Closing the feedback loop: an audit of the use of imiquimod for the treatment of genital warts

A retrospective case-note audit of 74 patients with 81 treatment episodes of anogenital warts with imiquimod from April 1999 until July 2000 was performed. The majority of patients had failed to clear their warts with other treatments, had recurrences after other treatments, or had other medical problems complicating their genital wart treatment. The overall clinically confirmed complete clearance rate was 33%. This is lower than other published data, but may be so because it includes patients with immunosuppression and difficult-to-treat warts. The complete clearance rate in immunocompetent patients was 37%. In addition, in this audit of clinical practice 17% of the patients did not return for full response to be assessed. The complete clearance rate in those who were able to tolerate treatment and who returned for follow-up was 45%. Based on the results of the audit we have extended the indications for the use of imiquimod in the clinic treatment guidelines. Patients are now offered imiquimod if six or more episodes of other treatments fail to give a good response. Earlier treatment with imiquimod is also offered to those patients with recurrent anogenital warts, and it is recommended as a first-line therapy for patients with multiple keratinized warts.     

Imiquimod 5% cream is an acceptable treatment option for external anogenital warts in uncircumcised males

OBJECTIVES: To determine the safety and efficacy of imiquimod (Aldara) 5% cream in the treatment of prepuce-associated warts in uncircumcised males. METHODS: An open-label study in six UK medical centres with 35 uncircumcised males with prepuce-associated warts treated with imiquimod 5% cream three times per week for up to 16 weeks. Other anogenital warts were also treated. RESULTS: Three times weekly application of imiquimod was found to be safe, with erythema as the most commonly reported local skin reaction. Forty per cent of patients had complete clearance of anogenital warts within 16 weeks. CONCLUSIONS: Imiquimod cream at a dosing regimen of three times per week, is effective and has an acceptable safety profile in the treatment of prepuce associated warts and other external anogenital warts in uncircumcised males.     

Human papillomavirus typing of warts and response to cryotherapy

Background Cutaneous warts are common and caused by a number of different types of human papillomaviruses (HPVs). Objective The aim of this study was to investigate the HPV types causing common warts and to determine any association between the HPV type and the duration of warts and response to cryotherapy. Methods Eighty wart samples from 76 immunocompetent patients were taken from warts by paring prior to cryotherapy and analysed by in situ hybridization (ISH) with HPV probes specific to HPV 1, 2, 3, 4, 7, 10 and 57 and PCR analysis using degenerate cutaneous HPV primers with subsequent DNA sequencing. Each patient's details, including site, duration and response of the wart to cryotherapy were recorded. Cryotherapy was performed at 2 week intervals for a maximum of 12 weeks. Results An HPV type was identified in 65 samples. The majority of warts (58 samples) were typed as HPV 2/27/57 by ISH and/or PCR. Three of the 18 samples that were HPV negative with ISH were HPV positive by PCR. Response to treatment did not correlate with HPV type, duration or location. In the 21 wart parings taken from patients aged 16 and under, response to treatment did not correlate with HPV type but warts of shorter duration were more likely to resolve with cryotherapy treatment than longer standing lesions. Conclusion This study demonstrates that HPV type can be determined from wart parings. HPV‐2 related viruses are the prevalent HPV types causing common warts on the hands and feet in this population.     

Nonavalent human papillomavirus vaccination as alternative treatment for genital warts

Genital warts caused by the human papillomavirus (HPV) are the most common sexually transmitted disease and have a negative impact on quality of life. Of the more than 200 different types of HPV, low‐risk types 6 and 11 are mainly responsible for the development of condyloma acuminata. Despite a large arsenal of local therapies such as numerous topical agents, CO₂ laser ablation, and surgical removal, genital warts tend to be recalcitrant. HPV vaccination is mainly used as a preventive strategy to prevent genital warts, cervical cancer, and other anogenital cancers. However, in a few cases, HPV vaccination has been shown to be a good treatment alternative for patients with recalcitrant skin warts. Here we report five cases of recalcitrant genital warts that responded well to treatment with the nonavalent HPV vaccine. HPV vaccines could be beneficial as a noninvasive treatment alternative for recalcitrant genital warts.     

Comparison of cryotherapy session intervals in the treatment of external genital warts

A review of the literature found that the cryotherapy method used to treat external genital warts (EGWs) has been applied with varying intervals between sessions. However, no study has compared the intervals between sessions. The files of 312 patients who were diagnosed with genital warts and underwent cryotherapy were retrospectively reviewed. The patients were divided into two groups: 7–8 days between cryotherapy treatments and 14–21 days between cryotherapy treatments. The number of sessions and recurrence status were recorded for each patient. Cryotherapy methods applied with short intervals, such as 7–8 days, are more effective, requiring fewer sessions and less time when compared with longer intervals (p < 0.0001).     

