Estandarización de PCR en tiempo real para detección y cuantificación de los oncogenes E7 de seis Virus del Papiloma Humano de Alto Riesgo

El cáncer de cuello uterino es causado por la infección persistente del epitelio cervical con los genotipos de alto riesgo del Virus del Papiloma Humano. Para su detección se realizan pruebas moleculares que detectan el gen L1 del VPH. Este gen puede perderse hasta en el 11 % de los casos durante la integración del ADN viral en el genoma del hospedero originando falsos negativos. Por otra parte, el oncogén E7 se expresa durante todas las etapas de progresión de la enfermedad. El objetivo de este trabajo fue estandarizar una PCR en tiempo real del oncogén E7 (E7-qPCR) para genotipificación y cuantificación de 6 VPH-AR. Los resultados muestran que la E7- qPCR amplificó VPH-16, -18, -31, -33, -35 y -45 con una alta sensibilidad con límites de detección desde 102 copias, eficiencias entre 90 y 110 %, valores R2 > 0,97 y análisis de curva de fusión que revelan productos específicos.

Cervical cancer is caused by persistent infection of the cervical epithelium with the high-risk genotypes of the Human Papilloma Virus (HR-HPV). For its detection, molecular tests are carried out that detect the L1 gene of HPV. This gene can be lost in up to 11 % of cases during the integration of viral DNA into the host genome, causing false negatives. On the other hand, the E7 oncogene is expressed during all stages of disease progression. The aim of this work was to standardize a real-time PCR of the E7 oncogene (E7-qPCR) for genotyping and quantification of 6 HR-HPV. The results show that the E7-qPCR amplified HPV-16, -18, -31, -33, -35 and -45 with high sensitivity with detection limits from 102 copies, efficiencies between 90 and 110 %, R2 values >0,97 and melting curve analysis revealing specific products.

Seroprevalencia de SARS-CoV-2 y factores asociados en migrantes con vocación de permanencia, Bucaramanga, Colombia / SARS-CoV-2 seroprevalence and associated factors among migrants with a vocation for permanence, Bucaramanga, Colombia / Soroprevalência de SARS-CoV-2 e fatores associados em migrantes com vocação de permanência, Bucaramanga, Colômbia

Introducción: Existen pocos reportes que evalúen la seroprevalencia contra SARS-CoV-2 en población migrante en el mundo. Estos estudios ayudan a conocer la exposición al virus en las poblaciones para implementar acciones que reduzcan el impacto de la infección por SARS-CoV-2. Objetivo: Determinar la seroprevalencia contra SARS CoV-2 en migrantes con vocación de permanencia en Bucaramanga, e identificar factores asociados a la infección previa por SARS-CoV-2. Materiales y métodos: Estudio de corte transversal analítico con muestreo consecutivo. Se incluyeron migrantes adultos en Bucaramanga durante febrero/2021. Se realizaron encuestas e inmunoensayos de quimioluminiscencia para IgM e IgG contra SARS-CoV-2 en suero. Se calcularon razones de prevalencia (RP) con regresión log-binomial. Resultados:Se incluyeron 462 participantes. La seroprevalencia de IgM fue 11,7% (IC95% 9,1­14,9), de IgG fue 32,9% (IC95% 28,8­37,3) y de IgM o IgG fue 36,1% (IC95% 31,9-40,6). Exposición a un caso confirmado (RP:1,54; IC95%1,04-2,29) o sospechoso (RP:1,56; IC95%1,13-2,16) de COVID-19, seis o más convivientes (RP:1,52; IC95%1,05-2,20), estancia en Colombia ≥2 años (RP:1,43; IC95%1,11-1,92) y presencia de síntomas (RP:1,62; IC95%1,26 - 2,10) se asociaron con mayor seroprevalencia de IgG. Discusión:En Bucaramanga, la seroprevalencia en migrantes fue similar a la de migrantes en Kuwait, pero menor que en Paris y Singapur. Conclusión: En migrantes con vocación de permanencia la seroprevalencia contra SARS-CoV-2 fue similar a la reportada en residentes de Bucaramanga. El contacto con casos sospechosos/confirmados de COVID-19 y las condiciones de hacinamiento fueron algunos de los factores asociados a la seroprevalencia.

