Treatment Of External Genital Warts Research Articles

Assessment of sinecatechins 10% ointment used as proactive sequential therapy in recurrence rate of genital warts lesions after cryotherapy. The PACT-II Trial (postablation immunomodulator treatment of condylomata with sinecatechins): a prospective assessor-blinded, multicenter, pilot trial.

Cryotherapy is commonly used as ablative treatment of external genital warts (EGW). However, after cryotherapy recurrence of lesions affects on average 45% (42-70%) of subjects in the 6 months after the treatment. Sinecatechins 10% are an effective topical treatment of EGW. A low recurrence rate (<6%) was observed in pivotal phase 3 trials conducted with this product. Topical sinecatechins have demonstrated to significantly reduce the recurrence rate of EGW in subjects treated with laser therapy (The PACT-I trial). So far, no prospective data are available regarding the efficacy of sinecathechins as immunomodulator sequential therapy after cryotherapy in EGW subjects. The purpose of this study was to assess the rate of recurrence lesions after the use of topical sinecatechins 10%, as sequential proactive immunomodulation treatment after cryotherapy in subjects with EGW (The PACT-II Trial: the postablation immunomodulator treatment of condylomata with sinecatechins trial) (Trial Registration number: ISRCTN44037479). In a prospective, assessor-blinded, multicenter trial a total of 55 subjects with a diagnosis of multiple EGW (36 men and 19 women, mean age 47±10 years) and a mean lesion number of 9±7, after their informed consent, were enrolled in the study. All subjects were treated with cryotherapy (an average of 2 sessions). After the ablative treatment, all subjects were instructed to apply sinecatechin 10% ointment 3 times daily for 4 consecutive months. The primary study endpoint was the evaluation (assessor-blinded) of recurrent lesions after 6 months (2 month of follow-up after the conclusion of topical treatment). The secondary study endpoints were the appearance of new EGW lesions (lesions affecting area not treated by cryotherapy) and the local tolerability. At baseline, the mean number of EGW lesions were 9±7. After cryotherapy, the mean lesions number were reduced to 1.6±1.8. At month 4, EGW mean lesion number were 0.2±0.4 (P=0.0001 vs. after cryotherapy). At month 6, recurrence of lesions was detected in 10 subjects (18%; 95% CI: 9-30%) with an average of 1.4 lesions. Of these recurrent lesions, 6 occurred in completely healed lesions site after cryotherapy and 8 in partially healed ones. New lesions (outside the cryotherapy treated area) were observed in 10 subjects. The product was very well tolerated. No serious side effects were reported. Three subjects reported moderate skin irritation on the application site. The PACT-II Trial has shown that the recurrence rate of EGW lesions after successful cryotherapy using sinecatechins as immunomodulator sequential therapy is lower in comparison with the percentage documented in the literature without sequential therapy (20 vs. 45%). These results are in line with already published data evaluating the role of sinecatechins after laser therapy (PACT-I trial). Future comparative, double-blind controlled trials assessing the efficacy of different proactive strategies are warranted.

Complications and dosing frequency of 5% imiquimod for genital warts in a young man

A clinical decision report using: Fife KH, Ferenczy A, Douglas JM Jr, et al. Treatment of external genital warts in men using 5% imiquimod cream applied three times a week, once daily, twice daily, or three times a day. Sex Transm Dis. 2001;28(4):226-231. https://doi.org/10.1097/00007435-200104000-00007 for a patient with genital warts and an unstable social support network.

Effectiveness and Safety of Ablative Er:YAG Laser Treatment of External Genital Warts

Background: The aim of this study is to evaluate effectiveness and safety of the use of ablative Er:YAG laser for removal of external genital warts (EGW), also called condylomata acuminata (CA).Methods: This is a retrospective cohort study performed at Gynecology Clinic Juna in Ljubljana, Slovenia. All patients older than 18 years that were clinically diagnosed with EGW and were treated with ablative Er:YAG laser between January 2012 and December 2017 were included in the study.Results: A total of 133 female patients (mean age 39.6 ± 12.9 years, range: 19–80) with EGW were eligible to be included in this study. EGW have been present from one to seven months, with a mean presence of 2.1 ± 2.0 months. The majority of the warts were on the labia, major some also on the mons pubis. The size of the lesions was 2–8 mm. The majority of patients, who completed therapy (74 patients out of 116; 64 %) received only one treatment and 82 % of the patients (n = 95) showed complete clearance of the lesions, without recurrence observed to date of analysis. Complete clearance was achieved after an average of 1.33 treatment sessions. Recurrence was reported by 21 patients (18 %). Recorded adverse effects of laser treatment were mild and transient.Conclusion: Er:YAG laser removal of EGW is a simple, quick and safe procedure, particularly suitable for large volume EGW or those that are located in anatomical sites difficult to access by other techniques.

