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Concordance of HPV load and HPV mRNA for 16 carcinogenic/possibly carcinogenic HPV types in paired smear/tissue cervical cancer specimens

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Abstract

HPV types with high viral load are associated with cervical abnormalities. However, viral load measurements and concordance of HPV loads and viral mRNA have not been demonstrated for all high-risk/possibly high-risk (HR-/pHR-)HPV types in cervical cancer (CxCa). Especially, the biological role of co-infecting HR-/pHR-HPV types with low viral load has not been thoroughly investigated. Using BSGP5+/6+-PCR/MPG genotyping, we analyzed viral loads for all currently defined 51 mucosal HPV types in 74 cervical smears from patients with CxCa and compared this data with HPV DNA and mRNA status in these patients’ corresponding CxCa tissues. All cervical smear/tissue pairs were HPV DNA+. Overall HPV type agreement within pairs was 99% (complete agreement in 50%, partial agreement in 49%, and complete disagreement in 1% of cases). The proportion of multiple HPV types was significantly higher in smears compared to tissues (p<0.0001). High load HPV infections (>1 copy/cell) were found in 88% of HPV DNA+ smears, and were significantly associated with the presence of respective HPV DNA (kappa=0.685, CI: 0.567-0.803), and HPV mRNA (kappa=0.693, CI: 0.566-0.820) in CxCa tissues. In total, 93% (67/72) of high load HR-/pHR-HPV infections identified in smears were also present in corresponding CxCa tissues, and 93% (62/67) of these were HPV mRNA+. On the other hand, 78% (42/54) of low load HR-/pHR-HPV infections identified in smears were not detectable in tissues, including 11 out of 15 low load HPV16 infections. This data demonstrates that the presence of high HPV loads in CxCa smears predicts biologically active HR-/pHR-HPV types in tumor tissues.

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Acknowledgements

We thank Prof. Otoniel Martinez-Maza for his support during the preparation of this manuscript.

Author information

Authors and Affiliations

  1. Division of Molecular Diagnostics of Oncogenic Infections, Research Program Infection, Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Gordana Halec, Bolormaa Dondog, Michael Pawlita & Markus Schmitt

  2. Obstetrics and Gynecology Department, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095-7363, USA

    Gordana Halec

  3. GATC Biotech AG, Konstanz, Germany

    Markus Schmitt

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  1. Gordana Halec
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  2. Bolormaa Dondog
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Contributions

Authors GH, BD, MS, and MP designed and/or performed experiments, analyzed the data, contributed reagents/materials/analysis tools, and wrote the paper.

Corresponding author

Correspondence to Gordana Halec.

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Disclosure of interests

MP and MS have received research support through cooperation contracts of DKFZ with Roche and Qiagen in the field of development of HPV diagnostics. They are inventors on patents owned by DKFZ in the field of HPV diagnostics. Authors GH and BD have no conflict.

Details of ethics approval

Ethics approvals were obtained as described in detail in Dondog et al., CEPB, 2008, PMID: 23034864. In short: On arrival at the study clinic, all participants read and signed an informed consent form explaining the main research goals, sample collection procedures, potential benefits and harms, and confidentiality of data collected for the study. The informed consent form respected the recommendations of the ethical review committees of the IARC and the Mongolian Health Ministry, which both approved the study.

Funding

Research grants from the Qiagen and Roche were awarded to Drs. Schmitt and Pawlita in the field of HPV diagnostics. These agencies were not involved in data analysis or interpretation.

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Halec, G., Dondog, B., Pawlita, M. et al. Concordance of HPV load and HPV mRNA for 16 carcinogenic/possibly carcinogenic HPV types in paired smear/tissue cervical cancer specimens. Arch Virol 162, 3313–3327 (2017). https://doi.org/10.1007/s00705-017-3452-8

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  • DOI: https://doi.org/10.1007/s00705-017-3452-8

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