Artemisinin and its Derivatives – Novel Treatment Options for HPV-infection and Cervical Dysplasia

Potent antiviral agents to treat high risk HPV-infections and resulting intraepithelial lesions have not been developed. Surgical intervention is currently standard of care for pre-invasive cervical dysplasia and overtreatment out of concern for progression or underlying high grade lesions is found frequently. Effective and inexpensive treatment options would be of great medical and economic benefit. Many neoplastic cells, including cervical cancers, overexpress transferrin-receptors to increase their iron uptake. We therefore hypothesized that artemisinin-derivatives, active principles of the medical herb Artemisia annua and currently the most effective iron-dependent antimalarials available, might proof useful for the treatment of HPV-infected and tumorgenic cells. We demonstrate in this study that DHA, artesunate, and two newly designed artemisinin derived trioxane dimers selectively display strong cytotoxic effects on HPV-infected and transformed cells with high intracellular iron concentrations. Artemisinin derivatives induce apoptosis via the iron dependent formation of free radicals and the activation of the mitochondrial apoptotic pathway. Most importantly, we show in vivo that DHA inhibits mucosal tumor formation, but not infection, induced by papillomaviruses in animals. Our findings suggest that artemisinin derivatives may be clinically useful as potent chemotherapeutic agents for the treatment of cervical cancer and its precursors. Their stability and hydrophobicity make them excellent candidates for not only systemic but also topical application, which could greatly simplify the treatment of early cervical lesions, including those in immunocompromised patients.

HPV - HPV-infection - cervical cancer - cervical dysplasia