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| 번호 | 제목 | 등록일 | 조회수 |
|---|---|---|---|
| 113 | Topical Cidofovir (HPMPC) Is an Effective Adjuvant to Surgical Treatment of Anogenital Condylomata Acuminata [2003년 8월 DCR] | 2011-11-17 | 3466 |
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G. Coremans, Ph.D.,* V. Margaritis, M.D.,* R. Snoeck, Ph.D.,‡ J. Wyndaele, M.D.,*E. De Clercq, Ph.D.,‡ K. Geboes, Ph.D.†
From the Departments of *Gastroenterology and †Pathology, University Hospital Gasthuisberg and ‡Rega Institute for Medical Research, Leuven, Belgium
PURPOSE: Human papilloma virus infections of the anogenital region are very common and cause condylomata acuminata; cervical, penile, vulvar, or perianal intraepithelial neoplasia; and more rarely, invasive cancer. The currently available therapies often result in painful, extensive, slowhealing ulcerations and frequent early relapses. This study was aimed at determining the efficacy of topical application of the antiviral agent cidofovir at 1 percent.
METHODS: Twenty patients treated with coagulations were compared with 27 patients treated with cidofovir. Lesions refractory to cidofovir were cleared up with additional coagulations. The number of patients previously treated for condylomata did not differ between the two groups. Significantly more
patients treated with cidofovir, however, had an impaired immune status (37 percent) compared with the patients treated with coagulations (5 percent). RESULTS: Cidofovir alone cured the lesions in 32 percent of the patients and induced partial regression in 60 percent. However, in smokers, complete resolution of the condylomata occurred only in 16.6 percent compared with 66 percent of nonsmokers (P = 0.03). The number of coagulation sessions was much lower (P < 0.0005) in the cidofovir treated group (1 +/- 0.8 vs. 2.9 +/- 2). Furthermore, the relapse rate was significantly lower in the cidofovir group (3.7 vs. 55). All recurrences in the electrocoagulation group occurred within four months of confirmed lesion clearance. Topical applications of cidofovir 1 percent were well tolerated. Thirty-three percent of the patients reported only mild pain caused by erosive dermatitis. In contrast, coagulations caused painful ulcerations that necessitated the use of analgesics in all patients treated this way.
CONCLUSIONS: Topical applications of cidofovir, an antiviral compound with activity against human
papilloma virus, is effective in the majority of patients with perianal condylomata and is a valuable adjuvant to surgical treatment of these lesions. A variety of human papilloma virus (HPV) serotypes cause clinical and subclinical lesions of the
anogenital region and latent infection of the skin. HPV-induced lesions may present as soft, pink, sessile masses or slightly elevated pigmented lesions with a smooth or a rough surface. Flat lesions, only visible with enhancing techniques, may also occur. These lesions may harbor intraepithelial neoplasia, all or none of which may be associated with dysplasia or carcinoma in situ and invasive epithelioma. Areas of latent infection can only be detected by sensitive probes for HPV DNA, such as in situ hybridization and the polymerase chain reaction technique. Most currently used therapies, including resection, diathermocoagulation and laser coagulation, cryotherapy, and topical application of cytotoxic substances, result in slowly healing, painful ulcerations that cause significant morbidity and high early relapse rates. Latent HPV infections account for the high recurrence rate of papillomatous lesions despite cytodestructive therapies. Recently developed antiviral and immunomodulating substances are aimed at not just removing the papillomatous lesions but also reducing the viral load. (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC) is an acyclic nucleoside phosphonate analog with antiviral activity against DNA viruses, including HPV. This antiviral agent, also known as cidofovir (Vistide®, Pharmacia, Brussels, Belgium), was reported to be effective in topical application in immune-compromised patients with severe relapsing anogenital HPV-induced lesions and in patients with HPV-induced cervix intraepithelial neoplasia grade. The aim of the present study was to evaluate the efficacy, recurrence rate, tolerance, and safety of topical cidofovir in patients with anogenital condylomata acuminata and to assess whether smoking affects the outcome of the antiviral therapy.
