Podophyllotoxin Cream Research Articles

Imiquimod versus podophyllotoxin, with and without human papillomavirus vaccine, for anogenital warts: the HIPvac factorial RCT.

The comparative efficacy, and cost-effectiveness, of imiquimod or podophyllotoxin cream, either alone or in combination with the quadrivalent HPV vaccine (Gardasil®, Merck Sharp & Dohme Corp., Merck & Co., Inc., Whitehouse Station, NJ, USA) in the treatment and prevention of recurrence of anogenital warts is not known. The objective was to compare the efficacy of imiquimod and podophyllotoxin creams to treat anogenital warts and to assess whether or not the addition of quadrivalent human papillomavirus vaccine increases wart clearance or prevention of recurrence. A randomised, controlled, multicentre, partially blinded factorial trial. Participants were randomised equally to four groups, combining either topical treatment with quadrivalent human papillomavirus vaccine or placebo. Randomisation was stratified by gender, a history of previous warts and human immunodeficiency virus status. There was an accompanying economic evaluation, conducted from the provider perspective over the trial duration. The setting was 22 sexual health clinics in England and Wales. Participants were patients with a first or repeat episode of anogenital warts who had not been treated in the previous 3 months and had not previously received quadrivalent human papillomavirus vaccine. Participants were randomised to 5% imiquimod cream (Aldara®; Meda Pharmaceuticals, Takeley, UK) for up to 16 weeks or 0.15% podophyllotoxin cream (Warticon®; GlaxoSmithKlein plc, Brentford, UK) for 4 weeks, which was extended to up to 16 weeks if warts persisted. Participants were simultaneously randomised to quadrivalent human papillomavirus vaccine (Gardasil) or saline control at 0, 8 and 24 weeks. Cryotherapy was permitted after week 4 at the discretion of the investigator. The main outcome measures were a combined primary outcome of wart clearance at week 16 and remaining wart free at week 48. Efficacy analysis was by logistic regression with multiple imputation for missing follow-up values; economic evaluation considered the costs per quality-adjusted life-year. A total of 503 participants were enrolled and attended at least one follow-up visit. The mean age was 31 years, 66% of participants were male (24% of males were men who have sex with men), 50% had a previous history of warts and 2% were living with human immunodeficiency virus. For the primary outcome, the adjusted odds ratio for imiquimod cream versus podophyllotoxin cream was 0.81 (95% confidence interval 0.54 to 1.23), and for quadrivalent human papillomavirus vaccine versus placebo, the adjusted odds ratio was 1.46 (95% confidence interval 0.97 to 2.20). For the components of the primary outcome, the adjusted odds ratio for wart free at week 16 for imiquimod versus podophyllotoxin was 0.77 (95% confidence interval 0.52 to 1.14) and for quadrivalent human papillomavirus vaccine versus placebo was 1.30 (95% confidence interval 0.89 to 1.91). The adjusted odds ratio for remaining wart free at 48 weeks (in those who were wart free at week 16) for imiquimod versus podophyllotoxin was 0.98 (95% confidence interval 0.54 to 1.78) and for quadrivalent human papillomavirus vaccine versus placebo was 1.39 (95% confidence interval 0.73 to 2.63). Podophyllotoxin plus quadrivalent human papillomavirus vaccine had inconclusive cost-effectiveness compared with podophyllotoxin alone. Hepatitis A vaccine as control was replaced by a saline placebo in a non-identical syringe, administered by someone outside the research team, for logistical reasons. Sample size was reduced from 1000 to 500 because of slow recruitment and other delays. A benefit of the vaccine was not demonstrated in this trial. The odds of clearance at week 16 and remaining clear at week 48 were 46% higher with vaccine, and consistent effects were seen for both wart clearance and recurrence separately, but these differences were not statistically significant. Imiquimod and podophyllotoxin creams had similar efficacy for wart clearance, but with a wide confidence interval. The trial results do not support earlier evidence of a lower recurrence with use of imiquimod than with use of podophyllotoxin. Podophyllotoxin without quadrivalent human papillomavirus vaccine is the most cost-effective strategy at the current vaccine list price. A further larger trial is needed to definitively investigate the effect of the vaccine; studies of the immune response in vaccine recipients are needed to investigate the mechanism of action. Current Controlled Trials. Current Controlled Trials ISRCTN32729817 and EudraCT 2013-002951-14. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 47. See the NIHR Journals Library website for further project information.

