Estimation of the costs of invasive cervical cancer treatment in Brazil: A micro-costing study / Estimativa dos custos do tratamento do câncer do colo do útero invasivo no Brasil: um estudo de microcustos

Abstract Objective Themain objective of the present study was to estimate the annual treatment costs of invasive cervical cancer (ICC) per patient at an oncology center in Brazil from a societal perspective by considering direct medical, direct nonmedical, and indirect costs. Methods A cost analysis descriptive study, in which direct medical, direct nonmedical, and indirect costs were collected using a microcosting approach, was conducted between May 2014 and July 2016 from a societal perspective. The study population consisted of women diagnosed with ICC admitted to a tertiary hospital in Recife, state of Pernambuco, Brazil. The annual cost per patient was estimated in terms of the value of American Dollars (US$) in 2016. Results From a societal perspective, the annual ICC treatment cost per patient was US $ 2,219.73. Direct medical costs were responsible for 81.2% of the total value, of which radiotherapy and outpatient chemotherapy had the largest share. Under the base-case assumption, the estimated cost to the national budget of a year of ICC treatment in the Brazilian population was US$ 25,954,195.04. Conclusion We found a high economic impact of health care systems treating ICC in a poor region of Brazil. These estimates could be applicable to further evaluations of the cost-effectiveness of preventing and treating ICC.

Resumo Objetivo O objetivo principal do presente estudo foi estimar os custos anuais por paciente do tratamento do câncer do colo do útero (CCU) invasivo em um centro de oncologia no Brasil, sob a perspectiva da sociedade, considerando os custos diretos médicos, diretos não médicos e indiretos. Métodos Foi realizado um estudo descritivo de análise de custos, no qual os custos médicos diretos, não médicos diretos e indiretos foram coletados por meio de uma abordagem de microcustos, realizado entre maio de 2014 e julho de 2016 sob a perspectiva da sociedade. A população do estudo foi composta por mulheres diagnosticadas com CCU invasivo internadas em um hospital terciário em Recife, PE, Brasil. O custo anual por paciente foi estimado emtermos de dólares americanos (US$) para o ano de 2016. Resultados O custo anual do tratamento do CCU invasivo sob a perspectiva da sociedade foi de US$ 2.219,73 por paciente. Os custos médicos diretos foram responsáveis por 81,2% do valor total, dos quais a radioterapia e a quimioterapia ambulatorial tiveram a maior participação. Sob o pressuposto do caso base, o custo estimado para o orçamento nacional de um ano de tratamento do CCU invasivo na população brasileira foi de US$ 25.954.195,04. Conclusão Foi encontrado um alto impacto econômico dos sistemas de saúde para o tratamento do CCU invasivo em uma região pobre do Brasil. Essas estimativas poderão ser aplicáveis emavaliações adicionais do custo-efetividade da prevenção e tratamento do CCU.

Cost of a human papillomavirus vaccination project, Zimbabwe

Objective To determine the cost of Zimbabwe's human papillomavirus (HPV) vaccination demonstration project. Methods The government of Zimbabwe conducted the project from 2014­2015, delivering two doses of HPV vaccine to 10-year-old girls in two districts. School delivery was the primary vaccination strategy, with health facilities and outreach as secondary strategies. A retrospective cost analysis was conducted from the provider perspective. Financial costs (government expenditure) and economic costs (financial plus the value of existing or donated resources including vaccines) were calculated by activity, per dose and per fully immunized girl. Results The project delivered 11 599 vaccine doses, resulting in 5724 fully immunized girls (5540 at schools, 168 at health facilities and 16 at outreach points). The financial cost for service delivery per fully immunized girl was United States dollars (US$) 5.34 in schools, US$ 34.90 at health facilities and US$ 288.63 at outreach; the economic costs were US$ 17.39, US$ 41.25 and US$ 635.84, respectively. The mean financial cost per dose was US$ 19.76 and per fully immunized girl was US$ 40.03 (economic costs were US$ 45.00 and US$ 91.19, respectively).The largest number of doses delivered (5788) occurred during the second vaccination round (the second group's first dose concurrently delivered with the first group's second dose), resulting in the lowest financial and economic service delivery costs per dose: US$ 1.97 and US$ 6.79, respectively. Conclusion The mean service delivery cost was lower in schools (primary strategy) and when more girls were vaccinated in each round, demonstrating scale efficiency

