A nationwide pilot study on breast cancer screening in Peru.

Introduction: A high prevalence of advanced breast cancer (BC) is a common scenario in Latin America. In Peru, the frequency of BC at Stages III/IV is ≈50% despite implementation of a programme for breast cancer screening (BCS) along the country. We carried out a study to assess the feasibility and develop an instrument to evaluate the knowledge, barriers and perception about BCS in a nationwide pilot study in Peru among candidates for BCS. Methods: We conducted a systematic review of 2,558 reports indexed in PubMed, Scopus, Web of Science, Medline-Ovid and EMBASE, regarding to our study theme. In total, 111 were selected and a 51-items survey was developed (eight items about sociodemographic characteristics). Patients were recruited in public hospitals or private clinics, in rural and urban areas of nine departments of Peru. Results: We surveyed 488 women from: Lima (150), Cajamarca (93), Ica (59), Arequipa (56), Loreto (48), Ancash (38), Junín (15), Puerto Maldonado (15) and Huancavelica (14); 27.9% of them were from rural areas. The mean of age was 53.3 years (standard deviation ± 9.1). Regarding education level, 29.8% had primary, 33.2% secondary and 37.0% higher education. In total, 28.7% of women did not know the term 'mammogram' and 47.1% reported never receiving a BCS (36.9% from urban and 73.5% from rural population). In women that underwent BCS, only 67% knew it is for healthy women. In total, 54.1% of patients had low levels of knowledge about risk factors for BC (i.e. 87.5% of women respond that injuries in the breast produce cancer). Cultural, economic and geographic barriers were significantly associated with having a mammogram where 56.9% of participants considered a cost ≤ 7 USD as appropriate. Mammogram was perceived as too painful for 54.9% of women. In addition, women with a self-perception of low-risk for BC and a fatalistic perception of cancer were less likely to have a BCS. Conclusion: We found that it is feasible to conduct a large-scale study in Peru. The results of this pilot study highlight an urgent need of extensive education and awareness about BCS in Peru.

Impact of Targeted Therapy on the Survival of Patients With Advanced-Stage Non-small Cell Lung Cancer in Oncosalud - AUNA.

BACKGROUND: Lung cancer is still a prevalent and fatal neoplasm in developing countries. In the last decades, chemotherapy (CHT) maintenance occupied an important role in the treatment, as well as targeted therapies. We aimed to evaluate the survival impact of targeted therapy in advanced lung cancer at a private Peruvian institution (Oncosalud - AUNA). METHODS: We reviewed retrospectively medical records of patients with advanced-stage non-small cell lung cancer (NSCLS) (clinical stage III-IV) who received CHT and maintenance treatment with target therapy (TT) or CHT. The impact was assessed by progression-free survival (PFS) and overall survival (OS) using the Kaplan-Meier method, and comparisons of survival curves were performed using log-rank or Breslow test and Cox model. RESULTS: The median age of the patients was 65 years. Clinical characteristics, as well as the treatment type, showed no significant difference between the two groups. The maintenance schedule in those receiving CHT was generally pemetrexed (70%) and in those receiving TT was erlotinib (60.7%). In patients receiving TT, the median PFS was 13 months compared to 7 months in those receiving CHT; likewise, the median OS was 45 and 17 months, respectively. The PFS and OS curves showed significant differences (P < .05), achieving a better survival in subjects treated with TT. CONCLUSION: Progression-Free Survival and OS were superior in patients who received targeted therapy than those treated only with CHT, the 2 years rate of PFS and OS was nearly double to those who received only CHT-based treatments.

Life expectancy and cancer survival in Oncosalud: outcomes over a 15-year period in a Peruvian private institution.

