Evaluación clínica y análisis económico de las tecnologías para el tamizaje de las lesiones precursoras del cáncer del cuello uterino / Clinical evaluation and economic analysis of technologies for screening cervical cancer precursor lesions

CONTEXTO: A nivel mundial, el cáncer del cuello uterino (CCU) ocupa el 4to lugar entre las neoplasias más frecuentes en las mujeres, con una incidencia estimada de 604,127 casos nuevos y 341,831 muertes en 2020; aproximadamente el 90% de los nuevos casos y muertes tuvieron lugar en países de ingresos medios y bajos. En México, se estima que cada año se diagnostican 9439 nuevos casos de CCU siendo la segunda causa de cáncer en mujeres de forma general y el tercer cáncer más común en mujeres de 15 a 44 años. El CCU es un problema global de salud pública, con una carga particularmente alta en muchos países de medios y bajos ingresos. La eficacia comprobada de las medidas de intervención, como la vacunación contra los tipos más oncogénicos del VPH, hacen que éste tipo de cáncer sea una enfermedad prevenible en gran medida. Se ha observado una reducción de la incidencia y mortalidad del CCU predominantemente en países con un índice de Desarrollo Humano Alto, donde los servicios de detección de alta calidad, tratamiento oportuno y atención de seguimiento están disponibles de forma rutinaria. Más del 85% de las afectadas son generalmente mujeres jóvenes, con un nivel educativo bajo que viven en los países más pobres del mundo. Muchas son también madres de niños pequeños cuya supervivencia se ve afectada posteriormente por la muerte prematura de sus madres. Por lo tanto, el CCU representa una enorme carga de salud para las mujeres, sus familias y las comunidades. Dado que la enfermedad afecta principalmente a las mujeres en sus mejores años de edad adulta, la enfermedad y la muerte por éste tipo de cáncer ejerce una presión emocional y financiera sobre las familias, las comunidades y los sistemas de salud. A pesar de ser una enfermedad prevenible y curable si se detecta a tiempo y se trata oportunamente, sigue siendo uno de los cánceres más comunes y causa de muerte en las mujeres de todo el mundo. La mayoría de las lesiones precancerosas (99.8%) y CCU se atribuyen al virus del papiloma humano (VPH). Esta infección es muy común porque se transmite fácilmente a través del contacto sexual y la mayoría de las personas la adquieren poco después de iniciar su actividad sexual. En lo general, más del 90% de las infecciones por el VPH se eliminan por el sistema inmunitario. EVALUACIÓN CLÍNICA: La prueba de tamizaje más eficaz para NIC2+ es la detección del VPH, con una sensibilidad de 89.9% a 94%, comparada con la citología agrupada (incluye CC y CBL), CC, CBL y la inspección visual con ácido acético (IVAA) que tienen sensibilidades más bajas (70% a 72.9%, 62.5%, 72.9% y 69%, respectivamente). Además, es importante considerar que la prueba de detección del VPH es objetiva mientras que las otras son operador-dependientes y subjetivas (Koliopoulos 2017) (Mustafa 2016). Respecto de la especificidad agrupada de las pruebas de tamizaje para NIC2+, la detección del VPH es la menos específica (89.9% a 90%) comparada con la citología agrupada (90.3% a 95%), CC (96.6%), CBL (90.3%). De igual manera, al compararse con la IVAA es menos específica (84% vs. 87%) (Koliopoulos 2017) (Mustafa 2016). En general, las pruebas de tamizaje para la detección de lesiones precancerosas del cuello uterino son seguras (Melnikow 2018). EVALUACIÓN ECONÓMICA: A nivel internacional en países de altos y medianos ingresos la prueba de ADN del VPH es la opción más costo ­ efectiva, pero en países con recursos limitados la prueba de IVAA es la mejor alternativa. Por otro lado, la citología posee una limitada costo ­ efectividad ocasionada en parte por la necesidad de infraestructura y recursos humanos capacitados. Por lo anterior, en México se sugiere utilizar la prueba de ADN. En el caso de la citología, se deben considerar las implicaciones organizacionales y de costos asociadas a su sustitución como tamizaje primario. Un Análisis de Impacto Presupuestal (AIP) a 5 años, encontró que al utilizar la prueba del VPH (PCR para identificación de ADN viral) en mujeres de 25 a 64 años, alcanzando la cobertura del 70% en el último año del análisis, se requieren $520 Millones de Pesos (MDP) en promedio anual, lo que se traduce en la necesidad de incrementar los recursos asignados a tamizaje del VPH en un 51.7% en promedio anual. En un escenario donde el costo de la prueba se reduzca en 20% o 30% (lo cual es probable) el gasto adicional sería de $354 MDP y de $271 MDP respectivamente, ambos en promedio anual; lo que equivale al 40.8% y 33.9% en promedio anual de recursos adicionales (comparados con los recursos actuales destinados al tamizaje del CCU) para llevar a cabo la prueba del VPH. MÉTODOS: Para identificar la evidencia de la precisión y seguridad de las pruebas de tamizaje para la detección del CCU, se buscaron revisiones sistemáticas existentes relevantes y de alta calidad. Se realizó una búsqueda de estudios en las bases de datos de Medline (PubMed) y Cochrane Library incluyendo tanto términos controlados MeSH como términos libres. Se limitó a documentos publicados desde el 1 de enero de 2016 a mayo del 2023 y en idioma inglés o español. La selección de estudios y extracción de los datos fueron realizados por un revisor y verificados por otro. Los datos se resumieron y clasificaron en función de los resultados. La revisión sistemática de la evidencia económica se concentró en evaluaciones completas, publicadas a febrero de 2023, las cuales abordan tanto los costos como los beneficios en salud12 asociados al uso de pruebas de ADN del VPH comparado con IVAA, citología convencional y en base líquida en mujeres de los 25 a los 69 años de edad, obtenidas de las bases de datos Pubmed, Value in Health y University of York Centre of Reviews and Dissemination. RESULTADOS: Los resultados del AIP mostraron que el escenario actual del tamizaje del CCU tiene un costo de $1,006 MDP mientras que en el escenario futuro el costo es de $1,527 MDP, ambos en promedio anual; lo que implicaría un gasto adicional de $520 MDP y en términos porcentuales representaría la necesidad de un incremento del 51.7% (ambos montos en promedio anual) en los recursos asignados para el tamizaje del VPH. El análisis de sensibilidad encontró que al reducir el costo en un 20% de la prueba el gasto adicional se reduciría a los $354 MDP (lo que representaría la necesidad de un incremento del 40.8% en los recursos asignados al tamizaje del VPH) en promedio anual. En el mismo sentido, si el costo se redujera en un 30%, el gasto adicional sería de $271 MDP lo que en términos porcentuales representaría la necesidad de un incremento del 33.9% en los recursos asignados al tamizaje del VPH. CONCLUSIONES: La evidencia clínica analizada, de moderada calidad, mostró que la detección del VPH es la prueba más sensible, aunque menos específica, que otras pruebas de tamizaje para la identificación de lesiones precancerosas del cuello uterino como la citología cervical y la IVAA, con un perfil de seguridad adecuado. Tomando en consideración los resultados obtenidos en el presente trabajo, así como las recomendaciones emitidas por la Organización Mundial de la Salud (OMS), 26 es de suma importancia adoptar medidas de salud pública necesarias que permitan la implementación de la detección del VPH como la prueba estándar de tamizaje de lesiones precancerosas del cuello uterino en lugar de la citología cervical o la IVAA ya que tiene una alta sensibilidad y es objetiva, lo cual podría coadyuvar en el cumplimiento de las metas de la Estrategia Mundial para Acelerar la Eliminación del Cáncer del Cuello Uterino como Problema de Salud Pública en nuestro país, específicamente para que el 70% de las mujeres mexicanas sean examinadas mediante una prueba de alta precisión antes de los 35 años. Dos revisiones sistemáticas de evaluaciones económicas concluyeron que la prueba de ADN o la IVAA serían alternativas costo ­ efectivas en comparación con la citología. Cuál de las dos primeras es la mejor opción, depende del costo de la prueba de ADN, el rendimiento de la prueba de IVAA o la cantidad de recursos financieros disponibles. En este sentido, una revisión que incluyó en su mayoría evaluaciones de países de altos y medianos ingresos concluyó que la prueba de ADN es la opción más costo efectiva.

