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Abstract: Routine use of human papillomavirus (HPV) vaccines is recommended in adolescents under 15 years of age worldwide. Still, effective programs remain suboptimal for several factors, making the WHO strategy to eradicate cervical cancer public health with an uncertain future. Objective: To review the literature on the effectiveness, long-term protection, and safety of HPV vaccination programs and vaccination as adjuvant management. This review aims to describe the current state of vaccination programs and demonstrate the long-term protection and safety of vaccines implemented worldwide targeting adolescent girls, with the most recent published evidence of the three prophylactic HPV vaccines - bivalent (bHPV), quadrivalent (qHPV), and nonavalent (nHPV)-. We mainly focus on publications evaluating efficacy, dosing schemes, and HPV vaccination, as well as studies contributing to the mounting evidence for the real-life effectiveness of prophylactic HPV vaccines from several countries. Findings: Human Papillomavirus vaccination programs have made remarkable strides in preventing HPV-related diseases; countries with robust vaccination efforts have witnessed substantial reductions in HPV-related diseases with a decline in high-grade cervical abnormalities and genital warts (54%-83%). However, global coverage remains uneven, with disparities between high-income (HICs) and low-income countries (LMICs). The long-term efficacy of the available human papillomavirus (HPV) goes up to 9.4 years and continues to be immunogenic and well tolerated with an excellent safety profile. Conclusions and relevance: As these are crucial topics in HPV vaccination, it is essential to establish systems for continued monitoring of vaccine immunogenicity, efficacy, and safety over time.
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mRNA vaccine technology is the most interesting final product of decades of research. This new platform for public health is simple to transfer to low-income countries and can be used against diverse agents, including cancer. It is environmentally clean, relatively low-cost, and does not use animals for its production. Most importantly, mRNA vaccines have been highly efficacious in avoiding serious disease and death from COVID-19. Yet, at the highest point of the pandemic, many voices, including some from prominent positions, opposed their use. Similarly, the Human Papillomavirus (HPV) vaccines, which are highly effective, very safe, and probably confer long life protection against its HPV types, faced strong parents' hesitancy. Vaccine hesitancy has been the subject of extensive research, focusing primarily on factors associated with the public, the political environment, and messaging strategies. However, the issue of unfair worldwide access to the COVID-19 vaccines has recently sparked significant debate about the vaccine industry's role. Recent data demonstrated that the system's perceived unfairness with the masses is behind the growing populist anti-vaccine movements worldwide. The association between populism and antivaccine attitudes has been reported at country and individual levels. The anti-science attitudes behind vaccine hesitancy emerge when the scientist is not found credible due to the suspicion that they had monetary investments in pharmaceutical companies. Here, I argue that the obscurity of the vaccine market, but also its unfairness, are important factors contributing to vaccine hesitancy. The purpose of this commentary is to stimulate a review of current market regulations and to improve its transparency and fairness, particularly in the context of public health emergencies. By doing so, a new pandemic would find us better prepared. The general population and much of the healthcare community often ignore the years of dedicated work and substantial public funding that enabled the discovery and design of vaccines. Conversely, pharmaceutical companies often over-emphasize their investments in research and development. A decade ago, Marcia Angell provided a detailed breakdown of pharmaceutical expenses, revealing that marketing and administration costs were 2.5 times higher than research and development expenses; recently, Olivier Wouters confirmed the high expenditures of the pharmaceutical industry in lobbying and political campaign contributions. In this commentary, I will present the cases of HPV and COVID-19 vaccines as examples of when vaccines, instead of being public health goods, became market goods, creating large inequities and health costs. This failure is a structural cause behind more ideological vaccine hesitancy, less studied so far.
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O presente estudo trata-se de uma análise na literatura sobre o aspecto bioético da autonomia em relação a imunização contra Hepatite B e HPV na adolescência. Foi realizada uma revisão bibliográfica baseada no método prisma onde foram incluídos artigos em português e inglês os quais foram pesquisados nas plataformas Scientific Electronic Library Online (SciELO), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) e National Library of Medicine (PUBMED), utilizando os seguintes descritores Hepatitis B Vaccines, bioethics, Humans. Os resultados demostraram a eficiência dos profissionais de saúde no contato com o indivíduo e o convencimento deste através de um diálogo aberto e criação de vínculos. Evidenciou-se ainda o estudo evidenciou o direito a autonomia progressiva do paciente, no qual este ganha o direito a algumas escolhas como as imunizações de doenças sexualmente transmissíveis, como é o caso da Hepatite B e HPV, no entanto é necessário que o adolescente seja instruído sobre a imunização. Assim sendo, reconhece-se o direito a autonomia progressiva do adolescente, referente a escolha das imunizações contra a Hepatite B e HPV, entretanto, deve-se considerar que estes indivíduos sejam instruídos sobre os benefícios individuais e/ou coletivos da vacinação, contemplados por atividades de educação em saúde por profissionais qualificados, objetivando ampliar a cobertura global de imunização com doenças que caracterizam problemas de saúde pública.
