Burden of genital warts in Colombia: an observational study / Carga das verrugas genitais na Colômbia: um estudo observacional

Introduction: Genital warts are benign lesions caused by sexual transmission of human papillomavirus types 6 and 11, with significant impact on healthcare resource use and patients' quality of life. Objective: To describe the epidemiology of genital warts in adults visiting a physician office for any reason, physician practice patterns, and healthcare resource use and costs in Colombia. Methods: Participants were a convenience sample of 53 physicians in 5 specialties: primary care (15), gynecology (24), urology (12), proctology (1), and dermatology (1). Physicians completed a survey and daily log of all patients 18-60 years old seen over 10 days in their practices in 2016-2017. The physician survey recorded genital warts consultation and management patterns. The daily log recorded patient demographic information and genital warts diagnosis. Results: Among 6,393 patients logged by physicians, the genital warts prevalence was 2.03% (95%CI 1.69­2.38) and incidence 1.30% (95%CI 1.02­1.58). Primary care physicians referred most of their genital warts cases for treatment (female: mean 63.3%, SD=44.8; male: mean 58.3%, SD=43.8). Treatment of non-resistant episodes (<6-month duration) lasted an average of 37.4 days (SD=29.4) and required an average of 4.0 (SD=1.9) office visits for females and 3.0 (SD=1.7) for males. The overall mean cost of an episode of care was USD558.13 (SD=507.30). Conclusion: Genital warts cases reported by most participant physicians were mainly direct-consult, but patients were typically treated by specialists. Much of the genital warts health care utilization and costs reported could be prevented by immunization with the quadrivalent or nonavalent HPV vaccine.

Introdução: As verrugas genitais são lesões benignas, de transmissão sexual, causadas pelo papilomavírus humano tipos 6 e 11 e que causam impacto significativo no uso de recursos de saúde e na qualidade de vida dos pacientes. Objetivo: Descrever a epidemiologia das verrugas genitais em adultos que buscaram atendimento médico ambulatorial por qualquer motivo, incluindo padrões de prática médica, uso de recursos de saúde e custos na Colômbia. Métodos: foi utilizada uma amostra de conveniência composta por 53 médicos em 5 especialidades: clínico geral (15), ginecologia (24), urologia (12), proctologia (1) e dermatologia (1). Os médicos completaram um questionário e registros diários de todos os pacientes com idade entre 18 e 60 anos atendidos durante 10 dias em seus consultórios em 2016-2017. O questionário registrou os padrões de prática médica e de tratamento de verrugas genitais. Os registros diários continham informações demográficas do paciente e o diagnóstico de verrugas genitais. Resultados: Entre 6.393 atendimentos médicos, a prevalência das verrugas genitais foi de 2,03% (IC95% 1,69­2,38) e a incidência de 1,30% (IC95% 1,02­1,58). Os clínicos gerais encaminharam a maioria dos pacientes com verrugas genitais para tratamento (mulheres: média de 63,3%, DP=44,8; homens: média de 58,3%, DP=43,8). O tratamento dos casos não-persistentes (<6 meses de duração) durou em média 37,4 dias (DP=29,4) e requereu uma média de 4,0 (DP=1,9) consultas para mulheres e 3,0 (DP=1,7) para homens. O custo médio geral do tratamento foi de US$ 558,13 (SD=507,30). Conclusão: Os casos de verrugas genitais relatados pela maioria dos médicos participantes derivaram-se principalmente de atendimentos primários e os pacientes foram tratados geralmente por especialistas. Grande parte da utilização de recursos e custos relacionados a verrugas genitais poderia ser evitada pela imunização com a vacina papilomavírus humano 4-valente ou 9-valente.

The EVerT2 (Effective Verruca Treatments 2) trial: a randomized controlled trial of needling vs. nonsurgical debridement for the treatment of plantar verrucae.

BACKGROUND: Verrucae are a common foot skin pathology, which can in some cases persist for many years. Plantar verrucae can be unsightly and painful. There are a range of treatment options including needling. OBJECTIVES: The EVerT2 (Effective Verruca Treatments 2) trial aimed to evaluate the clinical and cost-effectiveness of the needling procedure for the treatment of plantar verrucae, relative to callus debridement. METHODS: This single-centre randomized controlled trial recruited 60 participants (aged ≥ 18 years with a plantar verruca). Participants were randomized 1 : 1 to the intervention group (needling) or the control group (debridement of the overlying callus). The primary outcome was clearance of the index verruca at 12 weeks after randomization. Secondary outcomes included recurrence of the verruca, clearance of all verrucae, number of verrucae, size of the index verruca, pain and participant satisfaction at 12 and 24 weeks. A cost-effectiveness analysis was carried out from the National Health Service perspective over 12 weeks. RESULTS: Sixty eligible patients were randomized (needling group n = 29, 48%; debridement group n = 31, 52%) and 53 were included in the primary analysis (needling n = 28, 97%; debridement n = 25, 81%). Clearance of the index verruca occurred in eight (15%) participants (needling n = 4, 14%; debridement n = 4, 16%; P = 0·86). The needling intervention costs were on average £14·33 (95% confidence interval 5·32-23·35) more per patient than for debridement. CONCLUSIONS: There is no evidence that the needling technique is more clinically or cost-effective than callus debridement. The results show a significant improvement in pain outcomes after needling compared with the debridement treatment alone.