Uso de la auto-toma para determinación del Virus del Papiloma Humano en el programa de cribado de cáncer de cérvix / Use of self-sampling for the detection of human papillomavirus in cervical cancer screening

INTRODUCCIÓN: El cáncer de cuello uterino o cérvix es el cuarto tumor más común entre las mujeres en todo el mundo. En las últimas décadas, la mortalidad debida al cáncer de cérvix ha ido disminuyendo progresivamente, en parte debido a la implementación generalizada de programas de cribado poblacional. La prueba habitual para la realización del cribado ha sido durante años la toma de citología cervical (Papanicolaou) por un profesional sanitario. Sin embargo, este método presenta algunas limitaciones potenciales. La infección persistente con tipos oncogénicos de alto riesgo del virus del papiloma humano (VPH) es un requisito previo para el desarrollo de cáncer de cuello uterino. Se han desarrollado pruebas de detección de ADN de VPH de alto riesgo de causar el desarrollo de cáncer de cérvix como una estrategia para superar las limitaciones potenciales de la citología cervical. Con el fin de mejorar la participación en el cribado se han desarrollado recientemente dispositivos de auto-toma para la detección de ADN de VPH de alto riesgo, con los que las mujeres pueden recolectar células cervicales por sí mismas. OBJETIVOS: Comparar la exactitud diagnóstica de los métodos de la auto-toma de VPH de alto riesgo en comparación con la obtenida de las muestras tomadas por el profesional de salud para detectar lesiones neoplásicas intraepiteliales de cérvix NIC2+/NIC3+. Analizar la eficiencia de la auto-toma como estrategia primaria de cribado de cáncer de cérvix en comparación a otros métodos de cribado existentes. Describir las preferencias de las mujeres en relación con el uso de auto-toma de VPH como método de cribado. METODOLOGÍA: Se desarrollaron revisiones sistemáticas (RS), siguiendo, como guía, el Manual C ochrane para RS de Intervenciones (Cochrane Handbook for Systematic Reviews of Interventions). RESULTADOS: La detección de VPH mediante auto-toma usando pruebas de amplificación de señal es probablemente menos sensible, y podría ser menos especifica que la toma por personal sanitario para lesiones NIC2+. Para lesiones NIC3+, la auto-toma podría ser menos sensible, pero podría haber poca o ninguna diferencia en la especificidad en comparación a la toma por personal sanitario. La detección de VPH mediante auto-toma usando pruebas de PCR presenta poca o ninguna diferencia en sensibilidad, así como podría haber poca o ninguna diferencia en especificidad para detectar lesiones NIC2+ y NIC3+ en comparación con la toma de muestras por personal sanitario. La estrategia de cribado mediante la auto-toma es probablemente más eficiente en comparación con un programa de cribado basado en la detección de ADN de VPH de alto riesgo a partir de muestras tomadas por un profesional de la salud, independientemente de si se acompaña o no de un cribado por citología previo, o del nivel de cobertura vacunal para VPH. Los potenciales beneficios en el cambio a un programa de detección de VPH con auto-toma se basan en el supuesto de que se produzca un incremento en la participación de al menos 6% y que la sensibilidad no sea inferior al 5% en relación con la toma de muestra por el profesional de salud. Esto implica que el tipo de método de análisis recomendado sería el de PCR y que se deberían implementar medidas que favorezcan una mayor participación en los programas de cribado. La mayoría de las mujeres consideran aceptable el uso de auto-toma como método de obtención de muestra vaginal para la detección de ADN de VPH y que la auto-toma es fácil de realizar. La mayoría de las mujeres preferirían el uso de auto-toma en lugar de la toma por un profesional de salud. CONCLUSIONES: La detección de VPH mediante auto-toma usando pruebas de PCR presenta poca o ninguna diferencia en sensibilidad y en especificidad para detectar lesiones NIC2+ y NIC3+ en comparación con la toma de muestras por personal sanitario. La estrategia de cribado mediante la auto-toma es probablemente más eficiente en comparación con un programa de cribado basado en la detección de ADN de VPH de alto riesgo a partir de muestras tomadas por un profesional de la salud, siempre que el tipo de método de análisis recomendado sea el de PCR y se implementen medidas que favorezcan una mayor participación en los programas de cribado. La mayoría de las mujeres consideran aceptable el uso de auto-toma como método de obtención de muestra vaginal para la detección de ADN de VPH y que la auto-toma resulta fácil de realizar. La mayoría de las mujeres preferirían el uso de auto-toma en lugar de la toma por un profesional de salud.

INTRODUCTION: Cervical cancer is the fourth most common type of cancer among women worldwide. In recent decades, mortality due to cervical cancer has progressively decreased, in part due to widespread population screening programs. For many years, the most common type of test for screening purposes was cervical cytological (Papanicolaou) smear testing performed by a clinician. Nonetheless, this method has some potential limitations. Persistent infection with high-risk cancer-causing strains of human papillomavirus (HPV) is considered necessary for the development of cervical cancer. In this context, tests have been developed to identify DNA from HPV strains associated with a high risk of developing cervical cancer to overcome the potential limitations of cervical cytological sampling. Recently, seeking to increase screening participation rates, self-sampling kits have been developed for the detection of DNA from high-risk HPV strains, these enabling women to take their own samples of cervicovaginal cells. OBJECTIVES: To compare the diagnostic accuracy of self-sampling compared to that of clinician-collected samples for the detection of high-risk HPV strains for identifying grade 2 or 3 cervical intraepithelial neoplasia (CIN 2 or 3 respectively). To assess the performance of self-sampling compared to that of other existing screening methods as a primary strategy for cervical cancer screening. To describe the preferences of women regarding the use of HPV self-sampling as a screening method. METHODOLOGY: Systemic reviews were conducted, following the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: The detection of HPV by self-sampling using signal amplification methods is likely to be less sensitive and may be less specific than clinician sampling for CIN 2. In the case of CIN 3, self-sampling may be less sensitive but there may be little or no difference in terms of specificity compared to clinician sampling. On the other hand, the detection of HPV by self-sampling using polymerase chain reaction (PCR) methods shows little or no difference in terms of sensitivity, and similarly, there may be little or no difference in terms of specificity, for identifying CIN 2 or 3 lesions, compared to clinician sampling. The strategy of screening by self-sampling is probably more efficient than a screening program based on clinician-collected samples for the detection of DNA from high-risk HPV strains, regardless of whether there is a prior cytology-based screening and HPV vaccine coverage. The potential benefits of moving towards an HPV detection program using self-sampling rely on the expectation that participation rates will increase by at least 6% and that the sensitivity will not be more than 5% lower than that observed with clinician-collected samples. It also implies that the recommended type of analysis is PCR and that measures should be taken to encourage participation in screening programs. The majority of women consider the use of self-sampling as a method for obtaining a cervicovaginal sample for detecting HPV DNA to be acceptable and that self-sampling is easy to perform. Further, the majority of women would prefer this sampling method to the collection of samples by a clinician. CONCLUSIONS: HPV self-sampling for detecting HPV using PCR has few or no differences compared to clinician sampling in terms of sensitivity and specificity for CIN 2 and CIN 3. Self-sampling-based screening is probably more efficient than clinician-sampling-based screening programs for detecting DNA from high-risk HPV strains, provided that PCR is used for the analysis and measures are put in place to encourage greater participation in screening programs. Most women consider cervicovaginal self-sampling for detecting DNA from HPV acceptable and that the procedure is easy. Moreover, most would prefer self-sampling to clinician sampling.

Efectividad clínica y seguridad del cribado neonatal de la atrofia muscular espinal / Clinical effectiveness and safety of newborn screening for spinal muscular atrophy

INTRODUCCIÓN: La atrofia muscular espinal (AME) es una enfermedad neuromuscular hereditaria caracterizada por una degeneración progresiva de las neuronas motoras medulares que conducen a debilidad proximal muscular simétrica y atrofia de los grupos musculares. Aunque es una enfermedad rara, representa la causa genética más frecuente de mortalidad infantil. La reciente autorización de 3 nuevos fármacos modificadores de la enfermedad ha supuesto que la AME, en alguna de sus formas clínicas, deje de considerarse una enfermedad intratable. Como consecuencia, la Dirección General de Salud Pública del Ministerio de Sanidad solicita a la Red Española de Agencias de Evaluación de Tecnologías Sanitarias y Prestaciones del Sistema Nacional de Salud un informe sobre el estado de situación en cuanto a la evidencia sobre la inclusión de la AME dentro de un programa de cribado neonatal. OBJETIVO: Valorar la seguridad y la efectividad clínica del programa de cribado neonatal de AME. MÉTODO: Se realizó una revisión sistemática de la literatura en las siguientes bases de datos referenciales hasta junio de 2022: Medline, EMBASE, Web of Science, Cochrane Library. También se buscó en la base de datos del Centre for Reviews and Dissemination (CRD), en el Nacional Institute for Health and Care Excellence (NICE), en la plataforma de la Red Española de Agencias de Evaluación de Tecnologías Sanitarias y Prestaciones del Sistema Nacional de Salud (RedETS), European Medicines Agency (EMA), Agencia Española del Medicamento y Productos Sanitarios (AEMPS), Canadian Agency for Drugs and Technologies (CADTH), así como una revisión secundaria a partir de las referencias bibliográficas de los artículos recuperados. Se realizó selección, extracción de datos y evaluación del riesgo de sesgo de los estudios incluidos. La información se sintetizó de forma cualitativa. RESULTADOS: Se incluyeron 9 estudios que describieron experiencias de cribado realizadas en varios países. Los datos sobre los programas de cribado se basaron en estudios descriptivos sin grupo control, con un número reducidos de casos diagnosticados. No obstante, estos estudios mostraron que los niños con 2-3 copias del gen SMN2 cribados y tratados antes del inicio de los síntomas continuaron asintomáticos durante el seguimiento. Los fallecimientos se produjeron en niños no tratados con 2 copias SMN2. CONCLUSIONES: Los datos recuperados sugieren disminución de la mortalidad y mejoras en la evolución clínica entre los niños con 2 copias del gen SMN2 cribados y tratados con fármacos modificadores de la enfermedad (nivel de evidencia bajo).

