, 2013, Mikolajczak et al., 2012, Ksiazek et al., 2011 and Derkay and Wiatrak, 2008). Although there were some anecdotal reports documenting serious

adverse reactions in RRP in off-label use of CDV (Tjon Pian Gi et al., 2012), a multicentre retrospective chart review involving 16 hospitals from 11 countries worldwide with 635 RRP patients (of whom 275 were treated with CDV) was performed. In this study, no clinical evidence was found for more long-term nephrotoxicity, neutropenia or laryngeal malignancies after intralesional administration Target Selective Inhibitor Library concentration of CDV (Tjon Pian Gi et al., 2013). In another recent study, it was concluded that CDV remains the leading option for adjuvant treatment of patients with RRP of all ages whose disease is difficult to manage with surgery alone. CDV represents an option to reduce the risks of frequent surgical debulking and airway obstruction in children and adults with recurrent or severe disease (Derkay

et al., 2013). CDV is nowadays recognized as an adjuvant therapy for the management of this disease (Tjon Pian Gi et al., 2013 and Graupp et al., 2013). A type specific real-time PCR to measure HPV6 and HPV11 DNA loads in patients with recurrent respiratory papillomatosis treated with CDV, indicated that the drug significantly reduced viral load following intralesional application (Mikolajczak et al., 2012). Although CDV has been reported to be ineffective in the treatment of epidermodysplasia Proteases inhibitor verruciformis (a rare inherited disease characterized by widespread HPV infection of the skin) (Preiser et al., 2000), a more recent study documented its efficacy against epidermodysplasia verruciformis caused by novel HPV types (Darwich et al., 2011). The anti-proliferative effects of CDV against HPV-induced transformation have intensively been studied the last years. The first studies showing the cytostatic activity of the drug against cervical carcinoma cells date from 1998 (Andrei et al., 1998a), where CDV and related Cell Penetrating Peptide ANPs displayed

time-dependent anti-proliferative effects, in contrast to what is normally seen with chemotherapeutic drugs. HPV- and PyV-transformed cells appeared to be more sensitive to the effects of CDV due to the fact that the viral oncoproteins induce cellular proliferation making the cells more sensitive to the anti-proliferative drug effects. Thus, the activity of CDV against HPV- and PyV-transformed cells may be explained, at least in part, by an inhibitory effect of the compound on rapidly dividing cells, and the presence of the HPV or PyV genome might enhance the sensitivity of the cells to CDV. When various cell lines not containing HPV (i.e. human melanomas, lung carcinomas, colon carcinomas, breast carcinomas) were tested, CDV also showed an anti-proliferative effect (Andrei et al., 1998a).