Expression of Skp2 in cervical squamous cell carcinoma and precancerous lesions and its correlation with HPV16/18 infection

Abstract

To study the expression of Skp2 in cervical squamous cell carcinoma (SCC) and its precancerous lesions, and to investigate its relationship with human papillomavirus (HPV) infection. The expression of Skp2 protein and HPV16/18 DNA was determined using immunohistochemistry and in-situ hybridization in 30 cases of normal cervical squamous epithelium, 29 cases of low-grade intraepithelial neoplasia, 31 cases of high-grade intraepithelial neoplasia and 31 cases of cervical SCC. Skp2 expression was not detected in normal cervical squamous epithelium and no significant difference was obtained statistically on Skp2 expression between normal cervical squamous epithelium and low-grade intraepithelial neoplasia (P > 0.05). However, the expression of Skp2 gradually increased with elevation of epithelial lesion grading in an order from low to high grade and to cervical SCC (P < 0.01). The positive rate of HPV16/18 DNA in cases of normal cervical squamous epithelium, low-grade, high-grade intraepithelial neoplasia and cervical SCC was significantly different (P < 0.01), although both high-grade intraepithelial neoplasia and cervical SCC had a similar high HPV infection rate up to 96.8%. There was no correlation obtained between Skp2 expression and HPV16/18 infection in low-grade intraepithelial neoplasia. In contrast, expression of Skp2 and HPV infection were significantly correlated in both high-grade intraepithelial neoplasia and cervical SCC (gammaH = 0.373, gammaC = 0.416, P < 0.05). Abnormal expression of Skp2 is present mainly in high-grade cervical intraepithelial neoplasia and invasive carcinoma, which may be considered as a surrogate marker for the high-grade lesions. Skp2 may play a key role in the development of cervical squamous carcinoma induced by HPV16/18 infection, through E7-Skp2-Rb signaling pathway.