BACKGROUND: There is a large gap in the data on cancer outcomes in Latin America, making it difficult to establish adequate cancer control policies in the region. The aim of our study was to describe the survival, life expectancy estimates and life expectancy changes over time for a large cohort of Peruvian patients insured with Oncosalud, a private healthcare system. PATIENTS AND METHODS: We evaluated a retrospective cohort of patients diagnosed between 2000 and 2015 in Oncosalud (Lima-Peru). Cases included colon, rectum, stomach, bladder, breast, prostate and non-melanoma skin cancers. Survival was evaluated with the Kaplan-Meier methodology. The standard period life table was used to estimate the excess mortality risks of patients in our cohort compared to the population covered by the Peruvian Superintendence of Banks, Insurance Companies and Pension Funds (SBS). The years of life lost was estimated based on SBS population, matching patients by age and sex. RESULTS: A large cohort of 7,687 Peruvian cancer patients managed in a 15-year period was eligible. If patients survive 5 years after a cancer diagnosis, life expectancy tends to be close to that of a population without cancer. The number of years of life lost at diagnosis was higher at the youngest ages, steadily decreasing thereafter. During the first years after cancer diagnosis, young patients face a much higher loss in life expectancy than older ones. Patients suffering from colon, rectum, stomach and bladder cancer are the most affected by the years of life lost. CONCLUSION: In cancer patients surviving ≥ 5 years, life expectancy becomes similar to that observed in a population with similar socioeconomic characteristics. The estimated survival rate in our cohort is higher than that reported by public cancer registries in Peru. This could be explained by the different socio-economic background and access to specialised cancer care.

Telemedicine and the current opportunities for the management of oncological patients in Peru in the context of COVID-19 pandemic.

COVID-19 pandemic is the more challenging public health emergency of the century, producing the collapse of health systems and unprecedented levels of morbidity and mortality around the world, especially in low resource settings. Patients with chronic diseases are the most affected, not only due to the high susceptibility to SARS-CoV-2 infection but also due to the decrease in opportunities for timely care. In this dark landscape, telemedicine, before limited to very specific scenarios, has become one of our main tools to manage cancer patients, particularly in Latin America where COVID-19 has had a strong impact on the public health. Telemedicine can provide rapid access to specialized cancer care in a scenario complicated, reducing the exposure of patients and healthcare personnel to the SARS-CoV-2. In this review, we would like to share our experience and our workflow using telemedicine at Oncosalud-AUNA, a private clinic in Peru.

Barriers in Latin America for the management of locally advanced breast cancer.

Breast cancer (BC) is a highly prevalent malignancy in Latin American women, most cases being diagnosed at locally advanced or metastatic stages when options for cancer care are limited. Despite its label as a public health problem in the region, Latin American BC patients face several barriers in accessing standard of care treatment when compared with patients from developed countries. In this review, we analyse the landscape of the four main identified barriers in the region: i) high burden of locally advanced/advanced BC; ii) inadequate access to medical resources; iii) deficient access to specialised cancer care and iv) insufficient BC research in Latin America. Unfortunately, these barriers represent the main factors associated with the BC poor outcomes seen in the region. Targeted actions should be conducted independently by each country and as a region to overcome these limitations and create an enhanced model of BC care.

Gender and outcomes in non-small cell lung cancer: an old prognostic variable comes back for targeted therapy and immunotherapy?

BACKGROUND: There are well-known differences in gender outcome in non-small cell lung cancer (NSCLC) and other cancers. In this work, we evaluated several randomised clinical trials to explore the gender influence in the outcome of patients with NSCLC treated with targeted therapy and immunotherapy. METHODS: We performed a series of meta-analysis to compare the gender outcome in the routine setting for overall survival and progression-free survival (PFS) in phase III randomised clinical trials comparing EGFR inhibitors versus chemotherapy (OPTIMAL, LUX-lung 3, LUX-lung 6, EURTAC, ENSURE and WTJOG); ALK inhibitors versus chemotherapy (ASCEND 4, ASCEND 5, PROFILE 1014 and NCT009323893) and anti-PD1 checkpoint inhibitors versus chemotherapy (CheckMate 017, CheckMate 026, CheckMate 057, KEYNOTE 010 and KEYNOTE 024). RESULTS: Female patients with NSCLC have a reduced risk of death compared with men (HR=0.73; 95% CI 0.67 to 0.79; p<0.00001). Women had a better benefit from EGFR inhibitors than men (HR=0.34; 95% CI 0.28 to 0.40; p<0.00001 vs HR=0.44; 95% CI 0.34 to 0.56; p<0.00001, respectively). The benefit from ALK inhibitors was similar for both genders (HR=0.51; 95% CI 0.42 to 0.61; p<0.00001 vs HR=0.48; 95% CI 0.39 to 0.59; p<0.00001, for women and men, respectively). Anti-PD1 inhibitors significantly improved the PFS in male patients when compared with chemotherapy (HR=0.76; 95% CI 0.68 to 0.86; p<0.00001); in contrast, women showed no benefit in 5/5 randomised trials (HR=1.03; 95% CI 0.89 to 1.20; p=0.69). CONCLUSIONS: In this exploratory study, some targeted treatments were influenced by gender. Despite differences in outcomes that could be attributed to different histology, EGFR and smoking status, gender should be evaluated more deeply as prognostic variable in patients with NSCLC.

