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Insulin-Like Growth Factor Axis and Oncogenic Human Papillomavirus Natural History

¹ Albert Einstein College of Medicine, Bronx, New York; ² Yale University, New Haven, Connecticut; ³ Maimonides Medical Center and State University of New York Downstate, Brooklyn, New York; ⁴ Southern Illinois University School of Medicine, Springfield, Illinois; ⁵ National Institute of Child Health and Human Development, NIH, Bethesda, Maryland; ⁶ Johns Hopkins University, Baltimore, Maryland; ⁷ University of Southern California, Los Angeles, California; ⁸ University of Virginia, Charlottesville, Virginia; and ⁹ University of California at San Francisco, San Francisco, California

Requests for reprints: Howard D. Strickler, Department of Epidemiology and Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Belfer 1308, Bronx, NY 10461. Phone: 718-430-4055. E-mail: strickle{at}aecom.yu.edu

High serum levels of insulin-like growth factor-I (IGF-I) are reported to be a risk factor for several common cancers, and recent cross-sectional data suggest a possible additional association of IGF-I with cervical neoplasia. To prospectively assess whether circulating IGF-I levels influence the natural history of oncogenic human papillomavirus (HPV), the viral cause of cervical cancer, we conducted a pilot investigation of 137 women who underwent semiannual type-specific HPV DNA PCR testing and cervical cytology. Total IGF-I and IGF binding protein-3 (IGFBP-3), the most abundant IGFBP in circulation, were measured using baseline serum specimens. Having a high IGF-I/IGFBP-3 ratio was associated with increased persistence of oncogenic HPV infection [that is, a lower rate of clearance; adjusted hazard ratio (AHR), 0.14; 95% confidence interval (95% CI), 0.04-0.57], whereas IGFBP-3 was inversely associated with both the incident detection of oncogenic HPV (AHR, 0.35; 95% CI, 0.13-0.93) and the incidence of oncogenic HPV-positive cervical neoplasia (that is, squamous intraepithelial lesions at risk of progression; AHR, 0.07; 95% CI, 0.01-0.66). These prospective data provide initial evidence that the IGF axis may influence the natural history of oncogenic HPV. (Cancer Epidemiol Biomarkers Prev 2008;17(1):245–8)