Papillomavirus from the bench to the clinics

[Excerpt] Human papillomavirus (HPV) represents an exciting subject of study because it is currently established as an essential etiological factor of uterine cervical cancer and strongly implicated in the development of other genital cancers as well, in addition to benign genital warts. Additionally, substantial amount of new data have been elaborated linking HPV with head and neck cancer and, more tentatively, also with esophageal, breast, prostate, and lung cancers. Despite the existing controversies, the possible link of HPV infection with these nongenital carcinomas opens a new fascinating era of HPV research. [...

Estado de salud y barreras en la atención de niños con defectos congénitos nacidos entre el 2011 y el 2017 en dos instituciones de salud de Cali

Introduction: Birth defects affect 2-3% of births contributing an important load to the causes of infant morbidity and mortality during the first five years of life. In Colombia, they are the second cause of infant mortality according to reports from the Departamento Administrativo Nacional de Estadística (DANE) 2011.Objective: To describe the state of health and barriers in the health care of children with congenital defects born between 2011 and 2017 in two institutions of Cali.Materials and methods: We conducted a descriptive cross-sectional observational study. We included babies born between January, 2011, and December, 2017, with at least one congenital defect who were followed up by telephone.Results: Out of 54,193 births during the period, 1,389 (2.56%) newborns had at least one congenital defect. All cases were classified according to the prognostic scale and 881 were included in the follow-up. The most frequent congenital defect was congenital cardiac malformation with 88 cases (9.99%), followed by malformation/defect of the kidney with 73 cases (8.29%), Down syndrome with 72 cases (8.17%), and testicular abnormalities with 56 cases (6.36%). Out of the 454 cases with effective follow-up, 161 (35.46%) of the caregivers stated that they had experienced at least one type of barrier during health care.Conclusion: Follow-up programs should be implemented for patients with birth defects to contribute to reducing morbidity and mortality.Introducción. Los defectos congénitos afectan entre el 2 y el 3 % de los recién nacidos, y son una carga importante entre las causas de morbilidad y mortalidad infantil en los primeros cinco años de vida. En Colombia, fueron la segunda causa de mortalidad infantil según los reportes del Departamento Administrativo Nacional de Estadística (DANE) para el 2011.Objetivo. Describir el estado de salud y las barreras en la atención de niños con defectos congénitos nacidos entre el 2011 y el 2017 en dos instituciones de salud de Cali.Materiales y métodos. Se hizo un estudio observacional descriptivo de corte transversal. Se incluyeron los nacidos entre enero de 2011 y diciembre de 2017 con, al menos, un defecto congénito, a quienes se les hizo seguimiento telefónico.Resultados. De 54.193 nacidos en el período analizado, 1.389 (2,56 %) tenían, por lo menos, un defecto congénito. Todos los casos se clasificaron según la escala de pronóstico y se incluyeron 881 en el seguimiento. El defecto congénito más frecuente fue la malformación congénita cardíaca, con 88 (9,99 %) casos; en segundo lugar, las malformaciones o defectos del riñón, con 73 (8,29 %) casos; en tercer lugar, el síndrome de Down, con 72 (8,17 %) casos, y en cuarto lugar, las anormalidades testiculares, con 56 (6,36 %). Ciento sesenta y uno (35,46 %) de los cuidadores de los 454 casos con seguimiento efectivo, manifestaron haber encontrado, por lo menos, un tipo de barrera en la atención.Conclusión. Se deben implementar programas de seguimiento de los pacientes con defectos congénitos, que contribuyan a disminuir la morbimortalidad

Human papillomavirus vaccination in national immunization programs: impact and perspectives