El presente estudio es un análisis de la literatura sobre el aspecto bioético de la autonomía en relación con la inmunización contra la Hepatitis B y el VPH en la adolescencia. Se realizó una revisión bibliográfica basada en el método del prisma, que incluyó artículos en portugués e inglés que fueron buscados en la Biblioteca Científica Electrónica en Línea (SciELO), Literatura Latinoamericana y del Caribe en Ciencias de la Salud (LILACS) y la Biblioteca Nacional de Medicina (PUBMED), utilizando los siguientes descriptores Vacunas Hepatitis B, bioética, Humanos. Los resultados demostraron la eficiencia de los profesionales de la salud en contactar al individuo y convencerlo a través de un diálogo abierto y creación de vínculos. También se evidenció que el estudio evidenció el derecho del paciente a la autonomía progresiva, en la que adquiere el derecho a algunas opciones como las inmunizaciones de enfermedades de transmisión sexual, como la Hepatitis B y el VPH, sin embargo, es necesario que el adolescente sea educado sobre la inmunización. Por lo tanto, se reconoce el derecho del adolescente a la autonomía progresiva, en cuanto a la elección de las vacunas contra la Hepatitis B y el VPH, sin embargo, se debe considerar que estos individuos sean educados sobre los beneficios individuales y/o colectivos de la vacunación, contemplados por las actividades de educación en salud por profesionales calificados, con el objetivo de ampliar la cobertura mundial de inmunización con enfermedades que caracterizan los problemas de salud pública.
The present study is an analysis of the literature on the bioethical aspect of autonomy in relation to immunization against Hepatitis B and HPV in adolescence. A bibliographic review was carried out based on the prism method, which included articles in Portuguese and English which were searched on the Scientific Electronic Library Online (SCIELO), Latin American and Caribbean Literature on Health Sciences (LILACS) and the National Library of Medicine (PUBMED), using the following descriptors Hepatitis B Vaccines, bioethics, Humans. The results demonstrated the efficiency of health professionals in contacting the individual and convincing him/her through an open dialogue and creation of bonds. It was also evidenced the study evidenced the patient's right to progressive autonomy, in which he gains the right to some choices such as immunizations of sexually transmitted diseases, such as Hepatitis B and HPV, however it is necessary for the adolescent to be educated about immunization. Therefore, the adolescent's right to progressive autonomy is recognized, regarding the choice of immunizations against Hepatitis B and HPV, however, it must be considered that these individuals are instructed on the individual and/or collective benefits of vaccination, contemplated by health education activities by qualified professionals, aiming to expand the global coverage of immunization with diseases that characterize public health problems.
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HumanosRESUMEN
Objective: To analyze the number of applied HPV vaccine doses before (from April 2019 to March 2020) and after (from April 2020 to September 2020) social distancing measures in response to the COVID-19 pandemic in states and regions of Brazil. Methods: Ecological time-series study, using data from the Brazilian National Immunization Program (PNI). Using the Mann-Whitney test, we evaluated the difference between the median number of applied doses during the periods April 2019 to March 2020 and from April 2020 to September 2020. Spatial analysis identified clusters with a high or low percentage reduction in the median applied doses. Prais-Winsten regression models identified temporal trends in the applieddoses from both periods. Results: There was a significant reduction in the median HPV vaccine doses applied, formation of spatial clusters and, after a sharp drop in the number of applieddoses during the months following social distancing. There was a tendency to increase the applied vaccines doses. Conclusion: The COVID-19 pandemic resulted in reduction of the number of HPV vaccine doses applied as a possible effect of restrictive measures caused by the pandemic.
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Alphapapillomavirus , COVID-19 , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Brasil/epidemiología , COVID-19/epidemiología , COVID-19/prevención & control , Humanos , Pandemias/prevención & control , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/uso terapéutico , VacunaciónRESUMEN
INTRODUCTION: The influence of vaccination on composition of the human microbiome at distinct sites has been recognized as an essential component in the development of new vaccine strategies. The HPV vaccine is widely used to prevent cervical cancer; however, the influence of HPV vaccine on the vaginal microbiota has not been previously investigated. In his study, we performed an initial characterization of the microbiome and cytokine composition in the vagina following administration of the bivalent vaccine against HPV 16/18. MATERIAL AND METHODS: In this exploratory study, fifteen women between 18 and 40 years received three doses of the HPV-16/18 AS04-adjuvanted vaccine (Cervarix®). Cervicovaginal samples were collected before the first dose and 30 days after the third dose. HPV genotyping was performed by the XGEN Flow Chip technique. The cytokines IFN-γ, IL-2, IL-12p70, TNF-α, GM-CSF, IL-4, IL-5, IL-10, and IL-13 were quantitated by multiplex immunoassay. The vaginal microbiome was identified by analysis of the V3/V4 region of the bacterial 16S rRNA gene. RESULTS: The most abundant bacterial species in the vaginal microbiome was Lactobacillus crispatus, followed by L. iners. Bacterial diversity and dominant organisms were unchanged following vaccination. Small decreases in levels of pro and anti-inflammatory cytokines were observed following HPV vaccination, but there was no association between vaginal cytokine levels and microbiome composition. CONCLUSION: Vaginal microbiome is not altered following administration of the standard three-dose HPV-16/18 AS04-adjuvanted (Cervarix®) vaccine.
