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Periungual warts represent a treatment challenge because of its high recurrence rate and recalcitrance. These are benign lesions produced by the human papilloma virus (HPV) that often do not respond to habitual treatment. Cidofovir is a potent antiviral drug that acts inactivating viral DNA polymerase. Topical cidofovir for the treatment of HPV-related cutaneous and mucous lesions is becoming increasingly common. Our aim was to assess the efficacy and safety of cidofovir cream for the treatment of viral periungual warts. We undertook a retrospective observational study of patients with periungual warts who received treatment with topical cidofovir between January 2010 and December 2013 at the Dermatology Service of the Hospital Costa del Sol, Marbella, Spain. Data were recorded about the rate of treatment response, the adverse effects and recurrences, as well as the characteristics of the patient cohort. We identified 41 patients who had received some previous treatment. The concentration of cidofovir was 3% in all cases, usually applied twice a day (in 37 of the 41 cases). A greater or lesser response was noted in 35 cases. There were six recurrences in the follow-up period. Topical cidofovir seems to be a useful alternative for the therapeutic management of recalcitrant periungual common warts that fail to respond to usual treatment. Our experience with the use of this antiviral agent has been satisfactory, although in our opinion, it should be reserved for specific cases as its economical cost represents an important limitation., (© 2014 Wiley Periodicals, Inc.)

Plantar warts are a common reason for dermatological consultations and their treatment can occasionally be a challenge. Plantar warts are benign lesions produced by the human papillomavirus (HPV) that often fail to respond to habitual treatment. Cidofovir is a potent antiviral drug that acts competitively, inhibiting viral DNA polymerase. Our aim was to assess the efficacy and safety of cidofovir cream for the treatment of viral plantar warts. We undertook a retrospective observational study of patients with plantar warts who received treatment with topical cidofovir between July 2008 and July 2011 at the Dermatology Service of the Hospital Costa del Sol, Marbella, Spain. Data about the rate of treatment response, the adverse effects, and recurrences, as well as the characteristics of the patient cohort, were recorded. We identified 35 patients who had received some previous treatment. The usual concentration was 3% (in 33 of 35 cases), applied twice a day (in 31 of 35 cases). A greater or lesser response was noted in 28 cases. There were two recurrences. Topical cidofovir seems to be a useful alternative for the therapeutic management of recalcitrant plantar common warts that fail to respond to usual treatment., (© 2013 Wiley Periodicals, Inc.)

Cutaneous warts are caused by infection of the epidermis with human papillomavirus (HPV). Cryotherapy using liquid nitrogen is one of the most common local treatments. In this study, we used a novel ex vivo approach to compare the efficacy of a new product with conventional liquid-nitrogen cryotherapy by studying epidermal histology and assessing the presence of HPV types 1 and 2 DNA in plantar warts. The studied formulation, which acts by tissues mummification, is a combination of nitric acid, organic acids and metallic salts. We found that, similar to liquid nitrogen, the studied product induced alterations in the wart structure. In addition, unlike liquid nitrogen, this product also reduced the amount of HPV DNA. The results suggest that there is a poor correlation between the histological response and the antiviral efficacy of standard wart treatment., (© The Author(s) CED © 2012 British Association of Dermatologists.)

Background: Cutaneous warts are often recalcitrant to conventional therapy in immunocompromised patients. Cidofovir is a potent antiviral agent shown to have a broad spectrum of action against DNA virus, including human papillomavirus., Objective: To determine the efficacy of intralesional cidofovir in the treatment of florid warts in an immunocompromised renal transplant patient., Method: The patient received seven injections of intralesional cidofovir at 4 week intervals in his numerous palmar warts., Conclusion: Based on our results, intralesional cidofovir is a promising therapeutic modality in the treatment of cutaneous warts in the renal transplant population.

Background: The challenge of immunosuppression in pediatric renal transplantation is to balance preventing rejection while avoiding infectious complications. A dermatological complication of immunosuppression is viral warts, which cause significant disfigurement and increase the risk of skin malignancy., Methods: We present three pediatric and adolescent renal allograft recipients with multiple, recalcitrant verrucae vulgares lesions and one patient with molluscum contagiosum who were switched from mycophenolate mofetil to leflunomide. Teriflunomide metabolite levels were carefully maintained between 50,000 and 100,000 ng/mL to balance its immunosuppressive and antiviral properties. No adverse events requiring discontinuation of leflunomide were encountered., Results: Switching from mycophenolate mofetil to leflunomide successfully cleared verrucae vulgares and molluscum lesions in all four renal transplant patients., Conclusions: The ability to minimize and even resolve warts can improve quality of life by reducing risk of skin malignancies and emotional distress in solid organ transplant patients. Leflunomide is a potential therapeutic option for posttransplantation patients with skin warts because it serves both as an adjunct to the immunosuppressive regimen and an antiviral agent.

