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

Abstract

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 typespecific 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 HPVpositive 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)

Molecular and Circulatory Expression of Insulin Growth Factors in Indian Females with Advanced Cervical Cancer

“…Levels of IGF-I in young women may be inversely associated with high-grade cervical intraepithelial neoplasia, a precursor to cervical cancer (Schaffer et al, 2007). Our results showed strong association of IGFs with the HPV status in Indian patients with advanced cancer cervix and are in concordance with the findings of the previous studies (Mathur et al, 2003;Wu et al, 2003;Schaffer et al, 2007;Harris et al, 2008;Lee et al, 2010).…”

“…It has been shown in animal models that circulating IGF-I levels may play a significant role in carcinogenesis (Shen et al, 2006). Some studies have suggested that serum levels of IGF-I, IGF-II or IGFBP-III may be useful biomarkers for assessing risk of SIL or cervical cancer development (Mathur et al, 2003;Wu et al, 2003;Schaffer et al, 2007;Harris et al, 2008;Lee et al, 2010). In this study, we have explored the expression of the IGF system in cervical cancer patients and evaluated its potential association with HPV status by analysing its circulatory and cellular expression.…”

“…Recent studies reported additional evidence of an association between the IGF axis and cervical neoplasia (Mathur et al, 2003;Wu et al, 2003;Schaffer et al, 2007;Harris et al, 2008;Lee et al, 2010). A study investigated the association of IGF-I system and clinical outcome of cervical cancer, by analysing the serum levels of IGF-I, 2 and IGFBP-III, and tissue expression in the patient with different HPV status (Wu et al, 2003).…”

“…Another study demonstrated that the plasma levels of IGF-I and the IGF-I/IGFBP-III molar ratio might be useful for the early detection of cervical lesions (Lee et al, 2010). Another group prospectively assessed the influence of circulating IGF-I levels on the natural history of oncogenic HPV (Harris et al, 2008). Levels of IGF-I in young women may be inversely associated with high-grade cervical intraepithelial neoplasia, a precursor to cervical cancer (Schaffer et al, 2007).…”

New Biomarkers for Cervical Cancer – Perspectives from the IGF System

“…A recent prospective study reported a possible influence of the IGF axis on the natural history of oncogenic HPV and the development of cervical neoplasia (Harris et al, 2008). A high IGF-I/IGFBP-3 ratio was associated with increased persistence of oncogenic HPV infection [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).…”