The EVERT (effective verruca treatments) trial protocol: a randomised controlled trial to evaluate cryotherapy versus salicylic acid for the treatment of verrucae.

BACKGROUND: Verrucae are a common, infectious and sometimes painful problem. The optimal treatment for verrucae is unclear due to a lack of high quality randomised controlled trials. The primary objective of this study is to compare the clinical effectiveness of two common treatments for verrucae: cryotherapy using liquid nitrogen versus salicylic acid. Secondary objectives include a comparison of the cost-effectiveness of the treatments, and an investigation of time to clearance of verrucae, recurrence/clearance of verrucae at six months, patient satisfaction with treatment, pain associated with treatment, and use of painkillers for the treatments. METHODS/DESIGN: This is an open, pragmatic, multicentre, randomised controlled trial with two parallel groups: cryotherapy using liquid nitrogen delivered by a healthcare professional for a maximum of 4 treatments (treatments 2-3 weeks apart) or daily self-treatment with 50% salicylic acid for a maximum of 8 weeks. Two hundred and sixty-six patients aged 12 years and over with a verruca are being enrolled into the study. The primary outcome is complete clearance of all verrucae as observed on digital photographs taken at 12 weeks compared with baseline and assessed by an independent healthcare professional. Secondary outcomes include self-reported time to clearance of verrucae, self-reported clearance of verrucae at 6 months, cost-effectiveness of the treatments compared to one another, and patient acceptability of both treatments including possible side effects such as pain. The primary analysis will be intention to treat. It is planned that recruitment will be completed by December 2009 and results will be available by June 2010. TRIAL REGISTRATION: Current Controlled Trials ISRCTN18994246.

The economic burden of noncervical human papillomavirus disease in the United States.

OBJECTIVE: The purpose of this study was (1) to estimate the direct medical costs of 7 major noncervical human papillomavirus (HPV)-related conditions that include genital cancers, mouth and oropharyngeal cancers, anogenital warts, and juvenile-onset recurrent respiratory papillomatosis, and (2) to approximate the economic burden of noncervical HPV disease. STUDY DESIGN: For each condition, we synthesized the best available secondary data to produce lifetime cost per case estimates, which were expressed in present value. Using an incidence-based approach, we then applied these costs to develop an aggregate measure of economic burden. RESULTS: The economic burden that was associated with noncervical HPV-6-, -11-, -16-, and -18-related conditions in the US population in the year 2003 approximates $418 million (range, $160 million to $1.6 billion). CONCLUSION: The economic burden of noncervical HPV disease is substantial. Analyses that assess the value of investments in HPV prevention and control programs should take into account the costs and morbidity and mortality rates that are associated with these conditions.

Human papillomavirus: burden of illness and treatment cost considerations.

The monetary and personal costs to society of human papillomavirus (HPV) infection are enormous. In order to make a comparison of different treatment methods we reviewed the entire literature on HPV treatment from January 1966 to December 2003 using MEDLINE, with particular reference to published meta-analyses, randomized controlled and comparative studies. Patient-applied therapies offer patients the possibility of convenient and, on the whole, pain-free treatment. Podofilox (podophyllotoxin) and salicylic acid for genital and extragenital warts, respectively, have the additional advantage of being the most cost-effective treatments and, on this basis, they are to be commended as appropriate first-line agents. The second-line treatment of choice for common warts is cryotherapy. For recalcitrant common warts possible options include inosine pranobex with cryotherapy or electrosurgery, imiquimod with paring and occlusion, intralesional bleomycin, or diphencyprone. Alternative first-line and second-line treatments for genital warts would be either some form of surgical removal or imiquimod. The first option may be the cheapest but this has to be balanced against a degree of post-operative morbidity. Limited data from comparative studies do not show any clear difference in efficacy between cryotherapy, trichloroacetic acid, scissor excision, electrosurgery, and laser surgery in the treatment of genital warts, and the cost effectiveness of these therapies is probably similar to that of imiquimod. Cryotherapy and trichloroacetic acid are relatively expensive and inconvenient for patients and should be reserved as third-line treatments with certain exceptions, such as cryotherapy for meatal warts. The duration of treatment is significantly related to the number of warts present, the area covered by the warts, and the length of time the warts have been present. For recalcitrant anogenital warts third-line treatment options that show promise include surgery in combination with imiquimod or cidofovir cream. For squamous intraepithelial lesions that cannot easily be excised or physically ablated current treatment options include imiquimod and fluorouracil cream. The latter is an inexpensive option but causes the greatest morbidity. It is hoped that cidofovir may be added to this list if it becomes commercially available, and that protective and therapeutic HPV vaccines will transform the management of HPV in the future.