Evaluación costo-efectividad de dos alternativas de vacunación para el virus del papiloma humano en la prevención del cáncer cervical uterino / Evaluation of the cost-effectiveness of two alternative human papillomavirus vaccines as prophylaxis against uterine cervical cancer

RESUMEN Objetivos. Determinar la relación costo-efectividad de la vacunación contra el (virus del papiloma humano) VPH y el tamiz de lesiones cervicales, frente a un programa de tamiz solo. Materiales y métodos. Se realizó una evaluación costo-efectividad y se empleó un modelo de Markov, con un horizonte temporal de 70 años y tres alternativas de prevención para el (cáncer del cuello uterino) CCU (tamiz solo, tamiz + vacuna bivalente, y tamiz + vacuna cuadrivalente), en una cohorte hipotética de niñas de diez años, desde la perspectiva del Ministerio de Salud. Resultados. La vacunación contra el VPH y tamiz es más costo-efectiva que el tamiz solo a partir de una voluntad de pago de S/ 2000 (USD 1 290,32). En el análisis determinístico, la vacuna bivalente es marginalmente más costo-efectiva que la vacuna cuadrivalente (S/ 48 [USD 30,97] frente a S/ 166 [USD 107,10] por AVAC, respectivamente). Sin embargo, en el análisis probabilístico ambas intervenciones generan nubes de puntos superpuestos, con una tendencia de la vacuna cuadrivalente a ser más costo-efectiva. Es decir, ambas son costo-efectivas y, por ende, intercambiables. El modelo fue especialmente sensible a variaciones de la cobertura y en la prevalencia de infección persistente por genotipos oncológicos no incluidos en la vacuna. Conclusiones. A partir de una disponibilidad de pago de S/ 2000 [USD 1 290,32] el tamiz y la vacunación son más costo-efectivos que el tamiz solo. La diferencia de costo-efectividad entre ambas vacunas carece de robustez probabilística y ambas vacunas pueden considerarse intercambiables desde la perspectiva costo-efectividad.

ABSTRACT Objectives. To determine the cost-effectiveness of human papillomavirus (HPV) vaccination and cervical lesion screening versus screening alone for the prevention of uterine cervical cancer (UCC). Materials and methods. This cost-effectiveness evaluation from the perspective of the Ministry of Health employed a Markov model with a 70-year time horizon and three alternatives for UCC prevention (screening alone, screening + bivalent vaccine, and screening + quadrivalent vaccine) in a hypothetical cohort of 10-year-old girls. Results. Our model, which was particularly sensitive to variations in coverage and in the prevalence of persistent infection by oncologic genotypes not included in the vaccine, revealed that HPV vaccination and screening is more cost-effective than screening alone, assuming a payment availability from S/ 2 000 (US dollars (USD) 1 290.32) per subject. In the deterministic analysis, the bivalent vaccine was marginally more cost-effective than the quadrivalent vaccine (S/ 48 [USD 30.97] vs. S/ 166 [USD 107.10] per quality-adjusted life-year, respectively). However, in the probabilistic analysis, both interventions generated clouds of overlapping points and were thus cost-effective and interchangeable, although the quadrivalent vaccine tended to be more cost-effective. Conclusions. Assuming a payment availability from S/ 2000 [USD 1,290.32], screening and vaccination were more cost-effective than screening alone. The difference in cost-effectiveness between the two vaccines lacked probabilistic robustness, and therefore the vaccines can be considered interchangeable from a cost-effectiveness perspective.