Human Papillomaviruses are present in virtually all cases of cervical cancer and are also linked with anogenital warts and other precancerous lesions which can be primarily prevented by HPV vaccination. We searched the PubMed, Scopus, Web of Science and Embase databases (between January 1st, 2011 and February 28th, 2017) and WHO (World Health Organization) and countries’ health organizations websites for data on HPV vaccination programs and its effectiveness. For the review on the Brazilian Immunization program, we additionally searched SciELO database and websites of the Brazilian Ministry of Health and the Information System of the National Immunization Program (SI-PNI). As of April 2017, about 40% of the countries had introduced HPV vaccines in their national immunization programs, targeting almost always children and teenage females between 9 and 13 years of age. Most of these are high-income countries but low- and middle-income countries are recently implementing the vaccination program with financial support of public and private organizations. Since the introduction of HPV vaccination, numerous articles present data on its effectiveness in real world supporting the effectiveness of an immunization program in the prevention of HPV infection and related diseases in both genders. The Brazilian HPV vaccination program began in 2014 for 9-13 years old girls and has recently been expanded to include boys and young males. This review aims to update information on HPV vaccination programs worldwide highlighting the Brazilian immunization program. Data on the impact and effectiveness of HPV vaccines on infection and related diseases is presented. Moreover, the reasons for different coverage rates, reflected in low-vaccine uptake, are discussed. Finally, the present review addresses the socioeconomic barriers as well as the key determinants of long-term program success and strategies to improve access and adherence to HPV vaccination.O Papilomavírus Humano (HPV) está presente em praticamente todos os casos de câncer do colo do útero e também em verrugas anogenitais e outras lesões pré-cancerígenas diversas, que podem ser prevenidos primariamente via vacinação. Até abril de 2017, cerca de 40% dos países já haviam introduzido a vacina de HPV em seus programas nacionais de imunização, tendo por alvo quase sempre meninas entre 9 e 13 anos de idade. A maioria desses países são de alta renda, mas países de média e baixa renda têm implementado recentemente programas de vacinação com o apoio de organizações de financiamento públicas e privadas. Desde a introdução da vacinação de HPV, inúmeros artigos apresentam dados sobre sua efetividade no mundo real, apoiando a efetividade de um programa de imunização na prevenção da infecção e na redução das doenças relacionadas ao HPV em ambos os sexos. O programa brasileiro de vacinação contra o HPV iniciou-se em 2014 para meninas de 9 a 13 anos de idade e, recentemente, foi ampliado para meninos. Este artigo de revisão visa atualizar os dados de implementação de vacina de HPV em diferentes países do mundo, enfatizando o programa brasileiro. Além disso, são apresentados os dados de impacto e efetividade da vacina de HPV em relação à redução de infecções e doenças causados pelos tipos de HPV contidos nas vacinas. Ainda, são apontadas as razões para as diferentes taxas de cobertura e dificuldades observadas na implementação dos programas, considerando barreiras sociais e econômicas. Finalmente, são discutidos os principais determinantes de sucesso a longo prazo e estratégias para melhorar o acesso e a aderência aos programas de vacinação

Innate immunity and HPV: friends or foes

Most human papillomavirus infections are readily cleared by the host immune response. However, in some individuals, human papillomavirus can establish a persistent infection. The persistence of high-risk human papillomavirus infection is the major risk factor for cervical cancer development. These viruses have developed mechanisms to evade the host immune system, which is an important step in persistence and, ultimately, in tumor development. Several cell types, receptors, transcription factors and inflammatory mediators involved in the antiviral immune response are viral targets and contribute to tumorigenesis. These targets include antigen-presenting cells, macrophages, natural killer cells, Toll-like receptors, nuclear factor kappa B and several cytokines and chemokines, such as interleukins, interferon and tumor necrosis factor. In the present review, we address both the main innate immune response mechanisms involved in HPV infection clearance and the viral strategies that promote viral persistence and may contribute to cancer development. Finally, we discuss the possibility of exploiting this knowledge to develop effective therapeutic strategies

Juvenile-onset recurrent respiratory papillomatosis with pulmonary involvement and carcinomatous transformation