Topically applied treatments for external genital warts in nonimmunocompromised patients: a systematic review and network meta-analysis.

Selecting a topical treatment from among the numerous topical agents for external genital warts remains challenging without clear evidence. Our aim was to evaluate comparatively the efficacy and safety of topical agents for external genital warts using a network meta-analysis. We included all randomized controlled trials that evaluated any topically applied treatment for external genital warts. Using the R package netmeta, network meta-analyses were performed with a frequentist approach. We identified 41 relevant studies comprising 6371 patients. Among conventional agents, podophyllotoxin 0·5% solution (odds ratio 1·94, 95% confidence interval 1·02-3·71) was significantly more efficacious than imiquimod 5% cream for lesion clearance; however, it was associated with a higher overall adverse event rate. Sinecatechins 15% ointment (odds ratio 0·21, 95% confidence interval 0·12-0·34) was significantly less efficacious than imiquimod 5% cream. Idoxuridine, polyhexamethylene biguanide, cidofovir and SB206 showed comparable therapeutic efficacies with conventional therapies. None of the treatments were significantly different from each other with respect to recurrence, patients with severe adverse events, or patients who withdrew because of treatment-related adverse events. Conventional modalities were efficacious and well tolerated, although each of them had their advantages and disadvantages. Additional efficacy and safety studies are warranted for unconventional agents.

A Placebo-Controlled Study Using VP-102 in the Treatment of External Genital Warts

A Placebo-Controlled Study Using VP-102 in the Treatment of External Genital Warts

Efficacy of sinecatechins 10% as proactive sequential therapy of external genital warts after laser CO2 ablative therapy: The PACT study (post-ablation immunomodulator treatment of condylomata with sinecatechins): a randomized, masked outcome assessment, multicenter trial.

External genital warts (EGW) are the most common viral sexually transmitted infection. Ablative treatments like cryotherapy, curettage, and CO2 laser therapies offer rapid onset of effect, fast clearance, and reduction of virus load. However, these procedures are associated with high recurrence rates (RRs) ranging from 20% to 77% in the short and medium terms and do not provide sustained clearance. After laser therapy removal of EGW, an RR up to 77% has been reported. Topical sinecatechins (TS) 10% is a patient-applied regimen for the treatment of EGW with a low RR (<6.5%) at three months after completion of the therapy in the pivotal trials conducted so far. Sinecatechins can be considered a suitable proactive sequential therapy (PST) after ablative strategies to obtain a low RR. So far, no prospective data are available regarding the efficacy of sinecatechins 10% as PST. We evaluated the efficacy and tolerability of TS 10% ointment applied twice daily in subjects with "difficult to treat" EGW after CO2 laser ablative treatment in a prospective controlled trial. A total of 87 subjects (76 men and 11 women; mean age 42 years) were enrolled in this three-month masked outcome assessment parallel group trial with imbalanced randomization allocation (2:1). One week after a successful CO2 laser treatment, 60 subjects were randomized to TS 10% treatment and 27 subjects to no treatment (control group: ConTRol (CTR); no sequential therapy). All patients had a history of an average of 4.5 previous ablative treatments in the last 12 months due to recurrent EGW. Mean (standard deviation) baseline number of treated lesions was 6.5 (2.7). One subject in the TS arm dropped out due to burning sensation after the application of the product. Therefore, 86 subjects completed the study. After three months, in the TS group, three subjects presented new EGW lesions (RR: 5%) on treated sites. In the CTR group, eight subjects presented new EGW lesions (RR: 29%) on treated sites (p = 0.0024; odds ratio: 0.16; 95% confidence interval: 0.04-0.68). In the TS group, 34 subjects (56%) reported mild to moderate erythema or burning sensation at the application site. In this prospective multicenter trial, the use of TS 10% as PST after ablative treatment with CO2 laser was associated with a lower recurrence rate of new EGW lesions in the short term in comparison with the control group. Comparative larger trials are warranted to evaluate the role of this approach as PST (Trial Registration Number: ISRCTN44037479).