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Bacterias , Citocinas , Microbiota , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Vagina , Adulto , Bacterias/efectos de los fármacos , Bacterias/genética , Citocinas/inmunología , Femenino , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Microbiota/efectos de los fármacos , Microbiota/genética , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/farmacología , ARN Ribosómico 16S/genética , Vagina/microbiología , Adulto JovenRESUMEN
OBJECTIVE: This study aims to discover the most prevalent high-risk (hr) HPV genotypes in the regions of Loreto and La Libertad, Peru. METHODS: In 2015, cervical cell samples were collected during pelvic examinations from women in the geographically distinct regions of Loreto and La Libertad, Peru. In 2017, additional samples were collected in La Libertad. A total of 429 women between the ages of 18 and 65 years living in these regions were enrolled in the study. All samples were analyzed by polymerase chain reaction for the hrHPV genotypes 16, 18, and 35. RESULTS: Sample collection from 126 women in 2015 in Loreto revealed an hrHPV incidence of 15.9% (20 of 126), with 60% (12 of 126) of HPV infections due to hrHPV 16. Samples from La Libertad revealed an hrHPV incidence of 14.5% incidence (44 of 303) (among 303 women). Of these infections, 38% (17) were attributable to hrHPV type 35 and 20% (9) were due to hrHPV type 16. CONCLUSION: The prevalence of hrHPV genotypes in Peru may differ from those observed in North America and Europe. Loreto appears to follow the prevalence trend observed in North America, with hrHPV type 16 accounting for the majority of cases. However, hrHPV type 35 may account for a greater contribution to the cervical cancer burden in La Libertad. Further research, specifically on cervical tumor specimens, is needed.
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Alphapapillomavirus , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Adolescente , Adulto , Anciano , Femenino , Genotipo , Humanos , Persona de Mediana Edad , Papillomaviridae/genética , Infecciones por Papillomavirus/epidemiología , Perú/epidemiología , Prevalencia , Neoplasias del Cuello Uterino/epidemiología , Adulto JovenRESUMEN
Anal canal cancer is one of the human papilloma virus (HPV)-associated diseases with increasing incidence. High-risk sexual behaviour and the resurgence of human immunodeficiency virus (HIV) infection, associated with low HPV vaccine coverage, are risk factors for the increased incidence of this cancer. In this paper, the authors point out pertinent questions regarding the greater exposure of the population to some risk factors and discuss the latest epidemiological data of these factors, particularly those of concern to emerging countries like Brazil. The authors also discuss policies adopted that have not been successful to combat the HIV and HPV rise and that have direct consequences on the incidence of anal canal cancer.
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Resumen: OBJETIVO: Evaluar la inmunogenicidad de los distintos tipos de vacunas terapéuticas y de su efecto en las lesiones causadas por el virus del papiloma humano (VPH) después de su aplicación. Además, analizar los estudios de seguridad y las perspectivas de las vacunas terapéuticas contra el VPH. METODOLOGÍA: Estudio retrospectivo efectuado mediante la búsqueda bibliográfica sistemática en la base de datos PubMed, sin restricción de fecha de publicación. Criterio de inclusión: ensayos clínicos aleatorizados (metanálisis y revisiones sistemáticas). Criterios de exclusión: ensayos clínicos en fase preclínica del desarrollo y publicaciones en idiomas distintos al inglés o español. RESULTADOS: Se seleccionaron 30 artículos publicados entre 2000 y 2020. Entre ellos, 5 ensayos clínicos aleatorizados con vacunas terapéuticas que ya han finalizado o aún están en estudio. Las 25 publicaciones restantes incluyen: metanálisis y revisiones sistemáticas de aspectos seleccionados con objetivos primarios y secundarios. CONCLUSIONES: Las vacunas terapéuticas contra VPH se encuentran en fase experimental; hasta ahora se han conseguido resultados prometedores con algunas de ellas. Si bien existen distintos tipos de vacunas terapéuticas, los mejores resultados se han conseguido con las basadas en ADN. Las vacunas VGX-3100 y TS, en fase III, han demostrado diferencias significativas en el aclaramiento viral y la regresión de las lesiones de alto grado en pacientes vacunadas. Una vacuna terapéutica efectiva tendría una repercusión inmediata en la morbilidad y mortalidad por lesiones asociadas al virus.
Abstract: OBJECTIVE: To assess the immunogenicity of different types of therapeutic vaccines and their effect on human papillomavirus (HPV) lesions after application. In addition, to analyze the safety studies and prospects of therapeutic HPV vaccines. METHODOLOGY: Retrospective study based on a systematic literature search of the PubMed database, with no publication date restrictions. Inclusion criteria: randomized clinical trials (meta-analyses and systematic reviews). Exclusion criteria: clinical trials in the pre-clinical phase of development and publications in languages other than English or Spanish. RESULTS: 30 articles published between 2000 and 2020 were selected. Among them, 5 randomized clinical trials with therapeutic vaccines that have already been completed or are still under study. The remaining 25 publications include: meta-analyses and systematic reviews of selected aspects with primary and secondary objectives. CONCLUSIONS: Therapeutic HPV vaccines are in the experimental phase; so far promising results have been achieved with some of them. Although different types of therapeutic vaccines exist, the best results have been achieved with DNA-based vaccines. The VGX-3100 and TS vaccines, in phase III, have demonstrated significant differences in viral clearance and regression of high-grade lesions in vaccinated patients. An effective therapeutic vaccine would have an immediate impact on morbidity and mortality from virus-associated lesions.
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Abstract: Objective: To evaluate the effectiveness of a combined strategy of human papillomavirus virus (HPV) vaccination and high-risk HPV screening to reduce the occurrence of anogenital and oropharyngeal neoplasms among men who have sex with men, people with HIV, homeless people, transgender women, female sex workers and rape victims. Materials and methods: This mixed methods study evaluates the effectiveness of a combined vaccination-screening strategy to reduce HPV prevalence/incidence and occurrence of cervical intraepithelial neoplasms grade 2+ and/or anal intraepithelial neoplasms grade 2+, using Kaplan-Meier. The time-to-event method will evaluate time from positive results for specific anogenital HPV to incidence of anogenital lesions containing that HPV type. Results: People vaccinated against HPV and screened for HPV as a primary test will have lower prevalence and incidence of HPV infection and consequently lower frequency of HPV-related anogenital and oropharyngeal lesions. Conclusions: This study will generate scientific evidence on effectiveness of a combined vaccination-screening strategy to reduce the burden of HPV-associated neoplasms.
