Intralesional bivalent and quadrivalent human papillomavirus vaccines didn't significantly enhance the response of multiple anogenital warts when co-administered with intralesional Candida antigen immunotherapy. A randomized controlled trial.

Treatment of anogenital warts (AGWs) is challenging. Candida antigen immunotherapy has been proven to be a safe and relatively effective therapeutic modality; nevertheless, some patients may experience a partial or no response. Combining Candida antigen with other immunotherapies has been proposed to improve the cure rate. Immunotherapy with human papillomavirus (HPV) vaccines has been tried with conflicting outcomes. This study aimed to  assess the efficacy and safety of intralesional Candida antigen, either alone or in combination with intralesional bivalent or quadrivalent HPV vaccines, for treating multiple AGWs. Eighty patients with multiple AGWs were included and randomly assigned to four equal groups: group A treated with intralesional Candida antigen only; group B treated with intralesional bivalent HPV vaccine (Cervarix) and Candida; group C treated with intralesional quadrivalent HPV vaccine (Gardasil) and Candida; and group D (control) treated with intralesional saline. Complete clearance of lesions was detected in 40%, 20%, and 60% of patients in Candida monotherapy, Cervarix/Candida, and Gardasil/Candida groups, respectively, whereas 40%, 60%, and 20% of patients in the three groups, respectively, showed partial response. Only 10% of the control group had a partial response. Therapeutic outcomes were significantly better in the three treatment groups compared to the control group, with no statistically significant difference between the Candida monotherapy group and the combination groups, but the response was significantly better in the Gardasil/Candida group than in the Cervarix/Candida group. No statistically significant difference was found between the studied groups regarding the development of side effects. Moreover, no recurrence was detected in any of the groups throughout the 3-month follow-up period.  Based on our results, combining intralesional HPV vaccines with Candida antigen immunotherapy may have no significant benefit for treating multiple AGWs. Candida antigen may be recommended as a relatively effective and inexpensive therapeutic modality. The combination of Gardasil and Candida was also effective but very expensive. The results of the Cervarix/Candida combination were unsatisfactory.  This clinical trial was registered and approved prospectively by the ethical review board at Faculty of Medicine, Zagazig University.

Evaluation of needling-induced autoinoculation in the management of genital warts.

BACKGROUND: Genital warts caused by human papillomavirus (HPV) are one of the most common sexually transmitted infections. Long latency, lesions' multiplicity, high recurrence rate, and the tendency to malignant transformation are essential challenges during management. Traditional treatment modalities are known to be lesion-directed while intralesional immunotherapy was introduced to act beyond individual lesions and to confront the previous challenges through injection of known antigens, such as measles, mumps and rubella (MMR) vaccine, to stimulate the immune system against HPV. Needling-induced autoinoculation is also considred as an immunotherapeutic procedure that does not include the injection of antigens. We evaluated the efficacy of needling-induced autoinoculation in the management of genital warts. METHODS: Fifty patients with multiple recurrent (≥4) genital warts were divided into two equal groups. One group was subjected to needling-induced autoinoculation and the other was subjected to intralesional MMR injection every 2 weeks for a maximum of three sessions. Follow-up was done for 8 weeks after the last session. RESULTS: Both needling and MMR showed statistically significant therapeutic outcome. Needling showed significant improvement with regard to the number (P = 0.000) and size (P = 0.003) of lesions. In parallel, MMR showed significant improvement with regard to the number (P = 0.001) and size (P = 0.021) of lesions. There was no statistically significant difference between both treatments outcomes in regard to number (P = 0.860) and size (P = 0.929) of lesions. CONCLUSIONS: Both needling and MMR are effective immunotherapeutic modalities in management of genital warts. Needling-induced autoinoculation, being more safe and inexpensive, may be considered as a competing choice.

Successful treatment of anogenital warts with single dose Bacillus Calmette Guerin vaccine without prior sensitization in tuberculosis endemic country: Two case report.

Anogenital Warts (AGWs) are benign proliferations caused by Human Papillomavirus (HPV) infection on the genital or anal areas. Various therapeutic options are available for the treatment of AGWs but there is no best or ideal therapy, and the recurrence of AGWs is significantly high. A promising new therapy that is currently being evaluated is immunotherapy with the intralesional Bacillus Calmette-Guérin (BCG) vaccine. Two cases of a 23-year-old woman and a 41-year-old man were presented with manifestations of condyloma acuminata type AGWs. The patients were immunocompetent and received single dose intralesional BCG vaccine on the largest lesion. Clinical improvements of AGWs lesions were noted starting on the 14th day after receiving therapy by the disappearance of some lesions with no recurrence and side effects. Intralesional BCG vaccine activates the immune system, treats other AGWs lesions that do not receive an intralesional injection, and also prevents recurrence. Although the intralesional BCG vaccine is effective for treating AGWs, further evaluation is still needed for its recurrence.