Introduction:There are few reports assessing anti-SARS-CoV-2 seroprevalence in the migrant population in the world. These studies help to understand the exposure of populations to the virus to take actions to reduce the impact of SARS-CoV-2 infection. Objetive: To determine the anti-SARS-CoV-2 seroprevalence in migrants with a vocation for permanence in Bucaramanga and to identify factors associated with previous SARS-CoV-2 infection. Materials and Methods:Analytical cross-sectional study using consecutive sampling, which included adult migrants in Bucaramanga in February 2021. Surveys were conducted, and chemiluminescent immunoassays were performed to detect IgM and IgG antibodies to SARS-CoV-2 in serum samples. Prevalence ratios (PR) were estimated using a log-binomial regression model. Results:The study enrolled 462 participants. IgM seroprevalence was 11.7% (95% CI 9.1­14.9), IgG seroprevalence was 32.9% (95% CI 28.8­37.3), and IgM or IgG seroprevalence was 36.1% (95% CI 31.9­40.6). Contact with a confirmed case of COVID-19 (PR:1.54; 95% CI 1.04-2.29) or suspected case (PR:1.56; 95% CI 1.13­2.16); living with six or more people (PR: 1.52; 95% CI 1.05­2.20); stay in Colombia ≥ 2 years (PR:1.43; 95% CI 1.11­1.92), and presence of symptoms (PR:1.62; 95%CI 1.26­2.10) were some factors associated with higher IgG seroprevalence. Discussion: In Bucaramanga, SARS-CoV-2 seroprevalence among migrants was similar to the seroprevalences of migrants in Kuwait but lower than migrants in Paris and Singapore. Conclusions: The anti-SARS-CoV-2 seroprevalence among migrants with a vocation for permanence was similar to that reported among residents of Bucaramanga. Contact with suspected or confirmed COVID-19 cases and crowded conditions were some of the factors associated with seroprevalence.

Introdução: Existem poucos relatos que avaliam a soroprevalência contra SARS-CoV-2 na população migrante no mundo. Esses estudos ajudam a conhecer a exposição ao vírus nas populações para implementar ações que reduzam o impacto da infecção por SARS-CoV-2. Objetivo: Determinar a soroprevalência contra SARS CoV-2 em migrantes que pretendem permanecer em Bucaramanga e identificar fatores associados à infecção anterior por SARS-CoV-2. Materiais e Métodos: Estudo analítico transversal com amostragem consecutiva. Foram incluídos migrantes adultos em Bucaramanga durante fevereiro/2021. Foram realizados levantamentos e imunoensaios de quimioluminescência para IgM e IgG contra SARS-CoV-2 no soro. As razões de prevalência (RP) foram calculadas com regressão log-binomial. Resultados: foram incluídos 462 participantes. A soroprevalência de IgM foi de 11,7% (IC 95% 9,1-14,9), de IgG foi de 32,9% (IC 95% 28,8-37,3) e de IgM ou IgG foi de 36,1% (IC95% 31,9-40,6). Exposição a um caso confirmado (RP: 1,54; IC 95% 1,04-2,29) ou caso suspeito (RP: 1,56; IC 95% 1,13-2,16) de COVID-19, seis ou mais coabitantes (RP: 1,52; IC 95% 1,05 -2,20), permanência na Colômbia ≥2 anos (RP: 1,43; IC 95% 1,11-1,92) e presença de sintomas (RP: 1,62; IC95%1,26 - 2,10) foram associados a maior soroprevalência de IgG. Discussão: Em Bucaramanga, a soroprevalência em migrantes foi semelhante à de migrantes no Kuwait, mas menor do que em Paris e Cingapura. Conclusão: Em migrantes com vocação de permanência, a soroprevalência contra SARS-CoV-2 foi semelhante à relatada em residentes de Bucaramanga. O contato com casos suspeitos/confirmados de COVID-19 e as condições de superlotação foram alguns dos fatores associados à soroprevalência.