INTRODUCTION: Spinal muscular atrophy (SMA) is an inherited neuromuscular disease characterized by progressive degeneration of spinal motor neurons leading to symmetric proximal muscle weakness and atrophy of muscle groups. Although it is a rare disease, it represents the most frequent genetic cause of infant mortality. The recent authorization of 3 new disease-modifying drugs has meant that SMA, in some of its clinical forms, is no longer considered an intractable disease. As a consequence, the Dirección General de Salud Pública of Ministry of Health requests the Spanish Network of Health Technology Assessment Agencies and Health Services Provision for a report on the status of the evidence regarding the inclusion of SMA within a neonatal screening program. OBJECTIVE: To assess the safety and clinical effectiveness of the SMA neonatal screening program. METHODS: A systematic literature review was conducted in the following reference databases up to June 2022: Medline, EMBASE, Web of Science, Cochrane Library. Additionally, searches were performed in the Centre for Reviews and Dissemination (CRD) database, the National Institute for Health and Care Excellence (NICE), the platform of the Spanish Network of Health Technology Assessment Agencies and Health Services Provision (RedETS), European Medicines Agency (EMA), Spanish Agency of Medicines and Medical Devices (AEMPS), Canadian Agency for Drugs and Technologies (CADTH), as well as a secondary review based on the bibliographic references of the retrieved articles. Selection, data extraction, and assessment of the risk of bias of the included studies were performed. The information was synthesized qualitatively. RESULTS: Nine studies describing screening experiences conducted in various countries were included. The data on screening programs were based on descriptive studies without a control group, with a small number of diagnosed cases. However, these studies showed that children with 2-3 copies of the SMN2 gene who were screened and treated before the onset of symptoms remained asymptomatic during follow-up. Deaths occurred in untreated children with 2 copies of SMN2. CONCLUSION: The localized evidence suggests a decrease in mortality and improvements in clinical outcomes among children with 2 copies of the SMN2 gene who were screened and treated with disease-modifying drugs (low level of evidence).

Análisis de la efectividad clínica y coste-efectividad de la ampliación a 74 años del cribado del cáncer colorrectal en la población general / Clinical effectiveness and cost-effectiveness of the extension of colorectal cancer screening up to 74 years of age in general population

INTRODUCCIÓN: El cáncer colorrectal (CCR) es uno de los tipos de cáncer más comunes en todo el mundo y representa una de las principales causas de mortalidad relacionada con el cáncer. El CCR se origina en el colon o en el recto y suele desarrollarse a partir de pólipos que crecen en la pared intestinal. Estos pólipos pueden progresar a lesiones premalignas y malignas (CCR) que pueden propagarse a otras partes del cuerpo. La detección temprana del CCR mediante el cribado poblacional puede mejorar significativamente las tasas de supervivencia y reducir el coste del tratamiento. El cribado poblacional del CCR ha demostrado ser una herramienta efectiva para detectar esta enfermedad en una etapa temprana, aumentando las posibilidades de curación y mejorando el pronóstico de estas personas. Los métodos más utilizados en el cribado poblacional de CCR son la prueba de sangre oculta en heces (SOH), la sigmoidoscopia y la colonoscopia. En España, el programa de cribado de CCR se incorporó a la cartera común de servicios del Sistema Nacional de Salud (

INTRODUCTION: Colorectal cancer (CRC) is one of the most common types of cancer worldwide and represents a leading cause of cancer-related mortality. CRC originates in the colon or rectum and usually develops from polyps that grow in the intestinal wall. These polyps can progress to premalignant and malignant lesions (CRC) that can spread to other parts of the body. Early detection of CRC through population screening can significantly improve survival rates and reduce the cost of treatment. Population screening for CRC has proven to be an effective tool to detect this disease at an early stage, increasing the chances of cure and improving the prognosis of these people. There are several methods to perform screening for CRC in general population. The faecal occult blood test (FOBT), sigmoidoscopy and colonoscopy are currently the most used in population screening. In Spain, the CRC screening program was incorporated into the common portfolio of services of the National Health System (NHS) in 2014. The program offers the general population between 50 and 69 years of age a free FOBT test every two years. AIMS: To assess the effectiveness, safety and cost-effectiveness, ethical, patient, social, legal, organizational and environmental considerations, as well as to describe the research needs of expanding population-based CRC screening up to 74 years of age. METHODOLOGY: A systematic review (SR) was carried out of: 1) SR that evaluated the effectiveness/safety and/or diagnostic performance of population screening for CRC using FOBT tests (guaiac and immunological) as the first screening test followed by colonoscopy, as well as possible differences according to age groups and 2) economic evaluations that evaluated the cost-effectiveness of this screening strategy for the groups of interest. A search strategy was developed around the terms colorectal neoplasms, mass screening, and faecal occult blood in the electronic databases: MEDLINE, EMBASE, CINAHL, in several databases of IberoAmerican publications (IBECS, BRISA, LILACS, WPRIM, ARGMSAL, BINACIS, LIPECS), and in The Cost-Effectiveness Analysis (CEA) Registry in April 2023. The assessment of the methodological quality of the effectiveness and safety SRs was evaluated by two independent reviewers with the AMSTAR-2 scale and the economic evaluations were evaluated following the criteria of Drummond et al. The data extracted were those related to the identification of the study (authors, publication date, country where the study was carried out, funding, etc.), the design and methodology and the results of the study (CRC incidence, mortality, sensitivity and specificity, costs, effectiveness results and incremental cost-effectiveness ratio (ICER)). These data were collected in electronic sheets in Excel format (Microsoft) designed ad hoc. Only numerical results were extracted from the comparisons of interest: screening in the population aged 50-75 versus not screening and screening in the population aged 50-70 versus 50-75. A complete de novo economic evaluation was conducted out in which the costs and health outcomes of extending population-based CRC screening to age 74 were assessed from the perspective of the NHS. The analysis was based on a decision model that synthesizes the information obtained in the literature on the incidence of the disease, the effectiveness of screening, as well as the consequences of CRC (in terms of both costs and QALYs). In order to do this, a mathematical model was built that combines a decision tree and a Markov model with annual cycles. The time horizon was patient lifetime and a discount of a 3% was applied to both costs and effects. In addition, probabilistic and deterministic sensitivity analysis were carried out. Finally, a 5-year budget impact analysis (from 2023 to 2027) was performed to inform about the cost of extending current population screening for CRC in Spain to age 74. A scoping review was carried out through a series of manual searches in Google, Google Scholar and Pubmed using different combinations of keywords and their derivations using the search terms specific to the aspects evaluated in that section: ethics, acceptability, patient issues, organization, barriers, facilitators, implementation, equity, ageism, qualitative, interview. In addition, a patient association was contacted to find out their perspective. RESULTS: There is high-quality evidence, based on several population-based randomized trials with variable completion age, that the use of guaiac reduction-based FOBT screening (gFOBT) reduces CRC mortality (RR = 0.88, 95%CI: 0.82-0.93; k = 8; n = 598 933), but not its incidence or mortality from any cause. One trial showed that biennial gFOBT does not reduce mortality in patients between 70-80 years old, and in those aged 60-69 years it only did so in men (RR = 0.42, 95%CI: 0.27-0.66). There is low-quality evidence that screening with the immunological detection test for FOBT (iFOBT) up to age 69 reduces CRC mortality (RR = 0.90, 95%CI: 0.84, 0.95; an observational study). There is good quality evidence that iFOBT shows a sensitivity greater than 70% in the detection of CRC. There is no evidence of differences in effectiveness according to age. In terms of diagnostic performance, one study observed a worse sensitivity and specificity of the program in the range of 70-75 years, compared to 50-59 and 60-69. Given the non-invasive nature of faecal tests, the adverse effects of screening program refer to the possible complications of colonoscopy. There is evidence of a good safety profile of colonoscopy after a positive results of FOBT, with bleeding rates of 17.5 (95%CI: 7.6, 27.5) per 10,000 procedures, and perforation rates of 5.7 (95%CI 2.8, 8.7) per 10,000 procedures. Four systematic reviews of economic evaluations and 11 costeffectiveness references (corresponding to 10 studies) were included. No SRs were identified that exactly addressed the research question of this report. The included SRs concluded that all or almost all CRC screening strategies are cost-effective compared to no screening. All costeffectiveness studies, regardless of the test used for the FOBT analysis, concluded that biennial screening in the age group 50 to 74 (or 75) is costeffective compared to no screening. All ICERs, after being transformed into 2023 Spanish euros, were less than €20,000/QALY or €/LY. The results of the de novo economic evaluation model carried out show that the extension of CRC screening up to 74 years of age is a dominant alternative (less expensive and more effective) compared to current screening up to 69 years of age. The results of the sensitivity analysis indicate that these results are robust. The budget impact analysis indicates that the expansion of CRC population screening could mean an expense for the NHS that could reach € 10,918,777 in the fifth year of its expansion throughout the national territory, assuming 100% coverage and a rate participation of 36.26%. A manual scoping search was carried out in May 2023 and was expanded in November 2023. In this search of electronic databases and websites, 21 potentially relevant articles and a conference abstract were identified to be analysed in detail in full text. All of them were excluded due to the objective of this section. Only one ethical aspect was identified related to territorial inequality due to the different degrees of implementation and age coverage of the CRC screening program. This territorial inequality could decrease with the extension of the age to 74 years. CONCLUSIONS: Based on the evidence synthesized in the identified SRs and the primary studies included in them, as well as in the economic evaluations included in this report, it is not possible to answer the research question about the convenience of extending CRC screening from 69 to 74 years. There is high-quality evidence that gFOBT reduces CRC mortality in screening with variable completion age. Regarding differences by age, a population trial initiated in the 1980s in the United States did not obtain a significant effect from biennial screening in people between 70 and 80 years of age. In the case of iFOBT, the direct evidence is low quality, indicating a significant reduction in CRC mortality in patients up to 69 years of age with a mean follow-up of three years. There is no evidence of differential effectiveness according to age, and only one study reported differences in diagnostic performance, with worse sensitivity and specificity in the range of 70-75 years. The de novo cost-effectiveness analysis carried out in this report with data from Spain concludes that the extension of CRC population screening to 74 years of age is a dominant alternative from the NHS perspective (that is, less expensive and more effective alternative). The budget impact analysis estimates that the extension of CRC population screening up to 74 years of age could mean an additional expense of between €10,208,165 and €10,918,777 in the first and fifth year of its extension respectively. This analysis assumed 100% coverage and a participation rate of 36.26%.

