Using focus groups to plan culturally acceptable primary cervical cancer screening in Grenada, West Indies / Uso de grupos focales para planificar exámenes primarios de detección del cáncer cervicouterino culturalmente aceptables en Granada, Caribe / Uso de grupos focais para planejar estratégias culturalmente aceitáveis para rastreamento de câncer do colo do útero primário em Granada, Índias Ocidentais

ABSTRACT Objective. To document Grenadian women's knowledge about cervical cancer and human papillomavirus (HPV) infection, as well as their attitudes towards primary cervical cancer screening methods. Methods. In this qualitative study, we used focus groups in Grenada to gather information concerning women's knowledge about, attitudes towards and perceptions of screening for cervical cancer and general knowledge about HPV. Ten focus groups comprising 73 participants representing 5 of the 6 parishes in Grenada were conducted with women aged 19-59. Participants were asked about pelvic exams, Pap smears, HPV, reasons for seeking or avoiding cervical cancer screening and how different modalities of testing might affect their decision-making. Responses were then coded and organized into common themes. Results. While many respondents had heard of HPV, far fewer knew about its causative role in cervical cancer, how to prevent HPV infection or testing for the high-risk HPV types that cause almost all cases of cervical cancer. Many participants were aware that cervical cancer screening was beneficial, but numerous barriers to obtaining that screening were noted, including concerns about privacy and stigma, potential discomfort, and the cost and inconvenience involved. Conclusions. Our findings have implications for future cervical cancer screening efforts in Grenada. Central to these efforts should be a focus on educating Grenadians about the role of HPV infection in cervical cancer and the importance of early detection through screening. In addition, addressing issues of stigma and privacy are key to eliminating cervical cancer in Grenada.

RESUMEN Objetivo. Documentar los conocimientos de las mujeres granadinas sobre el cáncer cervicouterino y la infección por el virus de los papilomas humanos (VPH), así como sus actitudes hacia los métodos primarios de detección del cáncer cervicouterino. Métodos. En este estudio cualitativo, se han empleado grupos focales en Granada para recopilar información sobre los conocimientos, las actitudes y las percepciones de las mujeres sobre la detección del cáncer cervicouterino y nociones generales sobre el VPH. Participaron 73 mujeres de 19 a 59 años de edad, representantes de 5 de las 6 parroquias de Granada. Se formaron diez grupos focales, a los que se les preguntó sobre los exámenes pélvicos, las pruebas de Papanicolaou, el VPH, las razones para buscar o evitar la detección del cáncer cervicouterino y cómo las diferentes modalidades de examen podrían afectar sus decisiones. Luego se codificaron las respuestas y se organizaron en temas comunes. Resultados. Si bien muchas participantes habían oído hablar del VPH, un número considerablemente menor conocía su relación causal con el cáncer cervicouterino, cómo prevenir la infección por VPH o los exámenes de detección de los tipos del VPH de alto riesgo que causan casi todos los casos de cáncer cervicouterino. Muchas participantes sabían que los exámenes de detección del cáncer de cuello uterino eran convenientes, pero mencionaron numerosos obstáculos para obtenerlos, como las preocupaciones sobre la privacidad y la estigmatización, posibles molestias, así como el costo y los inconvenientes relacionados. Conclusiones. Nuestros hallazgos tienen implicaciones para la futura labor de detección del cáncer cervicouterino en Granada. En esta labor debería ser esencial adoptar un enfoque dirigido a educar a las granadinas sobre la relación de la infección por VPH con el cáncer cervicouterino y la importancia de la detección temprana mediante exámenes. Además, combatir los problemas de estigmatización y privacidad es clave para eliminar el cáncer cervicouterino en Granada.

RESUMO Objetivo. Documentar o conhecimento das mulheres de Granada sobre o câncer do colo do útero e a infecção por papilomavírus humano (HPV), bem como suas atitudes em relação aos métodos de rastreamento de câncer do colo do útero primário. Métodos. Neste estudo qualitativo, usamos grupos focais em Granada para coletar informações sobre conhecimentos, atitudes e percepções das mulheres sobre o rastreamento de câncer do colo do útero e conhecimentos gerais sobre HPV. Foram conduzidos dez grupos focais, incluindo 73 participantes e representando 5 das 6 paróquias de Granada, com mulheres de 19 a 59 anos de idade. As participantes responderam perguntas sobre exames ginecológicos, Papanicolau, HPV, razões para procurar ou evitar o rastreamento de câncer do colo do útero e como diferentes modalidades de testes podem afetar sua tomada de decisão. As respostas foram codificadas e organizadas por temas comuns. Resultados. Muitas participantes já tinham ouvido falar do HPV, mas um número muito menor conhecia sua relação causal com o câncer do colo do útero, formas de prevenir a infecção por HPV ou os testes para os tipos de HPV de alto risco, que causam quase todos os casos de câncer do colo do útero. Muitas participantes sabiam que o rastreamento de câncer do colo do útero era benéfico, mas várias barreiras para o rastreamento foram indicadas, incluindo preocupações relacionadas à privacidade e ao estigma, o potencial desconforto e o custo e inconveniência envolvidos. Conclusões. Nossos achados têm implicações para as futuras iniciativas de rastreamento de câncer do colo do útero em Granada. Essas iniciativas devem se focar em educar a população de Granada sobre o papel da infecção por HPV no câncer do colo do útero e a importância da detecção precoce por meio do rastreamento. Além disso, é fundamental abordar questões de estigma e privacidade para eliminar o câncer do colo do útero em Granada.

Análisis del uso de las técnicas de tamizaje para la detección de cáncer cervicouterino en Chile / Analysis of the use of screening techniques for the detection of cervical cancer in Chile

El Cáncer Cervicouterino es una de las principales problemáticas en salud de las mujeres a nivel mundial. Las técnicas de tamizaje para la detección de Cáncer Cervicouterino han ido desarrollándose a través de la historia reciente tanto intencionada como casualmente, incorporando con cada nuevo descubrimiento a las nuevas tecnologías. Actualmente existen diversos procedimientos vigentes que van desde pruebas sencillas de inspección visual, pasando por las tradicionales muestras citológicas, hasta la utilización de tecnología molecular, y los usos que se les dan a estos métodos de cribado potencian la detección temprana del Cáncer Cervicouterino, razón por lo cual se realiza una revisión respecto de las técnicas de tamizajes disponibles y su aplicación en Chile.

