Affiliations: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC 29425, USA
Correspondence:
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Corresponding author: Subbi P. Mathur, Ph.D., Professor and Member, Hollings Cancer Center, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Medical University of South Carolina, Suite 634, 96 Jonathan Lucas Street, Charleston, SC 29425, USA. Tel.: +1 843 792 8354; Fax: +1 843 792 0533; E-mail: [email protected].
Abstract: Cervical cancer is a major gynecologic malignancy around the world. However, current diagnostic methods such as Pap smear and human papilloma virus (HPV) testing are insufficient for an early diagnosis of cervical cancer, follow-up on therapy efficacy or to identify the women who might progress to cervical cancer (only about 1–5% of the HPV-positive women will develop cervical cancer). Patients with atypical squamous cells of undetermined significance (ASC-US) clearly need a better screening test. Developing a non-invasive method for early diagnosis of cervical cancer is essential. Our in vitro and translational research data support the hypothesis that: 1. Squamous cell cervical cancer is related to specific upregulation of tissue and serum Insulin-like Growth Factor-II levels (IGF-II; 100% sensitivity and 100% specificity). Serum IGF-I, but not IGF-II levels are elevated in other gynecological, breast, lung and prostate cancers. Serum IGF-II test helps in diagnosing cervical cancer as early as ASC-US or cervical intraepithelial neoplasia (CIN)-I and in monitoring therapy efficacy (p ‹ 0.001 by Student's 't' test and Chi-square analysis). 2. Concomittant to increased serum IGF-II levels, IGF-Binding Protein 3 (IGF-BP3) levels are significantly decreased in persistent CIN and cervical cancer (p ‹ 0.0001). As IGF-BP3 modulates IGF-II biological activity, significantly decreased serum IGF-BP3 levels (levels normalize after therapy; p ‹ 0.001) may indicate a poor prognosis. Similar to serum IGF-II, serum IGF-BP3 levels help monitoring therapy efficacy in cervical cancer and advanced CIN. Measurement of serum IGF-II levels will help in early diagnosis of cervical cancer and monitoring of therapy outcome. Serum IGF-BP3 in conjunction with IGF-II levels may help in predicting prognosis as well as monitoring therapy efficacy.