Latin American Clinical Epidemiology Network Series - Paper 2: Apixaban was cost-effective vs. acenocoumarol in patients with nonvalvular atrial fibrillation with moderate to severe risk of embolism in Chile.

OBJECTIVE: Nonvalvular atrial fibrillation (NVAF) is a risk factor for ischemic stroke and systemic embolism. New oral anticoagulants are currently available. The objective of this study was to assess the incremental cost-utility ratio (ICUR) for apixaban vs. acenocoumarol in patients treated in Chile's public health system. STUDY DESIGN AND SETTING: We assessed cost-utility from the payer perspective with a lifetime Markov model. Epidemiologic characteristics, costs, and utilities were obtained from a Chilean cohort; data were completed with information from international literature. RESULTS: Incremental costs when using apixaban vs. acenocoumarol over a lifetime are CH$2,108,600 with an incremental effectiveness of 0.173 years of life gained (YLG) and 0.182 quality-adjusted life-year (QALY). The ICUR of apixaban vs. acenocoumarol was CH$12,188,439 per YLG and CH$11,585,714 per QALY. One to 3 times gross domestic product (GDP) per capita threshold is acceptable based on World Health Organization (WHO) norms. Chilean GDP per capita was CH$7,797,021 in 2013. The sensitivity analysis shows that these results are sensitive to the ischemic stroke risk with apixaban, and the intracranial hemorrhage risk due to the use of acenocoumarol. CONCLUSION: The use of apixaban in patients with NVAF in moderate-to-high risk of stroke is cost-effective, considering the payment threshold suggested by WHO.

Latin American Clinical Epidemiology Network Series - Paper 8: Ticagrelor was cost-effective vs. clopidogrel in acute coronary syndrome in Chile.

OBJECTIVE: To evaluate the incremental cost-effectiveness ratio (ICER) of the use of ticagrelor as a substitute for clopidogrel for secondary prevention of acute coronary syndrome in Chile. STUDY DESIGN AND SETTING: Cost-effectiveness analysis based on a Markov model: Safety and effectiveness data of ticagrelor were obtained from a systematic review of the literature. Costs are expressed in Chilean pesos (CLP) as of 2013. The evaluation was conducted from the payer standpoint. A probabilistic sensitivity analysis comprising discount rates and national cost variability was done. A budget impact analysis estimated for 2015 was conducted to calculate the total cost for both treatments. RESULTS: The ICER with a discount rate of 6% for ticagrelor vs. clopidogrel was CLP 4,893,126 per quality-adjusted life-year (QALY) gained (=9,689 US$). In the budget impact analysis for the baseline scenario, considering 100% of treatment, coverage, and adherence, ticagrelor represented an additional cost of CLP 5,233,854,272, for 979 QALYs gained compared with clopidogrel. CONCLUSIONS: Ticagrelor is cost-effective in comparison with clopidogrel for the secondary prevention of acute coronary syndrome. These findings are similar to those reported in other international cost-effectiveness studies.

Costo efectividad y análisis de impacto presupuestario del óxido nítrico inhalatorio neonatal en un hospital, desde la perspectiva del sistema público de salud / Cost effectiveness and budget impact analysis of inhaled nitric oxide in a neonatal unit from the perspective of the public health system