Cervical Cancer is one of the main problems in women's health worldwide. Screening techniques for the detection of Cervical Cancer have been developed throughout recent history both intentionally and incidentally, incorporating new technologies with each new discovery. Currently there are various procedures in force that range from simple visual inspection tests, through traditional cytological samples, to the use of molecular technology, and the uses that are given to these screening methods enhance the early detection of Cervical Cancer, which is why which is carried out a review regarding the available screening techniques and their application in Chile.

Influencia del cáncer cérvico-uterino y la alteración de la salud mental en pacientes menores de 25 años en Ecuador / Influence of cervico-uterine cancer and the alteration of mental health in patients under 25 years of age in Ecuador

INTRODUCCIÓN: Los problemas sanitarios en los pacientes que padecen cáncer cérvico-uterino influyen en la satisfacción personal y evitan una gran adherencia a la terapia médica, y además están relacionados con un número más notable de efectos secundarios y la estancia en la clínica de emergencia junto afecciones depresivas y problemas de ansiedad. OBJETIVO: Identificar la influencia del cáncer cérvico -uterino en las alteraciones en la salud mental de pacientes menores de 25 años en el Ecuador. METODOLOGÍA: La investigación fue de tipo cuantitativo, descriptivo, y de corte transversal. Se utilizaron encuestas de manera virtual dirigida a pacientes menores de 25 años que padecen de cáncer al cuello uterino en diversas Fundaciones que luchan contra el cáncer, contando con una muestra de 178 mujeres, estas se dividieron en 4 categorías: Salud mental, Estrés, Depresión y Total de escalas. RESULTADOS: El porcentaje que se obtuvo de manera general tuvo un rango variado, el 32,9% dio como resultado que la alteración que causa en la mujer es contundente, seguido del 30,6 que su afección en la salud mental es más baja. CONCLUSIÓN: Se concluye afirmando que el cáncer uterino es el segundo cáncer más prevalente en la mujer, el cual influye de manera progresiva en la salud mental, presentando reacciones negativas y percepciones, falta de control en las emociones, consecuentemente aquello debilita el sistema inmunológico previamente comprometido, generando alteraciones en el curso del tratamiento.

INTRODUCTION: Health problems in patients suffering from cervical-uterine cancer influence personal satisfaction and prevent a high adherence to medical therapy, and are also related to a more notable number of side effects and stay in the emergency clinic together depressive conditions and anxiety problems. OBJECTIVE: To identify the influence of cervical cancer -uterine in the alterations in the mental health of patients under 25 years in Ecuador. MATERIALS AND METHODS: The research was quantitative, descriptive, andcross-sectional. Surveys were used in a virtual way directed at patients under 25 years of age who suffer from cervical cancer in various Foundations that fight against cancer, with a sample of 178 women, these were divided into 4 categories: Mental health, Stress, Depression and Total stopovers. RESULTS: The percentage that was obtained in a general way had a varied range, 32.9% gave as a result that the alteration it causes in women is overwhelming, followed by 30.6 that their mental health condition is lower. CONCLUSION: It is concluded by stating that uterine cancer is the second most prevalent cancer in women, which progressively influences mental health, presenting negative reactions and perceptions, lack of control over emotions, consequently that weakens the previously compromised immune system, generating alterations in the course of treatment.

Medical students' knowledge of the human papillomavirus (HPV), cervical cancer, and HPV vaccination / Conhecimento dos alunos de medicina sobre papilomavírus humano (HPV), câncer cervical e vacinação contra HPV

Abstract: Introduction: Medical students still have many doubts regarding HPV (Human papillomavirus) and the vaccine against this virus. Objective: The study aimed to assess the University of Brasilia medical students' grasp of knowledge about HPV, its relationship with cancer, and the vaccine against the virus. Methods: A cross-sectional study was undertaken by applying a survey questionnaire on the topics. The evaluation involved 379 respondents, 72.7% of the 521 students from the 1st to the 6th years enrolled in the second semester of 2017. The statistical analyses included differences between means and proportions, effect size measures, and the correlation between the identified indicators. The study was approved by the Ethics Committee in Research on Human Beings of the School of Medicine (1,989,835). Results: The 50-item knowledge score increased progressively with the year attended by the medical students (r= .706, p< .001), and was higher among the sexually-active compared to celibate participants (t = 3.26, df = 275, p = 0.001, d = 0.37), as well as among participants with higher family income compared to those with lower family income (t= 2.91, df= 366, p= .004, d= .35). No significant score differences emerged between participants grouped by gender, sexual behavior, or HPV vaccination status. Furthermore, gender (female; OR= 6.5, p<.001), age range (<24 years; OR= 3.3, p= .001), sexuality (active; OR= 2.7, p= .002), but not overall knowledge were predictors of the wish to be vaccinated among the 297 unvaccinated students. Conclusion: The study revealed a strong correlation of medical students' HPV-related knowledge with medical school year and significantly higher scores among sexually active and higher-income respondents, but there were no essential differences between males and females or between vaccinated and unvaccinated students. Among the latter participants, gender, age, and sexuality, but not knowledge, were the best predictors of the wish to be vaccinated. The findings suggest the need for improving HPV screening and vaccination programs and educational strategies regarding HPV-related diseases.