Local Management of Anogenital Warts in Non-immunocompromised Adults: A Systematic Review and Meta-analyses of Randomized Controlled Trials.

IntroductionSeveral therapeutic options are available to manage anogenital warts (AGWs). However, no hierarchy of treatments is provided in the latest European and American recommendations. This study aimed to determine the efficacy and safety of local treatments for the management of AGWs.MethodsA search was conducted through 12 databases from inception to August 2018. All randomized controlled trials (RCTs) in which at least one parallel treatment group composed of immunocompetent adults with AGWs received at least one provider-administered or patient-administered treatment were included. Risk of bias assessment and meta-analyses of aggregated study data were performed on the basis of the Cochrane Handbook, and quality of evidence evaluation followed the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Primary endpoints were complete clearance and recurrence at 3 months.ResultsSeventy RCTs (9931 patients) were included. All but four RCTs had a high risk of bias. CO2 laser was slightly more efficacious than cryotherapy [risk ratio (RR) 2.05; 95% confidence interval (CI) 1.61–2.62], with fewer recurrences at 3 months (RR 0.28; 95% CI 0.09–0.89). Electrosurgery was slightly more efficacious than cryotherapy. No differences in efficacy or side effects were found between cryotherapy and imiquimod or trichloroacetic acid. Podophyllotoxin gel was slightly more efficacious than podophyllotoxin cream. 5-Fluorouracil (5-FU) was slightly more efficacious and caused less erosion than CO2 laser (RR 1.37; 95% CI 1.11–1.70).ConclusionThe vast majority of included RCTs had a low level of evidence, thereby preventing the establishment of a hierarchy of treatments. Nevertheless, our results provide an overview of the main AGW treatments available for general practitioners and specialists. While provider-administered treatments are superior, patient-administered treatments (e.g., imiquimod, podophyllotoxin) are useful solutions for compliant patients.Protocol registrationPROSPERO-CRD42015025827.Electronic supplementary materialThe online version of this article (10.1007/s13555-019-00328-z) contains supplementary material, which is available to authorized users.

Human papillomavirus infection: protocol for a randomised controlled trial of imiquimod cream (5%) versus podophyllotoxin cream (0.15%), in combination with quadrivalent human papillomavirus or control vaccination in the treatment and prevention of recurrence of anogenital warts (HIPvac trial)

BackgroundAnogenital warts are the second most common sexually transmitted infection diagnosed in sexual health services in England. About 90% of genital warts are caused by human papillomavirus (HPV) types 6 or 11, and half of episodes diagnosed are recurrences. The best and most cost-effective treatment for patients with anogenital warts is unknown. The commonly used treatments are self-administered topical agents, podophyllotoxin (0.15% cream) or imiquimod (5% cream), or cryotherapy with liquid nitrogen. Quadrivalent HPV (qHPV) vaccination is effective in preventing infection, and disease, but whether it has any therapeutic effect is not known.Methods and designTo investigate the efficacy of clearance and prevention of recurrence of external anogenital warts by topical treatments, podophyllotoxin 0.15% cream or imiquimod 5% cream, in combination with a three-dose regimen of qHPV or control vaccination. 500 adult patients presenting with external anogenital warts with either a first or subsequent episode of anogenital warts will be entered into this randomised, controlled partially blinded 2 × 2 factorial trial.DiscussionThe trial is expected to provide the first high-quality evidence of the comparative efficacy and cost-effectiveness of the two topical treatments in current use, as well as investigate the potential benefit of HPV vaccination, in the management of anogenital warts.Trial registrationThe trial was registered prior to starting recruitment under the following reference numbers: International Standard Randomized Controlled Trial Number (ISRCTN) Registry - ISRCTN32729817 (registered 25 July 2014); European Union Clinical Trials Register (EudraCT) - 2013-002951-14 (registered 26 June 2013).