Evaluación del programa de cribado de cáncer de pulmón / Evaluation of the lung cancer screening program

Introducción. El cáncer de pulmón (CP) es un crecimiento maligno de las células del pulmón o del sistema bronquial. Alrededor del 80% de los tumores pulmonares pueden clasificarse como carcinomas de células no pequeñas (CPCNP) y el 15% como carcinomas de células pequeñas o microcíticos (CPCP) que se caracterizan por su alta agresividad y crecimiento rápido. Los síntomas del CP son inespecíficos y suelen aparecer cuando la enfermedad ya se ha diseminado, lo que dificulta su diagnóstico precoz. En términos de mortalidad, es la primera causa de muerte por cáncer en España, responsable en 2020 de más de 21 900 fallecimientos (19.4% de la mortalidad total por cáncer). La adicción al tabaco, es con diferencia, la causa evitable más importante del CP, responsable del 90% de los casos en hombres y del 80% en mujeres, y el tabaquismo pasivo o exposición al humo del tabaco en personas no fumadoras aumenta el riesgo en un 20-30% comparado con los no fumadores no expuestos al humo pasivo. Otros factores de riesgo que aumentan el riesgo de desarrollar CP son la exposición ambiental o laboral a carcinógenos (como el radón o el asbesto), la presencia de enfermedad pulmonar (como la EPOC (Enfermedad Pulmonar obstructiva crónica) o la fibrosis pulmonar idiopática) o los antecedentes familiares de CP. Disponer de una prueba de cribado que detecte la enfermedad en una fase temprana ayudaría a m

Introduction Lung cancer (LC) is a malignant growth of cells in the lung or bronchial system. About 80% of lung tumours can be classified as non-small cell carcinomas (NSCLC) and 15% as small cell or microcytic carcinomas (SCMC) which are characterised by high aggressiveness and rapid growth. The symptoms of LC are non-specific and usually appear when the disease has already spread, which makes early diagnosis difficult. In terms of mortality, it is the leading cause of cancer death in Spain, responsible for more than 21 900 deaths in 2020 (19.4% of total cancer mortality). Tobacco addiction is by far the most important preventable cause of LC, responsible for 90% of cases in men and 80% in women, and passive smoking or exposure to tobacco smoke in non-smokers increases the risk by 20-30% compared to non-smokers not exposed to passive smoke. Other risk factors that increase the risk of developing LC are environmental or occupational exposure to carcinogens (such as radon or asbestos), the presence of lung disease (such as COPD or idiopathic pulmonary fibrosis) or a family history of LC. A screening test that detects the disease at an early stage would help to modify the clinical course of the disease, facilitating early diagnosis and treatment and thus improving survival by preventing disease progression. Imaging techniques are used for screening, with low-dose radiation computed tomography (LDCT) being the only test currently recommended. The use of biomarker panels in blood or exhaled air is also proposed, although they are currently at an early stage of development and validation. Early detection of LC by CBCT is increasingly being implemented as a population screening programme, however, there is some uncertainty in its risk-benefit ratio. In view of the fact that several large randomised clinical trials (RCTs) on LDCT screening have been conducted in recent years, it is necessary to reassess the new evidence on clinical effectiveness, efficiency, in terms of cost-effectiveness and budgetary impact, and to assess the degree of compliance with the essential requirements related to the incorporation of population-based screening programmes in the National Health System (NHS). Aims and Scope The main objective was to assess the comparative efficacy, safety and efficiency, and to analyse the ethical, social, and organisational aspects, as well as the possible environmental impact and research needs of screening in populations at high risk of developing LC. To this end, 8 research questions were established. The degree of compliance with the essential requirements for implementing a population screening programme in the NHS was also assessed. The target population consisted of adults, without LC at the time of diagnosis (confirmed or suspected), smokers or ex-smokers or with other risk factors (occupational or environmental exposure to carcinogens such as radon, asbestos or fine particles, COPD, idiopathic pulmonary fibrosis or with a family history of lung cancer). Research questions 1. What is the risk-benefit balance of screening for LC by LDCT in high-risk individuals compared to no screening or routine diagnosis? 2. What is the risk-benefit balance of adding molecular biomarkers to LDCT for LC screening in high-risk individuals compared to LDCT screening? 3. What is the cost-effectiveness of the LC screening programme? 4. What would be the budgetary impact for the NHS of implementing an LC screening programme in the at-risk population in Spain? 5. What is the risk-benefit balance of the organisational variants of systematic LC screening with LDCT (intervals, invitation) in high-risk individuals?? 6. What are the best strategies for informing the target population about an LC screening programme to optimise informed participation? 7. What are the potential ethical implications of implementing the screening programme? 8. What are the potential environmental impacts of implementing the screening programme? Efficacy and safety of LDCT screening Methodology For research questions 1 and 2, the results of the European collaborative network on health technology assessment (EUnetHTA) report "Lung cancer screening in high risk groups" were used as a starting point. Taking into account the time limit, specific literature searches in the general and specific databases were updated (last update December 2021). The selection of studies was peer-reviewed, independent and blinded, according to the inclusion and exclusion criteria established in the protocol. Data extraction was performed systematically in standardised tables. The validity of the studies and level of evidence was assessed using specific scales or tools according to the study design. The overall quality of the evidence (at the level of clinical outcome) was graded using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. In addition to comparing the results of individual studies, we performed meta-analysis and sensitivity analysis and examined effect modifiers using subgroup analyses, where methodologically possible. Efficacy and safety results of LDCT screening Bibliographic search: Nine randomised trials (DANTE, DLCST, ITALUNG, LSS, LUSI, MILD, NELSON, NLST and UKLS) were included. All included active and former smokers, and one (UKLS) also included people with other risk factors. In addition, 13 ongoing research studies were located. The last search was conducted on 31 December 2021 Characteristics of the studies included: the UKLS study was a feasibility study which, despite meeting the inclusion criteria, did not provide data on the variables of interest for assessing clinical effectiveness and was therefore not further detailed. The remaining 8 studies (90,836 randomised patients) differed in terms of the screening strategies used. Six studies (DANTE, DLCST, ITALUNG, LUSI, MILD and NELSON) compared LDCT screening versus no screening and were conducted in Europe (Italy, Denmark, Germany, Netherlands and Belgium) and the remaining 2 (LSS and NLST) compared BCTD screening versus chest radiography (CXR) and were conducted in the USA. The sample size ranged between 3000 and 4000, except in NELSON and NLST which were close to 16 000 and 53 500, respectively. The duration of the screening phase ranged from 1 to 6 years, and the expected follow-up period ranged from 5 to 10 years. The screening interval was 1 year in all studies except MILD and NELSON. MILD screened annually or every 2 years and in NELSON, the screening interval was extended from 1 to 2 years and then to 2.5 years. The studies included men and women who smoked before starting the study (at least 20 or 30 packs/year) or who had quit smoking less than 10 years before (15 years in the NLST). DANTE only included men and NELSON added women later in the study. The age range for inclusion of participants was set between ≥49 years and 75 years; MILD was the only study that did not set an upper age limit. The screening participation rate (adherence to screening) ranged from 81% to 96% in the intervention groups. Three studies (DLCST, LUSI, MILD) reported contamination between 1% and 7% (non-screening comparator), NLST 4% (Rx comparator) and the remaining studies provided no information. Assessment of risk of bias and quality of evidence: the risk of bias assessed with the Cochrane RoB tool was considered low in four studies (DLCST, ITALUNG, LUSI and NELSON) and high in the remaining four, due to uncertainty about the generation of the randomisation sequence (MILD, NLST), blinding (DANTE, MILD and NLST) or the independence of the results (LSS). At the outcome level, the risk of bias for mortality (overall and LC-specific), consequences of FPs and FNs and overdiagnosis was considered low in three studies (DLCST, ITALUNG and NELSON). For adverse events, the only study that provided information on adverse events was DANTE, which had a high risk of bias. In studies where the risk of bias at the study level was considered high, no specific assessment was made at the clinical outcome level. Depending on the outcome assessed, the quality of the evidence ranged from low to high. Clinical Results Mortality Regarding overall mortality, a meta-analysis was performed with data from 6 studies comparing LDCT screening versus no screening: 3 at low risk of bias (DLCST, ITALUNG and NELSON) and 3 at high risk (DANTE, MILD and LUSI). We used a random effects model and considered the longest follow-up period ranging from 8 to 11 years. No statistically significant differences in favour of screening were found both in the analysis of studies with low risk of bias (IRR: 0.93, 95% CI: 0.69-1.26, p=0.43, I2: 51.4%) and in the pooling of all studies (IRR: 0.95, 95% CI: 0.88-1.03, p=0.16, I2: 0%). To compare the effect of LDCT screening versus CXR, we used data from 2 studies with high risk of bias (LSS and NLST). Neither were significant differences observed between the two groups (IRR: 0.97, IC 95%: 0.92-1.02, p=0.17, I2 : 3.2%). In summary, no significant reduction in overall mortality was observed after screening for LC with LDCT, with little or no difference compared with no screening (high quality evidence; GRADE profiles).