Podophyllotoxin in Dermatology

ABSTRACT A drug, by definition, is a medicine or substance that has a physiological effect when ingested or introduced into the body. Medications are utilized daily in the field of dermatology to treat a variety of skin conditions, such as eczema, psoriasis, and warts. The purpose of this column is to highlight common medicines used in dermatology, focusing on their mechanisms of action, usage and function, and available alternatives. This article describes the features of podophyllotoxin, utilized in diluted solution as podofilox, a topical treatment for external genital warts, such as condylomata acuminata.

The Amelioration Effect of the Ethanolic Extract of Cnidium officinale in Mice with Imiquimod-induced Psoriasis-like Skin Lesion

Psoriasis is an auto-immune skin disease, which is characterized by the excessive generation of plaques on the skin with typically a long-lasting red, itchy and scaly symptoms. Imiquimod, which has been used for the treatment of external genital warts, actinic keratosis, and superficial basal cell carcinoma, induced of psoriasis-like skin disorders with skin erythema and thickness in mice. In the present study, we tried to find the bioactive herbal extract against imiquimod-induced psoriasis-like skin disorder in mice. During the searching of the herbal extract with anti-psoriatic effect, the ethanolic extract of Cnidium officinale ameliorated imiquimodinduced psoriasis-like skin disorder in mice. The morphological evaluation, H&E staining and Psoriasis Area and Severity Index (PASI) score showed that ear and back thickness, and erythema induced by imiquimod were significantly reversed after the treatment of the cream of the ethanolic extract of C. officinale. The overexpressed myeloperoxidase (MPO) and keratin 6A levels were decreased by the treatment of C. officinale cream. Also, IFN- γ, c-fos and IκB-α mRNA levels, which are related to the progression of psoriasis, were reduced by C. officinale cream. Thus, the ethanolic extract of C. officinale ameliorated psoriasis-like skin disorder induced by imiquimod and might be the therapeutic agent for psoriasis.

A Solanum incanum extract (SR-T100) regresses vulvar condyloma acuminatum and induces distinct autophagic and apoptotic responses in different types of HPV-infected cells

BackgroundThe Solanum species have been used for the treatment of warts, tumor and cancer in folk medicine. The S. incanum extract is an important traditional Chinese medicine in Taiwan since 1973. The purpose of the present study was to evaluate the efficacy and safety of Solanum incanum (synonym: Solanum undatum) extract (SR-T100), a water-soluble product primarily composed of alkaloid solamargine, for the treatment of human condyloma and to study the possible underlying anti-condyloma mechanisms.MethodsWe conducted a pilot study to test the effectiveness and side effects of SR-T100 gel (2.3% solamargine in Solanum incanum plant extract) for the treatment of external genital warts. We produced different types of human papillomavirus (HPV) E6/E7-infected cells by lentiviral technology and studied the differences in apoptosis and autophagy between these cells under the treatment of SR-T100.ResultsNineteen (73%) of 26 patients using the SR-T100 gel exhibited a response, and 16 (61.5%) patients achieved total clearance. Only one patient showed severe (grade 3-4) skin-related side effects. SR-T100 induced mitochondria-dependent apoptosis in HPV-infected cells. Cells expressing the high-risk HPV E6/E7 type were resistant to SR-T100-induced apoptosis. SR-T100 induced a greater autophagic response in HPV 16, 18-E6/E7 cells than in HPV 6b, 11-E6/E7 cells. Autophagy inhibition enhanced SR-T100-induced apoptosis in HPV 16, 18-E6/E7 cells, whereas apoptosis inhibition enhanced SR-T100-induced autophagy in HPV 6b, 11-E6/E7 cells.ConclusionsSR-T100 is effective for the treatment of human vulva condyloma, with few side effects. Compared with those with high-risk HPVs, cells with low-risk HPVs were more sensitive to SR-T100 treatment. Autophagy played a protective role in SR-T100-induced apoptosis in HPV-infected cells.Trial registrationNCT01676792; Registered: August 29, 2012 (retrospectively registered).

