Serum and tissue levels of insulin-like growth factor-I in women with dysplasia and HPV-positive cervical cancer

The ectocervical epithelium is the target of the oncogenic human papillomavirus (HPV), which acts as an etiological agent in the development of cervical carcinoma. However, the HPV-mediated transformation of human epithelial cells is a multi-step process dependant on unknown factors additional to the virus, which is a necessary but, in and of itself, insufficient catalyst. In the present study, we characterized the role of insulin-like growth factor-I (IGF-I) in this process. IGF-I is an endocrine hormone with an autocrine and paracrine role in many tissues. Our data demonstrated that autocrine secretion of IGF-I can contribute to HPV-induced carcinogenesis of the epithelium. An immunohistochemical study showed that IGF-I was present in the nuclei of the reproductive layer of the paraepidermal epithelium in 89% of cases of intraepithelial neoplasia (CIN I-III) and 60% of cases of invasive cervical cancer. The presence of IGF-I at a nuclear localization in the cells studied suggests that it may also have intranuclear actions.