Resumen: Objetivo: Evaluar la efectividad de una estrategia combinada de vacunación contra el virus de papiloma humano (VPH) y tamizaje de VPH de alto riesgo para reducir neoplasias anogenitales y orofaringeas entre hombres que tienen sexo con hombres, personas con VIH, personas en situación de calle, mujeres transgénero, trabajadoras sexuales y víctimas de violación. Material y métodos: Este estudio evaluará la efectividad de una estrategia combinada de vacunación y tamizaje para reducir la ocurrencia de neoplasias intraepiteliales cervicales grado 2+ o neoplasias intraepiteliales anales grado NIA2+ utilizando Kaplan-Meier. Se evaluará tiempo de resultados positivos para tipos específicos de VPH anogenital a incidencia de lesiones anogenitales con ese tipo de VPH. Resultados: Las personas vacunadas contra VPH y con tamizaje de VPH tendrán menor prevalencia e incidencia de infecciones por VPH y por ende menor frecuencia de lesiones anogenitales y orofaringeas relacionadas con VPH. Conclusiones: Este estudio generará evidencia científica sobre la efectividad de una estrategia combinada de vacunación y tamizaje para reducir la carga de neoplasias asociadas al VPH.
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Humanos , Masculino , Femenino , Adulto , Adulto Joven , Neoplasias del Ano/prevención & control , Neoplasias de la Boca/prevención & control , Carcinoma in Situ/prevención & control , Programas de Inmunización , Infecciones por Papillomavirus/epidemiología , Detección Precoz del Cáncer , Neoplasias del Ano/epidemiología , Comorbilidad , Infecciones por VIH/epidemiología , Riesgo , /epidemiología , Víctimas de Crimen , Poblaciones Vulnerables , Vacunas contra Papillomavirus , Marginación Social , México/epidemiologíaRESUMEN
OBJECTIVE: To evaluate the effectiveness of a combined strategy of human papillomavirus virus (HPV) vaccination and high-risk HPV screening to reduce the occurrence of anogenital and oropharyngeal neoplasms among men who have sex with men, people with HIV, homeless people, transgender women, female sex workers and rape victims. MATERIALS AND METHODS: This mixed methods study evaluates the effectiveness of a combined vaccination-screening strategy to reduce HPV prevalence/incidence and occurrence of cervical intraepithelial neoplasms grade 2+ and/or anal intraepithelial neoplasms grade 2+, using Kaplan-Meier. The time-to-event method will evaluate time from positive results for specific anogenital HPV to incidence of anogenital lesions containing that HPV type. RESULTS: People vaccinated against HPV and screened for HPV as a primary test will have lower prevalence and incidence of HPV infection and consequently lower frequency of HPV-related anogenital and oropharyngeal lesions. CONCLUSIONS: Thisstudy will generate scientific evidence on effectiveness of a combined vaccination-screening strategy to reduce the burden of HPV-associated neoplasms.
OBJETIVO: Evaluar la efectividad de una estrategia combinada de vacunación contra el virus de papiloma humano (VPH) y tamizaje de VPH de alto riesgo para reducir neoplasias anogenitales y orofaringeas entre hombres que tienen sexo con hombres, personas con VIH, personas en situación de calle, mujeres transgénero, trabajadoras sexuales y víctimas de violación. MATERIAL Y MÉTODOS: Este estudio evaluará la efectividad de una estrategia combinada de vacunación y tamizaje para reducir la ocurrencia de neoplasias intraepiteliales cervicales grado 2+ o neoplasias intraepiteliales anales grado NIA2+ utilizando Kaplan-Meier. Se evaluará tiempo de resultados positivos para tipos específicos deVPH anogenital a incidencia de lesiones anogenitales con ese tipo de VPH. RESULTADOS: Las personas vacunadas contra VPH y con tamizaje de VPH tendrán menor prevalencia e incidencia de infecciones por VPH y por ende menor frecuencia de lesiones anogenitales y orofaringeas relacionadas con VPH. CONCLUSIONES: Este estudio generará evidencia científica sobre la efectividad de una estrategia combinada de vacunación y tamizaje para reducir la carga de neoplasias asociadas al VPH.