Resumo: Introdução: Há ainda, entre os estudantes de Medicina, muitas dúvidas com relação ao papilomavírus humano (HPV) e à vacina contra esse vírus. Objetivo: Este estudo teve como objetivo avaliar a compreensão dos estudantes de Medicina da Universidade de Brasília acerca do HPV, da sua relação com o câncer e da vacina contra o vírus. Método: Foi realizado um estudo transversal por meio da aplicação de um questionário teste sobre os temas. A avaliação envolveu 379 respondentes, o que representava 72,7% dos 521 alunos do primeiro ao sexto ano matriculados no segundo semestre de 2017. As análises estatísticas incluíram diferenças entre médias e proporções, medidas de tamanho de efeito e a correlação entre os indicadores identificados. O estudo foi aprovado pelo Comitê de Ética em Pesquisa em Seres Humanos da Faculdade de Medicina (1,989,835). Resultado: A pontuação de conhecimento de 50 itens aumentou progressivamente com o ano do curso médico (r = 0,706, p <0,001) e foi maior entre os participantes sexualmente ativos em comparação com os celibatários (t = 3,26, df = 275, p = 0,001, d = 0,37), e entre os participantes com renda familiar mais alta em comparação com aqueles com renda mais baixa (t = 2,91, df = 366, p = 0,004, d = 0,35). Nenhuma diferença significativa de pontuação foi observada entre os participantes agrupados por gênero, comportamento sexual ou estado de vacinação contra o HPV. Além disso, sexo (feminino; OR = 6,5, p <0,001), faixa etária (<24 anos; OR = 3,3, p = 0,001) e sexualidade (ativo; OR = 2,7, p = 0,002), mas não o conhecimento geral, foram preditores do desejo de vacinação entre 297 alunos não vacinados. Conclusão: O estudo revelou uma forte correlação entre o conhecimento relacionado ao HPV dos estudantes de Medicina e o ano de estudo, e pontuações significativamente mais altas entre os respondentes sexualmente ativos e de renda superior, mas não houve nenhuma diferença essencial entre homens e mulheres ou entre alunos vacinados e não vacinados. Entre estes últimos, gênero, idade, sexualidade, e não o conhecimento foram os melhores preditores do desejo de vacinação. Os achados sugerem a necessidade de aperfeiçoamento em programas de triagem e vacinação para HPV e nas estratégias educacionais referentes às doenças relacionadas ao vírus.

Prevalencia de los genotipos de HPV en lesiones pre invasoras de alto grado de malignidad y cáncer de cuello uterino en la población del Hospital de Clínicas: Montevideo-Uruguay / Prevalence of HPV genotypes in cervical high risk intraepithelial lesions and cervical cancer in the population of Hospital de Clínicas: Montevideo-Uruguay / Prevalência de genótipos de HPV em lesões pré-invasivas com alto grau de malignidade e câncer de colo do útero na população do Hospital de Clínicas: Montevidéu, Uruguai

El Cáncer de Cuello Uterino (CCU) es un problema de Salud pública a nivel mundial. Su indiscutible asociación con el Virus del papiloma humano (HPV) hace necesario su estudio. El objetivo de este trabajo, es conocer la prevalencia de los diferentes genotipos de HPV, en lesiones pre invasoras de alto grado de malignidad (HSIL) y/o cáncer de cuello uterino. Material y Métodos: Todas las Mujeres que fueron derivadas a pol de TGI del H Clínicas entre enero del 2011 y diciembre de 2012, por un PAP sospechoso de lesión y en las que se confirmó luego un HSIL o cáncer cervical fueron tipificadas. Se recabaron datos de edad, tipo de lesión y genotipificación. La extracción de ADN viral se realizó a partir de muestras cervico vaginales conservadas en medio de transporte comercial (Sacace) mediante el kit QIAamp DNA Mini Kit (QIAGEN). Se buscaron 14 genotipos de alto riesgo. Resultados: Se tipificaron 75 pacientes, 19 con CCU y 56 con HSIL. El HPV 16 fue el más prevalente en un 61,5 % para las infecciones únicas y en un casi 100 % para las múltiples y un 60% para el total de las lesiones, seguido en prevalencia por los HPV 31,33 y 45. El HPV 18 fue muy poco prevalente. Conclusiones: En esta muestra, la prevalencia del HPV 16 está acorde con las publicaciones nacionales siendo el más frecuente. El HPV 18 tiene muy baja prevalencia siendo 2 casos en 75, siempre en infecciones múltiples.

Cervical Cancer (CC) is a public health problem worldwide. Its indisputable association with the Human Papilloma Virus (HPV) makes its study necessary. The objective of this work is to know the prevalence of the different HPV genotypes, in pre-invasive high-grade malignant lesions (HSIL) and / or cervical cancer. Material and Methods: All women who were referred to Low genital tract service in the Hospital de Clinicas between January 2011 and December 2012, for a PAP suspected of injury and in which HSIL or cervical cancer was later confirmed were typified. Data on age, type of lesion and genotyping were collected. The viral DNA extraction was carried out from cervico-vaginal samples preserved in commercial transport medium (Sacace) using the QIAamp DNA Mini Kit (QIAGEN). 14 high-risk genotypes were searched. Results: 75 patients were typified, 19 with CCU and 56 with HSIL. HPV 16 was the most prevalent in 61.5% for single infections and almost 100% for multiple infections and 60% for all lesions, followed in prevalence by HPV 31,33 and 45. The HPV 18 was very rare. Conclusions: In this sample, the prevalence of HPV 16 is in accordance with national publications, being the most frequent. HPV 18 has a very low prevalence, being 2 cases in 75, always in multiple infections.

O câncer cervical é um problema de saúde pública em todo o mundo. E um câncer com uma ligação comprovada com o vírus do papiloma humano. O objetivo é conhecer a prevalência dos diferentes genótipos do HPV em mulheres que apresentam neoplasias pré-invasivas de alto grau e câncer de colo do útero, que foram tratadas e diagnosticadas no Hospital de Clínicas entre janeiro de 2011 e dezembro de 2012. Material e Métodos: o estudo foi realizado em 75 pacientes do Hospital de Clinicas, com diagnóstico histológico de Câncer Cervical e lesões intraepiteliais de alto grau para as quais foi realizado o tipageme do HPV alto risco. Resultados: 75 pacientes foram tipificados, 19 com CCU e 56 com HSIL. O HPV 16 foi o mais prevalente em 61,5% para infecções únicas e quase 100% para infecções múltiplas e 60% para todas as lesões, seguido em prevalência pelo HPV 31,33 e 45. O HPV 18 era muito raro. Conclusões: Nesta amostra, a prevalência do HPV 16 está de acordo com as publicações nacionais, sendo a mais frequente. O HPV 18 tem prevalência muito baixa, sendo 2 casos em 75, sempre em infecções múltiplas.

Age patterns of human papillomavirus infection as primary screening test for cervical cancer and subsequent triage with visual inspection in Honduras / Patrones de edad de infección por el virus del papiloma humano como prueba primaria en el tamizaje de cáncer de cuello uterino y triaje posterior con inspección visual en Honduras

Abstract Objective: To evaluate age patterns in human papillomavirus (HPV) prevalence and visual inspection with acetic acid (VIA) positivity among women participating in cervical cancer screening in Honduras. Materials and methods: Data on the HPV status (careHPV) and subsequent VIA in HPV-positive women were retrieved from three provinces within the Public Health Sector. Results: Between 2015 and 2018, 60 883 women aged 15-85 years were screened. HPV was detected in 15%, with variation by age, peaking at 20-24 years (27.8%) decreasing to 16% at 30-49 years. Differences in point age-specific HPV prevalence were observed between provinces, but with similar age pattern. VIA was positive in 24.5% of the women aged 30-44 years. Conclusions: The age pattern of the HPV prevalence supports starting HPV testing at age 30+. The low positivity of VIA in ages close to menopause suggest underdetection of cervical lesions in this age group.