Cidofovir is a nucleoside analog of deoxycytidine with a strong activity against a broad spectrum of DNA viruses, including human papillomavirus. The first objective was to evaluate efficacy of cidofovir for the treatment of cutaneous viral warts, recalcitrant after conventional therapies or where the surgery approach is difficult for their location or extension. Second, the present authors propose to point out possible local and systemic side effects consequent to treatment. Two-hundred eighty patients affected by recalcitrant cutaneous viral warts, were treated with intralesional cidofovir 15 mg/mL once a month. The present authors stated that candidates were those who had made before at least two other treatments reported in the guideline for management of cutaneous viral warts. In 276 cases, warts completely cleared: 158 of those have a follow-up period longer than 12 months and 118 have a follow-up of 6 months. On the average, 3,2 injections were enough to solve the problem. Local side effects consisted of pain and burning sensation during the injections; itching, erythema, and post-inflammatory hyperpigmentation were observed. No cases of systemic side effects were noted. The treatment was well tolerated, and the warts were completely cleared without relapses. Intralesional cidofovir is emerging as an effective therapeutic alternative for warts that are unresponsive to conventional treatments., (© 2012 Wiley Periodicals, Inc.)

A case of extensive periungual viral warts in an immunocompetent patient that failed to respond to standard treatments over a 10-year period is reported. A rapid and complete response to treatment was achieved with oral acitretin.

We describe a 42-year-old man with AIDS and Hodgkin's lymphoma whose severe and recalcitrant cutaneous warts resolved following treatment with local 1% cidofovir. Clinically significant improvements were observed in a two-week period of therapy. In advanced HIV disease complicated by additional haematological malignancy, cutaneous warts may be difficult to treat and present a challenge for the attending physicians. In similar clinical condition topical anti-human papillomavirus therapy may prove to be safe and curative.

Lesions caused by verrucus vulgaris are commonly refractory to therapy and may become large, painful, or disfiguring in immunocompromised patients. Cidofovir is a potent nucleoside analog antiviral agent shown to have in vitro and in vivo activity against a broad spectrum of DNA viruses. We report a successful use of topical cidofovir to treat verruca vulgaris lesions in a highly immunocompromised patient, who was not considered a candidate for conventional therapy.

Papillomaviruses are infectious agents for human and animal epithelial tissue, and nearly 100 distinct human types (HPVs) have been identified. When these viruses infect cutaneous or mucosal skin they can initially cause clinical warts or persistent infection with little or no visible manifestations. Warts, while usually benign, can be painful or cosmetically unacceptable and often require medical treatment. Furthermore, infection with certain specific HPV types, such as 16 or 18 (as well as several others), is the major risk factor for a woman's development of cervical cancer. In addition to cervical cancer, papillomaviruses have also been implicated in cancers of the skin and respiratory track though the evidence is not yet as conclusive. It is clear that prevention or elimination of papillomavirus infections would ultimately reduce the incidence of cervical cancer and possibly other epithelial cancers as well. Unfortunately, progress in vaccine development has been slow and no specific anti-papillomavirus agents are available. The rational development of effective anti-papillomaviral treatments will require a detailed understanding of how these viruses replicate and interact with the host cell, and much progress has been made in this area over the last 10 years. These viruses have small DNA genomes with limited coding capacity, and their complete array of viral protein products is known. This review will discuss the known functions of the viral proteins with a focus on strategies to interdict their biological activities as a possible means of specific therapy.

Human papillomavirus (HPV) induced epithelial cell proliferation is responsible for a broad range of lesions. Treatment of such lesions is characterized by a high relapse rate. Four patients are described who were treated locally with cidofovir (cream 1% or injection of 2.5 mg/ml solution) for multi-treated relapsing HPV-associated lesions. Three of the four patients had a complete response. The fourth patient showed a clinical response in the first cycle of treatment, but new lesions appeared during four successive cycles of cidofovir., (Copyright 2002 Wiley-Liss, Inc.)

