48. Cidofovir treatment prevents invasion of invasive HPV-16-positive anal keratinocytes

Abstract

Background: The nucleotide analogue cidofovir has been shown to be effective in treating precancerous HPV-associated lesions located in the respiratory tract, cervix, vulva and anus. Cidofovir has been shown to have a 51% efficacy in the short-term treatment of high-grade perianal squamous intraepithelial lesions in HIV-infected persons. Less is known about the effect of cidofovir in treating more advanced stages of HPV-associated disease such as invasive cancer. Methods: We established an immortalised anal keratinocyte cell line (AKC2) following transfection of the HPV-16 genome into primary anal keratinocytes and long-term culture. AKC2 cells were invasive using in vitro collagen invasion assays. To determine the effect of cidofovir on invasion, AKC2 cells were treated for up to 7 days with different concentrations of cidofovir (10, 25 and 50 µg mL^–1) and studied using the collagen invasion assays. Untreated cells served as a control. Results: We detected a decrease in invasion of AKC2 cells (50%, 70% and 90% decrease) with 10, 25 and 50 µg mL^–1 cidofovir, respectively. Cellular toxicity was not detected in any of the cidofovir-treated samples. Preliminary data suggest that cidofovir directly or indirectly impairs the formation of actin filaments and cellular filopodia, which are known to play a role in cellular invasion. Conclusions: Cidofovir inhibits invasion of HPV-16-transformed anal keratinocytes potentially through affecting pathways that are involved in actin filament formation. Cidofovir could potentially be useful as an adjuvant treatment for invasive anal cancers, and its mechanism of action in inhibiting cellular invasion requires further study.