Papilloma associated with recurrent respiratory papillomatosis (RRP), caused by human papilloma virus (HPV) infection types 6 and 11, is the most common benign neoplasm of the larynx. The clinical features of RRP vary widely from mild to aggressive forms. RRP in children is known as juvenile-onset recurrent respiratory papillomatosis (JORRP). Its outcome may be poor or even fatal due to the high rate of recurrence and eventual spread to the entire respiratory tract. Pulmonary invasion is reported to occur in 3.3% of patients with RRP, and malignant transformation in 0.5% of patients. We report the case of a 39-year-old female patient with a diagnosis of JORRP from the age of 3 years, with extensive bilateral pulmonary involvement and malignant transformation. Analysis of the papilloma and carcinomatous tissues revealed the presence of HPV type 11, which is associated with rapid and aggressive progression. We discussed the case on the basis of a literature review on pulmonary invasion, malignant transformation, and HPV 11 aggressiveness

Self-collection for high-risk HPV detection in Brazilian women using the care HPV™ test

Cervical cancer is the second most common cancer among Brazilian women. High-risk human papillomavirus (hr-HPV) persistence is the primary cause of cervical neoplasia. Early detection of hr-HPV is important for identifying women at risk for developing cervical lesions. Approximately 85% of new cases of cervical cancer worldwide and 50% of the total cervical cancer deaths occurred in developing countries. Here, a new methodology to support a cervical cancer screening program was evaluated in women from various Brazilian regions. METHODS: Two thousand women aged 18-77years were enrolled in an opportunistic cervical cancer screening program and were randomized into self-vaginal or health professional-guided cervical sampling groups. The Qiagen careHPV™ test was performed on all samples. Pap tests were performed on all women using liquid-based cytology. RESULTS: Positive hr-HPV results were obtained in 12.3% (245/2000) of women; similar rates were observed in self- or health professional-collected samples. Eighty-nine percent (1719/2000) of cervical cytologies classified as normal were negative to hr-HPV. Among the cytological samples, 36.6% classified as ASC-US+ were positive to hr-HPV, 78.8% were LSIL and 75.0% were HSIL. CONCLUSIONS: Self-sampled and health professional-sampled vaginal/cervical specimens did not differ in their rates of detection of hr-HPV. Therefore, HPV DNA testing in self-sampled vaginal cells is an alternative to primary screening in low-resource settings.The authors thank the following: Cancer Prevention Department Team, Cleyton Zanardo de Oliveira and Allini Mafra of the Researcher Support Team and the Pathology Depai Intent of the Barretos Cancer Hospital. Rui Manuel Reis and Andre Lopes Carvalho from the Molecular Oncology Center; Jose Eduardo Levi from Sao Paulo University; Cintia B. Oliveira, Raphael Haikel junior and Edmundo Mauad from Barretos Cancer Hospital. Luisa Lina Villa was supported by a grant from CNPq and FAPESP (INCT-HPV). Study Supported by CNPq - Process no 573799/2008-3 and FAPESP no 2008/57889-1. They also thank all volunteer women who participated of this study

Critical analyses of the introduction of liquid-based cytology in a public health service of the state of São Paulo, Brazil

OBJECTIVE The aim of this study was to compare the performance of the current conventional Pap smear with liquid-based cytology (LBC) preparations. STUDY DESIGN Women routinely undergoing their cytopathological and histopathological examinations at Fundação Oncocentro de São Paulo (FOSP) were recruited for LBC. Conventional smears were analyzed from women from other areas of the State of São Paulo with similar sociodemographic characteristics. RESULTS A total of 218,594 cases were analyzed, consisting of 206,999 conventional smears and 11,595 LBC. Among the conventional smears, 3.0% were of unsatisfactory preparation; conversely, unsatisfactory LBC preparations accounted for 0.3%. The ASC-H (atypical squamous cells - cannot exclude high-grade squamous intraepithelial lesion) frequency did not demonstrate any differences between the two methods. In contrast, the incidence of ASC-US (atypical squamous cells of undetermined significance) was almost twice as frequent between LBC and conventional smears, at 2.9 versus 1.6%, respectively. An equal percentage of high-grade squamous intraepithelial lesions were observed for the two methods, but not for low-grade squamous intraepithelial lesions, which were more significantly observed in LBC preparations than in conventional smears (2.2 vs. 0.7%). The index of positivity was importantly enhanced from 3.0% (conventional smears) to 5.7% (LBC). CONCLUSIONS LBC performed better than conventional smears, and we are truly confident that LBC can improve public health strategies aimed at reducing cervical lesions through prevention programs