El óxido nítrico inhalatorio (ONi) es actualmente la terapia de primera línea en la insuficiencia respiratoria hipoxémica grave del recién nacido; la mayor parte de los centros neonatales de regiones en Chile no cuentan con esta alternativa terapéutica. Objetivo: Determinar el costo-efectividad del ONi en el tratamiento de la insuficiencia respiratoria asociada a hipertensión pulmonar del recién nacido, comparado con el cuidado habitual y el traslado a un centro de mayor complejidad. Pacientes y método: Se modeló un árbol de decisiones clínicas desde la perspectiva del sistema de salud público chileno, se calcularon razones de costo-efectividad incremental (ICER), se realizó análisis de sensibilidad determinístico y probabilístico, se estimó el impacto presupuestario, software: TreeAge Health Care Pro 2014. Resultados: La alternativa ONi produce un aumento promedio en los costos de 11,7 millones de pesos por paciente tratado, con una razón de costo-efectividad incremental comparado con el cuidado habitual de 23 millones de pesos por muerte o caso de oxigenación extracorpórea evitada. Al sensibilizar los resultados por incidencia, encontramos que a partir de 7 casos tratados al año resulta menos costoso el óxido nítrico que el traslado a un centro de mayor complejidad. Conclusiones: Desde la perspectiva de un hospital regional chileno incorporar ONi en el manejo de la insuficiencia respiratoria neonatal resulta la alternativa óptima en la mayoría de los escenarios posibles.

Inhaled nitric oxide (iNO) is currently the first-line therapy in severe hypoxaemic respiratory failure of the newborn. Most of regional neonatal centres in Chile do not have this therapeutic alternative. Objective: To determine the cost effectiveness of inhaled nitric oxide in the treatment of respiratory failure associated with pulmonary hypertension of the newborn compared to the usual care, including the transfer to a more complex unit. Patients and method: A clinical decision tree was designed from the perspective of Chilean Public Health Service. Incremental cost effectiveness rates (ICER) were calculated, deterministic sensitivity analysis was performed, and probabilistic budget impact was estimated using: TreeAge Pro Healthcare 2014 software. Results: The iNO option leads to an increase in mean cost of $ 11.7 million Chilean pesos (€ 15,000) per patient treated, with an ICER compared with the usual care of $ 23 million pesos (€ 30,000) in case of death or ECMO avoided. By sensitising the results by incidence, it was found that from 7 cases and upwards treated annually, inhaled nitric oxide is less costly than the transfer to a more complex unit. Conclusions: From the perspective of a Chilean regional hospital, incorporating inhaled nitric oxide into the management of neonatal respiratory failure is the optimal alternative in most scenarios.

Control of cervical cancer in Peru: Current barriers and challenges for the future.

Cervical cancer is the leading malignant neoplasm in Peruvian women. This malignancy is a public health problem and several efforts were previously performed to develop cancer control plans. Geographical, cultural, structural, infrastructural and procedural barriers can limit the implementation of such strategies. Several previous studies have characterized human papilloma virus (HPV) epidemiology, where prevalence of high-risk HPV in adult females is ~12% and the prevalence in cervical cancer is 90-95%. The predominant barriers for the control of cervical cancer are lack of specialists in remote villages, education/cultural issues, loss of patients in follow-up, lack of access to HPV testing and lack of compliance for HPV vaccination. A good strategy for the prevention and early detection of high-risk HPV, pre-malignant neoplasms and cervical cancer, identified by interventional studies, is the self-sampling test, which assists with overcoming the cultural and geographic barriers. The current cancer control plan, termed 'Plan Esperanza', is performed with massive training of health professionals and social sensitization campaigns leading to filling the gaps regarding education and, in addition, it provides cancer care coverage for poorer individuals. In our experience at Oncosalud-AUNA, with a cohort of ~750,000 affiliates using a pre-paid system with annual screenings for cervical cancer for women, offered free-of-charge, a lower incidence of this malignancy (5.8/100,000) is now observed compared with the national incidence (32.7/100,000). As in other countries, the HPV vaccination can be a cost-utility strategy to reduce the high burdens of cervical cancer in Peru, a rapid and cheap HPV molecular sub-typification is rapidly required.

[Cost effectiveness and budget impact analysis of inhaled nitric oxide in a neonatal unit from the perspective of the public health system]. / Costo efectividad y análisis de impacto presupuestario del óxido nítrico inhalatorio neonatal en un hospital, desde la perspectiva del sistema público de salud.