Resumen Objetivo: Evaluar la prevalencia del virus del papiloma humano (VPH) y la positividad a la inspección visual con ácido acético (IVA) de cáncer cervicouterico, según edad en mujeres tamizadas en Honduras. Material y métodos: Se extrajo información sobre la prueba de VPH (careHPV) y de IVA en tres provincias en el ámbito de la Atención Pública en Salud. Resultados: Durante 2015-2018, 60 883 mujeres de 15-85 años fueron tamizadas, 15% fueron VPH positivas con valores máximos en mujeres de 20-24 años (27.8%), con una disminución a 16% entre 30-49 años. Se observaron diferencias mínimas entre provincias, con un patrón de edad similar. La IVA fue positiva en 24.5% en mujeres de 30-44 años, con una posterior disminución. Conclusiones: La curva de prevalencia del VPH respalda el tamizar con VPH a los 30+ años. La baja positividad de la IVA en edades cercanas a la menopausia sugiere una subdetección de lesiones cervicales en este grupo.

Immunology of cervical cancer

ABSTRACT Optimal function of the immune system allows the recognition and elimination of infected and tumor cells. However, these cells can develop mechanisms to evade the cellular immune response. In human papillomavirus (HPV) infection, dysregulation of major histocompatibility complex Class I molecules and other components of the innate immune system promote the survival of infected cells by allowing the infection to persist which, in turn, favors the development of cancer. Further, tumor cells possess inherent mechanisms designed to block the recognition and activation of cytotoxic lymphocytes: particularly, HPV proteins such as E1 and E2 and oncoproteins E5, E6, and E7 that inhibit immune mechanisms and/or stimulate the expression of immunosuppressive cytokines. These mechanisms include a decrease in receptor activation and costimulating molecules on the surface of immune cells, as well as the constitutive expression of molecules that inhibit their function, which allow HPV persistence and tumor progression. Immunotherapy-based therapeutic options are positioned as excellent candidates for the treatment of cervical cancer.

Avaliação do perfil de mulheres atendidas em centros de referência em saúde de Porto Alegre/RS e relação de alterações citológicas detectadas no exame citopatológico e a presença do HPV / Profile evaluation of women that attended reference health centers in Porto Alegre/RS and the relationship between cytological alterations detected in cytopathological examination and presence of HPV / Evaluación del perfil de las mujeres atendidas en los centros de referencia de salud de Porto Alegre / RS y la relación de las alteraciones citológicas detectadas en el examen citopatológico con la presencia de VPH

Justificativas e Objetivos: Câncer de colo de útero é considerado um problema de saúde pública mundial. Seu diagnóstico é realizado através do exame citopatológico (EC) e seu desenvolvimento relacionado à infecção pelo papilomavírus humano (HPV). Este estudo objetiva avaliar o perfil de mulheres atendidas em centros de referência em saúde de Porto Alegre, Rio Grande do Sul, assim como a relação de alterações observadas ao EC com presença do HPV. Métodos: Estudo transversal realizado em mulheres atendidas em unidades básicas de saúde e um ambulatório de referência de hospital público terciário, no período de julho de 2014 a janeiro de 2017. Coletaram-se amostras representativas da endo/ectocérvice para realização do EC e investigadas quanto à presença molecular do HPV. Resultados: Foram analisadas 169 mulheres com idade média entre 31 e 40 anos, das quais 125 (74%) informaram que a sexarca ocorreu na faixa de 15-20 anos e 37,9% relatou ter tido de três a cinco parceiros sexuais. Em relação ao EC, 71 (42%) apresentaram resultado negativo para lesão intraepitelial ou malignidade e 98 (58%) alguma anormalidade de células escamosas: 20 (11,8%) atipias; 22 (13%) lesão intraepitelial escamosa de baixo grau e 56 (32,6%) lesão intraepitelial de alto grau (HSIL). Cinquenta (29,6%) apresentaram positividade para HPV, destas 56,4% foram diagnosticadas com HSIL (p<0,01). Conclusão: Os resultados revelam alta frequência de HPV em amostras com alterações citopatológicas, em mulheres jovens e com grau de exposição ao HPV, reforçando a importância do papel da sua identificação precoce na investigação da carcinogênese cervical.(AU)

Background and Objectives: Cervical cancer is considered a worldwide public health problem. Its diagnosis is made through cytopathological examination and its development related to human papillomavirus (HPV) infection. This study aims to evaluate the profile of women treated at reference health centers in Porto Alegre, Rio Grande do Sul, as well as the relation of changes observed to cytopathological examination with the presence of HPV. Methods: This is a cross-sectional study carried out in women treated at basic health units and a referral clinic of a public tertiary hospital, from July 2014 to January 2017. Representative samples of the endo/ectocervix were collected to perform the cytopathological examination and investigated for the molecular presence of HPV. Results: 169 women with mean age between 31 and 40 years were analyzed, of whom 125 (74%) reported that the onset of sexual activity occurred in the 15-20 years age group, and 37.9% reported having had three to five sexual partners. In relation to cytopathological examination, 71 (42%) had a negative result for intraepithelial lesion or malignancy and 98 (58%) some squamous cell abnormality: 20 (11.8%) atypical; 22 (13%) low-grade squamous intraepithelial lesion and 56 (32.6%) high-grade intraepithelial lesion (HSIL). Fifty (29.6%) were positive for HPV, of which 56.4% were diagnosed with HSIL (p < 0.01). Conclusion: The results reveal a high frequency of HPV in samples with cytopathological changes, in young women and with a degree of exposure to HPV, reinforcing the importance of the role of its early identification in the investigation of cervical carcinogenesis.(AU)

