Human immunodeficiency virus (HIV) and oncogenic human papillomavirus (HPV) are involved in hepatocyte growth factor (HGF) and c-Met overexpression in squamous preneoplastic intraepithelial lesions of the uterine cervix

F Walker, MD PhD ^{a, b}, S Kermorgant, PhD ^b , E Soustre ^a, I Prevost ^a, C Bedel ^a, D Henin, MD ^a, T Lehy, PhD DSc ^b

The HIV-positive population is especially exposed to cervical intraepithelial neoplasia (CIN) linked to oncogenic HPV. HGF and its receptor, c-Met, are involved in tumor progression. In the female genital tract, c-Met is overexpressed in ovarian cancers but no information exists concerning HGF and c-Met expression in low- and high-grade CIN. AIM. To analyze the influence of HPV(s) and HIV on the expression of HGF and c-Met in CIN. METHODS. HPV(s) were identified by in situ molecular techniques. HGF and c-Met proteins were revealed by immunohistochemistry and their level of expression estimated by quantitatification in normal cervical epithelium of 10 healthy women, accuminata condylomas and flat condylomas with CIN, infected or not by oncogenic HPVs, from 40 HIV-negative and 48 HIV-positive women. RESULTS. 1) In CIN with oncogenic HPV(s), the number of epithelial cell layers augmented significantly during progression of lesions. It augmented also in HIV-positive versus HIV-negative women (P<0.025 to P<0.01) ; 2) In HIV-negative women, the number and percentage of HGF and c-Met immunostained cell layers as well as the immunostaining intensity dramatically increased in oncogenic HPV lesions versus normal mucosa and accuminata condylomas infected by non-oncogenic HPV; 3) Furthermore, these parameters were still enhanced for CIN of grades 1 and 2 and accuminata condylomas (P<0.025 to P<0.0001) in HIV-positive versus HIV-negative women. CONCLUSIONS. Oncogenic HPV(s) and HIV participate in HGF and c-Met overexpression in preneoplastic intraepithelial lesions of the uterine cervix. Strongly up-regulated HGF/c-Met complex may stimulate cell proliferation in accuminata condylomas and tumor progression in oncogenic HPV lesions, particularly in HIV-positive population.

KEY WORDS: Accuminata condyloma, cervical intraepithelial neoplasia, immunocytochemistry, cell layer quantification, HPV in situ hybridization.

For more information, contact francine.walker@bch.ap-hop.paris.fr

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Viral Oncogenesis.

http://www.cancerprev.org/Journal/Issues/26/101/996/4335