Effectiveness of Naturally Acquired and Vaccine-Induced Immune Responses to SARS-CoV-2 Mu Variant.

SARS-CoV-2 Mu variant emerged in Colombia in 2021 and spread globally. In 49 serum samples from vaccinees and COVID-19 survivors in Colombia, neutralization was significantly lower (p<0.0001) for Mu than a parental strain and variants of concern. Only the Omicron variant of concern demonstrated higher immune evasion.

Cohort profile: Colombian Cohort for the Early Prediction of Preterm Birth (COLPRET): early prediction of preterm birth based on personal medical history, clinical characteristics, vaginal microbiome, biophysical characteristics of the cervix and maternal serum biochemical markers.

PURPOSE: Preterm birth (PTB) is a public health issue. Interventions to prolong the length of gestation have not achieved the expected results, as the selection of population at risk of PTB is still a challenge. Cervical length (CL) is the most accepted biomarker, however in the best scenario the CL identifies half of the patients. It is unlikely that a single measure identifies all pregnant women who will deliver before 37 weeks of gestation, considering the multiple pathways theory. We planned this cohort to study the link between the vaginal microbiome, the proteome, metabolome candidates, characteristics of the cervix and the PTB. PARTICIPANTS: Pregnant women in the first trimester of a singleton pregnancy are invited to participate in the study. We are collecting biological samples, including vaginal fluid and blood from every patient, also performing ultrasound measurement that includes Consistency Cervical Index (CCI) and CL. The main outcome is the delivery of a neonate before 37 weeks of gestation. FINDINGS TO DATE: We have recruited 244 pregnant women. They all have measurements of the CL and CCI. A vaginal sample for microbiome analysis has been collected in the 244 patients. Most of them agreed to blood collection, 216 (89%). By August 2021, 100 participants had already delivered. Eleven participants (11 %) had a spontaneous PTB. FUTURE PLANS: A reference value chart for the first trimester CCI will be created. We will gather information regarding the feasibility, reproducibility and limitations of CCI. Proteomic and metabolomic analyses will be done to identify the best candidates, and we will validate their use as predictors. Finally, we plan to integrate clinical data, ultrasound measurements and biological profiles into an algorithm to obtain a multidimensional biomarker to identify the individual risk for PTB.

Biofilm formation and its effects on microbiologically influenced corrosion of carbon steel in oilfield injection water via electrochemical techniques and scanning electron microscopy.

In this study, changes in the electrochemical conditions of oil fields caused by biofilms with sulfate-reducing bacteria have been studied as they promote localized pitting damage, reservoir souring problems, and many other processes including well plugging that lead to increased production costs. Biofilm formation and its effects on 1020 carbon steel surfaces were evaluated in a discontinuous electrochemical reactor by using a bacterial consortium isolated from the injection water of a Colombian oil field. Sulfide concentration and pH values were observed to decrease, which was consistent with the exponential planktonic sulfate-reducing bacterial growth. The formation of a biofilm that adheres to a porous layer of corrosion products was identified using scanning electron microscopy and energy-dispersive X-ray spectroscopy. The morphology of the films revealed the presence of the biofilm and corrosion product crystals. Open circuit potential presented a negative shift in the potential during the first 24 h in a biotic cell. Electrochemical impedance spectroscopy showed a change in the behavior of the resistive zone for both systems, a charge transfer trend in the abiotic cell, and a transformation of the charge transfer process to a diffusive process in the biotic cell after 48 h. The polarization resistance showed its lowest resistivity 74.95 Ω·cm-2 during the first 48 h, while the corrosion rate was estimated as 3.37 mpy. This research contributes to the understanding of corrosion mechanisms in the metal-solution interface via detailed monitoring of biofilm growth.