Vacina como agente de imunização contra o HPV / Vaccines as an agent for immunization against HPV

Considerada uma infecção de alta prevalência em todo o mundo, o papiloma vírus humano (HPV) é um DNA vírus que infecta a mucosa genital e possui grande potencial oncogênico, sendo relacionado ao risco aumentado de lesões do trato genital inferior, como o câncer cervical. Este câncer é responsável pela morte de cerca de 231 mil mulheres por ano no mundo, o que torna o HPV um grande problema para a saúde pública. Sabendo que a maneira mais eficaz e com melhor custo-benefício para controlar uma doença infecciosa é o desenvolvimento de vacinas, duas profiláticas foram desenvolvidas e aprovadas no Brasil, uma bivalente e outra quadrivalente. Essa revisão de literatura se propõe a apresentar as características do vírus HPV, os tipos de vacinas presentes no mercado, suas indicações e contraindicações, seus efeitos adversos, sua eficácia, seus títulos de anticorpos (GMT) e seu custo-efetividade.

Considered a highly prevalent infection throughout the world, the human papillomavirus (HPV) is a DNA virus that infects the genital mucosa and has high carcinogenic potential, being related to an increased risk of lower genital tract lesions, such as cervical cancer. This cancer is responsible for the deaths of about 231,000 women per year worldwide, which means that HPV is a major problem for public health. Knowing that the most effective and cost-effective way to control an infectious disease is the development of vaccines, two prophylactic vaccines have been developed and approved in Brazil, one of which is bivalent and the other is tetravalent. This review of the literature seeks to present the characteristics of the HPV virus, types of vaccines available on the market, their indications and contraindications, their adverse effects, their effectiveness, their geometric mean titer (GMT) and their cost-effectiveness.

Disposición de los padres a pagar por una vacuna contra el virus del papiloma humano para sus hijas adolescentes: región del Maule, Chile / Parents willingness to pay for a human papillomavirus vaccine to protect their adolescent daughters: maule Region, Chile

Objetivo. Determinar la disposición de los padres de hijas adolescentes a pagar por una vacuna contra el virus del papiloma humano en la Región del Maule, Chile. Material y métodos. Se utilizó una muestra de 386 padres con hijas entre 12 y 18 años, representativa de las cinco ciudades de mayor población de la Región del Maule, estratificada socioeconómicamente. La disposición a pagar se obtuvo usando el método de valoración contingente en su formato dicotómico doble. Resultados. Los padres están dispuestos a pagar en promedio 126.538 pesos chilenos para vacunar a sus hijas contra el virus; el precio y número de hijas afecta negativamente la probabilidad de la disposición a pagar, y el ingreso familiar afecta positivamente dicha probabilidad. Conclusión. Existe la posibilidad de utilizar financiamiento compartido entre el Estado y los padres de las potenciales hijas que puedan recibir la vacuna contra el virus del papiloma humano para reducir la incidencia de cáncer de cuello uterino.

Objective. To determine the willingness to pay of parents of teenage daughters for a vaccine against human papillomavirus in the Maule Region, Chile. Materials and methods. A sample of 386 parents with daughters between 12 and 18 years old, representing the five largest cities of the Region of Maule, socioeconomically stratified. WTP was obtained using the contingent valuation method in double bounded format. Results. Parents are willing to pay an average of US$ 252.71 to vaccinate their daughters against virus, where the price and number of daughters negatively affects the probability of willingness to pay, and family income positively affects the probability. Conclusion. There is a possibility of using shared funding between the government and the parents of potential daughter to be affected by the human papillomavirus to reduce cervical cancer events.

Cost-effectiveness of the vaccine against human papillomavirus in the brazilian Amazon region / Custo-efetividade da vacina contra o papilomavírus humano na região Amazônica brasileira

OBJECTIVE: To assess the cost-utility of the human papillomavirus (HPV) vaccination on the prevention of cervical cancer in the Brazilian Amazon region. METHODS: AMarkov cohort modelwas developed to simulate the natural evolution of HPV and its progress to cervical cancer, considering the current preventive programs and treatment costs. The one-year transition probabilities were mainly based on empirical data of local and national studies. The model evaluated the addition of the vaccine to three cervical cancer-screening scenarios (0, 3 or 10 exams throughout life). RESULTS: The scenario of three Pap tests resulted in satisfactory calibration (base case). The addition of HPV vaccination would reduce by 35% the incidence of cervical cancer (70% vaccination coverage). The incremental cost-effectiveness ratio was US$ 825 for each quality-adjusted life year gained. The sensitivity analysis confirms the robustness of this result, and duration of immunity was the parameter with greater variation in incremental cost-effectiveness ratio. CONCLUSION: Vaccination has a favorable profile in terms of cost-utility, and its inclusion in the immunization schedule would result in a substantial reduction in incidence and mortality of invasive cervical cancer in the Brazilian Amazon region.