Assessing the annual economic burden of preventing and treating anogenital human papillomavirus-related disease in the US: analytic framework and review of the literature.

The anogenital human papillomavirus (HPV) is estimated to be the most commonly occurring sexually transmitted infection in the US. Comprehensive estimates of the annual economic burden associated with the prevention and treatment of anogenital HPV-related disease in the US population are currently unavailable. The purpose of this paper is to (i) outline an analytic framework from which to estimate the annual economic burden of preventing and treating anogenital HPV-related disease in the US; (ii) review available US literature concerning the annual economic burden of HPV; and (iii) highlight gaps in current knowledge where further study is particularly warranted. Among eight US studies identified that describe the annual economic burden pertaining to one or more aspects of anogenital HPV-related disease, three met the review eligibility criteria (published between 1990 and 2004, examined multiple facets of annual anogenital HPV-related economic burden, and clearly articulated the data and methods used in the estimation process). All costs were adjusted to 2004 US dollars. Estimates of the annual direct medical costs associated with cervical cancer were comparable across studies (range 300-400 million US dollars). In contrast, there was a wide range across studies for estimates of the annual direct medical costs associated with cervical intraepithelial neoplasia (range 700 million US dollars-2.3 billion US dollars). Only one study reported direct medical costs for anogenital warts (200 million US dollars) and routine cervical cancer screening (2.3 billion US dollars). No studies examined direct medical costs attributable to HPV-related anal, penile, vaginal or vulvar cancers, or the work and productivity losses resulting from time spent receiving medical care, morbidity or mortality. Current economic burden estimates would suggest annual direct medical costs associated with the prevention and treatment of anogenital warts and cervical HPV-related disease of at least 4 billion US dollars. This figure would likely rise to at least 5 billion US dollars per year if direct medical costs associated with other disease entities caused by the sexual transmission of HPV were included, with further additions to the economic burden totalling in the billions of dollars if work and productivity losses were incorporated, a research priority for future studies.

The cost-effectiveness of patient-applied treatments for anogenital warts.

A model was developed to estimate the cost-effectiveness of podophyllotoxin and imiquimod for self-treatment of anogenital warts. The effectiveness endpoint was sustained clearance after treatment and a subsequent follow-up period of approximately 12 weeks. Effectiveness of podophyllotoxin was estimated from a quantitative summary of nine placebo-controlled trials, while effectiveness of imiquimod was based on a quantitative summary of six placebo-controlled trials. Costs were considered from a UK health service provider perspective; drug acquisition costs were obtained from the British National Formulary and health service costs of clinic attendance were based on a recent survey of GUM clinics. The impact of uncertainty was explored in a wide range of one-way and probabilistic (multi-way) sensitivity analyses. The cost per sustained clearance was 313 for podophyllotoxin and 606 for imiquimod. The modest and statistically insignificant incremental effectiveness of imiquimod was purchased at high cost-2476 per additional sustained clearance. Sensitivity analyses showed the economic superiority of podophyllotoxin to be robust and statistically very significant.

Comparing therapy costs for physician treatment of warts.

To compare the cost of several common modalities used to treat non-genital warts in immunocompetent patients, we identified studies published in English using standard search strategies and evaluated the literature for the following common non-genital wart therapies: cryotherapy with liquid nitrogen, carbon dioxide and pulsed-dye laser therapy, topical squaric acid, intralesional bleomycin, intralesional interferon alpha injections, and intralesional immunotherapy with Candida antigens. Standard treatment algorithms, compiled by dermatologists experienced in the treatment of patients with moderate wart burdens, were utilized for cost-comparison analyses. Based on the cost analysis model, the least expensive treatment option for non-genital warts were carbon dioxide laser therapy (157 dollars) and Candida antigen injections (190 dollars). The other treatment modalities examined ranged from 495 dollars (bleomycin) to 1227 dollars (interferon alpha). Although treatment with the carbon dioxide laser therapy is the least expensive, pain and post-procedure complications limit the use of this modality.