Importancia de los interferones tipo I en la respuesta inmune antiviral contra el Virus del Papiloma Humano / Importance of type I interferons in the antiviral immune response against the Human Papillomavirus

Resumen Los interferones (IFNs) son citoquinas fundamentales en la modulación de la inmunidad innata y adaptativa del hospedero, el papel de los IFNs tipo I en el control de la infección por el Virus del Papiloma Humano (VPH) es crucial para una eficiente respuesta antiviral del huésped. Esta revisión profundiza sobre las funciones de los IFNs tipo I en la infección causada por el VPH y los mecanismos de evasión de este virus para inactivar los IFNs tipo I, todos estos mecanismos necesarios para el desarrollo y progresión de lesiones malignas en los tejidos infectados por el VPH.

Abstract The interferons (IFNs) are very important cytokines in the interface between innate and adaptive immunity of the host, the role type I IFNs in the control of HPV is pivotal for an efficient immune response, so a wide knowledge about this topic will contribute understanding HPV pathogenicity mechanism. This review focuses on the HPV evasion mechanisms for the type I IFNs which are necessary for a malignant lesion development, otherwise develops knowledge about the type I IFNs functions on the HPV infection.

A Novel Strategy for Cervical Cancer Prevention Using Cervical-Vaginal Self-Collected Samples Shows High Acceptability in Women Living in Low-Income Conditions from Bucaramanga, Colombia.

INTRODUCTION: Human papillomavirus molecular detection prevents cervical cancer (CC). To widen its use, cervical-vaginal self-collection devices are proposed. Our aim was to determine the acceptability of self-sampled cervical-vaginal protocol and the reproducibility of results using HPV detection brushes in a low-income Colombian population between 35 and 65 years old. METHODS: Cross-sectional study including women classified as medium to high-risk for developing CC by using a short-standardized survey. After receiving instructions, women self-collected a cervical-vaginal sample. Subsequently, a perception survey was conducted. RESULTS: Four hundred and twenty-three women performed self-collected sampling. The median age was 46.5 years (IQR 40-52), 56.5% were housewives, and 55.1% had finished elementary school. About 99% of the population (n=419) considered that they understood the instructions, 19.4% (n=82) reported having concerns about the self-collected sample, 9.2% (n=39) distrusted the results because of the self-collection, 7.3% (n=31) felt uncomfortable with the procedure, and 9.7% (n=41) reported some pain. The majority would recommend the procedure to others (99%), 88.5% of the sampled population preferred the self-collected method, 4% preferred conventional cytology, and 7.3% were not sure. The reasons behind favoring the self-collected procedure included privacy (n= 149, 40.1%), comfort (n=110, 29.7%), easiness (n=52, 14%), reliability (n=46, 12.4%), and less painful (n=110, 29.7%). The percentage of HPV detection agreement between the self-collected and the healthcare professional-collected procedures was 98.99% (Cohen's Kappa=0.9774). CONCLUSION: Women living in low-income households in Bucaramanga, Colombia preferred the self-sampling procedure because it was easy to use, convenient, and private, resulting in 98% acceptability, and positioning it as an excellent tool for CC prevention.

SARS-CoV-2: generalidades bioquímicas y métodos de diagnóstico / SARS-CoV-2: biochemical aspects and diagnostic methods

Resumen El 31 de diciembre de 2019 la comisión municipal de salud de Wuhan (provincia de Hubei, China) informa sobre un inusitado brote de casos de neumonía en la ciudad. Posteriormente se determina que se trata de un nuevo coronavirus designado inicialmente como 2019-nCoV y posteriormente, SARS-CoV-2. El SARS-CoV-2 infecta y se replica en los neumocitos y macrófagos del sistema respiratorio específicamente en el parénquima pulmonar en donde reside el receptor celular ACE-2. Esta revisión describe aspectos relacionados con la transmisión, prevención, generalidades bioquímicas del SARS-CoV-2 y métodos diagnósticos del COVID-19. Inicialmente se describe la forma de transmisión del virus y algunas recomendaciones generales para su prevención. Posteriormente, se hace una descripción detallada de los aspectos bioquímicos del SARS-CoV-2, su ciclo infeccioso y la estructura de la proteína S, la cual está involucrada con el proceso de ingreso del virus a la célula. Finalmente, se describen los métodos y pruebas de laboratorio para el diagnóstico del COVID-19.

