Journal of Cancer Research and Clinical Oncology

, Volume 133, Issue 4, pp 235–245

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

Authors

    • Department of Gynecology and ObstetricsUniversity Hospital of Duesseldorf
  • Nicolas Wentzensen
    • Department of Molecular Pathology/Applied Tumor Biology, Institute of PathologyRuprecht Karls University
  • Svetlana Vinokurova
    • Department of Molecular Pathology/Applied Tumor Biology, Institute of PathologyRuprecht Karls University
  • Magnus von Knebel-Doeberitz
    • Department of Molecular Pathology/Applied Tumor Biology, Institute of PathologyRuprecht Karls University
  • Cristopher Poremba
    • Department of PathologyHeinrich Heine University
  • Hans G. Bender
    • Department of Gynecology and ObstetricsUniversity Hospital of Duesseldorf
  • Volkmar Kueppers
    • Dysplasia Clinic
Original Paper

DOI: 10.1007/s00432-006-0162-0

Cite this article as:
Hampl, M., Wentzensen, N., Vinokurova, S. et al. J Cancer Res Clin Oncol (2007) 133: 235. doi:10.1007/s00432-006-0162-0

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.

Keywords

HPV typesMulticentricityCINVAINVINAINp16 expression

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

Copyright information

© Springer-Verlag 2006