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Neoplasias del Ano/prevención & control , Carcinoma in Situ/prevención & control , Detección Precoz del Cáncer , Programas de Inmunización , Neoplasias de la Boca/prevención & control , Infecciones por Papillomavirus/epidemiología , Neoplasias del Cuello Uterino/prevención & control , Poblaciones Vulnerables , Adulto , Neoplasias del Ano/epidemiología , Neoplasias del Ano/virología , Carcinoma in Situ/epidemiología , Carcinoma in Situ/virología , Comorbilidad , Víctimas de Crimen , Femenino , Infecciones por VIH/epidemiología , Humanos , Masculino , México/epidemiología , Neoplasias de la Boca/virología , Vacunas contra Papillomavirus , Evaluación de Programas y Proyectos de Salud , Riesgo , Conducta Sexual , Minorías Sexuales y de Género , Marginación Social , Población Urbana , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/virología , Vacunación/estadística & datos numéricos , Adulto Joven , Displasia del Cuello del Útero/epidemiología , Displasia del Cuello del Útero/prevención & control , Displasia del Cuello del Útero/virologíaRESUMEN
BACKGROUND: Cervical cancer (CC) and genital warts (GW) are a significant public health issue in Venezuela. Our objective was to assess the cost-effectiveness of the two available vaccines, bivalent and quadrivalent, against Human Papillomavirus (HPV) in Venezuelan girls in order to inform decision-makers. METHODS: A previously published Markov cohort model, informed by the best available evidence, was adapted to the Venezuelan context to evaluate the effects of vaccination on health and healthcare costs from the perspective of the healthcare payer in an 11-year-old girls cohort of 264,489. Costs and quality-adjusted life years (QALYs) were discounted at 5%. Eight scenarios were analyzed to depict the cost-effectiveness under alternative vaccine prices, exchange rates and dosing schemes. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: Compared to screening only, the bivalent and quadrivalent vaccines were cost-saving in all scenarios, avoiding 2,310 and 2,143 deaths, 4,781 and 4,431 CCs up to 18,459 GW for the quadrivalent vaccine and gaining 4,486 and 4,395 discounted QALYs respectively. For both vaccines, the main determinants of variations in the incremental costs-effectiveness ratio after running deterministic and probabilistic sensitivity analyses were transition probabilities, vaccine and cancer-treatment costs and HPV 16 and 18 distribution in CC cases. When comparing vaccines, none of them was consistently more cost-effective than the other. In sensitivity analyses, for these comparisons, the main determinants were GW incidence, the level of cross-protection and, for some scenarios, vaccines costs. CONCLUSIONS: Immunization with the bivalent or quadrivalent HPV vaccines showed to be cost-saving or cost-effective in Venezuela, falling below the threshold of one Gross Domestic Product (GDP) per capita (104,404 VEF) per QALY gained. Deterministic and probabilistic sensitivity analyses confirmed the robustness of these results.
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Condiloma Acuminado/prevención & control , Análisis Costo-Beneficio/estadística & datos numéricos , Costos de la Atención en Salud/estadística & datos numéricos , Cadenas de Markov , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/economía , Neoplasias del Cuello Uterino/prevención & control , Adulto , Niño , Estudios de Cohortes , Condiloma Acuminado/economía , Análisis Costo-Beneficio/economía , Femenino , Humanos , Infecciones por Papillomavirus/economía , Vacunas contra Papillomavirus/administración & dosificación , Años de Vida Ajustados por Calidad de Vida , Neoplasias del Cuello Uterino/economía , VenezuelaRESUMEN
Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) encompassing conditions linked to previous exposure to an adjuvant substance. The clinical picture is very heterogeneous, from mild to severe manifestations, including death. However, the systematic analysis of severe ASIA cases has not been performed. The aim of this study was to systematically review the literature on severe ASIA cases. A systematic review of the literature was performed investigating severe ASIA cases. All publications were identified through PubMed, EMBASE, MEDLINE and Cochrane. Articles published from 2011 to 2016 were included. Severe ASIA was arbitrarily defined as follows: major organ involvement, life-threatening conditions, intensive treatment, disability, hospitalization and outcome (survival and death). Cases described before 2011 were excluded. From 2011 to 2016, we identified 4479 ASIA cases, of them 305 fulfilled arbitrary criteria of severe ASIA including our case presentation and 11 deaths. The majority of severe ASIA cases were related to HPV vaccine, silicone, influenza vaccine and mineral oil injections. The interval from exposition to severe manifestation was from 2 days to 23 years. (1) This is the first study that analyzes all cases published on ASIA with severe manifestations. (2) The current HPV vaccine is both effective and generally safe. However, it should be noted that severe autoimmune side effects have been reported in several studies. Severe ASIA may be observed after influenza vaccines, and other vaccines. (3) Efforts should be made to discover the connection between adjuvants, autoimmunity and autoimmune diseases, because there is an increase in cases severe and life-threatening of ASIA.
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Adyuvantes Farmacéuticos/efectos adversos , Enfermedades Autoinmunes/inducido químicamente , Humanos , SíndromeRESUMEN
UNLABELLED: Aim To estimate relative contribution and time trends of HPV types in cervical cancer in Cali, Colombia over a 50 years' period. METHODS: Paraffin blocks of 736 cervical cancer histological confirmed cases were retrieved from the pathology laboratory at Hospital Universitario del Valle (Cali, Colombia) and HPV genotyped using SPF10-PCR/DEIA/LiPA25 (version 1) assay. Marginal effect of age and year of diagnosis in secular trends of HPV type prevalence among HPV+ cases were assessed by robust Poisson regression analysis. RESULTS: 64.7% (95%CI: 59.9-69.2) of squamous cell carcinomas (SCCs) were attributed to HPV 16 and 18, 78.2% (95%CI: 74-82) to HPV 16, 18, 31, 33 and 45 and 84.8% (95%CI: 81-88.1) to HPV 16, 18, 31, 33, 45, 52 and 58 while ninety-three percent of adenocarcinomas (ADCs) were attributed to HPV 16, 18 and 45 only. The prevalence of specific HPV types did not change over the 50-year period. A significant downward trend of prevalence ratios of HPV16 (âP=0.017) and α7 but HPV 18 (i.e., HPV 39, 45, 68, 70, âP=0.024) with increasing age at diagnosis was observed. In contrast, the prevalence ratio to other HPV genotypes of α9 but HPV 16 genotypes (i.e., HPV 31, 33, 35, 52, 58, 67, âP=0.002) increased with increasing age at diagnosis. CONCLUSION: No changes were observed in the relative contribution of HPV types in cervical cancer in Cali, Colombia during the 50 years. In this population, an HPV vaccine including the HPV 16, 18, 31, 33, 45, 52 and 58 genotypes may have the potential to prevent â¼85% and 93% of SCC and ADC cases respectively.