Anogenital squamous cell carcinoma in neglected patient

Skin squamous cell carcinomas (SCCs) are arguably the second most common carcinoma of the skin and are responsible for the majority of non-melanoma skin cancer deaths. Gynecologist treated a Caucasian 56-years old female patient for genital wart with podophyllotoxin cream. She did not achieve complete response and therefore she has interrupted the therapy and the collaboration with the gynecologist. At the time of evaluation the lesion had a size of man's palm in anogenital region and showed characteristic features of neoplasm. The regional lymph nodes have produced infiltrated painful bubo. PCR analysis for HPV proved negative. Histopathology revealed well-differentiated squamous cell keratinizing carcinoma from the tumor as well as from the regional lymph node packet. Staging computed tomography scans proved negative and pelvis scans disclosed regional lymphadenopathy underlying the tumor. Palliative radiation therapy (by linear accelerator) was administered for the oversized tumor to the total TD 50.0Gy. The patient died 6 months after diagnostic assessment from cardio-respiratory failure. Staging computed tomography before her death did not disclose distinct metastases in her inner organs. Well-differentiated squamous cell keratinizing carcinoma could be growing endophytically affecting the underlying adipose tissue and musculature, with spreading into the regional lymph nodes. The rate of metastases into inner organs seems to vary according to the aggressiveness and metastatic behavior of each SCC. The case report calls for attention to the importance of collaboration among various specialists assisting in the diagnosis and management of skin neoplasm (Fig. 5, Ref. 12). Full Text in PDF www.elis.sk.

CONDYLOMATA ACUMINATA TREATMENT WITH CARBON DIOXIDE LASER IN COMPARISON WITH 0.15% PODOPHYLLOTOXIN CREAM

The clinical manifestations and HIV testing was analyzed in 137 patients with condylomata acuminata. A pulsed carbon dioxide laser was used to treat 60 patients and 0.15% podophyllotoxin cream was used in 30 patients. Condylomatous lesions were seen at a high rate (87.6%), and the number of patients testing positive for HIV was comparatively high (8%). The first pulsed laser carbon dioxide treatment gave a cure rate of 81.7% as compared with a 40% cure rate with topical cream (p < 0,001). Scars were noted in 8.3% of patients treated with pulsed carbon dioxide laser. The results of the study suggest that carbon dioxide laser is a safe, effective and easy-to-deliver therapeutic approach for the treatment of condylomata acuminata, and that the autosimultaneous LLLT component of laser radiation in the periphery of the photothermal destruction contributed greatly to this efficacy.

Randomised controlled trial and economic evaluation of podophyllotoxin solution, podophyllotoxin cream, and podophyllin in the treatment of genital warts

Objectives: To evaluate the efficacy and cost effectiveness of self applied podophyllotoxin 0.5% solution and podophyllotoxin 0.15% cream, compared to clinic applied 25% podophyllin in the treatment of genital warts...

Er:YAG laser followed by topical podophyllotoxin for hard‐to‐treat palmoplantar warts

BACKGROUND AND OBJECTIVES: Palmoplantar warts are often hard to treat. They tend to relapse and the course of therapy is frustrating in many cases. The erbium:YAG laser (Er:YAG) with a wavelength of 2.94 μm is capable of achieving a rapid and precise ablation of warts, but about 14% of patients are non‐responders as shown in a previous study. Podophyllotoxin is an established antimitotic agent derived from podophyllum plant resin, approved for human papilloma virus (HPV)‐induced genital warts. The combination of both ablative Er:YAG laser and topical 0.5% podophyllotoxin solution in hard‐to‐treat palmoplantar HPV warts was investigated.PATIENTS AND METHODS: Thirty‐five patients with hard‐to‐treat warts (palmar or plantar) with a mean age of (32.2±12.1) years, range 17–50 years, with various pretreatments that had failed, were treated once by Er:YAG laser ablation with a spot size of 3 mm, a frequency between 8 Hz and 10 Hz, and a fluence of 5.7–11.3 J/cm2. After wound healing, topical podophyllotoxin 0.5% solution was applied for 3 days followed by a break of 4 days. Four to six treatment cycles with podophyllotoxin were performed.RESULTS: After laser treatment followed by topical podophyllotoxin cream a complete response was observed in 31 patients (88.6%). Two patients with plantar warts and a complete response showed a relapse within 3 months after treatment (5.7%). None of the patients developed pigmentary changes, wound infections or scarring.CONCLUSION: The therapy of hard‐to‐treat warts with a combination of Er:YAG laser and topical podophyllotoxin is safe and effective. Compared with laser alone, the CR percentage seems to be higher and the percentage of relapses reduced.