Abstract On December 31, 2019, Wuhan Municipal Health Commission (Hubei Province, China) reports on an unusual outbreak of pneumonia cases in the city. Subsequently it is determined that it is a new coronavirus initially designated as 2019-nCoV and later, SARS-CoV-2. SARS-CoV-2 infects and replicates in pneumocytes and macrophages of the respiratory system specifically in the lung parenchyma where the ACE-2 cell receptor resides. This review describes aspects related to the transmission, prevention, biochemical generalities of SARS-CoV-2 and diagnostic methods of COVID-19. Initially, it describes the form of virus transmission and general recommendations for its prevention. Subsequently, a detailed description is made of the biochemical aspects of SARS-CoV-2, its infectious cycle and the structure of protein S, which is involved in the process of entry of the virus into the cell. Finally, the methods and laboratory tests for the diagnosis of COVID-19 are described.

Prueba de concepto de una pcr multiplex de primera generación (cualitativa) para detección del oncogén e7 de vphs de alto riesgo

Introducción: Infección persistente con el virus de papiloma humano de alto riesgo (VPH-AR) causa cáncer de cuello uterino (CCU). Existen ensayos moleculares para la detección y la genotipificación del gen L1 de VPH, sin embargo, L1 puede perderse durante la integración viral. La expresión e integración del oncogén E7 es fundamental para el desarrollo de CCU. Objetivo: Estandarizar una PCR multiplex (mPCR) del oncogén E7 (E7-mPCR) para genotipificación de los VPH-AR de mayor frecuencia en CCU (VPH-16, -18, -31, -33, -45 y -52). Métodos: Se obtuvieron cepillados cervicales de voluntarias y se analizaron amplificando por PCR el gen L1 con subsecuente hibridación reversa. Posteriormente, se escogieron 59 muestras positivas para VPH-AR y se analizaron por E7-mPCR. Resultados: Se evidenció una elevada concordancia entre los resultados del ensayo E7- mPCR y los de la PCR de L1 (concordancia observada de 95,1%, Kappa de Cohen = 0,88), encontrándose mayor número de infecciones por VPH- AR en el 15,8% con E7-mPCR. Conclusión: E7-mPCR es una herramienta diagnóstica con alta concordancia y económica que puede adaptarse a una plataforma de mayor complejidad para procesar y detectar mayor cantidad de muestras y genotipos de VPH-AR.

Introduction: The persistent infection of the high-risk Human Papiloma Virus (VPH-AR in Spanish) causes uterine cervix cancer (CCU in Spanish). There are molecular essays for detection and genotyping of gen L1 of VPH. However, L1 may get lost during the viral integration. The expression and integration of oncogene E7 is fundamental for the development of CCU. Objective: To standardize a multiplex PCR (mPCR) of oncogene E7 (E7-mPCR) for genotyping the VPH- AR of highest frequency in CCU (VPH-16, -18, -31, -33, -45 y -52). Method: We obtained cervix brushing simples from volunteers and we analyzed them by amplifying the L1 gene through PCR with a subsequent reverse hybridization. After that, we chose 59 positive VPH- AR samples and we analyzed them for E7-mPCR. Results: We found out a high concordance between the results of the essay E7-mPCR and those of L1 PC (Observed concordance was of 95.1%, Cohen's Kappa = 0.88), and we revealed a higher number of infections for VPH-AR in a 15.8% with E7-mPCR. Conclusion: E7-mPCR is an economic diagnostic tool with high concordance which can be adapted to a platform with more complexity to process and detect a higher number of samples and VPH-AR genotypes.