Genital human papillomavirus infection identification by molecular biology among asymptomatic women

OBJECTIVE: To evaluate whether epidemiological factors may be associated to genital human papillomavirus (HPV) infection. METHODS: A cross-sectional study was carried out among 975 women seen at a public health service for cervical cancer screening in Porto Alegre, Brazil. Women were considered infected if tested positive to HPV either by Polymerase Chain Reaction (PCR) or Hybrid Capture II (HC-II) methods. Women with genital HPV infection were compared to women without infection drawn from the same population. RESULTS: The study enrolled 975 women. The HPV prevalence (both methods combined) in this population was 27%. However, when each diagnostic method is analyzed separately, HPV prevalence was 15% and 16% for HC-II and PCR, respectively. Unconditional multiple logistic regression was used to correlate disease status to women characteristics. A positive association was found with HPV infection for the following variables: years of schooling (11 years: OR=2.05; 95%CI =1.31; 3.20), married (OR=1.69; 95%CI=0.78; 2.00), number of lifetime sexual partners (2 partners: OR=1.67; 95%CI=1.01; 2.77; 4 or +: OR=2.18; 95%CI=1.15; 4.13), age at first intercourse (15-16 years: OR=4.05; 95%CI=0.89; 18.29). CONCLUSIONS: Various factors may contribute to genital HPV infection, especially those related to sexual behavior (young age at first intercourse, high number of lifetime sexual partners, and marital status), and those related to social and economic status (years of schooling).OBJETIVO: Verificar a associação entre fatores epidemiológicos e infecção genital pelo papilomavírus humano (HPV). MÉTODOS: Realizou-se estudo transversal com 975 mulheres atendidas em um serviço público de rastreamento para o câncer cervical, em Porto Alegre, Brasil. As mulheres foram consideradas infectadas pelo HPV quando apresentaram o teste de DNA positivo para esse vírus, tanto pelo método de captura híbrida II (CH II) como pelo método de reação em cadeia da polimerase (PCR). Mulheres infectadas pelo HPV foram comparadas com mulheres não infectadas oriundas da mesma população. RESULTADOS: Foram estudadas 975 mulheres. A prevalência observada de HPV (pela combinação dos métodos de DNA) foi de 27%. Quando a análise de cada método de DNA foi feito isoladamente, a prevalência de HPV-DNA foi de 15% para a CH II e de 16% para PCR. Regressão logística múltipla incondicional foi utilizada na identificação dos fatores associados à infecção pelo HPV. Foi encontrada associação positiva com as seguintes variáveis: anos de escolaridade (11 anos: OR=2,05; IC95%=1,31; 3,20; referência: até oito anos de escolaridade); ser casada (OR=1,69; IC95%=0,78; 2,00; referência: ser solteira); parceiros sexuais ao longo da vida (dois parceiros: OR=1,67; IC95%=1,01; 2,77; quatro ou mais: OR=2,18; IC95%=1,15; 4,13; referência: um parceiro); idade da primeira relação sexual (15-16 anos: OR=4,05; IC95%=0,89; 18,29; referência: >; ou = 22 anos). CONCLUSÕES: Vários fatores parecem estar associados à presença de infecção genital pelo HPV, especialmente aqueles referentes ao comportamento sexual (idade da primeira relação sexual, número de parceiros sexuais ao longo da vida e estado marital) e aqueles relacionados à situação socioeconômica (escolaridade)

Human Papillomavirus prevalence among women with cervical intraepithelial neoplasia III and invasive cervical cancer from Goiânia, Brazil