Justificación y objetivos: El cáncer de cuello uterino se considera un problema de salud pública en todo el mundo. Su diagnóstico se realiza mediante el examen citopatológico (EC), y su desarrollo está relacionado con la infección por el virus del papiloma humano (VPH). Este estudio objetivó evaluar el perfil de mujeres atendidas en los centros de referencia en salud de Porto Alegre, Rio Grande do Sul (Brasil), así como la relación de las alteraciones observadas en el EC con la presencia del VPH. Métodos: Estudio transversal realizado en las mujeres atendidas por unidades de atención primaria y por una clínica ambulatoria de referencia del hospital público terciario en la ciudad de Porto Alegre, en el período de julio de 2014 a enero de 2017. Se recolectaron muestras representativas de endo/ectocérvice para realizar la CE, las cuales se clasificaron según el sistema Bethesda y se investigaron la presencia molecular del VPH. Resultados: Analizamos 169 mujeres con promedio de edad entre 31 y 40 años, de las cuales 125 (74%) informaron que el sexarche ocurrió en el rango de 15-20 años. La mayoría (37,9%) informó haber tenido de 3 a 5 parejas sexuales; y el 37,3% estaban usando anticonceptivos orales. Con respecto a la EC, 71 (42%) se clasificaron como negativos para lesión intraepitelial o malignidad; y el 98 (58%) tenían alguna anormalidad de células escamosas: 20 (11,8%) de atipias; 22 (13,0%) lesión intraepitelial escamosa de bajo grado y 56 (32,6%) lesión intraepitelial de alto grado (HSIL). La frecuencia de positividad del VPH encontrada fue de 50 (29,6%), de estas un 56,4% fueron diagnosticadas con HSIL (p<0,01). Conclusiones: Estos resultados revelan una alta frecuencia de VPH en muestras con alteraciones citopatológicas presentes en mujeres jóvenes con cierto grado de exposición al VPH, lo que refuerza la importancia de identificarse tempranamente en el análisis de la carcinogénesis cervical.(AU)

The contribution of Latin American research to HPV epidemiology and natural history knowledge

Our aim was to review the major contributions of studies conducted in different Latin American (LA) countries to the field of human papillomavirus (HPV) epidemiology, natural history, risk of disease, and prevention strategies, mainly in the uterine cervix. Although cytological screening is established in several countries in LA, incidence and mortality rates from cervical cancer (CC) are still extremely high. Finally, data from large cohort studies conducted in LA countries provided seminal data to propose primary and secondary prevention modalities: the HPV vaccine has been introduced in the national immunization programs of several LA countries and multiple screening experiences using HPV testing are under evaluation in the region.

Knowledge of human papillomavirus and Pap test among Brazilian university students

SUMMARY OBJECTIVE: Human papillomavirus (HPV) is the most prevalent sexually transmitted virus in the world and is associated with an increased risk of cervical cancer. The most effective approach to cervical cancer control continues to be screening through the preventive Papanicolaou test (Pap test). This study analyzes the knowledge of university students of health science programs as well as undergraduate courses in other areas of knowledge on important questions regarding HPV. METHOD: Four hundred and seventy-three university students completed a questionnaire assessing their overall knowledge regarding HPV infection, cervical cancer, and the Pap test. A descriptive analysis is presented, and multivariate analysis using logistic regression identified factors associated with HPV/cervical cancer information. RESULTS: Knowledge was higher for simple HPV-related and Pap test questions but was lower for HPV interrelations with genital warts and cervical cancer. Being from the health science fields and having high income were factors associated with greater knowledge. Only the minority of the participants recognized all the situations that increased the risk of virus infection presented in the questionnaire. CONCLUSIONS: These findings highlight the need for educational campaigns regarding HPV infection, its potential as a cervical cancer agent and the forms of prevention available.

RESUMO OBJETIVO: O papilomavírus humano (HPV) é o vírus sexualmente transmissível mais prevalente no mundo, estando a infecção por este agente associada a um aumento do risco do câncer de colo uterino. A abordagem mais eficaz para o controle desse tipo de câncer continua sendo a triagem por meio do exame preventivo (Papanicolaou). Este estudo analisa o conhecimento de estudantes universitárias de cursos da área da saúde, bem como cursos de graduação de outras áreas do conhecimento com relação a questões importantes sobre o HPV. MÉTODO: Quatrocentas e setenta e três estudantes universitárias responderam a um questionário que avaliava os conhecimentos sobre a infecção pelo HPV, o câncer de colo do útero e o exame preventivo. Após análise descritiva, foi feita a análise multivariada por regressão logística para identificação dos fatores associados à informação sobre o HPV/câncer de colo do útero. RESULTADOS: O conhecimento das universitárias foi maior para questões simples relacionadas ao HPV e ao exame preventivo, mas foi menor para as correlações do HPV com verrugas genitais e com o câncer de colo do útero. Ser aluna da área da saúde e ter alta renda foram fatores associados ao maior conhecimento. Somente uma minoria das participantes reconheceu todas as situações que aumentavam o risco de infecção pelo HPV apresentadas no questionário. CONCLUSÃO: Os resultados evidenciam a necessidade de realização de campanhas educativas sobre a infecção pelo HPV, do seu potencial como agente de câncer do colo uterino e as formas de prevenção disponíveis.

Detección y tipificación del Virus Papiloma Humano en el marco del tamizaje virológico para la detección de lesiones del cuello uterino en Asunción, Paraguay / Detection and typing of Human Papilloma Virus during a virological screening for detection of cervical lesions in Asunción, Paraguay

En Paraguay la incidencia de cáncer de cuello uterino (CCU) es superior a las observadas en otros países de la región. El agente etiológico asociado al CCU es el virus papiloma humano (VPH), esencialmente tipos de alto riesgo oncogénicos. El objetivo es describir aspectos epidemiológicos de la infección genital por el virus papiloma humano de alto riesgo (VPH-AR) en mujeres de 25 a 64 años que consultaron en servicios de Patología Cervical del MSPyBS, de mayo a diciembre de 2013. Se utilizó el Cobas 4800 HPV Test (Roche) que permite la detección individual de VPH-16 y VPH-18 y un pool de otros VPH-AR que incluye 12 genotipos de alto riesgo. Los otros VPH-AR fueron tipificados por hibridación reversa en línea (RLB). Entre las 495 mujeres incluidas, se detectaron 72 casos positivos (14,5%) de VPH-AR. Se identificaron 19 tipos virales; siendo el más frecuente VPH-16 (2,1%), seguido del VPH-31, 33, 58 y 66; el VPH-18 aparece en sexto lugar. Este trabajo aporta los primeros datos sobre la implementación de técnicas moleculares para detección y tipificación de VPH como parte del sistema de salud pública de Paraguay. El predominio de VPH-16, confirma su amplia circulación a nivel mundial y dado su mayor potencial oncogénico, representa una alerta a considerar, en especial en las mujeres mayores de 30 años portadoras de una infección persistente. Estos resultados apoyan la importancia de la implementación criteriosa y la utilización apropiada de las pruebas moleculares actualmente disponibles para la prevención y control del CCU(AU)