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Adenocarcinoma/epidemiología , Carcinoma de Células Escamosas/epidemiología , Papillomaviridae/genética , Infecciones por Papillomavirus/epidemiología , Neoplasias del Cuello Uterino/epidemiología , Adenocarcinoma/virología , Adulto , Anciano , Carcinoma de Células Escamosas/virología , Colombia/epidemiología , Femenino , Genotipo , Humanos , Persona de Mediana Edad , Invasividad Neoplásica , Papillomaviridae/clasificación , Infecciones por Papillomavirus/virología , Reacción en Cadena de la Polimerasa , Prevalencia , Factores de Tiempo , Neoplasias del Cuello Uterino/virologíaRESUMEN
OBJECTIVES: To evaluate the impact and cost-effectiveness of introducing universal human papillomavirus (HPV) vaccination into the National Immunization Program (NIP) in Brazil. METHODS: The Excel-based CERVIVAC decision support model was used to compare two strategies: (1) status quo (with current screening program) and (2) vaccination of a cohort of 11-year-old girls. National parameters for the epidemiology and costs of cervical cancer were estimated in depth. The estimates were based on data from the health information systems of the public health system, the PNAD 2008 national household survey, and relevant scientific literature on Brazil. Costs are expressed in 2008 United States dollars (US$), and a 5% discount rate is applied to both future costs and future health benefits. RESULTS: Introducing the HPV vaccine would reduce the burden of disease. The model estimated there would be 229 deaths avoided and 6677 disability-adjusted life years (DALYs) averted in the vaccinated cohort. The incremental cost-effectiveness ratios (ICERs) per DALY averted from the perspectives of the government (US$ 7663), health system (US$ 7412), and society (US$ 7298) would be considered cost-effective, according to the parameters adopted by the World Health Organization. In the sensitivity analysis, the ICERs were most sensitive to variations in discount rate, disease burden, vaccine efficacy, and proportion of cervical cancer caused by types 16 and 18. However, universal HPV vaccination remained a cost-effective strategy in most variations of the key estimates. CONCLUSIONS: Vaccine introduction could contribute additional benefits in controlling cervical cancer, but it requires large investments by the NIP. Among the essential conditions for attaining the expected favorable results are immunization program sustainability, equity in a population perspective, improvement of the screening program, and development of a surveillance system.
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Infecciones por Papillomavirus/economía , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/economía , Vacunas contra Papillomavirus/inmunología , Neoplasias del Cuello Uterino/economía , Neoplasias del Cuello Uterino/prevención & control , Vacunación/economía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Niño , Análisis Costo-Beneficio , Femenino , Política de Salud , Humanos , Programas de Inmunización , Persona de Mediana Edad , Modelos Estadísticos , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Vacunas contra Papillomavirus/administración & dosificación , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/etiología , Vacunación/métodos , Adulto JovenRESUMEN
OBJECTIVE: Among women in Belize, cervical cancer is both the leading cancer and the leading cause of cancer deaths. Both the quadrivalent and bivalent human papillomavirus (HPV) vaccines are licensed in Belize. The Ministry of Health of Belize convened a multidisciplinary team to estimate the costs, health benefits, and cost-effectiveness of adding an HPV vaccine to the national immunization schedule. METHODOLOGY: The CERVIVAC cost-effectiveness model (Version 1.123) was used to assess the lifetime health and economic outcomes of vaccinating one cohort of girls aged 10 years against HPV. The comparator was no HPV vaccination. The PAHO Revolving Fund negotiated price of US$ 13.79 per dose was used (for the quadrivalent vaccine) and national data sources were used to define demography, cervical cancer incidence and mortality, cervical cancer treatment costs, and vaccine delivery costs. Estimates from international agencies were used in scenario analysis. RESULTS: In a cohort of â¼4000 Belizean girls tracked over a lifetime, HPV vaccination is estimated to prevent 69 new cases of cervical cancer (undiscounted), and 51 cervical cancer deaths (undiscounted). Considering the potential cervical cancer treatment costs and lost wages avoided by households (societal perspective), the cost per disability-adjusted life year (DALY) averted was estimated to be US$ 429. This increased to US$ 1320 when cervical cancer treatment costs and lost wages were excluded from the analysis. Both estimates are far below the gross domestic product (GDP) per capita of Belize (US$ 4795). The lifetime health care costs saved by the women and their families represent more than 60% of the investment cost needed by the Government for the vaccine. CONCLUSION: Routine HPV vaccination would be highly cost-effective in Belize. If affordable, efforts should be made to expedite the introduction of this vaccine into the Belizean national immunization program.