OBJETIVO: Avaliar a custo-efetividade da vacinação contra o papilomavírus humano (HPV) na prevenção do câncer de colo de útero na região Amazônica brasileira. MÉTODOS: Um modelo de coorte Markov foi desenvolvido para simular a história natural do HPV e seu progresso para câncer de colo de útero, considerando os atuais programas de prevenção e os custos de tratamento. As probabilidades de um ano de transição foram baseadas principalmente em dados empíricos de estudos locais e nacionais. O modelo avaliou a adição da vacina a três cenários de rastreio de câncer de colo de útero (0, 3 ou 10 exames ao longo da vida). RESULTADOS: O cenário de três exames de Papanicolau resultou em calibração satisfatória (caso base). A adição de vacinação contra o HPV reduziria em 35% a incidência de câncer de colo de útero (70% de cobertura de vacinação). A razão incremental de custo-efetividade foi US$ 825 para cada ano de vida ajustado para qualidade ganho. A análise de sensibilidade confirma a robustez deste resultado, e a duração de imunidade foi o parâmetro com maior variação na razão incremental de custo-efetividade. CONCLUSÃO A vacinação tem um perfil favorável em termos de custo-utilidade, e sua inclusão no calendário de imunização resultaria em redução substancial de incidência e de mortalidade relacionadas ao câncer de colo de útero na região Amazônica brasileira.

Vacina contra HPV na prevenção de câncer de colo do útero / HPV vaccine to prevent cervical cancer

O vírus do Papiloma Humano (HPV, sigla em Inglês) é um vírus cuja transmissão se dá por via sexual e com alto potencial de transmissão, sendo que a proximadamente 75% dos indivíduos que iniciam a vida sexual tornam-se infectados em algum momento da vida. Na década de 1990 foi comprovado que a infecção pelo HPV é causa necessária, ainda que não suficiente, para o desenvolvimento do câncer de colo uterino, que é um relevante problema de saúde pública, particularmente nas regiões mais pobres do mundo. Outros fatores foram identificados como associados à presença de lesões pré-cancerosas e desenvolvimento do câncer de colo do útero: início precoce da atividade sexual, promiscuidade do parceiro, sexo anal, múltiplos parceiros, imunossupressão, multiparidade, precocidade da idade materna no primeiro parto, fumo, uso a longo prazo de contraceptivos hormonais, co-infecção por Chlamydia trachomatis ou vírus Herpes simplex e fatores relacionados à dieta. No entanto, a maioria das infecções por HPV é assintomática e auto-resolutiva, ou seja, nem toda infecção irá evoluir para o câncer, e pelo menos 80% delas regridem sem intervenções. As vacinas contra HPV são preparadas a partir de partículas virais semelhantes ao vírus (VLP, do inglês virus-like particle), produzidas por tecnologia recombinante, oriundas da proteína L1 do capsídeo viral dos tipos de HPV, altamente purificadas e capazes de gerar resposta imunológica. Como as VLP não contêm DNA (ácido desoxirribonucléico) viral, não são capazes de infectar células, se reproduzirem ou causarem doenças. Existem duas vacinas disponíveis no mercado: A vacina bivalente recombinante contra HPV 16 e 18, fabricada pela Glaxo Smith Kline. Nome comercial: Cervarix; A vacina quadrivalente recombinante contra HPV 6, 11, 16 e 18, fabricada pela Merck Sharp & Dohme. Nome comercial: Gardasil. A evidência científica disponível atualmente confirma que a vacina contra o HPV é eficaz na prevenção de lesões precursoras do câncer de colo do útero (NIC 2 e 3), as quais são diretamente relacionadas ao aparecimento do carcinoma. Porém, deve ser apontado que, para garantir a eficácia na prevenção do câncer de colo do útero propriamente dito, os estudos devem acompanhar as meninas incluídas por tempo suficiente para o desenvolvimento das neoplasias, qual seja superior a 20 anos em média. Com relação à segurança, considerando que a vacina foi implementada em diversos países do mundo e está sendo utilizada por milhões de crianças e mulheres, pode-se concluir que ela é segura e não está relacionada a eventos adversos graves. Pelo exposto, a CONITEC, em sua 17ª reunião ordinária, considerou que ambas as vacinas hoje disponíveis são similares em eficácia e segurança para a finalidade estudada, qual seja a prevenção de lesões precursoras do câncer de colo uterino, e recomendou a incorporação da vacina quadrivalente contra o HPV no SUS, considerando a proposta selecionada para a parceria de desenvolvimento produtivo (PDP), bem como a observância às normas definidas pelo Programa Nacional de Imunização (PNI). A Portaria nº 54, de 18 de novembro de 2013 - Torna pública a decisão incorporar a vacina quadrivalente contra HPV na prevenção do câncer de colo do útero no Sistema Único de Saúde - SUS.