Methodological quality of systematic reviews of the local management of anogenital warts: a systematic review using AMSTAR II, ROBIS and PRISMA.

INTRODUCTION: Anogenital warts (AGWs) are among the most common STDs. Many therapy options are available but are not codified. Systematic reviews (SRs) and meta-analyses (MAs) are helpful to elaborate recommendations on the management of AGWs. The objective of our study was to assess the quality and consistency of SRs for the local management of AGWs using three international tools. METHODS: Seven electronic databases were searched from inception to 10 January 2022 for this SR. The intervention of interest was any local treatment of AGWs. There was no restriction on language and population. The methodological quality, reporting quality and risk of bias (ROB) of the included SRs for the local treatments of AGWs were assessed independently by two investigators with A Measurement Tool to Assess systematic Reviews version II (AMSTAR II), Risk of Bias in Systematic Reviews (ROBIS) and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). RESULTS: Twenty-two SRs/MAs met all inclusion criteria. According to the results of the AMSTAR II, nine included reviews were rated critically as being of low quality, and only five were of high quality. Based on the ROBIS tool, only nine SRs/MAs had a low ROB. The domain-assessed 'study eligibility criteria' were mostly rated at a low ROB, unlike the other domains. With PRISMA, the reporting checklist was relatively complete for ten SRs/MAs, but some reporting weaknesses remained in the topics of the abstract, protocol and registration, ROB and funding. DISCUSSION: Several therapy options are available for the local management of AGWs and are widely studied. However, due to the many ROB and low quality of these SRs/MAs, only a few of them have the sufficient methodological quality to support guidelines. PROSPERO REGISTRATION NUMBER: CRD42021265175.

Updated estimate of the annual direct medical cost of screening and treatment for human papillomavirus associated disease in the United States.

The annual direct medical cost attributable to human papillomavirus (HPV) in the United States over the period 2004-2007 was estimated at $9.36 billion in 2012 (updated to 2020 dollars). The purpose of this report was to update that estimate to account for the impact of HPV vaccination on HPV-attributable disease, reductions in the frequency of cervical cancer screening, and new data on the cost per case of treating HPV-attributable cancers. Based primarily on data from the literature, we estimated the annual direct medical cost burden as the sum of the costs of cervical cancer screening and follow-up and the cost of treating HPV-attributable cancers, anogenital warts, and recurrent respiratory papillomatosis (RRP). We estimated the total direct medical cost of HPV to be $9.01 billion annually over the period 2014-2018 (2020 U.S. dollars). Of this total cost, 55.0% was for routine cervical cancer screening and follow-up, 43.8% was for treatment of HPV-attributable cancer, and less than 2% was for treating anogenital warts and RRP. Although our updated estimate of the direct medical cost of HPV is slightly lower than the previous estimate, it would have been substantially lower had we not incorporated more recent, higher cancer treatment costs.

Abordagens terapêuticas do Condiloma Acuminado em crianças e adolescentes / Therapeutic approaches to Condyloma Acuminatum in children and adolescents

Objetivos: A infecção pelo papiloma vírus humano dos tipos 6 e 11 pode evoluir para Condiloma Acuminado. Sua transmissão é principalmente via sexual, de forma que a presença dessas verrugas em crianças deve ser consi-derada sinal de alarme para investigação de abuso. Eventualmente, contudo, ocorre por autoinoculação ou fômites. O tratamento é desafiador, dado que apesar do extenso arsenal, a recorrência se faz comum. A presente revisão siste-mática advém a comparar taxas de sucesso das estratégias terapêuticas, objetivando fornecer substrato para escolhaacertada no tratamento da doença em crianças e adolescentes. Métodos: Foi realizada Revisão Sistemática baseada no GuidelinePreferred Report Items for Systematic Reviews and Meta-Analyses (PRISMA), registrada na Plataforma PROSPERO sob identificação CRD42021262090. Resultados: 211 estudos foram encontrados nasdatabases con-sultadas, de forma que 30 atenderam as propostas de critérios estabelecidos na pesquisa sistematizada. Esses pas-saram extração de dados para síntese qualitativa, demonstrando eficácia de métodos não-invasivos a invasivos.Conclusões: Mediante bons resultados em resolução da doença e reduzidos efeitos adversos, a terapia mais popular entre os autores foi o Imiquimode. A pesquisa chamou atenção à necessidade de estudos mais robustos e metodo-logias mais complexas acerca das abordagens terapêuticas do Condiloma Acuminado em crianças e adolescentes. (AU)