Asunto(s)
Vacuna Tetravalente Recombinante contra el Virus del Papiloma Humano Tipos 6, 11 , 16, 18/economía , Vacuna Tetravalente Recombinante contra el Virus del Papiloma Humano Tipos 6, 11 , 16, 18/inmunología , Infecciones por Papillomavirus/economía , Infecciones por Papillomavirus/prevención & control , Neoplasias del Cuello Uterino/economía , Neoplasias del Cuello Uterino/prevención & control , Vacunación/economía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Belice/epidemiología , Niño , Análisis Costo-Beneficio , Femenino , Vacuna Tetravalente Recombinante contra el Virus del Papiloma Humano Tipos 6, 11 , 16, 18/administración & dosificación , Humanos , Persona de Mediana Edad , Modelos Estadísticos , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/etiología , Vacunación/métodos , Adulto JovenRESUMEN
BACKGROUND: Carcinoma of the cervix is ranked second among the top 5 cancers affecting women globally. Parallel to other cancers, it is also a complex disease involving numerous factors such as human papillomavirus (HPV) infection followed by the activity of oncogenes and environmental factors. The incidence rate of the disease remains high in developing countries due to lack of awareness, followed by mass screening programs, various socioeconomic issues, and low usage of preventive vaccines. Over the past 3 decades, extensive research has taken place in cervical malignancy to elucidate the role of host genes in the pathogenesis of the disease, yet it remains one of the most prevalent diseases. It is imperative that recent genome-wide techniques be used to determine whether carcinogenesis of oncogenes is associated with cervical cancer at the molecular level and to translate that knowledge into developing diagnostic and therapeutic tools. OBJECTIVE: The aim of this study was to discuss HPV predominance with their genotype distribution worldwide, and in India, as well as to discuss the newly identified oncogenes related to cervical cancer in current scenario. FINDINGS: Using data from various databases and robust technologies, oncogenes associated with cervical malignancies were identified and are explained in concise manner. CONCLUSION: Due to the advent of recent technologies, new candidate genes are explored and can be used as precise biomarkers for screening and developing drug targets.
Asunto(s)
Adenocarcinoma/virología , Carcinoma de Células Escamosas/virología , Proteínas Oncogénicas Virales/genética , Papillomaviridae/genética , Infecciones por Papillomavirus/virología , Neoplasias del Cuello Uterino/virología , Quinasas de la Proteína-Quinasa Activada por el AMP , Adenocarcinoma/epidemiología , Adenocarcinoma/genética , Adenocarcinoma/prevención & control , Brasil/epidemiología , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/prevención & control , Fosfatidilinositol 3-Quinasa Clase I , Etiopía/epidemiología , Asia Oriental/epidemiología , Femenino , Genotipo , Ghana/epidemiología , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Papillomavirus Humano 31 , Humanos , India/epidemiología , América Latina/epidemiología , México/epidemiología , Mutación , Nigeria/epidemiología , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/genética , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/uso terapéutico , Fosfatidilinositol 3-Quinasas/genética , Prevalencia , Proteínas Serina-Treonina Quinasas/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Arabia Saudita/epidemiología , Sudáfrica/epidemiología , Proteína p53 Supresora de Tumor/genética , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/prevención & controlRESUMEN
Worldwide, cervical cancer is the third most common cancer in women, and the first or second most common in developing countries. Cervical cancer remains in Colombia the first cause of cancer mortality and the second cause of cancer incidence among women, despite the existence of screening programs during the last 3 decades. Bucaramanga, Manizales and Cali reported rates around 20 per 100,000 and Pasto 27 per 100,000. The Cali cancer registry has reported a progressive decrease in the age standardized incidence and mortality rates of cervical cancer over the past 40 years. Reasons for the decline in incidence and mortality of cervical cancer are multiple and probably include: improvement in socio-economic conditions, decrease in parity rates and some effect of screening programs. Human papilloma Virus is the main cause of cervical cancer, HPV natural history studies have now revealed that HPVs are the commonest of the sexually transmitted infec¬tions in most populations. Most HPV exposures result in sponta¬neous clearance without clinical manifestations and only a small fraction of the infected persons, known as chronic or persistent carriers, will retain the virus and progress to precancerous and cancer. HPV 16 and 18 account for 70% of cervical cancer and the 8 most common types. (HPV 16, 18, 45, 33, 31, 52, 58 and 35) account for about 90% of cervical cancer. Case-control studies also allowed the identification of the following cofactors that acting together with HPV increase the risk of progression from HPV persistent infection to cervical cancer: tobacco, high parity, long term use of oral contraceptives and past infections with herpes simplex type 2 and Chlamydia trachomatis. The demonstration that infection with certain types of human papillomavirus (HPV) is not only the main cause but also a necessary cause of cervical cancer has led to great advances in the prevention of this disease on two fronts: (i) Primary prevention by the use of prophylactic HPV vaccines; and (ii) secondary prevention by increasing the accuracy of cervical cancer screening.