Indicadores de desempeño de un programa de rastreo de cáncer colorrectal en la provincia del Neuquén, Argentina, 2015-2019 / Performance indicators of a colorectal cancer screening program in the province of Neuquén, Argentina, 2015-2019

INTRODUCCIÓN: El cáncer colorrectal (CCR) es una causa frecuente de mortalidad en adultos. El objetivo de este estudio fue mostrar resultados de la implementación del Programa de Rastreo de Cáncer Colorrectal (PRCCR) en la provincia del Neuquén, Argentina. MÉTODOS: Se realizó un estudio retrospectivo con análisis de resultados de sangre oculta en materia fecal (SOMF) y videocolonoscopía (VCC) en personas de 50-75 años, en efectores del sistema de salud pública en 2015-2019. Se determinó porcentaje de participación, resultados de SOMF, realización de colonoscopía en pacientes con SOMF positiva y sus hallazgos, y valor predictivo positivo (VPP) para detección de lesiones y de CCR. RESULTADOS: Se analizaron 11 189 SOMF. La participación promedio fue 6,52% de la población objetivo. Tuvieron SOMF positiva el 24,6% de los participantes; de ellos, realizaron la VCC un 24%. Se encontró lesión significativa en el 24,8% (pólipos adenomatosos 21,9%, cáncer 2,9%), con un VPP para la detección de lesiones del 34,3%. Tuvieron adenomas avanzados el 7,4%. Repitieron la SOMF tras un resultado negativo (segunda o tercera ronda) el 17,6% de los pacientes, y realizaron una VCC de control tras el hallazgo de un pólipo adenomatoso el 13,7%. DISCUSIÓN: El PRCCR en Neuquén muestra algunos indicadores que deben mejorarse (cobertura, realización de VCC) y otros adecuados (frecuencia de lesiones). Ante las dificultades se pueden plantear medidas más focalizadas, como la aplicación de escalas de riesgo de CCR, rastreo bianual, etc.

INTRODUCTION: Colorectal cancer (CRC) is a leading cause of mortality among adults. The objective of this study was to show results of the implementation of the colorectal cancer screening program (CRCSP) in the province of Neuquén, Argentina. METHODS: A retrospective study was conducted, with analysis of fecal occult blood test (FOBT) results in people aged 50 to 75 years, in public hospitals between 2015- 2019. Participation rate, FOBT results, colonoscopy (CC) performance in patients with positive FOBT and their findings, and positive predictive value (PPV) for detection of lesions and CRC were determined. RESULTS: A total of 11,189 FOBT were requested. The average participation was 6.52% of the target population, 24.6% of the participants had positive FOBT, and 24% of them had a CC performed. A significant lesion was found in 24.8% (adenomatous polyps 21.9%, cancer 2.9%), with a PPV for the detection of lesions of 34.3%. Furthermore, 7.4% had advanced adenomas, 17.6% of the patients repeated the FOBT after a negative result (second or third round), and 13.7% had a control CC performed after the finding of an adenomatous polyp. DISCUSSION: The CRCSP in Neuquén shows some indicators that need to be improved (coverage, conduction of CC) and others that are adequate (frequency of findings). In view of these difficulties, some more focused screening measures can be considered, such as use of CRC risk scales, bi-annual screening, etc.

Rastreo de cáncer colorrectal Análisis de resultados en la provincia de Neuquén, Argentina, 2015-2019 / Colorectal cancer screening: analysis of results in the Province of Neuquén, Argentina, 2015-2019

INTRODUCCIÓN: El Programa de Prevención de Tumores de la Provincia del Neuquén recomienda la Sangre Oculta en Materia Fecal Inmunológica (SOMFi) como intervención de rastreo, con posterior confirmación por videocolonoscopía (VCC) en pacientes con resultado positivo. El objetivo del estudio fue conocer los resultados de la utilización de SOMFi, la realización de VCC confirmatoria y sus hallazgos. MÉTODOS: Se realizó un estudio retrospectivo, que analizó los resultados de SOMFi obtenidos en personas de 50 a 75 años en todos los efectores del Sistema de Salud Pública de Neuquén en el período 2015-2019 sobre la base de registros informáticos provinciales y de cada centro de endoscopía. Se determinó la frecuencia de resultados de SOMFi, de VCC en los pacientes con SOMFi positiva y sus hallazgos. RESULTADOS: De 9909 muestras analizadas, 23,1% fueron positivas. Se realizó VCC confirmatoria en 24,1% de los pacientes con SOMFi positiva; presentaron cáncer el 3,7% de los casos, pólipos el 35% y estudio normal el 61,3%. Los tipos histológicos de los pólipos fueron: tubular (49%), hiperplásico (21,3%), tubulovelloso (20%), aserrado (7,2%) y otros tipos (2,5%). DISCUSIÓN: La frecuencia de SOMFi positiva fue mayor a la publicada. Solo el 20% de los pacientes realizó VCC confirmatoria. La frecuencia de cáncer y pólipos encontrados fue similar a la de otros estudios publicados. Debe incrementarse la realización de VCC confirmatoria.(AU)

INTRODUCTION: Neuquén Province Cancer Prevention Program recommends Fecal Immunochemical Test (FIT) as a screening intervention, with subsequent confirmation by video-colonoscopy (VCC) in patients with a positive result. The objective of the study was to know the results of the use of FIT, the performance of confirmatory VCC and its findings. METHODS: A retrospective study was carried out. It analyzed the results of FIT in people aged 50-75 years, considering tests conducted in all agents of the Neuquén Public Health System in 2015- 2019 based on provincial computer records and data from each endoscopy center. The frequency of FIT results, VCC in patients with positive FIT and findings was determined. RESULTS: Of 9909 samples analyzed, 23.1% were positive. Confirmatory VCC was performed in 24.1% of the patients with positive FIT, with 3.7% having cancer, 35% with polyps and 61.3% of normal studies. The histological types of the polyps were tubular (49%), hyperplastic (21.3%), tubulovillous (20%), serrated (7.2%) and other types (2.5%). DISCUSSION: The frequency of positive FIT was higher than published. Only one in five patients with positive FIT underwent confirmatory VCC. The frequency of cancer and polyps was similar to the one found in other published studies. It is necessary to increase the number of confirmatory VCC.AU)

Costo-efectividad del rastreo de cáncer colorrectal en provincias argentinas seleccionadas / Cost-Effectiveness of Colorectal Cancer Screening in Selected Argentine Provinces

INTRODUCCIÓN: El cáncer colorrectal (CCR) es una de las principales causas de mortalidad en adultos. En Argentina es la segunda entre las neoplasias, y se observan diferencias en la mortalidad entre las distintas provincias. El rastreo de CCR es subutilizado en Argentina, donde el sistema de salud se encuentra fragmentado. OBJETIVOS: Analizar la costo-efectividad (CE) de diversas estrategias de rastreo basadas en el test de sangre oculta en materia fecal inmunohistoquímico (SOMFihq) anual desde distintos subsectores provinciales. MÉTODOS: Se construyó un modelo de Markov, que permitió comparar tres estrategias: rastreo en población de 50 a 74 años, rastreo en población de 50 a 64 años y no rastreo. RESULTADOS: Se encontraron diferencias de costos y variabilidad clínica. El rastreo a población de 50-74 años presentó una razón de CE incremental levemente mayor que el rastreo en población de 50-64 años, con valores inferiores al producto bruto geográfico per cápita. Este resultado se mostró robusto en el análisis de sensibilidad. CONCLUSIONES: Los resultados comparados en siete subsectores de salud regionales de Argentina ­con diferencias epidemiológicas, organizacionales, de capacidad instalada y de recursos, con su variabilidad de práctica clínica y sus diferentes costos­ indican de manera robusta que el rastreo de CCR se mantiene costo-efectivo en diversos escenarios. Analizar la CE de intervenciones sanitarias en Argentina requiere tener en cuenta el contexto local de los diferentes subsectores de salud.