Objectives: Infection with human papillomavirus types 6 and 11 can progress to Condyloma acuminata. Its transmission is mainly sexual, so these warts in children should be considered an alarm signal for abuse investigation. Eventually, however, it occurs by autoinoculation or fomites. Treatment is challenging, given that despite the extensive arsenal, recurrence is common. The present systematic review compares the success rates of therapeutic strategies, aiming to provide a substrate for the right choice in the treatment of the disease in children and adolescents. Methods: Asystematic review was performed based on the guideline for Preferred Report Items for Systematic Reviews and Meta-Analyses (PRISMA), registered on the PROSPERO Platform under identification CRD42021262090. Results: 211 studies were found in thedatabasesconsulted, and 30 met the proposed criteria established in the systematic research. These passed data extraction for qualitative synthesis, demonstrating the effectiveness of non-invasive to invasive methods. Conclusions: Due to good results in disease resolution and reduced adverse effects, the most popular therapy among the authors was Imiquimod. The research called attention to the need for more robust studies and more complex methodologies about the therapeutic approaches of Condyloma Acuminatum in children and adolescents. (AU)

Experiencia en cirugía de condilomas anales en mayores de 15 años / Experience in anal condyloma surgery in patients older than 15 years

Resumen Objetivo: Describir la experiencia en cirugía electiva de condilomas anales en pacientes mayores de 15 años en un hospital terciario de la Región Metropolitana. Material y Método: Estudio observacional retrospectivo y descriptivo, en el cual se analizan las intervenciones quirúrgicas electivas realizadas entre 2008 a 2021. Resultados: Dentro del período analizado se obtuvo 165 cirugías de condilomas anales, lo que corresponde a 137 pacientes en total. El 85% de los pacientes son de sexo masculino, el 68% de los pacientes son VIH positivo, un 87% de los pacientes MSM (hombres que tienen sexo con otros hombres) son VIH positivo, el 34% de los pacientes tiene antecedente de ETS, el 46% de los pacientes recibió terapia tópica como tratamiento preoperatorio o posoperatorio. Un 25% de los pacientes presenta recidiva en su historia personal, un 21% de los pacientes presenta lesiones anales intraepiteliales de alto grado, un 6% presenta carcinoma escamoso infiltrante. No hubo mortalidad descrita. Discusión: El presente estudio, describe la experiencia en cirugía de condilomas de un hospital terciario de la Región Metropolitana de Chile, cuya población corresponde a un estrato socioeconómico medio y bajo. Se logra describir a la población que es intervenida de condilomas acuminados, además de sus resultados quirúrgicos precoces y a largo plazo. Conclusión: El presente estudio, presenta una población de 137 pacientes operados de condilomas anales, a partir de los hallazgos de la cirugía. Se cumple el objetivo del estudio de caracterizar en un período de 12 años los resultados quirúrgicos de dicha serie, algo no reportado previamente en la literatura chilena.

Objective: To describe the experience in elective surgery for anal condylomas in patients over 15 years of age in a tertiary hospital in the Metropolitan Region. Materials and Method: Retrospective and descriptive observational study about elective surgical interventions performed between 2008 to 2021. Results: Within the analyzed period, 165 anal warts surgeries were obtained, corresponding to 137 patients. 85% of the patients are male, 68% are HIV positive, 87% of the MSM patients are HIV positive, 34% of the patients have a history of STDs, 46% of the patients received topical therapy as preoperative or postoperative treatment. 25% present recurrence in their personal history, 21% present high-grade anal intraepithelial lesions, 6% present infiltrating squamous carcinoma. There was no reported mortality. Discussion: The present study describes the experience in condyloma surgery in a tertiary hospital in the Metropolitan Region of Chile, whose population corresponds to a medium and low socioeconomic stratum. It is possible to describe the population that undergoes surgery for this reason, in addition to its early and long-term surgical results. Conclusion: The present study presents a population of 137 patients operated on for anal condylomas, based on the findings of the surgery. The objective of the study to characterize the surgical results of this series over a 12-year period is fulfilled, something not previously reported in the Chilean literature.

Asian guidelines for condyloma acuminatum.