Possible role of interleukin 21 and interleukin 33 in patients with genital warts

Genital warts (GWs) are most prevalent sexually transmitted infections, presenting especially among the sexually active young population of both sexes. Efficient cell‐mediated immunity is needed for regression of GWs. To clarify the reactivity of cellular immunity among patients with GWs by means of measurements of their levels of serum interleukin (IL)‐21 and IL‐33, hence, to identify the possible role of IL‐21 and IL‐33 in GWs, this study aimed to evaluate serum levels of IL‐21 and IL‐33 among patients with GWs in comparison with the results of the controls. Levels of serum IL‐21 and IL‐33 were assayed utilizing commercially enzyme‐linked immune‐sorbent assay kits in 45 patients with GWs and 45 healthy control subjects. Levels of serum IL‐21 and IL‐33 were significantly decreased among patients with GWs in comparison with the controls (p < .0001). There was a highly significant positive correlation between IL‐21 and IL‐33 (r = .73, p < .0001). Low levels of serum IL‐21 and IL‐33 could have a contributive role in development, persistence, severity, and recurrence of GWs which rely basically on the defectiveness of cell‐mediated immunity. This could receive new light on nonconventional strategies for the prospective medical therapies of GWs by means of regulation of IL‐21 and IL‐33.     

Human papillomavirus (HPV) viral load and HPV type in the clinical outcome of HIV-positive patients treated with imiquimod for anogenital warts and anal intraepithelial neoplasia

OBJECTIVE: To evaluate the efficacy of 5% imiquimod in HIV-positive male patients with anogenital warts or anal intraepithelial neoplasia (AIN), and to elucidate whether human papillomavirus (HPV) type and viral load were important for clinical outcome and recurrences. METHODS: Thirty-seven patients with histologically proven anogenital warts or AIN were enrolled. Topical 5% imiquimod was applied three times per week for more than 8 h overnight for 16 weeks, although patients were allowed to continue therapy for 4 more weeks if they did not have complete clearance of lesions. RESULTS: Mean age was 34 years. The perianal area was the main lesion location. Thirty-three patients had CD4 counts of < 500 cells/mm(3). Eighteen patients had a histopathological diagnosis of AIN-1. Main HPV types detected corresponded to low-risk HPV types. At 20 weeks of therapy, 46% patients achieved total clearance whereas 14 patients had > 50% clearance. Recurrence was observed in 5 of 17 patients who cleared. Clearance was not influenced by patients' CD4 counts, wart location, HIV viral load or HPV viral load. CONCLUSIONS: The assumption that visible perianal warts are benign lesions in HIV-positive patients has to be reevaluated since an important number of such lesions could correspond to low-grade anal disease, which in turn could progress to high-grade anal disease or cancer. In addition, our results in this preliminary study indicate that imiquimod appears to be effective in treating AIN in HIV-positive patients. Further studies are needed to document its utility to prevent high-grade dysplasia and/or anal cancer.     

Treatment of genital warts in males by pulsed dye laser

Objective: To determine the safety and efficacy of the flashlamp‐pumped pulsed dye laser for the treatment of uncomplicated genital warts in adult males. Methods: This was a prospective observational study set in the outpatient clinics of the Department of Andrology and Sexually Transmitted Diseases, National Institute of Laser Enhanced Sciences, the Dermatology Clinic, Cairo University, and the Department of Dermatology and Venereology, Suez Canal University. A total of 174 adult male patients with 550 uncomplicated anogenital warts were included. Selective photothermolysis and photocoagulation of the lesions with the flashlamp‐pumped pulsed dye laser was carried out. A pulsed dye laser (wavelength 585?nm, 450?s pulse duration; Cynosure, USA) was used with the following settings: spot size 5–7?mm; fluence 9–10 J/cm². Results: Complete resolution of treated warts was achieved in 96% of lesions. Side effects were limited, transient and infrequent. Lesion recurrence rate was 5%. Conclusion: The pulsed dye laser has been found to be safe, effective and satisfactory for the treatment of anogenital warts in males. It could be used to selectively destroy warts without damaging the surrounding skin.     

Clearance of genital warts in pregnant women by mild local hyperthermia: a pilot report

Genital warts acquired during pregnancy tend to grow fast, and management is challenging. We treated two cases of primipara with extensive genital warts by local hyperthermia at 44°C for 30 minutes a day for 3 consecutive days plus 2 additional days 1 week later, then once a week till there showed signs of clinical regression. The warty lesions in the patients resolved in 5 and 7 weeks, respectively. There was no sign of recurrence during a 6‐month follow‐up. This suggests that local hyperthermia seems to be a promising method for treating genital warts in pregnant women.     

Recent advances in management of genital ulcer disease and anogenital warts

ABSTRACT:   Genital ulcer disease (GUD) constitutes a major public health problem. Most of them are the result of sexually transmitted diseases. Genital herpes, syphilis, lymphogranuloma venereum, granuloma venereum, or chancroid are the commonly encountered GUD. The treatment modalities for these disorders have changed with advent and use of drugs such as azithromycin. The treatment modalities differ in patients with HIV disease. Further vaccines for herpes genitalis and human papilloma virus has opened new avenues in management of these diseases. In regions where there are no diagnostic facilities or where the costs of diagnostic tests are prohibitive, syndromic management of GUD is preferred.     