The report describes the establishment and characterization of a mouse xenograft transplantation model for the study of papillomavirus infection of bovine skin. Calf scrotal skin was inoculated with bovine papillomavirus type 2 before grafting it to the dorsum of severe combined immunodeficient mice. The grafted skin contained epidermis, dermis, and a thin layer of fat. After 5 months the induced warts not only showed histological features of papillomavirus infections but also tested positive for viral DNA and papillomavirus capsid antigen. The formation of infectious virions was demonstrated by inoculation of new transplants with crude extract from the induced warts as well as in a cell culture focus assay. Topical application of bromovinyl-2'-deoxyuridine led to a reduction in viral DNA content in the developing wart. This small-animal xenograft model should be useful for characterizing antiviral compounds and providing an understanding of the regulation of papillomavirus infections.

Warts can be difficult to diagnose and to treat in the setting of human immunodeficiency virus (HIV) infection. A 37-year-old woman with a background of HIV presented with a large verrucous plaque involving her right foot. Human papillomavirus (HPV)-66 was identified in the lesional skin biopsy sample and in scrapings obtained from her cervix. The wart rapidly responded to topical cidofovir therapy. HPV-66 is a novel HPV type to be associated with verruca vulgaris. Topical cidofovir should be further investigated as an alternative treatment modality for verruca vulgaris.

The present study examined topical effects of cidofovir on cutaneous rabbit warts. Based on an inoculum-dependency study, each New Zealand White rabbit was inoculated with a high and low titer of cottontail rabbit papillomavirus (CRPV) at four sites on each dorsolateral area. Inoculation with 50 ID(50) induced papillomas at 100% of the inoculation sites within 16+/-1 days, and the wart growth curve plateaued within approximately 7 weeks. With an inoculum of 5 ID(50), 80% of the inoculated sites developed papillomas within 21+/-1 days and their size plateaued at a later time. Cidofovir was applied topically twice daily on the inoculated sites at a concentration of 1% for 18 days, starting at three different time points. In the first experiment, treatment was initiated 7 days post-inoculation. One of the inoculated sides received cidofovir or the vehicle, PBS, while the other side was left untreated. With this treatment regimen, cidofovir significantly delayed the time of onset and the growth rate of papillomas induced with the high titer of inoculum. It completely prevented papilloma-induction on the sites inoculated with the low titer of CRPV. Reversible side-effects of cidofovir were observed on the directly treated area including erythema, necrosis, and flaking. Both therapeutic and side-effects were limited to the sites of direct exposure. In the second experiment, one of the two sides in each group of rabbits received cidofovir or vehicle starting on day 29 post-inoculation. With this treatment regimen, cidofovir significantly reduced wart growth against the low titer only. Topical treatment initiated on day 49 post-inoculation was not effective on warts initiated with either viral titer. These results demonstrated that topical cidofovir could be very effective against papillomavirus-induced wart growth if it is initiated early during the infection, especially against low titers of inoculum.

Recurrent respiratory papillomatosis (RRP) is a potentially devastating disease that can have significant morbidity, and can even result in mortality due to airway compromise or, less commonly, malignant transformation. Two distinct types of RRP exist: adult-onset RRP (AO-RRP) and juvenile-onset RRP (JO-RRP). Acquisition of human papillomavirus (HPV), the causative agent of RRP, is believed to occur in the peripartum period in the case of JO-RRP, with disease symptoms (primarily hoarseness) becoming apparent during the first several years of life. Treatment currently consists of surgical debulking of the papillomas to relieve airway obstruction. However, numerous antiviral therapies have also been evaluated, albeit primarily under uncontrolled settings. This article will review the biology, natural history and management of HPV infection, with particular emphasis on JO-RRP.

CTC-96, a cobalt containing complex, was tested as a putative topical therapeutic agent for the treatment of papillomavirus-induced tumors in our cottontail rabbit papillomavirus (CRPV)-rabbit model system. Following experimental infection of domestic rabbits with CRPV, CTC-96 was applied to infection sites twice daily, 5 days a week for a total of 8 weeks. Two levels of concentrations of aqueous CTC-96 were compared to placebo control-treated animals. With increasing dose of CTC-96 we observed tumors earlier, larger, and more often across eight infected sites on each animal.