Importancia del sistema de Bethesda en el diagnóstico citológico de lesiones precancerosas del cérvix / The importance of Bethesda system in the cytological diagnosis of the cervix pre-cancerous lesions

RESUMEN El cáncer cérvico uterino, causa alrededor de 250 000 muertes anuales en el mundo y alrededor de 400 en Cuba, a pesar del esfuerzo que realiza el MINSAP, a través del Programa de Pesquisaje. Con el mismo se puede obtener el diagnóstico de lesiones precursoras del cáncer de cuello uterino, este diagnóstico citológico se realiza en Cuba a través del método de Richard y Barron que demuestra que existe un progreso citológico aparente hasta llegar al cáncer, que comienza con neoplasia intraepitelial (NICI a NICIII y carcinoma in situ), hasta finalmente el cáncer invasor. Por otro lado existe el método de Bethesda que responde casi todas las interrogantes que la citología plantea para su enfrentamiento, evidentemente los mayores aportes y revisiones se enfocan al manejo de las citologías atípicas de significado incierto, ya que no sólo presentan un mayor número de posibles evaluaciones, sino que representan el mayor porcentaje de citologías alteradas y la inclusión del VPH en las lesiones de bajo grado. En Cuba todavía se clasifica por el método de Richard y no se utiliza el Bethesda. Por la alta incidencia de esta entidad el propósito de este trabajo es emitir consideraciones sobre la implementación del sistema de Bethesda en el diagnóstico citológico de lesiones precancerosas del cérvix.

ABSTRACT The cervical-uterine cancer causes almost 250 000 death a year around the world and around 400 in Cuba in spite of the efforts made by the Public Health Ministry through the Screening Program. With it, the diagnosis of lesions that are predecessors of the cervical cancer could be reached. This cytological diagnosis is carried out through the Richard and Barron method, showing that there is an apparent cytological progress leading to the cancer that begins with intraepithelial neoplasia (NICI and NICIII and carcinoma in-situ) and ends in the invasive cancer. From the other hand there is the Bethesda methods answering to all the questions cytology ask for confronting it. Obviously the biggest contributions and reviews are focused in the management of the atypical cytologies with uncertain significance since they not only have a higher number of possible evaluations, but also represent the highest percent of the altered cytologies and the inclusion of the HPV in low grade lesions. The classification in Cuba is still made by the Richard method and the Bethesda one is not used. Due to the high incidence of this entity, the aim of this article is exposing considerations on the implementation of the Bethesda system in the cytological diagnosis of cervix pre-cancerous lesions.

LncRNA CASC11 promotes the cervical cancer progression by activating Wnt/beta-catenin signaling pathway

BACKGROUND: Studies have shown that cancer susceptibility candidate 11 (CASC11), a newly discovered long non-coding RNA (lncRNA), was aberrantly overexpressed in hepatic carcinoma, gastric cancer and colorectal cancer. However, its effects on cervical cancer has been kept unknown up to now. The present study was aimed to investigate the relationship between lncRNA CASC11 and cervical cancer and further explore the mechanism of CASC11 effect on cervical cancer progression. MATERIALS: Quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expressions of CASC11 in cancerous and adjacent normal tissues of patients with cervical cancer as well as in cell lines. The proliferation, migration, invasion and apoptosis were assayed after transfecting the cell with si-CASC11 or pcDNA3.1-CASC11. TOP/FOP-Flash luciferase reporter assay and western blot were used to analysis the activation of Wnt/ß-catenin signaling pathway. Si-CASC11-transfected HeLa cells were subcutaneously inoculated into male athymic (nude) mice to investigate the effect of CASC11 on the tumor formation. RESULTS: We discovered that CASC11, the expression of which was positively associated with the tumor size and the FIGO staging and negatively related to the patients' survival rate, was up-regulated in the cervical cancer tissues and cell lines. Silencing CASC11 inhibited the proliferation, migration as well as invasion and promoted the cell apoptosis. Conversely, overexpression of CASC11 facilitated the cancer cell's proliferation, migration and invasion ability and suppressed the apoptosis. Further study showed that CASC11 promoted the migration and invasion of cervical cancer cells by activating Wnt/ß-catenin signaling pathway and silencing CASC11 inhibited the tumor growth in vivo. CONCLUSION: Our study demonstrated that CASC11 promoted the cervical cancer progression by activating Wnt/ß-catenin signaling pathway for the first time, which provides a new target or a potential diagnostic biomarker of the treatment for cervical cancer.

Optimización de una técnica de PCR convencional para detección de virus de papiloma humano tipo 16 y 18 / Optimization of a conventional PCR technique for detection of human papillomavirus type 16 and 18

El cáncer de cuello uterino es el segundo cáncer femenino más común a nivel mundial. El agente causal es el virus de papiloma humano (VPH). Se han identificado 13 tipos de virus de papiloma humano de alto riesgo oncogénico (VPH-AR), entre los cuales el VPH 16 y VPH 18 son los más frecuentemente detectados en cáncer de cuello uterino, siendo en Paraguay detectados en el 70% de casos de cáncer invasor. Por ello, el objetivo fue estandarizar y determinar el límite de detección de una técnica de PCR convencional para la detección de VPH 16 y 18. Para la detección de ADN de VPH 16 y 18, se observaron mejores resultados con 2mM de MgCl2 y 60°C para la temperatura de alineamiento. El límite de detección para las PCR fue de 14,6x10-11ng/µL para VPH 16 y 21,7x10-12ng/µL para VPH 18. Este trabajo servirá de base a otros estudios de detección e identificación de estos tipos virales por PCR, con miras a identificar un grupo de mujeres positivas para VPH-AR que poseen mayor riesgo de desarrollo de lesión y cáncer de cuello uterino y precisan de un seguimiento más cercano(AU