Disposición a pagar por vacunas contra el virus papiloma humano en la Región Metropolitana de Santiago de Chile / Willingness to pay for human papillomavirus vaccine in Metropolitan Santiago, Chile

Background: Human papillomavirus (HPV) infection is a risk factor for cervical cancer and can be prevented with the HPV vaccine. Aim: To explore the willingness of parents to pay for HPV vaccine for their offspring. Material and Methods: A survey about the willingness to pay for HPV vaccine was answered by 386 individuals of the highest socioeconomic level who had a daughter aged between 12 and 18 years. The survey included information about the risks of HPV infection. Results: Parents would pay a mean of US$ 758 for the vaccine. Twenty five percent of parents were not willing to pay for it. If the cost of the vaccine would be reduced by 50%, only 4% of parents would not pay for it. The willingness to pay is associated with the price of the vaccine, the income level of respondents and the size of the family. Conclusions: Most respondents would pay for HPV vaccine for their daughters, despite the relatively high cost.

Health and economic impact of human papillomavirus 16 and 18 vaccination of preadolescent girls and cervical cancer screening of adult women in Peru / Repercusiones sanitarias y económicas de la vacunación de niñas preadolescentes contra los tipos 16 y 18 del virus del papiloma humano y el tamizaje del cáncer cervicouterino en las mujeres adultas en el Perú

OBJECTIVE: To estimate the benefits, cost-effectiveness (i.e., value for money), and required financial costs (e.g., affordability) of adding human papillomavirus (HPV) vaccination to Peru's cervical cancer screening program. METHODS: Evidence (e.g., coverage, delivery costs) from an HPV vaccination demonstration project conducted in Peru was combined with epidemiological data in an empirically calibrated mathematical model to assess screening (HPV DNA testing three to five times per lifetime) and HPV vaccination under different cost, coverage, and efficacy assumptions. Model outcomes included lifetime risk of cancer reduction, cancer cases averted, lives saved, average life expectancy gains, short-term financial costs, and discounted long-term economic costs. RESULTS: Status quo low levels of screening (e.g., cytologic screening at 10.0% coverage) reduced lifetime risk of cervical cancer by 11.9%, compared to not screening. Adding vaccination of preadolescent girls at a coverage achieved in the demonstration program (82.0%) produced an additional 46.1% reduction, and would cost less than US$ 500 per year of life saved (YLS) at ~US$ 7/dose or ~US$ 1 300 at ~US$ 20/dose. One year of vaccination was estimated to cost ~US$ 5 million at ~US$ 5/dose or ~US$ 16 million at ~US$ 20/dose, including programmatic costs. Enhanced screening in adult women combined with preadolescent vaccination had incremental cost-effectiveness ratios lower than Peru's 2005 per capita gross domestic product (GDP; US$ 2 852, in 2009 US$), and would be considered cost-effective. CONCLUSIONS: Preadolescent HPV vaccination, followed by enhanced HPV DNA screening in adult women, could prevent two out of three cervical cancer deaths. Several strategies would be considered "good value" for resources invested, provided vaccine prices are low. While financial costs imply substantial immediate investments, the high-value payoff should motivate creative mechanisms for financing and scale-up of delivery programs.