El cáncer de cérvix uterino es la tercera causa más frecuente de cáncer en el mundo y la primera o segunda más común en países en desarrollo. El cáncer de cérvix persiste en Colombia como la primera causa de mortalidad por cáncer en las mujeres, a pesar de la existencia de programa de tamización durante las últimas tres décadas. Bucaramanga, Manizales y Cali reportan tasas de incidencia alrededor de 20 por 100.000 y Pasto, 27 por 100.000. El Registro poblacional de cáncer de Cali ha reportado un descenso progresivo en las tasas de incidencia y mortalidad por cáncer de cérvix durante los últimos 40 años. Las razones para la declinación de las tasas de incidencia y mortalidad por cáncer de cérvix son múltiples y probablemente incluyen: mejoría en las condiciones socio-económicas, descenso en las tasas de fecundidad y algún efecto de los programas de tamización. El virus del papiloma humano (VPH) es la principal causa de cáncer de cuello uterino. Los estudios de la historia natural del VPH han revelado que el VPH es la infección de transmisión sexual más común en la mayoría de las poblaciones. La exposición a VPH resulta en una resolución espontánea sin manifestaciones clínicas y únicamente una pequeña fracción de las personas infectadas, conocida como portadores crónicos, retendrá el virus y progresará a lesiones precursoras y cáncer. Los genotipos de VPH 16 y 18 son responsables del 70% del cáncer de cérvix y los 8 tipos más comunes (VPH 16, 18, 45, 33, 31, 52, 58 and 35), se asocian con cerca del 90% de todos los casos de cáncer cervical. Los estudios de casos y controles también han permitido identificar los siguientes cofactores que actúan junto con la infección con VPH para aumentar el riesgo de cáncer de cérvix: tabaco, multiparidad, uso prolongado de contraceptivos orales y antecedentes de infecciones por virus del herpex simple tipo 2 y Clamidia trachomatis. La demostración de que la infección por ciertos tipos de virus del papiloma humano (VPH) no sólo es la causa principal, sino, también, una causa necesaria del cáncer cervical, ha conducido a grandes avances en la prevención de esta enfermedad en dos frentes: (i) La prevención primaria mediante el uso de vacunas profilácticas contra el VPH, y (ii) La prevención secundaria mediante el aumento de la precisión de la detección del cáncer de cuello uterino.
RESUMEN
Worldwide, cervical cancer is the third most common cancer in women, and the first or second most common in developing countries. Cervical cancer remains in Colombia the first cause of cancer mortality and the second cause of cancer incidence among women, despite the existence of screening programs during the last 3 decades. Bucaramanga, Manizales and Cali reported rates around 20 per 100,000and Pasto 27 per 100,000. The Cali cancer registry has reported a progressive decrease in the age standardized incidence and mortality rates of cervical cancer over the past 40 years. Reasons for the decline in incidence and mortality of cervical cancer are multiple and probably include: improvement in socio-economic conditions, decrease in parity rates and some effect of screening programs. Human papilloma Virus is the main cause of cervical cancer, HPV natural history studies have now revealed that HPVs are the commonest of the sexually transmitted infections in most populations. Most HPV exposures result in spontaneous clearance without clinical manifestations and only a small fraction of the infected persons, known as chronic or persistent carriers, will retain the virus and progress to precancerous and cancer. HPV 16 and 18 account for 70% of cervical cancer and the 8 most common types. (HPV 16, 18, 45, 33, 31, 52, 58 and 35) account for about 90% of cervical cancer. Case-control studies also allowed the identification of the following cofactors that acting together with HPV increase the risk of progression from HPV persistent infection to cervical cancer: tobacco, high parity, long term use of oral contraceptives and past infections with herpes simplex type 2 and Chlamydia trachomatis. The demonstration that infection with certain types of human papillomavirus (HPV) is not only the main cause but also a necessary cause of cervical cancer has led to great advances in the prevention of this disease on two fronts: (i) Primary prevention by the use of prophylactic HPV vaccines; and (ii) secondary prevention by increasing the accuracy of cervical cancer screening.
El cáncer de cérvix uterino es la tercera causa más frecuente de cáncer en el mundo y la primera o segunda más común en países en desarrollo. El cáncer de cérvix persiste en Colombia como la primera causa de mortalidad por cáncer en las mujeres, a pesar de la existencia de programa de tamización durante las últimas tres décadas. Bucaramanga, Manizales y Cali reportan tasas de incidencia alrededor de 20 por 100,000 y Pasto, 27 por 100,000. El Registro poblacional de cáncer de Cali ha reportado un descenso progresivo en las tasas de incidencia y mortalidad por cáncer de cérvix durante los últimos 40 años. Las razones para la declinación de las tasas de incidencia y mortalidad por cáncer de cérvix son múltiples y probablemente incluyen: mejoría en las condiciones socio-económicas, descenso en las tasas de fecundidad y algún efecto de los programas de tamización. El virus del papiloma humano (VPH) es la principal causa de cáncer de cuello uterino. Los estudios de la historia natural del VPH han revelado que el VPH es la infección de transmisión sexual más común en la mayoría de las poblaciones. La exposición a VPH resulta en una resolución espontánea sin manifestaciones clínicas y únicamente una pequeña fracción de las personas infectadas, conocida como portadores crónicos, retendrá el virus y progresará a lesiones precursoras y cáncer. Los genotipos de VPH 16 y 18 son responsables del 70% del cáncer de cérvix y los 8 tipos más comunes (VPH 16, 18, 45, 33, 31, 52, 58 and 35), se asocian con cerca del 90% de todos los casos de cáncer cervical. Los estudios de casos y controles también han permitido identificar los siguientes cofactores que actúan junto con la infección con VPH para aumentar el riesgo de cáncer de cérvix: tabaco, multiparidad, uso prolongado de contraceptivos orales y antecedentes de infecciones por virus del herpex simple tipo 2 y Clamidya trachomatis. La demostración de que la infección por ciertos tipos de virus del papiloma humano (VPH) no sólo es la causa principal, sino, también, una causa necesaria del cáncer cervical, ha conducido a grandes avances en la prevención de esta enfermedad en dos frentes: (i) La prevención primaria mediante el uso de vacunas profilácticas contra el VPH, y (ii) La prevención secundaria mediante el aumento de la precisión de la detección del cáncer de cuello uterino.