Cervical cancer is the second most common female cancer worldwide. It is caused by the human papilloma virus (HPV). Thirteen genotypes of high oncogenic risk human papilloma viruses (HPV-HR) have been identified, among which types 16 and 18 are the most frequently detected in cervical cancer. In Paraguay, they are detected in 70% of the invasive cancer cases. Therefore, the objective was to standardize and determine the detection limit of a conventional PCR technique for the detection of HPV 16 and 18. Better results were observed with 2mM MgCl2 and 60°C for the alignment temperature in detection of HPV 16 and 18 DNA. The limit of detection was 14.6x10-11ng/µL for HPV 16 and 21.7x10-12ng/µL for HPV 18. This work will help other studies for the detection and identification of these viral types by PCR in order to identify a group of HPV-HR positive women who have higher risk for the development of lesions and cervical cancer and need a closer follow-up(AU)

Guidelines for HPV-DNA testing for cervical cancer screening in Brazil / Recomendações para o uso de testes de DNA-HPV no rastreamento do câncer do colo útero no Brasil

Abstract Evidence-based clinical guidelines ensure best practice protocols are available in health care. There is a widespread use of human papillomavirus deoxyribonucleic acid (HPVDNA) tests in Brazil, regardless of the lack of official guidelines. On behalf of the Brazilian Association for the Lower Genital Tract Pathology and Colposcopy (ABPTGIC, in the Portuguese acronym), a team of reviewers searched for published evidence and developed a set of recommendations for the use of HPV-DNA tests in cervical cancer screening in Brazil. The product of this process was debated and consensus was sought by the participants. One concern of the authors was the inclusion of these tests in the assessment of women with cytologic atypia and women treated for cervical intraepithelial neoplasia (CIN). Testing for HPV is recommended in an organized screening scenario to identify women with precursor lesions or asymptomatic cervical cancer older than 30 years of age, and it can be performed every 5 years. It also has value after the cytology showing atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions (LSILs) as a triage test for colposcopy, in the investigation of other cytological alterations when no abnormal findings are observed at colposcopy, seeking to exclude disease, or, further, after treatment of high-grade cervical intraepithelial neoplasia, to rule out residual disease.

Resumo O uso de diretrizes clínicas baseadas em evidências visa assegurar as melhores práticas na área de cuidado à saúde. O uso de testes de ácido desoxirribonucleico de papilomavírus humano (DNA-HPV) vem crescendo e se disseminando sem que existam recomendações de uso no cenário brasileiro.Emnomeda Associação Brasileira de Patologia doTrato Genital Inferior e Colposcopia (ABPTGIC), grupos de revisores pesquisaram evidências e formularamrecomendações para o uso dos testes de DNA-HPV no rastreamento do câncer do colo do útero, no seguimento de mulheres com atipias citológicas, e após tratamento de neoplasia intraepitelial cervical (NIC). O produto desse processo foi debatido e foi buscado consenso entre participantes. Os testes de DNA-HPV são recomendados num cenário de rastreamento organizado para identificação de mulheres portadoras de lesões precursoras ou câncer assintomático com mais de 30 anos e podem ser realizados a cada 5 anos. Também têm valor após a citologia mostrando células escamosas atípicas de significado indeterminado (ASC-US) ou lesão intraepitelial escamosa de baixo grau (LSIL) como teste de triagempara colposcopia, na investigação de outras alterações citológicas quando não são observados achados anormais à colposcopia, buscando excluir doença, ou, ainda, no seguimento após tratamento das neoplasias intraepiteliais de alto grau, para exclusão de doença residual.

Molecular epidemiology and phylogenetic analysis of human papillomavirus infection in women with cervical lesions and cancer from the coastal region of Ecuador / Epidemiología molecular y análisis filogenético de la infección por el virus del papiloma humano en mujeres con lesiones cervicales y cáncer en la región litoral del Ecuador

The aim of the present study was to gather information regarding the molecular epidemiology of Human papillomavirus (HPV) and related risk factors in a group of women with low- and high-grade cervical lesions and cancer from the coastal region of Ecuador. In addition, we studied the evolution of HPV variants from the most prevalent types and provided a temporal framework for their emergence, which may help to trace the source of dissemination within the region. We analyzed 166 samples, including 57 CIN1, 95 CIN2/3 and 14 cancer cases. HPV detection and typing was done by PCR-sequencing (MY09/MY11). HPV variants and estimation of the time to most recent common ancestor (tMRCA) was assessed through phylogeny and coalescence analysis. HPV DNA was found in 54.4% of CIN1, 74.7% of CIN2/3 and 78.6% of cancer samples. HPV16 (38.9%) and HPV58 (19.5%) were the most prevalent types. Risk factors for the development of cervical lesions/cancer were the following: three or more pregnancies (OR = 4.3), HPV infection (OR = 3.7 for high-risk types; OR = 3.5 for HPV16), among others. With regard to HPV evolution, HPV16 isolates belonged to lineages A (69%) and D (31%) whereas HPV58 isolates belonged only to lineage A. The period of emergence of HPV16 was in association with human populations (tMRCA = 91 052 years for HPV16A and 27000 years for HPV16D), whereas HPV58A preceded Homo sapiens evolution (322 257 years). This study provides novel data on HPV epidemiology and evolution in Ecuador, which will be fundamental in the vaccine era.

El objetivo del presente estudio fue aportar información sobre la epidemiología molecular del virus del papiloma humano (human papillomavirus [HPV]) y los factores de riesgo asociados al desarrollo de lesiones cervicales y cáncer en mujeres de la costa del Ecuador. Además, se estudiaron la evolución de las variantes de los HPV más prevalentes y el marco temporal de su emergencia, para ayudar a rastrear la fuente de dispersión en la región. Se analizaron 166 muestras, incluyendo 57 y 95 casos de neoplasia intraepitelial cervical tipo 1 (CIN1) y tipo 2/3 (CIN2/3), respectivamente, y 14 de casos de cáncer. La detección/tipificación de HPV se realizó por PCR-secuenciación (MY09/MY11). La caracterización de variantes y la datación del ancestro común más reciente (tMRCA) se realizaron mediante filogenia y coalescencia. Se encontró ADN de HPV en el 54,4% de las muestras de CIN1, el 74,7% de las muestras de CIN2/3 y el 78,6% de las muestras de cáncer. Los tipos HPV16 (38,9%) y HPV58 (19,5%) fueron los más frecuentes. Los factores de riesgo para el desarrollo de lesiones cervicales/cáncer fueron 3 o más embarazos (OR = 4,3) e infección por HPV (O = 3,7 para HPV de alto riesgo, OR = 3,5 para HPV16), entre otros. En cuanto a la evolución viral, los aislados del HPV16 pertenecían a los linajes A (69%) y D (31%), mientras que los aislados del HPV58 pertenecían únicamente al linaje A. El período de emergencia del HPV16 estuvo asociado a poblaciones humanas (tMRCA = 91.052 años para HPV16Ay 27.000 para HPV16D), mientras que el del HPV58A precedió a la evolución de Homo sapiens (322.257 años). Este estudio proporciona datos novedosos sobre la epidemiología y la evolución del HPV en Ecuador, los cuales serán fundamentales en la era de la vacuna.