Complete remission of recalcitrant genital warts with a combination approach of surgical debulking and oral isotretinoin in a patient with systemic lupus erythematosus

Genital warts in immunocompromised patients can be extensive and recalcitrant to treatment. We report a case of recalcitrant genital warts in a female patient with systemic lupus erythematosus (SLE), who achieved complete remission with a combination approach of surgical debulking and oral isotretinoin at an initial dose of 20 mg/day with a gradual taper of dose over 8 months. She had previously been treated with a combination of topical imiquimod cream and regular fortnightly liquid nitrogen. Although there was partial response, there was no complete clearance. Her condition worsened after topical imiquimod cream was stopped because of her pregnancy. She underwent a combination approach of surgical debulking and oral isotretinoin after her delivery and achieved full clearance for more than 2 years duration. Oral isotretinoin, especially in the treatment of recalcitrant genital warts, is a valuable and feasible option when other more conventional treatment methods have failed or are not possible. It can be used alone or in combination with other local or physical treatment methods.     

Topical treatment for human papillomavirus-associated genital warts in humans with the novel tellurium immunomodulator AS101: assessment of its safety and efficacy

Background  Various methods are currently used for the treatment of anogenital warts. However, a complete cure is unlikely, and the rate of recurrence is high.
Objectives  The purpose of this open-label, multicentre trial was to evaluate the safety and clinical efficacy of a new treatment using the immunomodulator ammonium trichloro (dioxoethylene- O , O ') tellurate (AS101; Biomas Ltd, Kefar Saba, Israel) 15% w/w cream to clear vulval/perianal condylomata acuminata.
Methods  Study participants comprised 48 women and 26 men, age range 18–62 years. Of the 48 woman, 44 were diagnosed with vulval condylomata and four with perianal condylomata. All 26 men were diagnosed with perianal condylomata. All the patients in the study received AS101 15% w/w cream twice a day. Maximal treatment duration was 16 weeks. To evaluate the safety and clinical efficacy, patients were examined and lesional areas photographed on a biweekly basis.
Results  By the end of the treatment, 56 of 74 (76%) patients were considered completely cleared. Complete cure was achieved in 35 of 44 (80%) patients with vulval condylomata and in 21 of 30 (70%) patients with perianal condylomata. No scarring of treated areas was observed. Complete cure was achieved within a time range of 10–109 days. The most frequent side-effects observed were mild-to-moderate itching, soreness, burning and erythema. In post-treatment follow up of up to 6 months, disease recurrence was observed in two patients (4%), at 105 and 144 days following completion of treatment.
Conclusions  AS101 15% w/w cream is an effective and safe, self-administered therapy used for the treatment of external vulval and perianal warts. The cream is applied topically twice daily for up to 16 weeks. A very low recurrence rate was reported.     

高频电离子联合艾拉光动力治疗男性复发性尖锐湿疣疗效观察

目的:分析并探讨高频电离子联合艾拉光动力治疗男性复发性尖锐湿疣的临床效果。方法:选取在我院接受治疗的男性复发性尖锐湿疣患者120例,随机分成两组,分别为观察组与对照组,每组60例。两组患者均给予高频电离子方案进行治疗,在此基础上,观察组联合艾拉光动力进行治疗。治疗后4周、8周和12周随访。观察随访结果,评估治疗效果和复发情况以及不良反应发生情况。结果:观察组治愈率为91.67%,复发率为8.33%。对照组治愈率为71.67%,复发率为28.33%。观察组治愈率明显高于对照组,复发率明显低于对照组(P0.05)。观察组不良反应发生率为6.67%,对照组不良反应发生率为31.67%。观察组不良反应发生率明显低于对照组(P0.05)。结论:高频电离子联合艾拉光动力治疗男性复发性尖锐湿疣效果显著,且复发率低,临床上值得推广。     

High prevalence of genital HPV infection among long‐term monogamous partners of women with cervical dysplasia or genital warts—Another reason for HPV vaccination of boys

We conducted a cross‐sectional study on the occurrence of a specific type of genital human papillomavirus (HPV) among long‐term monogamous male partners of women with cervical dysplasia and genital warts. The purpose of the study was to improve knowledge with regards to the management of these couples. The presence of genital HPV‐DNA was detected by PCR with broad spectrum primers followed by hybridization. 82 males met the study criteria, 41 in each group. Genital HPV‐DNA prevalence was 67.5% in the genital warts group and 72.2% in the cervical dysplasia group. The prevalence of high risk HPVs was higher in the cervical dysplasia group, while low risk HPVs were more prevalent in the genital warts group (p < .05). The prevalence of HPV in males was independent of the duration of the relationship (73.5% for 6–24 months and 66.7% for longer relationships). In conclusion, our results suggest that the prevalence of the genital HPV infection in both groups of male partners is comparable and very high, but the spectrum of HPV types varies significantly. The presence of the genital HPV infection in male sexual partners seems to be independent of the duration of the relationship. Applying the HPV vaccination to boys may prevent this phenomenon.