Er:YAG laser followed by topical podophyllotoxin for hard-to-treat palmoplantar warts

BACKGROUND AND OBJECTIVES: Palmoplantar warts are often hard to treat. They tend to relapse and the course of therapy is frustrating in many cases. The erbium:YAG laser (Er:YAG) with a wavelength of 2.94 μm is capable of achieving a rapid and precise ablation of warts, but about 14% of patients are non‐responders as shown in a previous study. Podophyllotoxin is an established antimitotic agent derived from podophyllum plant resin, approved for human papilloma virus (HPV)‐induced genital warts. The combination of both ablative Er:YAG laser and topical 0.5% podophyllotoxin solution in hard‐to‐treat palmoplantar HPV warts was investigated.PATIENTS AND METHODS: Thirty‐five patients with hard‐to‐treat warts (palmar or plantar) with a mean age of (32.2±12.1) years, range 17–50 years, with various pretreatments that had failed, were treated once by Er:YAG laser ablation with a spot size of 3 mm, a frequency between 8 Hz and 10 Hz, and a fluence of 5.7–11.3 J/cm2. After wound healing, topical podophyllotoxin 0.5% solution was applied for 3 days followed by a break of 4 days. Four to six treatment cycles with podophyllotoxin were performed.RESULTS: After laser treatment followed by topical podophyllotoxin cream a complete response was observed in 31 patients (88.6%). Two patients with plantar warts and a complete response showed a relapse within 3 months after treatment (5.7%). None of the patients developed pigmentary changes, wound infections or scarring.CONCLUSION: The therapy of hard‐to‐treat warts with a combination of Er:YAG laser and topical podophyllotoxin is safe and effective. Compared with laser alone, the CR percentage seems to be higher and the percentage of relapses reduced.

Topical treatment of venereal warts: a comparative open study of podophyllotoxin cream versus solution

Podophyllotoxin solution (0.5%) is licensed for use in the treatment of condylomata acuminata (genital warts) in men in a number of European countries. In some countries, approval also extends to treatment of genital warts in women. This controlled randomized prospective study evaluated the efficacy and safety of a cream formulation of podophyllotoxin at 2 concentrations (0.15% and 0.3%), using 0.5% podophyllotoxin solution as a reference treatment. Two separate studies were initiated, to assess the 3 treatment groups in (a) male patients, and (b) female patients. Statistical evaluation was based on a "response rate' calculated at each clinic visit. The mean "response rates' in the male patient study at 4 weeks were 75.1%, 79.0% and 85.6% in the 0.15% cream, 0.3% cream and 0.5% solution groups, respectively. The corresponding "response rates' for the female patient study were 86.2%, 92.6%, and 93.1%, respectively. The relapse rates for both male and female patients were 6.0% in the 0.15% cream group, 8.6% in the 0.3% cream group and 8.6% in the 0.5% solution group. The results show that there were no statistically significant differences between the 3 treatments with regard to both efficacy and safety. This was true for both the male and female patient groups.

Audits of the treatment of genital warts: closing the feedback loop.

An initial audit of the treatment of patients presenting to the GUM Department at Leeds General Infirmary with a first episode of anogenital warts was reported in 1993. Treatment was found to be unselective and poorly monitored and the results of treatment were disappointing. As a consequence, guidelines for the management of new patients presenting with genital warts were devised. In order to establish whether these guidelines had produced any improvements in outcome, a second audit was performed looking at the results of treatment in patients with new genital warts who attended 6 months or more after the new guidelines were introduced. Progress was documented for 6 months after presentation. There was a significant fall in the numbers of patients receiving podophyllin 25% solution as first-line treatment, and corresponding increases in the initial use of cryotherapy, trichloracetic acid and, in men, podophyllotoxin solution. (Podophyllotoxin was not licensed for use in women at the time of the second audit.) There were significant improvements in the outcome of treatment. Originally 44% of men had warts despite receiving treatment for 3 months, and 32% were still attending for treatment 6 months after presentation. After the introduction of treatment guidelines, these figures had fallen to 8% and 3% respectively. In the first audit 38% of women still had warts after 3 months' treatment but in the second audit this figure was reduced to 18%. At 6 months, the percentage of women still attending for treatment was halved from 12% in the first audit to 6% in the second audit. The mean number of clinic visits fell from 5 to 3 in men and from 9 to 6 in women. The treatment protocols have been modified and now include the use of podophyllotoxin cream and solution in both men and women.