Tipificación viral en el seguimiento de conización: rol pronóstico de la persistencia del HPV post cono con asa / Viral typing in conization monitoring: prognostic role of HPV persistence post cone with loop

RESUMEN Fundamento: La persistencia del virus papiloma posterior a la conización del cuello uterino, se ha considerado un factor de riesgo para la persistencia de lesiones intra epiteliales (LIE) causadas por virus papiloma. Para determinar la asociación entre persistencia de lesión cervical y la presencia del virus papiloma posterior a la conización del cuello uterino, se realizó un estudio observacional prospectivo en un grupo de 123 pacientes portadoras de lesiones intraepiteliales de alto grado (LIEAG) tratadas con conización. Material y métodos: Se siguieron a 123 pacientes portadoras de LIEAG, ingresadas a la Unidad de Patología Cervical entre Abril de 2013 y Abril de 2014, las que fueron seguidas por 2 años hasta Abril de 2016. Se realizó genotipificación antes, y entre 4 a 6 meses posterior a la conización. Los datos se tabularon considerando la edad, paridad, tipo de virus, persistencia de LIE, reconización o requerimiento de histerectomía posterior. Resultados: La mediana de la edad fue de 37 años, el 91% fueron multíparas, y solo el 9% fueron nulíparas. El 56% ingresó por NIE III y el 44% por NIE II. Los virus más frecuentes fueron el 16, 31,58, 52 y 56. La persistencia de virus papiloma se constató en el 37% de las pacientes conizadas. La persistencia de LIE se observó en el 27% de las pacientes que fueron positivas para virus papiloma posterior a la conización, en comparación a sólo el 5% en las que fueron negativas. Del total de pacientes positivas para virus papiloma posterior a la conización, 12 de ellas presentaron persistencia de lesión confirmadas histológicamente por biopsia cervical, 8 pacientes requirieron recono por LIE de alto grado, 2 pacientes fueron a histerectomía y en 2 casos se realizó seguimiento estricto por NIE I. Cuando la tipificación post cono fue negativa solamente 3 pacientes requirieron conización y en sólo una se realizó seguimiento estricto por NIE I. Conclusión: La persistencia del virus papiloma posterior a la conización se asocia a mayor persistencia de LIEAG, mayor frecuencia de reconización o histerectomía posterior.

ABSTRACT Backgroud: The persistence of papilloma virus after conization of the cervix has been considered a risk factor for the persistence of cervical intra epithelial lesion (CIN) caused by papilloma virus. Aim: In order to determine the association between cervical lesion persistence and the presence of papilloma virus after conization, a prospective observational study was performed in a group of 123 patients with intraepithelial lesions treated with conization. Material and methods: We followed 123 patients with high grade CIN who were admitted to the Cervical Pathology Unit, between April 2013 and April 2014; they were followed for 2 years until April 2016. Viral genotyping was done before, and among the 4 to 6 months after the LEEP. Data were tabulated considering age, parity, type of virus, persistence of CIN, reconization or requirement of posterior hysterectomy. Results: The median age was 37 years, 91% were multiparous, and only 9% were nulliparous. 56% had NIE III and 44% NIE II. The most frequent viruses were 16, 31, 58, 52 and 56. The persistence of papillomavirus was present in 37% of patients. The persistence of CIN was observed in 27% of patients who were positive for papilloma virus after conization, compared to only 5% in those who were negative. Of the total number of patients positive for papilloma virus, in 12 of them had intra epitelial lesions were confirmed by cervical biopsy, 8 patients required recone for high grade CIN, 2 patients underwent hysterectomy, and 2 patients underwent follows up strictly by CIN I. When post cone typing was negative only 3 patients required conization and only one was followed strictly by CIN I.

Hybrid capture as a tool for cervical lesions screening in HIV-infected women: insights from a Brazilian cohort

ABSTRACT Introduction: Cervical cancer remains an important burden for HIV-infected women in the era of combination antiretroviral therapy. Recommendations for cervical screening in these women diverge and may include high-risk HPV (HRHPV) testing. We aimed to evaluate the clinical usefulness of a single HRHPV testing for cervical screening of HIV-infected women. Methods: 723 HIV-infected women from a Brazilian prospective cohort were included between 1996 and 2012. Inclusion criteria were: normal cervical cytology at baseline and having a HRHPV-test at baseline. We calculated incidence rates of any squamous intraepithelial lesion (SIL) and high grade SIL+ (HSIL+) and negative predictive values (NPV) within 12 and 36 months. Hazard Ratios were obtained using Cox proportional hazards regression models. Results: Incidence rate for both outcomes was low (9.9 cases per 100 PY [95% CI 8.8-11.0] for any SIL and 1.3 cases per 100 PY [95% IC 0.9-1.8] for HSIL+). Women with a HRHPV positive status at baseline had 1.7-fold (95% CI 1.3-2.2) and 3.2-fold (95% CI 1.5-7.1) increased risk of presenting any SIL and HSIL+, respectively, during follow-up. Negative-HRHPV test presented high NPV for both periods and outcomes (any SIL: 92.4% [95% CI 89.7-94.6] for 12 months and 80.9% [95% CI 77.2-84.3] for 36 months; and HSIL+: 99.8% [95% CI 98.9-100.0] for 12 months and 99.0 [95% CI 97.6-99.7] for 36 months). Conclusions: Incidence of any and high grade cytological abnormality was significantly higher among HIV-infected women with positive-HRHPV test. A single negative-HRHPV test helped reassure follow-up free of cytological abnormalities through three years of follow-up in HIV-infected women with negative cytology.