Inhaled nitric oxide (iNO) is currently the first-line therapy in severe hypoxaemic respiratory failure of the newborn. Most of regional neonatal centres in Chile do not have this therapeutic alternative. OBJECTIVE: To determine the cost effectiveness of inhaled nitric oxide in the treatment of respiratory failure associated with pulmonary hypertension of the newborn compared to the usual care, including the transfer to a more complex unit. PATIENTS AND METHOD: A clinical decision tree was designed from the perspective of Chilean Public Health Service. Incremental cost effectiveness rates (ICER) were calculated, deterministic sensitivity analysis was performed, and probabilistic budget impact was estimated using: TreeAge Pro Healthcare 2014 software. RESULTS: The iNO option leads to an increase in mean cost of $ 11.7 million Chilean pesos (€15,000) per patient treated, with an ICER compared with the usual care of $23 million pesos (€30,000) in case of death or ECMO avoided. By sensitising the results by incidence, it was found that from 7 cases and upwards treated annually, inhaled nitric oxide is less costly than the transfer to a more complex unit. CONCLUSIONS: From the perspective of a Chilean regional hospital, incorporating inhaled nitric oxide into the management of neonatal respiratory failure is the optimal alternative in most scenarios.

Repeated observation of immune gene sets enrichment in women with non-small cell lung cancer.

There are different biological and clinical patterns of lung cancer between genders indicating intrinsic differences leading to increased sensitivity to cigarette smoke-induced DNA damage, mutational patterns of KRAS and better clinical outcomes in women while differences between genders at gene-expression levels was not previously reported. Here we show an enrichment of immune genes in NSCLC in women compared to men. We found in a GSEA analysis (by biological processes annotated from Gene Ontology) of six public datasets a repeated observation of immune gene sets enrichment in women. "Immune system process", "immune response", "defense response", "cellular defense response" and "regulation of immune system process" were the gene sets most over-represented while APOBEC3G, APOBEC3F, LAT, CD1D and CCL5 represented the top-five core genes. Characterization of immune cell composition with the platform CIBERSORT showed no differences between genders; however, there were differences when tumor tissues were compared to normal tissues. Our results suggest different immune responses in NSCLC between genders that could be related with the different clinical outcome.

Revisión Sistemática sobre los Efectos Adversos de la Fluoración del Agua / Systematic Review of the Adverse Effects of Water Fluoridation

Durante las últimas décadas, una considerable atención científica ha sido puesta en la seguridad de los fluoruros, dada la amplia variedad de fuentes de ingestión a la que la población se encuentra expuesta y los riesgos a la salud de las personas que esto puede acarrear. El objetivo de esta investigación fue determinar si la fluoración del agua a concentraciones de 0,6 a 1 ppm se asocian a una mayor proporción de efectos adversos en la población general al compararlo con concentraciones subóptimas. Se realizó una revisión sistemática de la literatura en MEDLINE, EMBASE, COCHRANE, SCIELO, LILACS, CRD, BBO, PAHO y WHOLIS, limitada desde el 2002 al 2012. Se incluyeron estudios primarios y secundarios en español, inglés y portugués con al menos dos poblaciones comparadas, una con niveles óptimos de flúor en agua (0,6­1 ppm) y otra sin fluoración del agua (<0,3 ppm) o con niveles subóptimos (>0,3 < 0,6 ppm). Dos investigadores de forma independiente realizaron evaluación de la calidad de los artículos seleccionados y que cumplieron los criterios de inclusión. La búsqueda arrojó 1024 artículos de los cuales 24 cumplieron los criterios de inclusión y 10 fueron incluidos como evidencia. Con excepción de fluorosis dental, no hay asociación entre fluoración del agua con fracturas óseas, cáncer u otro efecto adverso. A pesar de la mayor prevalencia de fluorosis en zonas fluoradas, esta fue principalmente del tipo cuestionable a leve y la proporción de fluorosis con daño estético no difiere significativamente de la presente en zonas sin fluoración del agua.