Introdução: a infecção persistente com o virus de papiloma humano de alto risco (HPV-AR) causa cáncer de colo do útero (CCU). Existem ensaios moleculares para detecção e para a genotipificação do gene L1 de HPV; contudo, L1 pode ser perdido durante a integrado viral. A expressão e integração do oncogênese E7 é fundamental para o desenvolvimento do CCU. Objetivo: padronizar uma PCR multiplex (mPCR) do oncogênese E7 (E7-mPCR) para genotipificação dos HPV-AR de maior frequência no CCU (HPV-16, -18, -31, -33, -45 e -52). Métodos: foram realizadas raspagens com escova cervical rodada em voluntárias e foram analisadas a partir da amplificação do gene L1 por PCR com subsequente hibridação inversa. Em seguida, foram escolhidas 59 amostras positivas para HPV-AR, as quais foram analisadas por E7-mPCR. Resultados: foi evidenciada elevada concordância entre os resultados do ensaio E7-mPCR e os da PCR de L1 (concordância observada de 95,1%, Kappa de Cohen = 0,88), encontrando-se maior número de infecções por HPV-AR em 15,8% com E7-mPCR. Conclusão: E7-mPCR é uma ferramenta diagnóstica com alta concordância e económica que pode ser adaptada a uma plataforma de maior complexidade para processar e detectar maior quantidade de amostras e genótipos de HPV-AR.

Sedentarismo y Sobrepeso/Obesidad asociados a la prevalencia de infección por Virus de Papiloma Humano de alto riesgo en mujeres de la zona norte de Bucaramanga / Sedentary lifestyle and overweight/obesity associated with prevalence of high risk human papillomavirus in vulnerable population from north region of Bucaramanga

Resumen Introducción: Para el desarrollo de cáncer de cuello de uterino la infección con el Virus de Papiloma Humano (VPH) es una causa necesaria. Sin embargo, la eliminación viral está asociada a múltiples factores, algunos modificables y otros no, que varían según las características poblacionales y áreas geográficas. Objetivo: Determinar factores asociados a la prevalencia de infección por virus de Papiloma Humano de alto riesgo en mujeres entre 35-65 años con riesgo moderado o alto de cáncer de cuello uterino de la zona norte de Bucaramanga. Metodología: Estudio analítico de corte transversal. A las mujeres clasificadas como de moderado/alto riesgo para cáncer de cuello uterino en una encuesta corta estandarizada, se les realizó una encuesta sobre factores potenciales asociados a infección, seguida de una autónoma de muestra cervical, que se utilizó para detección de DNA viral. Se realizó análisis múltiple de regresión log-binomial para obtener Razones de Prevalencia ajustadas (RPa). Resultados: Se entrevistaron 810 mujeres, de éstas 435 tuvieron moderado/alto riesgo para cáncer y se realizaron la autotoma. La prevalencia de infección por VPH de alto riesgo fue de 5,1% (IC 95% 3,2-7,6). El sedentarismo (RPa 2,51; IC95% 1,15-5,50) y el sobrepeso/obesidad (PRa 4,20; IC95% 1,00-15,51) se asociaron a mayor prevalencia. Además, hubo una tendencia de incremento en la prevalencia de infección en las usuarias de anticonceptivos inyectables; así como una tendencia de disminución de esta prevalencia según porciones de frutas y verduras consumidas diariamente. Conclusión: Factores modificables como sedentarismo y sobrepeso/obesidad, se asociaron independientemente a mayor prevalencia de infección por VPH en la población estudiada.

Abstract Introduction: Infection with Human Papillomavirus is mandatory for cervical cancer development. However, viral elimination is associated to multiple factors, according to the population characteristics and geographic areas, some are modifiable and others not. Objective: To determine the factors associated with the prevalence of high risk human papillomavirus infection in women between 35-65 years old with moderate or high risk of cervical cancer located at the northern zone of Bucaramanga. Methodology: Cross-sectional analytical study. Women classified as moderate/ high risk for cervical cancer in a short standardized survey, were surveyed on the side effects associated to chronic viral infection and self-sampling cervical test. Bivariate analysis and multiple analysis of log-binomial regression were performed. Results: 810 women were interviewed; 435 cases of high cancer risk were presented. The prevalence of high risk human papilloma virus infection was 5.1% (95% CI 3.2-7.6). The sedentary lifestyle (RPa 2.51, 95% CI 1.15-5.50) and overweight/obesity (PRa 4.20, 95% CI 1.00-15.51) were associated with higher prevalence. In addition, there was a trend of increased prevalence of infection among users of injectable contraceptives; as well as a tendency to decrease this prevalence according to portions of fruits and vegetables consumed daily. Conclusion: modifiable factors such as sedentary lifestyle and overweight / obesity were independently associated with a higher prevalence of infection by human high risk papilloma virus in the population studied.