OBJETIVO: Calcular los beneficios, la rentabilidad (relación costo-efectividad), y los costos financieros (asequibilidad) de añadir la vacunación contra el virus del papiloma humano (VPH) al programa de tamizaje del cáncer cervicouterino en el Perú. MÉTODOS: Se combinaron los datos probatorios (por ejemplo, cobertura, costos de prestación) de un proyecto piloto de vacunación contra el VPH llevado a cabo en el Perú con datos epidemiológicos, en un modelo matemático calibrado empíricamente para evaluar el tamizaje (prueba de ADN del VPH tres a cinco veces durante toda la vida) y la vacunación contra el VPH, según diferentes supuestos de costo, cobertura y eficacia. Los resultados del modelo incluían la reducción del riesgo de cáncer durante toda la vida, los casos de cáncer evitados, las vidas salvadas, los incrementos de la esperanza media de vida, los costos financieros a corto plazo y los costos económicos a largo plazo actualizados. RESULTADOS: Los bajos niveles de tamizaje actuales (cobertura del tamizaje citológico de 10,0 %) redujeron en 11,9 % el riesgo de cáncer cervicouterino durante toda la vida en comparación con la ausencia de tamizaje. La adición de la vacunación de las niñas preadolescentes con la cobertura alcanzada en el programa piloto (82,0 %) produjo una reducción adicional de 46,1 % y costaría menos de US$ 500 por cada año de vida salvado a US$ 7 la dosis, o de US$ 1 300 a US$ 20 la dosis. Se calculó que el costo de las vacunaciones de un año era aproximadamente de US$ 5 millones a unos US$ 5 la dosis o de aproximadamente US$ 16 millones a unos US$ 20 la dosis, incluidos los costos programáticos. La mejora del tamizaje en las mujeres adultas combinada con la vacunación de las preadolescentes mostraba cocientes de rentabilidad incremental inferiores al producto interno bruto per cápita del Perú en el año 2005 (PIB US$ 2 852, en dólares del 2009), y se consideraría rentable. CONCLUSIONES: La vacunación de las preadolescentes contra el VPH, junto con la mejora del tamizaje mediante la prueba de ADN del VPH en las mujeres adultas, podría prevenir dos de cada tres muertes debidas a cáncer cervicouterino. Varias estrategias se considerarían rentables en relación con los recursos invertidos, a condición de que el precio de la vacuna sea bajo. Aunque los costos financieros implican inversiones inmediatas sustanciales, el valor elevado de los beneficios debe motivar la elaboración de mecanismos creativos para financiar y extender los programas de prestación de servicios.

Costo-utilidad de la vacuna contra el virus de papiloma humano en mujeres peruanas / Cost- utility of the vaccine against the human papiloma virus in peruvian women

Objetivos. Estimar el costo-utilidad de la vacuna contra el Virus de Papiloma Humano (VPH) en las mujeres peruanas luego de la aplicación de la vacuna cuando tenían 10 años de edad. Materiales y métodos. Se realizó un análisis de costo-utilidad empleando el modelo oculto de Markov en una cohorte hipotética de mujeres peruanas, basado en la información de parámetros epidemiológicos, costos asociados al Cáncer de cuello uterino (CCU) y la eficacia y los costos de la vacunación contra el VPH. Los costos de la vacunación se estimaron desde la perspectiva del Ministerio de Salud de Perú y se compararon con los años de vida ajustados por calidad (AVAC) utilizando una tasa de descuento del 5 por ciento. Resultados. El costo anual de la vacunación fue de USD 16 861 490, para el tamizaje con Papanicolau fue de USD 3 060 793 y los costos asociados al CCU fueron de USD 15 580 000. La razón de costo-utilidad incremental (RCUI) fue de 6775 USD/AVAC. Conclusiones. La vacunación contra el VPH puede resultar costo-útil comparada con el no vacunar.

