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Comprehensive analysis of 130 multicentric intraepithelial female lower genital tract lesions by HPV typing and p16 expression profile

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Abstract

Purpose

HPV associated cervical transformation is characterized by well-defined steps, including persistent HPV infection and deregulated oncogene expression. Recent studies have suggested that a number of lower genital tract lesions are clonally related to cervical lesions. In the current study, HPV infections and oncogene expression were assessed in a large series of patients with multicentric lower genital tract disease to analyze the transformation steps in extracervical disease.

Methods

One hundred and thirty biopsies of 52 women treated for multicentric synchronous or metachronous lower genital tract intraepithelial neoplasias were collected. Up to seven multicentric specimens taken from one patient were studied with a maximum follow up of 20 years. HPV typing and p16ink4a immunostaining was performed.

Results

HPV DNA was present in 121 of 130 specimens (93%). HPV16 was frequently found in VIN, VaIN and AIN (73, 60 and 77%, respectively), whereas only 37% of CIN were HPV16 positive. Infections with identical HPV types in multicentric lesions were diagnosed in 46% of the HPV positive patients. p16INK4a expression was negative in the nine HPV negative lesions whereas about 90% of the high grade lesions showed diffuse p16 staining.

Conclusion

Our findings indicate that multicentric lower genital tract disease evolves through different pathways. Some cases were related to a high susceptibility towards HPV infections, while others exhibited features of clonal propagation of transformed cervical cell clones. The clinical management of the latter group is particularly challenging, because malignant cell clones can persist over a long time course.

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Abbreviations

HPV:

Human papillomavirus

PCR:

Polymerase chain reaction

HR:

High risk

VIN:

Vulvar intraepithelial neoplasia

VaIN:

Vaginal intraepithelial neoplasia

CIN:

Cervical intraepithelial neoplasia

AIN:

Anal intraepithelial neoplasia

DNA:

Desoxy-ribonucleic acid

LEEP:

Loop electrosurgical excision procedure

n.a.:

Not available

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Authors and Affiliations

  1. Department of Gynecology and Obstetrics, University Hospital of Duesseldorf, Moorenstr. 5, 40 225, Duesseldorf, Germany

    Monika Hampl & Hans G. Bender

  2. Department of Molecular Pathology/Applied Tumor Biology, Institute of Pathology, Ruprecht Karls University, Heidelberg, Germany

    Nicolas Wentzensen, Svetlana Vinokurova & Magnus von Knebel-Doeberitz

  3. Department of Pathology, Heinrich Heine University, Duesseldorf, Germany

    Cristopher Poremba

  4. Dysplasia Clinic, Koenigsalle, Duesseldorf, Germany

    Volkmar Kueppers

Authors
  1. Monika Hampl
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  2. Nicolas Wentzensen
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  3. Svetlana Vinokurova
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  4. Magnus von Knebel-Doeberitz
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  5. Cristopher Poremba
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  6. Hans G. Bender
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  7. Volkmar Kueppers
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Correspondence to Monika Hampl.

Additional information

Monika Hampl and Nicolas Wentzensen contributed equally to the work.

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Hampl, M., Wentzensen, N., Vinokurova, S. et al. Comprehensive analysis of 130 multicentric intraepithelial female lower genital tract lesions by HPV typing and p16 expression profile. J Cancer Res Clin Oncol 133, 235–245 (2007). https://doi.org/10.1007/s00432-006-0162-0

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  • DOI: https://doi.org/10.1007/s00432-006-0162-0

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