CONDYDAV : étude observationnelle multicentrique des patients présentant des condylomes dans les dispensaires antivénériens en France

Since 2007 in France, human papilloma virus (HPV) vaccination has been licensed for use as a vaccine against HPV 6, 11, 16 and 18. The impact on the epidemiology of external genital warts (EGWs) in a large population remains unclear. To determine epidemiologic and clinical features of patients presenting EGWs in France in the era of HPV vaccination. In this prospective, observational study, we analyzed clinical features and treatments between January 1st, 2012 and March 31, 2012 for patients consulting for EGWs at 15 STI clinics throughout France. A total of 372 men and 111 women were included; mean age 31.2 years. The women were younger than the men (31.7 and 28.9 years respectively P<0.05). Among the patients, 416 (85.7%) were heterosexual, 13 bisexual and 54 (11.2%) homosexual, including one female. Males reported more sexual partners in the last 12 months (more than 3 partners in 32.6% versus 11.9%, P<0.01). Among the men, 230 had involvement of the penis alone and 46 had involvement of the anus alone. Seventy-six patients had EGWs of the anus, and of these 26 were MSM. In females, 76 had an infection of the vulva alone and 22 co-infection of the vulva and anus. MSM and females were at higher risk than heterosexual males for anal involvement (P<0.0001 and P=0.004, respectively). Three women had been vaccinated: two with Gardasil® and one with Cervarix®. Cryotherapy was the preferred treatment. With the advent of HPV vaccination, a global strategy for the prevention and treatment of EGW should be implemented.

Combined treatment of anogenital HPV infection with cryodestruction, podophyllin 25% and post-ablation immunomodulation with sinecatechins 15% ointment - a retrospective analysis.

External genital warts, caused by human papillomavirus, have a significant clinical, epidemiological, and financial impact, including the risk for malignant transformation. Treatment modalities include: (a) destructive (ablative); (b) cytotoxic (proapoptotic) and (c) immunomodulatory, with success and recurrence rates varying from 23% to 94% and from 4.1% to 77%, respectively. Most studies evaluated only single modality therapy, with few reports examining a combined approach for external genital warts management. The introduction of sinecatechins ointment in recent years has resulted in very low recurrence rates of 4.1-10.6%, despite lower initial clearance rates than ablative methods. We present a retrospective review of 27 patients who underwent combined therapy for external genital warts by using one or two sessions of cryodestruction combined with 25% podophyllin as the cytotoxic agent, and post-ablation immunomodulation with topical sinecatechins 15% ointment. This approach resulted in an excellent initial clearance rate of 96.3% with a recurrence rate of 7.4% after a total period of six months of follow-up. We suggest the importance of the combined approach in external genital warts management including post-ablative immunomodulation to augment the immune response and combat the residual latent infection. We hope to encourage trials examining the combined approach to the treatment of external genital warts.

Imiquimod 2.5% and 3.75% for the treatment of external genital warts: Additional insights into efficacy

Imiquimod 2.5% and 3.75% for the treatment of external genital warts: Additional insights into efficacy

Imiquimod 2.5% and 3.75% for the treatment of external genital warts: Sex differences in a study of 981 randomized patients

Imiquimod 2.5% and 3.75% for the treatment of external genital warts: Sex differences in a study of 981 randomized patients

Imiquimod 2.5% and 3.75% for the treatment of external genital warts: Assessment of safety in 981 randomized patients

Imiquimod 2.5% and 3.75% for the treatment of external genital warts: Assessment of safety in 981 randomized patients

Imiquimod 2.5% and 3.75% for the treatment of external genital warts: Assessment of efficacy in 981 randomized patients

Imiquimod 2.5% and 3.75% for the treatment of external genital warts: Assessment of efficacy in 981 randomized patients

Visualization and treatment of subclinical actinic keratoses with topical imiquimod 5% cream: an observational study.

