Cidofovir is an acyclic nucleoside phosphonate that acts as an alternate substrate for DNA polymerase and thus competitively inhibits this enzyme. Cidofovir binds and inhibits both viral and cellular DNA polymerase, stopping replication. The mechanism of action of cidofovir in HPV infected cells is not fully understood, but it is believed that its ability to halt host cell replication machinery in proliferating cells leads to apoptosis, and virustatic control of HPV infection [ 12 ].

Although cidofovir is only FDA approved for CMV retinitis in human immunodeficiency virus (HIV) patients, there are many reports of successful topical and intralesional use for HPV lesions [ 13 14 ]. Intravenous cidofovir is avoided as it is associated with nephrotoxicity, ocular injury (anterior uveitis, retinal detachment, iritis and permanent loss of vision), and possible teratogenicity [ 15 ]. Although topical cidofovir has been used for warts on the oral mucosa, hands and anogenital region, most of the efficacy data has been collected based on the latter diagnosis [ 16 ]. In one study, 47% and 0 of patients had a complete response to topical 1% cidofovir and placebo respectively. Furthermore, 37% and 18% of patients had partial resolution with cidofovir and placebo respectively [ 17 ]. In children, off-label use of cidofovir has been used to control the growth of papillomas in recurrent respiratory papillomatosis (RRP), a benign, multi-focal neoplasm caused by HPV infection. Prospective studies have shown partial to complete resolution of mucosal papillomas [ 18 ]. Documented side effects of cidofovir in treating RRP include cutaneous rash, headache, local inflammatory response, vocal cord scarring, compromise of airway, disorders of hematologic and chemical parameters in blood [ 19 ]. Gilead, the makers of cidofovir, reported a ban on its off-label use of cidofovir in 2011 due to concern for its side effects.