INTRODUCTION: Colorectal cancer (CRC) is one of the main causes of mortality in adults. In Argentina it is the second among tumors, and there are differences between province mortality rates. CRC screening is underutilized in Argentina, where there is an important fragmentation of the health care system. OBJECTIVES: To assess the cost-effectiveness (CE) of different screening strategies based on annual immunochemical fecal occult blood test (IFOBT) for different health subsectors in the country. METHODS: A Markov model was developed, which allowed to compare three different strategies: screening population aged 50 to 74 years, screening population aged 50 to 64 years, and no screening. RESULTS: Differences in costs and clinical variability were found. Screening the population aged 50 to 74 years showed a slightly higher incremental CE ratio than screening the population aged 50 to 64, with values lower than per capita gross regional product. This result was robust in the sensitivity analysis. CONCLUSIONS: The compared results from seven regional health subsectors in Argentina, with their differences in epidemiology, organization, installed capacity and resources, as well as clinical variability and differences in costs, are robust in showing that CRC screening remains cost-effective under different scenarios. In order to analyze the CE in Argentina, it is necessary to take into account the local context of different health subsectors.

Rastreo con electrocardiograma en población general de 6 a 18 años / Tracing with electrocardiogram in the general population of 6 to 18 years

PREGUNTA DE INVESTIGACIÓN: ¿Es recomendable el rastreo con electrocardiograma en población general de 6 a 18 años con la finalidad de despistar patología cardiaca que pudiera desencadenarse con el ejercicio no competitivo, con resultados fatales? METODOLOGÍA: Se realizó una búsqueda bibliográfica donde se consultaron principalmente revisiones istemáticas, Guias de Práctica Clínica basadas en la evidencia, Evaluaciones de tecnologías Sanitarias y estudios epidemiológicos locales e internacionales. Se realizó una búsqueda bibliográfica en las siguientes fuentes, repositorios, buscadores y meta-buscadores: Cochrane, Gin, EBSCO, Pubmed-Medline, Lilacs, CRD de la Universidad de York, Tripdatabase, Epistemonikos y Google académico. Se solicitó al área de epidemiología el registro de muertes súbitas en población de Neuquén de la edad blanco. Para ampliar la información se consultó con especialistas locales en cardiología pediátrica, pediatría, medicina del deporte, medicina general y epidemiología, con interés en profesionales que se desempeñen en distintas zonas sanitarias de la provincia. REVISIONES SISTEMÁTICAS: Una revisión sistemática 27 que analizó los estudios publicados entre 1966 y 2013 termina concluyendo, luego de un exhaustivo análisis que existen suficientes dudas para recomendar que se realicen más estudios de investigación antes de aplicar el rastreo con ECG en niños. Entre los factores que consideran para esta recomendación, mencionan la falta de expertez y de recursos humanos capacitados para interpretar en ECG en niños. Por eso recomienda que el interrogatorio y el examen físico sean la base de la evaluación de riesgo de MSC en niños. RECOMENDACIONES Y GUÍAS ACTUALES: En Neuquén el Ministerio de Salud de Neuquén recomienda actualmente hacer un rastreo con interrogatorio, examen físico y electrocardiograma de 12 derivaciones a los 6 y a los 13 años de edad. Sin embargo, diversos participantes de las reuniones que se realizaron sobre este tema manifestaron opiniones en contra de ésta recomendación. La Dirección de Salud Colectiva encomendó al Comité Provincial de Biotecnologías un informe técnico sobre ésta recomendación. Diversas guías y consensos argentinos proponen realizar rastreo en población sana combinando el interrogatorio sobre antecedentes familiares y personales cardiovasculares, examen físico y electrocardiograma (ECG) para identificar causas de muerte súbita cardiaca (MSC). Pero otros consensos no incluyen este estudio complementario, reflejando el debate que existe sobre este tema. En su actualización 2014 un conjunto de Comités y Sociedades científicas pediátricas y del deporte de Argentina recomiendan la realización de rastreo con ECG en la adolescencia, pero no en la niñez.

Diretrizes para detecção precoce do câncer de mama no Brasil: relatório de recomendação / [Guidelines for early detection of breast cancer in Brazil: recommendation report]

INTRODUÇÃO: O câncer de mama é o tipo mais incidente na população feminina mundial e brasileira, excetuando-se os casos de câncer de pele não melanoma, e também uma das principais causas de morte por câncer em países desenvolvidos e em desenvolvimento. As taxas de incidência são maiores nos países desenvolvidos, embora tenham ocorrido, em alguns países, tendências para redução e estabilização na primeira década de 2000. As taxas de mortalidade variam entre diferentes regiões do mundo, com as maiores taxas nos países desenvolvidos. Nos países em desenvolvimento, o risco de morrer de câncer de mama, em geral, é menor em comparação com os países desenvolvidos . No Brasil, embora exista uma grande heterogeneidade na distribuição de casos novos e mortes por câncer de mama, as maiores taxas de incidência e mortalidade ocorrem nas Regiões Sul e Sudeste, e as menores taxas nas Regiões Norte e Nordeste. As políticas públicas relacionadas ao câncer de mama, desenvolvidas no Brasil desde meados dos anos 1980, foram impulsionadas, particularmente, em 1998, pelo Programa Viva Mulher. O incentivo federal em prol das ações para o Controle do Câncer de Mama sempre teve como objetivos principais: reduzir a exposição aos fatores de risco; diminuir a mortalidade; e melhorar a qualidade de vida da mulher com câncer de mama, estando esses em consonância com as diretrizes atuais da política de controle do câncer, publicadas pela Portaria GM/MS1 no 874, de 2013, e com a Política Nacional de Prevenção e Controle do Câncer. Mediante a realidade atual (internacional e nacional) quanto à crescente incorporação e utilização de novas tecnologias no sistema de saúde para fins de detecção precoce do câncer de mama, tornou-se necessário atualizar e aprofundar a discussão sobre as recomendações dessa modalidade de Controle do Câncer de Mama: Documento de Consenso. O Ministério de Saúde tem utilizado as evidências científicas como um dos instrumentos para decidir sobre questões relacionadas à incorporação e à utilização de novas tecnologias em saúde ou de tecnologias já incorporadas, mas indicadas para novos fins terapêuticos. Assim, houve a implementação institucional de um novo campo da pesquisa conhecido como Avaliação de Tecnologias em Saúde (ATS), que se tornou um importante instrumento para os tomadores de decisão na saúde, sejam eles gestores em saúde, clínicos, chefes de serviços, representantes de organizações civis e científicas, sejam inclusive do sistema judiciário. Essa iniciativa culmina com a publicação da Lei nº 12.401, em 2011, que estabelece que documentos com caráter de protocolos clínicos e diretrizes terapêuticas devem ser elaborados a partir do uso das melhores evidências científicas sobre a eficácia, a acurácia e a segurança das tecnologias em questão. MÉTODOS: A rigor, a escolha dos métodos empregados na atualização e na elaboração das novas diretrizes nacionais para a detecção precoce segue a tendência de governos e agências internacionais quanto à utilização de evidências científicas consistentes no processo de tomada de decisão na área da saúde. Nesse sentido, alinha-se também aos dispositivos administrativos e normativos vigentes no país, como a Portaria SAS/MS no 375, de 2009, e a própria Lei nº 12.401, de 2011, que estabelece que os documentos com caráter de protocolos clínicos e diretrizes terapêuticas devem ser elaborados a partir da metodologia do uso das melhores evidências científicas sobre a eficácia, a acurácia, a efetividade e a segurança das tecnologias em questão. A definição do escopo geral das Diretrizes foi fruto das conferências realizadas pelo Comitê Gestor, em que todas as especificidades e os pontos controversos a respeito da formulação da questão-chave foram dirimidos em conjunto com a equipe de especialistas. CONCLUSÃO: Espera-se com esta publicação contribuir para qualificar a tomada de decisão dos gestores em saúde quanto à organização da linha de cuidado do câncer de mama, assim como para apoiar os profissionais de saúde nas suas práticas clínicas e os pacientes nas suas escolhas frente a diferentes intervenções sanitárias. Esta proposta foi apreciada pelo Plenário da CONITEC, em sua 34ª Reunião Ordinária, realizada nos dias 1º e 2 de abril de 2015, que deliberou por unanimidade em recomendar a aprovação destas diretrizes (Registro de Deliberação nº 160/2015). A decisão de aprovar as Diretrizes Nacionais para a Detecção Precoce do Câncer de Mama se deu com a Portaria nº 59 publicada em 05/10/2015, no DOU nº 190, pág. 693.