Objetives. To estimate the cost-utility of the vaccine against the Human Papiloma Virus (HPV) in peruvian women after the application of the vaccine at 10 years of age. Materials and methods. A cost-utility analysis was performed using the Markov´s hidden model in a hypothetical cohort of peruvian women, based on the information on epidemiological parameters, costs associated to uterine cervical cancer (UCC) and the efficacy and costs of the vaccine against the HPV. The vaccination costs were estimated from the Peruvian Ministry of Health perspective and were compared against the quality-adjusted life years (QALYs), using a discount rate of 5 percent. Results. The annual cost of the vaccination was USD 16’861,490, for the Papanicoau screening it was USD 3’060,793 and the costs associated to the UCC were USD 15’580,000. The incremental cost utility ratio (ICUR) was 6,775 USD/QALY. Conclusions. Vaccination against HPV can be cost-utility compared to not vaccinating.

Desarrollo de una vacuna profiláctica de segunda generación contra el papilomavirus humano / Development of a second generation prophylactic vaccine against human papillomavirus

Los papilomavirus humanos (HPV) son el agente etiológico del cáncer cervical (CC), la segunda causa de muerte por cáncer en mujeres. Se estima que medio millón de nuevos cánceres se diagnostica cada año, ocurriendo la mayoría de ellos en países en vías de desarrollo debido a la ausencia o ineficiencia de los programas masivos de detección temprana. Recientemente se han introducido en el mercado dos vacunas profilácticas contra las principales cepas oncogénicas de HPV, la cepa 16 y 18, responsables por el 80% de todos los CC. Estas vacunas se obtienen en forma recombinante y han demostrado ser extremadamente seguras y eficaces. Sin embargo, su impacto inmediato en la incidencia de la infección por HPV en países en vías de desarrollo será mínimo, debido principalmente al alto costo de las mismas. Existe la necesidad de contar con vacunas de segunda generación, de bajo costo y de aplicación masiva que permitan disminuir sensiblemente el número de CC en la población. Con este objetivo hemos desarrollado una plataforma de expresión recombinante que permite obtener partículas tipo virus (VLPs) con las cuales es posible formular vacunas efectivas y accesibles contra la infección por HPV.

Human papillomaviruses (HPV) are the etiologic agent for cervical cancer (CC), the second cause of cancer death in women worldwide. It is estimated that half a million new cases are diagnosed each year, mostly in developing countries due to the lack of massive programs for early detection of the virus. Recently, two prophylactic vaccines against the main oncogenic HPV types 16 and 18 (responsible for 80% of CC) have been introduced into market. Both of these vaccines, obtained as recombinants, have been shown to be safe and effective; however, their high cost works against its immediate impact in the incidence of HPV infection in developing and low-income countries. There is a need to have in hand second generation, low cost vaccines of massive use that will decrease CC cases in a large extent. With this in mind, we have developed a recombinant expression platform that allows us to obtain virus-like particles (VLPs) to formulate both effective and accessible vaccines against HPV infection.

Avaliações econômicas do uso da vacina contra o Papilomavírus Humano (HPV) em meninas adolescentes: uma revisão sistemática / Economic evaluations of the use of a vaccine against human papillomavirus (HPV) in adolescent girls: a systematic review

O câncer de colo do útero persiste como um importante problema de saúde em todo o mundo, em particular nos países em desenvolvimento. Duas vacinas contra o papilomavirus humano (HPV) encontram-se atualmente disponíveis e aprovadas para uso em meninas adolescentes, antes do início da vida sexual: uma bivalente, contra os sorotipos 16 e 18 e outra quadrivalente, contra os sorotipos 6, 11, 16 e 18. Estes imunobiológicos têm por objetivo induzir uma imunidade contra o papilomavírus e, desta forma, atuar na prevenção primária do câncer do colo de útero. As avaliações econômicas podem ser um elemento que auxiliem nos processos de tomada de decisão sobre a incorporação da vacina em programas de imunização nacionais. Estas avaliações foram o objeto central deste trabalho, que teve como objetivo sintetizar as evidências procedentes de uma revisão sistemática da literatura de estudos de avaliação econômica da utilização da vacina contra o HPV em meninas adolescentes e pré-adolescentes. Foi realizada uma busca na literatura nas bases MEDLINE (via Pubmed), LILACS (via Bireme) e National Health Service Economic Evaluation Database (NHS EED) ate junho de 2010. Dois avaliadores, de forma independente, selecionaram estudos de avaliação econômica completa, que tivessem como foco a imunização para HPV em mulheres com as vacinas comercialmente disponíveis direcionada à população adolescente. Após a busca, 188 títulos foram identificados; destes, 39 estudos preencheram os critérios de elegibilidade e foram incluídos na revisão. Por tratar-se de uma revisão de avaliações econômicas, não foi realizada uma medida de síntese dos valores de relação incremental entre custos e efetividade. Os 39 artigos incluídos envolveram 51 avaliações econômicas em 26 países. Predominaram estudos de custo-utilidade (51%). Do ponto de vista da perspectiva da análise, predominou o dos sistemas de saúde (76,4%)...