Background. Imiquimod 5% is licensed for the treatment of external genital warts, superficial basal cell carcinoma, and actinic keratosis (AK) and is being used experimentally in various other dermato-oncological conditions. Objective. This observational study shall show that nonmelanoma skin cancer can be detected at its earliest subclinical stage by its reaction with imiquimod and can be cleared by finishing the course of treatment. Material and Methods. In this single arm trial 15 patients with chronically sun-exposed skin who had no clinical evidence of AK were treated with 5% imiquimod cream on the face or scalp for 4 weeks three times per week. Results. During treatment, all patients developed multiple areas with mild to moderate inflammatory skin reactions, such as erythema, induration, and scaling. Biopsies obtained from 12 patients prior to treatment revealed no malignancies. However, in cases with more pronounced inflammation during treatment, targeted biopsies indicated very early malignant alterations. Conclusion. Topical imiquimod treatment of chronically sun-exposed skin without overt clinical signs of AK is able to detect subclinical actinic keratoses (SAK) and to completely clear the lesions, even before they can be clinically diagnosed as AK. In such patients, imiquimod might be able to prevent the evolution of SCC.

Therapeutic options for external genital warts.

The primary goal of treatment for external genital warts (EGWs) is to eradicate visible lesions and address symptoms that may accompany them, but it does not address the underlying virus. Left untreated, warts may grow, remain the same, or spontaneously regress as a result of being cleared by the immune system. However, recurrence is common with or without treatment and may occur within 3 months of ending treatment in one-quarter to two-thirds of cases. Treatment options fall into two categories: provider or patient applied. Provider-based therapies include cryotherapy, trichloroacetic and bichloroacetic acid, electrocautery, surgical excision, and CO2 laser therapy. Patient-applied therapy choices include imiquimod and podophyllotoxin. Imiquimod 3.75% is a fairly new, patient-administered topical cream approved by Health Canada in 2011. Another recently approved patient-applied choice is sinecatechins, a green tea extract with immunomodulatory effects. Self-treatment options are attractive to patients because they offer privacy, convenience, and autonomy. In contrast, provider-administered therapies may boast increased precision (especially for areas that are hard to reach) and closer monitoring, which can be augmented by patient education and counseling. Available topical and surgical therapies vary widely in terms of cost, efficacy, adverse effects, dosage/frequency, and length of treatment. No one treatment is ideally suited to all patients or constitutes a gold standard. Treatment regimens must be tailored to each patient's needs and preferences. The health care provider's skills and experience will also factor into treatment decisions. In addition, the size, number, and location of lesions and whether the infection is new or recurrent will help guide the decision process toward the best treatment for a given patient.

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).

Current update on the treatment of genital warts

External genital warts (EGW) are currently the most common form of viral sexually transmitted disease found in the general population. EGW have been shown to occur as a direct result of infection with the human papillomavirus (HPV). Malignancy is typically associated with high-risk types of HPV; however, low-risk type association has been observed. Numerous therapies are presently indicated for use in the treatment of EGW, which can target lesions through multiple modalities including topically, surgically or via immune modulation. Therapies often differ dramatically with respect to cost, side-effect profiles, dosing schedules, duration of treatment and overall effectiveness. Routine HPV vaccination may play a powerful role in reducing the burden of disease by preventing viral infection and transmission. As HPV vaccination continues to gain widespread approval, it may prove instrumental in decreasing the incidence of HPV infection and eventually eradicating genital warts.

Overview of HPV-related Dermatoses and Applications of Sinecatechins Ointment

The incidence of Condyloma acuminata and other HPV-related dermatoses is increasing, with as many as one million new cases of infections diagnosed yearly. Therapeutic options that were once limited to in-office procedures or topical podophyllin toxins are now directed toward modifying the immune responses against the viral burden and minimizing recurrence potential. For years, compliance with follow-up and topical management has been limited due to issues with convenience, toxicities, and costs. There are now several pharmacological agents in the dermatology marketplace that can be incorporated into treatment regimens, either as monotherapy or in combination with in-office destruction modalities. One of the newer agents, Sinecatechins 15 % ointment (Veregen®), promotes localized antioxidative effects in conjunction with other proinflammatory actions. As the elucidations of the immune mechanisms that create viral diseases as well as other dermatoses continues to expand, so will the potential applications of this class of therapies. Several studies have supported its use in the treatment of external genital warts as well as other diseases. This article focuses on the pathogenesis and epidemiology of external genital warts and other manifestations of HPV, as well as on the history, mechanisms of action, and therapeutic applications of Sinecatechins 15 % ointment.