Mamografia para o rastreamento do câncer de mama em mulheres com idade abaixo dos 50 anos, entre 50 e 69 anos e com mais de 70 anos / Mammography for the screening of breast cancer in women aged under 50 years, between 50 and 69 years and over 70 years

INTRODUÇÃO: O câncer de mama é a principal causa de óbito por neoplasias malignas entre as mulheres. Em 2012, ocorreram 13.591 óbitos de mulheres por neoplasia maligna da mama no Brasil1. Os dados disponíveis, referentes ao período de 1979 a 2012 no Brasil, mostram uma tendência mantida de elevação nas taxas de mortalidade por câncer de mama (brutas e ajustadas por idade), por 100.000 mulheres, com taxa bruta de 13,73 por 100.000 mulheres em 2012 (em 1979 era de 5,77 por 100.000 mulheres). Para o ano de 2014, no Brasil, foram previstos 57.120 casos novos de câncer de mama, com um risco estimado de 56,09 casos a cada 100 mil mulheres. EVIDÊNCIAS CIENTÍFICAS: Para a elaboração do PTC, foram seguidas as recomendações das Diretrizes Metodológicas para elaboração de PTC do Ministério da Saúde. Foi realizada busca, no mês de novembro de 2014, nas bases de dados Medline (via Pubmed), Center for Reviews and Dissemination - CRD, Biblioteca Cochrane, Biblioteca Virtual em Saúde/L

Câncer de colo de útero: a vacina para prevenção do HPV e o desafio para a melhoria da qualidade do rastreamento no Brasil / Cervical cancer: the vaccine for HPV prevention and the challenge to improve the quality of screening in Brazil

INTRODUÇÃO: O câncer de colo de útero ou câncer cervical, embora passível de prevenção e cura, ainda é responsável por um grande número de mortes entre mulheres, especialmente em países em desenvolvimento. O Papilomavírus Humano (HPV) é fator necessário, ainda que não suficiente, para o desenvolvimento do câncer de colo do útero. Existem mais de 100 tipos de HPV, embora poucos sejam oncogênicos. A transmissão do HPV se dá pela via sexual, sendo essa infecção muito frequente na população. Na maior parte dos casos, a infecção cura-se espontaneamente, ou seja, a persistência da infecção e a evolução para o câncer são raras. As alterações das células que podem desencadear o câncer são descobertas facilmente no exame preventivo (Papanicolaou), por isso é importante a sua realização periódica. Quando essas alterações são identificadas e tratadas, é possível prevenir a doença em praticamente 100% dos casos. TECNOLOGIA: Outra estratégia de prevenção é a vacinação contra HPV. Duas vacinas estão, atualmente, registradas no Brasil, ambas prevenindo contra a infecção pelos dois subtipos oncogênicos mais prevalentes no Brasil e no mundo, os tipos 16 e 18. Há evidências de que ambas são seguras e eficazes na prevenção da infecção pelos subtipos incluídos em suas formulações, entretanto, esta eficácia é reduzida quando a mulher já teve contato com o vírus. Por conta disso, a população alvo dos programas de vacinação deve incluir, preferencialmente, meninas de 9 a 12 anos, o que representa um desafio, tendo em vista que a adesão a esquemas vacinais voltados a esse público tem se mostrado abaixo do ideal. RESULTADOS: Vários estudos de avaliação econômica sobre a utilização da vacina contra HPV foram feitos nos últimos anos, tanto em países desenvolvidos como em desenvolvimento, com o intuito de demonstrar a relação custo-efetividade de sua introdução nos sistemas de saúde. Das avaliações econômicas realizadas, destacam-se as que compararam os programas de rastreio já existentes em um dado país (como, por exemplo, o método Papanicolaou) com a vacina contra HPV combinada à prática de rastreio já utilizada. A maioria dos estudos da revisão sistemática, avaliada neste boletim, apontou que a vacina contra HPV, quando combinada aos métodos de rastreio tradicionais, é custo-efetiva. Com relação ao impacto orçamentário, segundo as estimativas adotadas neste boletim, deverá haver substancial incremento no orçamento do PNI/MS, caso seja introduzida a vacinação contra o HPV no sistema de saúde, pois ela comprometeria mais de 25% do orçamento atual desse programa. CONCLUSÃO: É importante ressaltar que a vacinação não substitui a realização do rastreamento dentro dos prazos preconizados. Ao contrário, mesmo em países que já incorporaram a vacina contra HPV, a recomendação é que todas as mulheres vacinadas devem continuar realizando o rastreamento de Papanicolaou, com a mesma periodicidade e faixa etária preconizadas anteriormente nos protocolos de rastreamento destes países.

Summary: Indications for positron­emission tomography (pet): a brief update

The purpose of this report is to provide an initial response to various questions concerning the expansion of the clinical indications for positron-emission tomography (PET) and PET-CT1 in oncology and for other types of diseases with regard to the current practice in Québec. A targeted literature review identified 28 health technology assessments and systematic reviews on this topic published between 2004 and 2010, from which information concerning PET clinical indications was extracted. These indications were placed in two categories: the initial indications (diagnostic characterization and tumour initial staging) and follow-up indications (evaluation of treatment response, disease progression, and evaluation of recurrences). In twelve cancers, initial and follow-up indications are accepted both in the literature and in Québec, with a low potential for expanding indications based on nuances or specificities that cannot be discussed in the context of this report. A potential expansion of the indications accepted in Québec was identified for six cancers, for two of which there is an international consensus, namely, glioma for the initial indications and gastrointestinal stromal tumours for both initial and follow-up indications. The other indications are the subject of debate because of a lack of interpretable evidence (kidney cancer for the initial indications and pancreatic cancer for the follow-up indications); emerging, thanks to the large number of recent studies (thyroid cancer for the initial indications); or included in another category (unspecified brain cancer placed together with glioma). With regard to non-oncological indications, only chronic osteomyelitis and prosthesis-related infections could constitute new, emerging indications. As for the utility of PET in planning radiotherapy treatments, this question could not be resolved because of a lack of evidence. This is an emerging and mainly experimental field, and there is presently no systematic review of the available data. The current research mainly concerns technical issues specific to each cancer. The Unité d'évaluation des technologies et des modes d'intervention en santé (UETMIS) at the Centre hospitalier universitaire de Québec (CHUQ) is analyzing now the literature on this new technological application and its potential use in Québec. In conclusion, the range of new or expanded indications for PET in relation to those currently accepted in Québec remains fairly limited. However, PET is a rapidly evolving technology, and its combined use with other technologies such as magnetic resonance imaging, is opening development prospects for new clinical applications. Following an agreement with the Ministère de la Santé et des Services sociaux, it was agreed that the most concerned professional associations with PET would be consulted to check if the results of this update on the indications accurately reflect the current state of knowledge and their application in Québec clinical practice. The minutes of the meetings are presented in Appendix E, and the main points are summarized in Section 5.

Efectividad del test de sangre oculta en materia fecal en el cribado poblacional del cáncer colorrectal en personas con riesgo medio / Effectiveness of the fecal occult blood test in population screening for colorectal cancer in persons at medium risk

Objetivo: Evaluar la evidencia disponible de la efectividad de la técnica de sangre oculta en materia fecal para la detección precoz del cáncer colorrectal, en población general con riesgo medio. Metodología: Se utilizó un método dual de revisión sistemática en las principales bases de datos generales y especializadas (Google, Pubmed, LILACS, Tripdatabase, INAHTA, COCHRANE, NGC, AUnETS), priorizando la búsqueda de revisiones sistemáticas o metanálisis y evaluaciones de tecnología sanitaria. Resultados: Se identificaron 2 evaluaciones de tecnología sanitaria, 4 revisiones sistemáticas y 1 revisión Cochrane, entre los años 2007 y 2010. Conclusiones: La mortalidad por cáncer colorrectal en población de riesgo medio, se reduce por el screening con el test de sangre oculta en materia fecal y tiene probabilidad de evitar aproximadamente 1 de cada 6 muertes por cáncer colorrectal. Evidencia limitada o indirecta de que el TIF tenga Sensibilidad /especificidad superior al de TSOMFg sin rehidratar para detección de CCR.(AU)

Efectividad de diferentes maniobras para prevenir la infección perinatal por virus de hepatitis B y C / Effectiveness of different maneuvers to prevent perinatal infection with hepatitis B and C virus

Esta ETS fue solicitada por las autoridades del Ministerio de Salud de la Nación a la Dirección de Calidad de \r\nlos Servicios de Salud, y tiene como objetivo evaluar la efectividad de diferentes estrategias preventivas de la \r\ninfección perinatal por virus de hepatitis B y C y el impacto de los programas de prevención de la hepatitis \r\nneonatal en diferentes países. Se estima que 400 millones de personas son portadores crónicos de alguna de estas infecciones y entre el 25% y el 40% morirán por carcinoma hepatocelular o complicaciones \r\nrelacionadas a cirrosis hepática. En Argentina 2,1 % de la población tiene anticuerpos positivos para hepatitis B crónica, colocando a nuestro país como un sitio de prevalencia intermedia o alta. 1,8 cada 100.000 \r\nhabitates están infectados por virus de hepatitis C. Si la madre es positiva a HBsAg y HBeAg, del 70% al \r\n90% de los niños se convierten en crónicamente infectados. La tasa de transmisión perinatal de la hepatitis C ronda el 5% pero aumenta al 15% en madres HIV positivas. Se realizó una búsqueda en TRIP DATA BASE, COCHRANE DATA BASE, LILACS; PUBMED; BVS; en buscadores genéricos de Internet como google, \r\nAgencias de Evaluación de Tecnologías Sanitarias, Agencias de Servicios Preventivos, sistemas nacionales \r\nde salud, además de sitios web de aseguradoras y prestadores de servicios de salud de Estados Unidos y \r\nCanadá. Se incluyeron revisiones sistemáticas, metanálisis, ensayos clínicos controlados aleatorizados, \r\nestudios de cohortes con grupos control y estudios de prevalencia, evaluaciones económicas, guías de \r\npráctica clínica basadas en la evidencia o evaluaciones de tecnología sanitaria, publicados desde el año 2004 hasta la fecha, a los que pudiera accederse a texto completo, en idioma español, inglés o francés. Se \r\nutilizaron palabras clave tales como "hepatitis perinatal prevention program" entre otras. Se encontró \r\nevidencia sobre la efectividad del rastreo universal de hepatitis B durante el embarazo, con la consecuente \r\nrealización de inmunoprofilaxis con inmunoglobulina específica asociada a vacuna en niños de madres \r\nportadoras de infección VHB, así como sobre la inmunización neonatal universal con vacuna de la hepatitis B, para disminuír la transmisión perinatal del virus, por lo que estas estrategias deberían ser consideradas para \r\nincluír en un Programa de Prevención de la infección perinatal por VHB. Los programas de vacunación \r\nuniversales han demostrado un impacto importante a largo plazo en varios países que los han implementado. La cesárea electiva podría ser efectiva para disminuír la transmisión perinatal del virus de la hepatitis B, \r\naunque la evidencia que existe actualmente sobre el tema no es de buena calidad, por lo que persisten las \r\ndudas en relación a esta indicación. Drogas antirretrovirales como lamivudina y telbivudina han demostrado \r\nsu efectividad para disminuír la transmisión perinatal de la infección por virus de hepatitis B si se \r\nadministran a las madres infectadas durante el tercer trimestre del embarazo, aunque se requieren más \r\nestudios que repliquen esos hallazgos y evalúen su seguridad a largo plazo antes de poder indicarlas de \r\nforma masiva. Al momento de la realización de esta ETS no se encontró evidencia que sustente la \r\nvacunación universal de las embarazadas contra la hepatitis B para disminuír la infección perinatal, ni \r\ntampoco el rastreo universal de infección por virus de la hepatitis C en el embarazo. Tampoco se encontró \r\nevidencia que avale la indicación de cesárea electiva en embarazadas portadoras de VHC ni la \r\ncontraindicación de la lactancia en madres infectadas con virus C. Los sistemas de salud y prestadores \r\nconsultados, cubren la vacunación universal de los neonatos contra la hepatitis B, así como el rastreo de \r\nhepatitis B en embarazadas, no así la indicación de cesárea en infectadas por virus de hepatitis B. No se \r\nencontró información sobre la cobertura de drogas antivirales en embarazadas infectadas por VHB como \r\nindicación específica de prevención de la transmisión perinatal. (AU)

