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Detection of E6-AP as a potential therapeutic target in cervical specimen of HPV-infected women

  • Gynecologic Oncology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

Silencing of HPV oncogenes or their human host client proteins using topically applied small interfering RNA (siRNA) may be an attractive nonsurgical strategy for CIN treatment. An exploratory clinical investigation was designed to evaluate E6-AP mRNA expression levels in different stages of cervical intraepithelial neoplasia and during the menstrual cycle.

Methods

In 38 premenopausal women aged 18–45 years referred to colposcopy clinic, analysis of serum hormones, cervical smears for cytology and HPV DNA, cervical biopsy, p16 immunohistochemistry and E6-AP mRNA expression levels in cervical smears and biopsies were performed. The intra-subject variability in E6-AP mRNA expression of vaginal smears was assessed and compared to cervical biopsy specimens.

Results

RNA of sufficient quantity and quality was available for E6-AP expression analysis from 97 % of the collected cervical smears and from 56 % of the collected biopsy samples. The normalized RNA levels from cervical smears were approximately tenfold higher compared to biopsies. There was little influence by the phase of the menstrual cycle or by CIN stage. Real-time PCR showed that the expression level of E6-AP is in a range (<28 C t) that would allow for detection of at least 100-fold modulation by a therapeutic agent (based on an assay LOD of C t = 36).

Conclusions

Our findings suggest a potential therapeutic approach using E6-AP siRNA as a specific molecular target in cervical intraepithelial neoplasia.

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Acknowledgments

This study was supported in part by a grant from the Novartis Institute of BioMedical Research.

Conflict of interest

The authors declare no financial, personal, or professional conflicts of interest.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Medical University Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    Peter Hillemanns, Matthias Jentschke, Philipp Soergel & Ralf Hass

  2. Translational Medicine/Infectious Diseases, Novartis Institutes for Biomedical Research, Inc., Cambridge, MA, 02139, USA

    Thomas G. Evans

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  1. Peter Hillemanns
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  2. Matthias Jentschke
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  3. Thomas G. Evans
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  4. Philipp Soergel
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  5. Ralf Hass
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Corresponding author

Correspondence to Peter Hillemanns.

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Hillemanns, P., Jentschke, M., Evans, T.G. et al. Detection of E6-AP as a potential therapeutic target in cervical specimen of HPV-infected women. Arch Gynecol Obstet 289, 1281–1286 (2014). https://doi.org/10.1007/s00404-013-3120-5

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  • DOI: https://doi.org/10.1007/s00404-013-3120-5

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