During the last decades, considerable scientific attention has been paid to the safety of fluoride, given the wide variety of sources of intake at which the population is exposed and the risks to the health of people this may produce. The aim was to determine whether water fluoridation at concentrations from 0.6 to 1 ppm is associated with a higher proportion of adverse effects in the general population when comparing them to suboptimal concentrations. A systematic review was conducted of the literature in MEDLINE, EMBASE, COCHRANE, SCIELO, LILACS, CRD, BBO, PAHO and WHOLIS, limited to 2002 to 2012. Included were primary and secondary studies in Spanish, English and Portuguese with at least two compared populations, one with optimal fluoride levels in the water (0.6­1 ppm) and another without water fluoridation (<0.3 ppm) or with suboptimal levels (>0.3 < 0.6ppm). Two researchers independently evaluated the quality of the articles selected and which met the inclusion criteria. The search revealed 1024 articles, of which 24 met the inclusion criteria and 10 were included as evidence. With the exception of dental fluorosis, there is no association between any other adverse effect and water fluoridation. Despite the greater prevalence of fluorosis in fluoride than in non-fluoride zones, this was mainly questionable to slight and the proportion of fluorosis with esthetic damage does not differ significantly from this in zones without water fluoridation.

[The main methodological aspects in Health Technology Assessment]. / Principales aspectos metodológicos en la Evaluación de Tecnologías Sanitarias.

This article reviews the most relevant methodological aspects involved in Health Technology Assessment (HTA). Firstly, it addresses the process of defining the research problem (or scoping). Then it explains some specific aspects of systematic reviews of evidence, as well as indirect and mixed comparisons of the effectiveness of interventions. It covers also the methods for economic evaluation in healthcare and the budget impact analysis of interventions. Finally, the paper provides an empirical insight on the methodological emphasis used by HTA agencies around the world, and reflects on the available capacities in our country in the topics discussed.

Carga de enfermedad atribuible al tabaquismo en Chile / Disease burden attributable to smoking in Chile

Objetivo: El objetivo inicial del proyecto, comenzado en el año 2005, fue seleccionar y desarrollar el marco metodológico más adecuado, así como elaborar un modelo económico común, con el fin de estimar la carga de enfermedad relacionada con el tabaquismo y la costo-efectividad de las intervenciones para controlar la epidemia del tabaco en América Latina.En este reporte se presentan los detalles del modelo económico, el proceso de calibración y validación para adecuarlo a la realidad de Chile y los resultados de carga de enfermedad atribuible al tabaquismo, medida tanto en términos de salud como económicos. Materiales e Métodos: Se describen a continuación los siguientes puntos relacionados con el desarrollo y utilización del modelo económico: 1) Etapa inicial de diagnóstico de situación, 2) Descripción del modelo, 3) Metodología utilizada para la selección de fuentes de información e incorporación de parámetros, 4) Proceso de calibración y validación, 5) Estimación de carga de enfermedad, 6) Aspectos metodológicos de los datos epidemiológicos considerados, y 7) Características de la información de costos de atención médica requerida para el modelo. Conclusión: En Chile el tabaquismo es responsable de una importante cantidad de muertes prematuras, enfermedad y costos sanitarios. El mayor peso está dado por las enfermedades cardiovasculares, la enfermedad pulmonar obstructiva crónica y el cáncer de pulmón. Su impacto en la mortalidad y en la calidad de vida es responsable en forma directa de la pérdida de 428.588 años de vida (por muerte prematura y discapacidad) cada año y explica el 18,5% de todas las muertes que se producen en el país. El tabaquismo genera además un costo directo anual de más de 1 billón de pesos chilenos. Es esperable que los resultados de este estudio contribuyan a tomar conciencia sobre los efectos del tabaco y sean un soporte para que los responsables de las políticas puedan llevar adelante intervenciones para reducir su consumo, lograr la implementación de mayores impuestos al tabaco e instalar las políticas de control promovidas por el Convenio Marco de la Organización Mundial de la Salud para el Control del Tabaco (CMCT-OMS).

Time trends of human papillomavirus types in invasive cervical cancer, from 1940 to 2007.