DISCUSSION
Currently available treatments for anogenital HPVinduced lesions are characterized by significant side
effects and high recurrence rates. These treatments are aimed mainly at removal of the papillomatous lesions and not at reducing the viral load and the persistent latent infection and high relapse rates associated therewith. Recently, the potential role of HPMPC in the treatment of condylomata acuminata has been suggested.
Although there are several reports on the effect of the antiviral agent HPMPC on HPV-induced papillomatous lesions, no prior studies have compared the long-term results of cidofovir with other treatments in patients with perianal condylomata. HPMPC was applied with success topically or intralesionally in HPV-induced lesions with and without intraepithelial neoplasia at the internal and external genitals (including vulvar, vaginal, penile, and cervical intraepithelial neoplasia), esophagus, and larynx. In the present study, HPMPC was compared with the standard treatment, repetitive coagulations. In the design of a study to compare two completely different treatment modalities,repetitive coagulations and topical antiviral therapy, the problem of coexistent internal lesions was difficult to resolve. Topical application of cidofovir, in contrast to coagulations, can only be applied on externally visible warts. The exclusion of all patients with coexistent internal lesions would have reduced the number of potential candidates for treatment by approximately 50 percent. The alternative, disregarding from analysis the relapses limited to internal lesions after complete clearing, was chosen in this study. The nonconcurrent, nonrandomized study design with the historic nature of the control group treated primarily with coagulations, retrospective analysis of the data of the control group, and differences in immune status between patients in both treatment groups are obvious limitations of this study. Although these factors must be taken into consideration when one interprets the results of the study,
they do not compromise the straightforward conclusions. The significantly higher incidence of impaired immunity in the cidofovir-treated patients (test group) compared with patients treated only with coagulation (control group) can be explained by the design of the study, which is nonconcurrent. Between 1992 and 2000, the incidence of patients infected with HIV and patients treated with immune-suppressive drugs for organ transplantation, systemic disease, or a variety of inflammatory diseases in the Belgian population was increasing steadily. HIV-positive patients were not stratified according to the degree of immune deficiency because the numbers were too small. Because all HIV-positive patients included in the test group received optimal treatment, the effect of HIV infection on the outcome of cidofovir treatment is expected to be minimal. Despite the higher incidence of impaired immune status in the test group compared with the control group, the relapse rate was significantly lower in the cidofovir-treated patients, further underlining that this topically applied antiviral agent is an effective adjuvant to surgical clearance of external HPV-induced lesions. The lesser amount of time needed to confirm complete clearance of the lesions in the test group can be
explained by a higher efficacy of cidofovir with or without coagulations than repetitive coagulations alone in preventing or postponing recurrence. Topically applied HPMPC resulted in complete resolution or partial regression of perianal condylomata in 92 percent of the patients, with only minimal side effects. HPMPC treatment also resulted in a very low recurrence rate after complete clearing of the condylomata without significantly prolonging the total treatment period. Furthermore, in most patients who had only partial regression of the lesions, the number and extent of the coagulations and the ensuing painful ulcerations could be greatly reduced. The natural history of HPV infection is likely influenced by the cell-mediated immune system. Smoking,
other sexually transmitted diseases, HIV infection, and immunosuppressive drugs stimulate HPV __EXPRESSION__ and promote persistent infections. In the present study, cidofovir was also effective in patients with impaired immunity. This is in accordance with previously reported experience. The literature indicates that smoking is a risk factor for developing condylomata and persisting HPV infection. The observation that the percentage of smokers was much higher in patients presenting with condylomata in the present study than in the general population appears to confirm the data of the literature. Our observation that cidofovir is less effective in smokers than in nonsmokers further points to the deleterious effect of smoking on the course of HPV infection. |
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