A single-blind study of podophyllotoxin cream 0.5% and podophyllotoxin solution 0.5% in male patients with genital warts.

To evaluate the efficacy-safety ratio of a new topical podophyllotoxin cream 0.5% compared with podophyllotoxin solution 0.5% (Condyline) in male patients with genital warts. In an observer-blinded controlled study a total of 136 and 133 wart lesions were treated with podophyllotoxin cream 0.5% and podophyllotoxin solution 0.5%, respectively. The preparations were applied twice daily for 3 days, repeated with 4 days intervals for a minimum of two and a maximum of four treatment cycles. At the conclusion of the study (8 weeks after completion of therapy) a significant reduction in mean wart area was observed in both the cream group (87.7, SD 8.4 to 20.6, SD 2.7) and in the solution group (92.3, SD 7.5 to 21.5, SD 2.8) (p < 0.01). At the same time all treated warts had completely cleared in 63% of patients in both study groups. Mild to moderate side effects occurred to the same extent in both podophyllotoxin cream and podophyllotoxin solution recipients. We conclude that podophyllotoxin 0.5% administered in a cream formulation does not give additional clinical benefits when compared with podophyllotoxin solution 0.5% in male patients with external genital warts.

Topical treatment of genital warts in men, an open study of podophyllotoxin cream compared with solution.

To evaluate the clinical efficacy of a 0.15% and a 0.3% cream formulation of podophyllotoxin in comparison with the 0.5% solution in the treatment of condylomata acuminata and to compare the treatment modalities regarding side effects. The study was designed as an open randomised trial. Ninety male patients with signs of penile HPV infection, with either acuminate or papular lesions, were randomised into three parallel treatment groups. The study medication comprised 0.15% and 0.3% cream and 0.5% solution of podophyllotoxin. The patients treated themselves twice daily for three consecutive days and if total regression of the warts was not achieved after this first treatment cycle, further treatment cycles at 7-day intervals were to be repeated up to a maximum of four treatments. The study was carried out in three outpatient clinics: two STD clinics, Department of Dermatology and Venereology, University Hospital (45 patients) and Institut Antoine Fournier, Paris (30 patients), and one military hospital, S1/FO 47/48, Sjukhusenheten, Enköping (15 patients). Statistical evaluation of the treatment effect was based on a "Response rate" calculation at each visit. The number of completely responding patients after the first, second, third and fourth cycle were 40 (44%), 61 (68%), 67 (74%) and 70 (78%), respectively. There was no statistically significant difference between the three treatments after four treatment cycles. However, the 0.15% cream had a significantly slower onset of efficacy as compared with the 0.3% cream and 0.5% solution. Adverse effects were less severe and less frequent with the 0.15% cream than with the other treatment modalities. Severe adverse effects were reported by 12 patients, of whom two were treated with 0.15% cream, five with 0.3% cream and five with 0.5% solution. Thirty-one patients were completely free from adverse effects. In this open randomised study with three parallel treatment groups, two cream formulations of 0.15% and 0.3% podophyllotoxin and a 0.5% solution of the same drug all showed an equally good response rate after four treatment cycles. Reported adverse effects were few and mild. The convenience of having different formulations to offer when prescribing treatment for condylomata must be considered.

Self-treatment Using a 0.5% Podophyllotoxin Cream of External Genital Condylomata Acuminata in Women

Self-treatment Using a 0.5% Podophyllotoxin Cream of External Genital Condylomata Acuminata in Women

Clinical efficacy of Condyline (0.5% podophyllotoxin) solution and cream versus podophyllin in the treatment of external condylomata acuminata

A single-blind randomized controlled trial was performed to compare the clinical efficacy of Condyline (0.5% podophyllotoxin) solution with Condyline (0.5% podophyllotoxin) cream and 20% podophylli...