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Naturally occurring systemic immune responses to HPV antigens do not predict regression of CIN2/3

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Abstract

Essentially all squamous cervical cancers and their precursor lesions, high grade cervical intraepithelial neoplasia (CIN2/3), are caused by persistent human papillomavirus (HPV) infection. However, not all CIN2/3 lesions progress to cancer. In a brief, observational study window monitoring subjects with CIN2/3 from protocol entry (biopsy diagnosis) to definitive therapy (cervical conization) at week 15, in a cohort of 50 subjects, we found that 26% of CIN2/3 lesions associated with HPV16, the genotype most commonly associated with disease, underwent complete histologic regression. Nonetheless, HPV16-specific T cell responses measured in peripheral blood obtained at the time of study entry and at the time of conization were marginally detectable directly ex vivo, and did not correlate with lesion regression. This finding suggests that, in the setting of natural infection, immune responses which are involved in elimination of cervical dysplastic epithelium are not represented to any great extent in the systemic circulation.

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Fig. 1

Abbreviations

HPV:

Human papillomavirus

CIN:

Cervical intraepithelial neoplasia

SCC:

Squamous cervical cancer

PBMC:

Peripheral blood mononuclear cells

ELISPOT:

Enzyme-linked immunosorbent spot assay

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Acknowledgments

This work was supported by the National Institutes of Health (P50 CA098252) and by the Dana Foundation (CLT).

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Authors and Affiliations

  1. Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Phipps 255, 600 North Wolfe St, Baltimore, MD, 21287, USA

    Cornelia L. Trimble

  2. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Christopher Thoburn & Ferdynand Kos

  3. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Shiwen Peng & T. C. Wu

Authors
  1. Cornelia L. Trimble
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  2. Shiwen Peng
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  3. Christopher Thoburn
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  4. Ferdynand Kos
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  5. T. C. Wu
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Correspondence to Cornelia L. Trimble.

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Trimble, C.L., Peng, S., Thoburn, C. et al. Naturally occurring systemic immune responses to HPV antigens do not predict regression of CIN2/3. Cancer Immunol Immunother 59, 799–803 (2010). https://doi.org/10.1007/s00262-009-0806-4

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  • DOI: https://doi.org/10.1007/s00262-009-0806-4

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