HPV & HPV vaccination: Issues in developing countries.

Cervical cancer is the second-most common cancer in women worldwide causing most cancer related deaths in women in developing countries including India. The most predominant etiological factor for cervical cancer is persistent infection of certain high-risk types of human papillomaviruses (HR-HPVs), while low-risk types are associated with benign cervical lesions and genital warts. In India, the most common (98%) oncogenic types are HPV types 16 and 18 with HPV 16 exclusively (80-90%) prevalent. Two recently developed virus-like particle (VLP) based prophylactic HPV vaccines, quadrivalent Gardasil (HPV 16/18/6/11) and Cervarix (HPV 16/18) offer great promise. Several other therapeutic vaccines are also in clinical trials and are yet to establish their efficacy. The use of already developed VLP vaccines in resource-poor regions is limited by several factors, most importantly the high cost of the vaccine. Therefore efforts are being made in India to develop cost-effective second-generation vaccines. Besides cost, there are several socio-cultural and ethical issues involved with the implementation of already developed vaccines including the acceptability of HPV vaccination by preadolescent girls and their parents in India.

HPV vaccination: the promise & problems.

Four-fifths of the cervical cancer burden in the world is experienced in developing countries. HPV genotypes 16 and 18 account for 70 per cent of cervical cancers and currently available vaccines targeting these two types confer a high degree of protection against HPV 16/18 infection and related cervical precancerous lesions. However, widespread implementation of HPV vaccination programs are challenged by the unaffordable high costs of the vaccines and the lack of effective vaccine delivery platforms for sexually naïve girls. Other unresolved issues include long-term protection, cross-protection against HPV types not included in the vaccine and whether booster doses will be needed. Sensitivities associated with a vaccine preventing a sexually transmitted infection in girls, lack of awareness, public demand and political will, lack of coordination between cancer control, sexual and reproductive health and vaccine delivery services are additional challenges. Reduced costs, simple vaccine regimes and strengthening vaccine delivery platforms for adolescents should eventually facilitate HPV vaccine introduction in developing countries.

Genotypes of the human papillomavirus: Relevance to Indian field trials of the vaccine.

Highly effective HPV vaccines are likely to become available for use in India shortly. The availability and validation of the vaccines to prevent oncogenic HPV infection associated lesions from progressing to cancer has clearly offered a cost effective long-term strategy to reduce the cervical cancer burden, particularly for developing countries where effective screening programmes are not available. The enthusiasm for these new vaccines duly justified, are we in reality targeting the actual delinquent by prompting these vaccines in India? The answer would be no as we may not be essentially implementing a rational fool-proof vaccine program which will aid in preventing HPV-related diseases, for the simple reason that there is a lack of understanding about the underlying HPV types responsible for cervical cancer in India. Field trials involving large populations form a major part of continued analysis in understanding any disease and India is still short of such a trial as far as cervical cancer is concerned. Conducting such studies, might also act as prevention programs that will save lives and improve public health in a substantive manner.

Cervical cancer screening & HPV vaccination: a comprehensive approach to cervical cancer control.

India with its highest share of global burden of cervical cancer has to implement a population based cervical cancer control program to reduce the number of deaths. There are new screening options available like visual inspection after acetic acid application (VIA) test, single visit approach to screening and treatment etc. Emergence of the two effective vaccines against human papillomavirus (HPV), the necessary cause of cervical cancer, has introduced a fresh lease of life to the cervical cancer control strategies. The current high cost of the vaccines is a major impediment to implement a vaccine-based primary prevention approach.