Place de la coloscopie virtuelle dans un programme organisé de dépistage du cancer colorectal / Place of virtual colonoscopy in an organized colorectal cancer screening program

Le cancer colorectal constitue la deuxième cause de mortalité par cancer au pays, mais demeure une maladie curable lorsqu'elle est dépistée précocement. Actuellement, la coloscopie standard est la technique de référence pour dépister et diagnostiquer les lésions colorectales cancéreuses et précancéreuses (polypes adénomateux). Depuis maintenant près d'une quinzaine d'années, une option de rechange moins effractive est disponible, soit la coloscopie virtuelle. Cette méthode d'imagerie utilise la tomodensitométrie hélicoïdale et le traitement informatisé des images pour obtenir des représentations bidimensionnelles et tridimensionnelles du côlon. Or, la Direction de la lutte contre le cancer (DLCC) du ministère de la Santé et des Services sociaux du Québec est actuellement à mettre sur pied un programme organisé de dépistage du cancer colorectal. Elle se questionne sur le rôle que pourrait occuper la coloscopie virtuelle dans son programme, précisément comme outil de deuxième intention. La DLCC a donc demandé à l'Agence d'évaluation des technologies et des modes d'intervention en santé de se pencher sur cette question. La présente note informative constitue un avis sur la performance de la coloscopie virtuelle et sur son rôle comme outil diagnostique chez les patients qui obtiennent un résultat positif à une recherche de sang occulte dans les selles (RSOS). Les résultats des plus récentes revues systématiques y sont présentés, ainsi que les conclusions et (ou) recommandations d'agences d'évaluation des technologies de la santé et de professionnels du domaine (guides de pratique clinique, consensus d'experts). Actuellement, la coloscopie virtuelle ne semble pas offrir une performance suffisante pour le diagnostic de l'ensemble des lésions colorectales significatives (cancers et polypes ≥ 6 mm). La coloscopie virtuelle n'est pas l'outil courant de choix pour diagnostiquer les cancers et polypes colorectaux chez les patients qui ont préalablement obtenu un résultat positif à un test de RSOS. Par contre, elle offre une utilité comme méthode diagnostique chez les patients pour lesquels une coloscopie standard est contre-indiquée ou n'a pu être complétée.(AU)

Screening mammography: a reassessment

INTRODUCTION: Eight trials examining the performance of screening mammography have been conducted in the USA, Sweden, the United Kingdom and Canada, beginning in 1963. A first report by the Conseil d'évaluation des technologies de la santé (CETS) published in 1990 concluded that screening mammography trials had shown reductions in mortality from breast cancer of 35%, with 45% in the subgroup of women aged 50 to 69. A second report in 1993 concluded that mammographic screening of women under 50 had not been shown to reduce mortality. By the year 1998, when Québec introduced the Programme québécois de dépistage du cancer du sein (PQDCS), all Canadian provinces and many other countries had organized screening programs in place. A recent Cochrane Collaboration Group review, challenging the belief that mammography screening is an effective tool for reducing breast cancer deaths, has raised concerns about the validity of the published randomized trials. This update addresses three questions: (1) What is the strength of the scientific evidence on which screening mammography programs are based? (2) What is the evidence in support of screening for women aged 40 to 49 years? (3) What are the implications of research studies for maximizing the effectiveness of modern programs such as the Programme québécois de dépistage du cancer du sein (PQDCS)? METHODOLOGIC ANALYSIS: An evaluation of efficacy trials essentially aims to determine whether the conditions under which the trials were performed and the results that were obtained can guide strategies. In practice, the reference strategy (no screening) may include some uncontrollable screening activities, which will weaken the contrast with the screening intervention. A valid study must be a fair comparison between screening and no screening. Thus screening and control cohorts should have the same baseline risk of breast cancer mortality, should be treated equally in all regards except concerning the screening or control intervention, and should have the information on their outcome measured in a way that is independent of their assignment to the screening or control group. Validity can be compromised by bias of known direction and by bias of unknown direction. In this evaluation, to further develop the notion of bias of known direction, we use the concept of strength of contrast. It corresponds to the degree to which a trial succeeds in bringing out the divergence between the two strategies compared and in measuring the effects that this divergence produces. Five elements are evaluated in this report which help assess the strength of contrast: -the technical contrast, or the nature of the difference between screening and control interventions; -the era in which these techniques are applied; -the quality of the intervention, including quality control measures; -rates of participation and contamination measured among screening and control cohorts; and -the timing of the measurement of the effects of screening on mortality (or timing dilution). DISCUSSION AND CONCLUSIONS: Question 1: What is the strength of the scientific evidence on which screening mammography programs are based? There are serious concerns regarding the validity of most of the trials supporting mammography screening, based on methodological weaknesses in the screening trials. Studies are highly heterogeneous with regard to the strength of the contrast that they studied, with numerous weaknesses identified in all the major studies, meaning that the potential of screening mammography has perhaps not been thoroughly explored. Using the best available data, one can conclude that there is fair evidence of moderate reduction of breast cancer mortality, of the order of 9 to 15%; data restricted to women over the age of 50 show greater reductions, of the order of 24 to 29%. Furthermore, our analysis has demonstrated that modern mammography, carried out under quality conditions that maximize its performance, has the potential to identify cancerous lesions earlier in their progression, and this may allow for some further reduction in mortality. Conclusion: Existing scientific trials, despite their flaws, support mammography screening programs. In addition, there are good reasons to believe that modern, well-conducted screening programs may achieve earlier detection and diagnosis of breast cancer and, perhaps, greater reductions in breast cancer mortality than what has been found in screening trials. Question 2: What is the evidence in support of screening mammography for women aged 40 to 49 years? There is much less data available to answer the question, since most study experience is in women over 50, even though some women in some of the studies started screening several years earlier than their fiftieth birthday. The best data available show no significant reduction in breast cancer mortality in women screened before the age of 50. In the absence of any convincing data that mammography is efficacious in this age group, harmful effects may outweigh any positive effects. Conclusion: Trial data published to date do not provide scientific justification to recommend screening for women younger than 50. However, this conclusion does not exclude the possibility that screening of individual women, based on a personalized risk assessment, could be of benefit. These conclusions should be reviewed when results from the UK Trial become available. Question 3: What are the implications of research studies for maximizing the effectiveness of modern programs such as the Programme québécois de dépistage du cancer du sein (PQDCS)? Although the PQDCS already includes rigorous control of the quality of films produced, certain aspects of the structure and process of trials examined under the rubric of strength of contrast can be transposed as additional quality norms. Notable among these are double reading of films and an annual reading volume sufficient to allow each radiologist to acquire and maintain the necessary expertise to detect breast cancer in its early stages. These aspects should also allow for a reduction in false positive rates and subsequent unnecessary diagnostic procedures. Moreover, high participation rates at each screening round will contribute to achieving and perhaps exceeding the mortality reductions obtained by screening trials. Conclusion: Modern screening programs such as the PQDCS may produce outcomes comparable or even superior to those observed in screening trials if they achieve a standard of quality equal to or better than the standard achieved by trials. Measures that should reduce false positive rates and assure high-quality screening include making sure that high-quality mammographic films are being produced, that readers have the necessary expertise to detect early cancer and avoid false positives, and double reading of a proportion of films. While participation rates should be as high as possible, efforts to increase participation should not overstate the benefits of mammography nor understate the risks and uncertainties which remain.