This study estimated the prevalence and distribution of human papillomavirus (HPV) types among women with cervical intraepithelial neoplasia (CIN) grade III and invasive cervical cancer from Goiás (Brazil Central Region). Seventy-four cases were analyzed and consisted of 18 CIN III, 48 squamous cell carcinomas, 4 adenocarcinomas, 1 adenosquamous carcinoma and 3 undifferentiated carcinomas. HPV-DNA sequences were examined in formalinfixed and paraffin-embedded tissues using primers from L1 region GP5+/GP6+. Polymerase chain reaction products were typed with dot blot hybridization using probes for HPV 16, 18, 31, 33, 45, 54, 6/11, 42/43/44, 51/52, 56/ 58. The prevalence of HPV was estimated to be 76% (56/74). HPV 16 was the most frequently found type, followed by HPV 33, 18 and 31. The prevalence of untyped HPV was 6%; 79% percent of the squamous cell carcinoma cases and 61% percent of the CIN III were positive for HPV and the prevalence rate of HPV types was the same for the total number of cases. According to other studies, HPV type 16 is the most prevalent virus in all Brazilian regions, but there is variation regarding to other types. Type 18 is the second most prevalent HPV in North, Southeast and South Brazil regions and types 31 and 33 are the second most prevalent HPV in Northeast and Central Brazil, respectively

Revisão sistemática de literatura sobre modelos de previsão de consumo de energia elétrica

The growing consumption of electrical energy, climate change and the development of new technologies demand improvements for efficient energy management. An adequate forecast of the energy consumption is relevant for the sustainable development of any country. This article proposes a systematic review of selected literature based on search chains formed by the terms forecasting, energy and consumptionapplied to the scientific databases. In the article are compared mostly the models/ techniques used, the considered variables and the error metrics used for obtaining knowledge on each one of the proposals, relieve its features and thus highlight the void in the literature that might be determinant for new research work. As conclusions are made evident the continuous use of neural networks for forecasting theenergy consumption, the importance of determining the input variables and the error measuring for evaluating the precision of the models. Finally, the development of a model for the CEE short term forecast of a Latin-American developing country based on the comparison and evaluation of different  techniques/models, variables and already existing tools is proposed as a new line of research.El creciente consumo de energía eléctrica, los cambios climáticos y el desarrollo de nuevas tecnologías exigen mejoras para la gestión eficiente de la energía. El adecuado pronóstico del consumo de energía es relevante para el desarrollo sostenible de cualquier país. En este artículo se propone una revisión sistemática de literatura seleccionada a partir de cadenas de búsqueda formada por las palabras forecasting, energyy consumptionaplicadas en las bases de datos científicas. Se comparan principalmente los modelos/técnicas utilizadas, las variables consideradas y las métricas de error usadas con el fin de obtener conocimiento de cada una de las propuestas, relevar sus características y así poder evidenciar el vacío en la literatura que podría determinar la semilla para un nuevo trabajo de investigación. Como conclusiones se observan el uso continuo de redes neuronales artificiales para el pronóstico de consumo, la importancia determinar las variables de entrada y la medición del error para evaluar la precisión de los modelos. Finalmente, como nueva línea de investigación se propone desarrollar un modelo para el pronóstico de corto plazo de CEE para un país latinoamericano en vías de desarrollo, a partir de la comparación y evaluación de diferentes técnicas/modelos, variables y herramientas ya existentes.O crescente consumo de energia elétrica, as mudanças climáticas e o desenvolvimento de novas tecnologias exigem melhoras para a gestão eficiente da energia. A adequada previsão do consumo de energia é relevante para desenvolver sustentável de qualquer país. Neste artigo, é proposta uma revisão sistemática de literatura selecionada a partir de redes de busca formada pelas palavras “forecasting”, “energy” e “consumption” aplicadas nas bases de dados científicas. São comparados, principalmente, os modelos ou técnicas utilizados, as variáveis consideradas e as medidas de erro usadas a fim de obter conhecimento de cada uma das propostas, destacar suas características e, assim, poder evidenciar a lacuna na literatura quepoderia determinar a semente para um novo trabalho de pesquisa. Como conclusões, são observados o uso contínuo de redes neurais artificiais para prognosticar o consumo, a importância de determinar variáveis de entrada e a medição do erro para avaliar a exatidão dos modelos. Finalmente, como nova linha de pesquisa,propõe-se desenvolver um modelo para prever, em curto prazo, de CEE para um país latino-americano em via de desenvolvimento, a partir da comparação e da avaliação de diferentes técnicas e modelos, variáveis e ferramentas já existentes