The present guidelines aim to provide comprehensive information on genital condyloma acuminata, including the epidemiology, clinical features, diagnosis and management. The guidelines provide evidence-based recommendations on the diagnosis, prevention and treatment of genital condyloma acuminata in adults in Asia, including patients with HIV co-infection. METHODOLOGY: A PubMed search was performed, using the keywords "condyloma acuminata", "anal wart", "anogenital wart", "genital wart" and "genital HPV". A total of 3031 results were found in publications during last six years. A careful review of the titles and abstracts was done to find all the studies pertaining to epidemiology, clinical features, diagnosis, treatment and prevention of condyloma acuminata. DIAGNOSIS: Various diagnostic procedures described are: 1. PCR (LE: 2b). 2. Serology (LE: 2b). 3. In-situ hybridization (LE: 3). PREVENTION: 1. Vaccination (LE: 1a): Quadrivalent vaccine reduced the frequency of anogenital warts in both vaccinated and unvaccinated contacts. According to the update Advisory Committee on Immunization Practices (ACIP) recommendations, the following protocol is recommended: (a). HPV vaccination at age 11 or 12 years for both males and females. (b). Catch-up vaccination for all persons through age 26 years. (c). Shared clinical decision-making regarding potential HPV vaccination for persons aged 27-45 years, who are at risk of new HPV infection. 2. Male circumcision (LE: 2a): conflicting evidence. HIV AND CONDYLOMA ACUMINATA: In HIV-affected individuals, the course of HPV is more aggressive, with a greater risk of treatment resistance, increased chances of intraepithelial neoplasia as well as cancers. TREATMENT: Physician administered. 1. Photodynamic therapy (LE: 1a). 2. Laser (LE: 2b). 3. Surgery (LE: 1a). 4. Electrosurgery (LE: 2c). 5. Cryotherapy (LE: 1b). 6. Immunotherapy (LE: 1b). 7. Podophyllin (LE: 1b). Provider administered. 1. Imiquimod 5%(LE: 1a). 2. Podophyllotoxin (LE: 1b). 3. Sinecatechins (LE: 1a). 4. Cidofovir (LE: 3). 5. 5- Fluorouracil (LE: 1a). 6. Interferon (LE: 1a).

Unrecognized Bowen's disease in previously treated condylomata acuminata: indication of a common etiology?

Bowen's disease (BD) is an intraepidermal squamous cell carcinoma (SCC) with the capacity to become invasive SCC giving rise to distant metastasis. In rare cases it can be associated with human papillomavirus (HPV) infection, specifically with HPV types 16, 18, 31, 32, and 34. Here we report a case of an immunocompetent white male, age 37, with an erythematous, irregularly-shaped patch in his suprapubic region, appearing 1 year after treatment for condylomata acuminata with cryotherapy and podophyllin in the same area. At the time of clinically active disease, a urethral smear was positive for high-risk HPV types. The lesion was considered a scar by several physicians because it emerged in an area of previous postinflammatory hyperpigmentation. The aim of this report is to raise awareness of the emerging causative association between anogenital HPV infection and the development of BD, which was the possible etiological agent in the case of the patient presented here. Hereby we also advocate primary preventive measures in terms of safe sexual habits and HPV vaccination.

Condyloma acuminatum mimicking cervical cancer in a pregnant woman and treatment with cryotherapy: A case report.

RATIONALE: Condyloma acuminata and anogenital warts are protruding papillomatous lesions caused by human papillomavirus. In pregnant women, condyloma acuminata over the cervical region may grow rapidly, mimicking cervical cancer. PATIENT CONCERNS: A pregnant woman at 14 weeks of gestation with condyloma acuminatum mimicking cervical cancer was referred to our hospital for further management. DIAGNOSIS: Condyloma acuminata. INTERVENTIONS: Tumor biopsy was performed twice, and the pathology confirmed condyloma acuminatum. Immunohistochemistry revealed focal positivity for p16 and Ki-67. Cryotherapy was performed and regular follow-up was performed at 2-week intervals. A small residual condyloma acuminata was found and treated with cryotherapy. OUTCOME: During the follow-up period, no recurrence of condyloma acuminata was noted. She delivered a baby at 37 weeks of gestation via cesarean section, without complications. LESSONS: Condyloma acuminata of the cervix may grow faster during pregnancy, mimicking cervical cancer. Multiple factors must be considered when treating condyloma acuminata during pregnancy. Cryotherapy is proposed as a 1st-line treatment in all trimesters because of its safety, convenience, and cost-effectiveness. Serial follow-up at 2-week intervals to observe post-cryotherapy conditions is recommended.

Meatal Intraurethral Warts Successfully Treated with 5-fluorouracil Cream.

Condyloma acuminatum relatively rarely involves the urethra, and when it does it is usually only in the most distal portion of the urethra. A number of treatments have been described for urethral condylomas. These treatments are extensive and variable, comprising laser treatment, electrosurgery, cryotherapy, and topical application of cytotoxic agents such as 80% trichloroacetic acid, 5-fluorouracil cream (5-FU), podophyllin, podophyllotoxin, and imiquimod. Laser is still considered to be therapy of choice for treatment of intrauretral condylomata. We present the case of a 25-year-old male patient with meatal intraurethral warts who was successfully treated with 5-FU, after many unsuccessful treatment attempts with laser treatment, electrosurgery, cryotherapy, imiquimod, and 80% trichloroacetic acid.