Contribution over time of human papillomavirus (HPV) types in human cancers has been poorly documented. Such data is fundamental to measure current HPV vaccines impact in the years to come. We estimated the HPV type-specific distribution in a large international series of invasive cervical cancer (ICC) over 70 years prior to vaccination. Paraffin embedded ICC cases diagnosed between 1940 and 2007 were retrieved from eleven countries in Central-South America, Asia and Europe. Included countries reported to have low-medium cervical cancer screening uptake. Information on age at and year of diagnosis was collected from medical records. After histological confirmation, HPV DNA detection was performed by SPF-10/DEIA/LiPA25 (version1). Logistic regression models were used for estimating the adjusted relative contributions (RC) of HPV16 and of HPV18 over time. Among 4,771 HPV DNA positive ICC cases, HPV16 and HPV18 were the two most common HPVs in all the decades with no statistically significant variations of their adjusted-RC from 1940-59 to 2000-07 (HPV16-from 61.5 to 62.1%, and HPV18-from 6.9 to 7.2%). As well, the RC of other HPV types did not varied over time. In the stratified analysis by histology, HPV16 adjusted-RC significantly increased across decades in adenocarcinomas. Regarding age, cases associated to either HPV16, 18 or 45 were younger than those with other HPV types in all the evaluated decades. The observed stability on the HPV type distribution predicts a high and stable impact of HPV vaccination in reducing the cervical cancer burden in future vaccinated generations.

Principales aspectos metodológicos en la Evaluación de Tecnologías Sanitarias / The main methodological aspects in Health Technology Assessment

This article reviews the most relevant methodological aspects involved in Health Technology Assessment (HTA). Firstly, it addresses the process of defining the research problem (or scoping). Then it explains some specific aspects of systematic reviews of evidence, as well as indirect and mixed comparisons of the effectiveness of interventions. It covers also the methods for economic evaluation in healthcare and the budget impact analysis of interventions. Finally, the paper provides an empirical insight on the methodological emphasis used by HTA agencies around the world, and reflects on the available capacities in our country in the topics discussed.

An economic evaluation of trastuzumab as adjuvant treatment of early HER2-positive breast cancer patients in Colombia / Evaluación económica del trastuzumab como tratamiento adyuvante en cáncer de mama HER2- positivo en Colombia

Objective: Trastuzumab (Herceptin®), a recombinant, humanized, monoclonal antibody targeting HER2 is well established as an effective treatment for HER2-positive breast cancer. Evidence from developed countries showed that trastuzumab was cost-effective; but there are few evidences in developing countries. This study assesses the cost-effectiveness of adjuvant trastuzumab treatment in Colombia. Methods: A Markov health-state transition model was built to estimate clinical and economic outcomes in HER2-positive breast cancer with or without 12 months trastuzumab adjuvant chemotherapy over a lifetime perspective with annual transition cycles. The model incorporated five health states (diseasefree, local recurrence, distant recurrence, cardiac failure, and death). Baseline event rates and 3-year hazard ratio (HR=0.51, IC 95% 0.44-0.59; p<0.0001) were derived from 4-year follow up of the N9831 and NSABP B-31 trial. Costs and utility weights were obtained from the literature and were discounted by 5% annually. Results: The model showed that the utilization of adjuvant trastuzumab treatment in early breast cancer can prolong 0.80 quality-adjusted life-years (QALY), compared with standard chemotherapy, an incremental cost-effectiveness ratio (ICER) of US$ 71,491 per QALY gained. Conclusion: The results suggest that 1-year adjuvant Trastuzumab treatment is not cost-effective in Colombia, using the definition of WHO cost-effectiveness threshold of 3 times GDP per capita.

Introducción. El trastuzumab es un anticuerpo monoclonal de reconocida efectividad para el tratamiento en mujeres con cáncer de mama positivo para HER2. Sin embargo, la mayoría de estudios de costo-efectividad se han llevado a cabo en países desarrollados. Objetivo. Determinar el costo-efectividad del tratamiento adyuvante con trastuzumab en mujeres con cáncer de mama HER2+ en Colombia. Materiales y métodos. Se construyó un modelo de Markov, con ciclos de transición anuales y desde la perspectiva del pagador, para estimar los resultados clínicos y económicos derivados de la administración de trastuzumab en mujeres con HER2 positivo. El modelo incorpora cinco estados de transición: libre de enfermedad, recurrencia local, metástasis, falla cardiaca y muerte. La tasa de eventos y la razón de tazas instantáneas (0,51; IC 95% 0,44-0,59; p<0,0001) se derivaron del reporte a cuatro años de los ensayos clínicos controlados N9831 y NSABP B-31. Los costos y las utilidades se estimados a partir de la literatura científica, utilizando una tasa de descuento del 5 % anual. Resultados. El modelo revela que la utilización de trastuzumab como tratamiento adyuvante prolonga la expectativa de vida ajustada por calidad en 0,8 años, en comparación con la quimioterapia sin trastuzumab; a una razón de costo efectividad incremental (sic.) de US$ 71.491 por año de vida ganado ajustado por calidad de vida. Conclusión. El tratamiento con trastuzumab durante un año no es costo-efectivo en Colombia, utilizando la definición de costo-efectividad de la OMS de menos de dos a tres veces el PIB per cápita por año de vida ganado ajustado por calidad de vida.

