojca Eržen
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  10. L. S. Hammes
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  11. S. Costa
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  12. Kari Syrjänen
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Corresponding author

Correspondence toKari Syrjänen.

Additional information

LAMS: Latin American Screening Study, funded by European Commission, INCO-DEV Contract # ICA4-CT-2001-10013.

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Syrjänen, S., Naud, P., Sarian, L. et al. Immunosuppressive cytokine Interleukin-10 (IL-10) is up-regulated in high-grade CIN but not associated with high-risk human papillomavirus (HPV) at baseline, outcomes of HR-HPV infections or incident CIN in the LAMS cohort.Virchows Arch 455, 505–515 (2009). https://doi.org/10.1007/s00428-009-0850-7

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