Prevalencia de lesiones premalignas de cuello uterino e infecci¢n por papilomavirus humano en madres del Comit‚ de Vaso de Leche de la Municipalidad de Surquillo / Cervical pre malignant lesions And PVH infection prevalence in women of the “Vaso de leche” committee in Surquillo district

Introducción: El papilomavirus humano (PVH) es el agente etiológico del cáncer de cuello uterino, siendo los subtipos de alto riesgo (16 y 18) los responsables de la mayoría de casos de esta neoplasia. El objetivo de este estudio fue determinar la prevalencia de lesiones premalignas de cuello uterino y factores de riesgo de PVH de alto grado. Métodos: Se realizó un estudio prospectivo, descriptivo y de corte transversal en madres menores de 55 años. La determinación de lesiones malignas fue realizada en 1142 mujeres mediante biopsia guiada por colposcopía en aquellas que presentaron citología anormal.El estudio de PVH se realizó mediante captura híbrida en 409 mujeres. Resultados: la prevalencia de infección con PVH de alto riesgo fue del 15,2%. La prevalencia de citología convencional anormal fue de 2,2%. La prevalencia de neoplasia interepitelial cervical (NIC) fue de 1.3% de los cuales 0,79% correspondieron a NIC II y NIC III. Adicionalmente se informa que fueron tomadas 214 muestras de citología de Base Líquida al grupo de captura híbrida, encontrándose 4,7% de anormalidades citológicas y 1,4% de NIC. Tanto en el análisis univariado y multivariado la ocupación y el estado civil muestran mayor significancia como factores de riesgo para la infección por PVH y realizarse el Papanicolaou (PAP) en los tres últimos años muestra mayor significancia como factor de riesgo para la presencia de citología anormal.

Introduction: Human papilomavirus (HPV) is the etiologic agent of cervical cancer, and its high risk subtypes (16, 18) are responsible of the majority of cases of this malignancy. The aim of this study was to determine the prevalence of the “cervical pre malign lesions”, high risk HPV subtypes and transversal study was made including mothers under 55 years. Malignant lesions determination was performed in 1142 women through colposcopy guide biopsy in those who presented abnormal cytology. The hybrid capture PVH infection prevalence was 15, 2%. Conventional abnormal cytology prevalence was 2, 2%. The intraepithelial cervical malignancy prevalence (NIC) was 1, 3%, 0,79% corresponding to NIC II and NIC III. Additionally, 214 samples were taken from the hybrid capture group to perform the “liquid base cytology” analysis, were the 4,4% corresponded to cytological abnormalities and the 1,4% to NIC. The univariated analysis showed that both occupation and marital status had more significance as risk factors for PVH infection, in the same way women who have had a Pap smear in the last 3 years showed more significance a as a risk factor for abnormal cytology.

Planning cancer control in Latin America and the Caribbean.

Non-communicable diseases, including cancer, are overtaking infectious disease as the leading health-care threat in middle-income and low-income countries. Latin American and Caribbean countries are struggling to respond to increasing morbidity and death from advanced disease. Health ministries and health-care systems in these countries face many challenges caring for patients with advanced cancer: inadequate funding; inequitable distribution of resources and services; inadequate numbers, training, and distribution of health-care personnel and equipment; lack of adequate care for many populations based on socioeconomic, geographic, ethnic, and other factors; and current systems geared toward the needs of wealthy, urban minorities at a cost to the entire population. This burgeoning cancer problem threatens to cause widespread suffering and economic peril to the countries of Latin America. Prompt and deliberate actions must be taken to avoid this scenario. Increasing efforts towards prevention of cancer and avoidance of advanced, stage IV disease will reduce suffering and mortality and will make overall cancer care more affordable. We hope the findings of our Commission and our recommendations will inspire Latin American stakeholders to redouble their efforts to address this increasing cancer burden and to prevent it from worsening and threatening their societies.