Achatina fulica (Mollusca: Achatinidae) Naturally Infected with Caenorhabditis briggsae (Dougherty and Nigon, 1949) (Nematoda: Rhabditidae).

Specimens of the African snail Achatina fulica, collected in Bucaramanga, Colombia, were examined for parasites. Numerous specimens of Caenorhabditis briggsae were collected from the digestive tract of the snails and identified by the structure of male spiculum, caudal bursa, gubernaculum and precloacal lip in males, triangular tooth in metarhabdion, and protandrous hermaphrodites with a female:male ratio of 15:1 and with morphometry. DNA sequences of the ITS2 region of the ribosomal gene array from worms in this study matched with 99% similarity to published sequences of C. briggsae. A redescription of the species is provided. This is the first record of the species in South America.

Genotipificación del Virus de Papiloma Humano en mujeres de la comuna norte de Bucaramanga / Genotypification of Human Papilloma Virus in women of the comuna Norte de Bucaramanga

Resumen Introducción: La infección persistente con Virus de Papiloma Humano de alto riesgo es causa necesaria para la aparición de cáncer de cérvix. Objetivo: Caracterizar molecularmente los genotipos circulantes de Virus de Papiloma Humano en población de la zona Norte de Bucaramanga. Métodos: Estudio de corte transversal en mujeres de 35 a 65 años con riesgo ≥3 puntos para desarrollar cáncer de cérvix determinado por una encuesta estandarizada. En una muestra cervico-vaginal por autotoma se realizaron pruebas moleculares por tecnología HPV Direct Flow CHIP. Resultados: Se encuestaron 810 mujeres, de éstas 435 (53,7%) se realizaron auto-toma por el riesgo presentado. La mediana de edad fue de 47,3 años (RIQ 41-53 años). Casi la totalidad de la población reside en estrato 1 y 2 (98,8%) y en su mayoría son del régimen subsidiado (87,2%). La prevalencia de infección fue de 10,6% (IC 95%: 7,8 - 13,8), para genotipos de alto riesgo fue de 3,9% (IC 95%: 2,3 - 6,2), de bajo riesgo de 3,5% (IC 95%: 1,4 - 5,6) y para genotipo indeterminado de 1,9%. El genotipo de alto riesgo más común fue VPH-59 y de bajo riesgo fue VPH-62/81. Hubo coinfección con genotipos alto/bajo riesgo en cinco mujeres y coinfección con dos genotipos de bajo riesgo en una mujer. Conclusión: la prevalencia de infección por Virus de Papiloma Humano en mujeres que habitan en zonas vulnerables de Bucaramanga es menor a la reportada en Bogotá y Cali (14,9% y 13%, respectivamente). No se encontró predominio de ningún genotipo de alto riesgo en particular.

Abstract Introduction: Persistent infection with high-risk Human Papilloma Virus is a necessary cause for the appearance of cervical cancer. Objective: Molecularly characterize circulating genotypes of Human Papilloma Virus in population of the north of Bucaramanga. Methods: Cross-sectional study in women aged from 35 to 65 years with risk ≥3 points for develop cervical cancer determined by a standardized survey. In a cervico-vaginal self-sampling probe a molecular test was performed by HPV Direct Flow CHIP technology. Results: 810 women were interviewed, of these 435 (53.7%) performed self-sampling due to the risk calculated. The median age was 47.3 years (RIQ 41-53 years). Almost the entire population resides in poor conditions (stratum1 and 2) (98.8%) and most of them are from the Colombian subsidized social security system (87.2%). The prevalence was 10.6% (CI 95%: 7.8 - 13.8), for high risk genotypes it was 3.9% (CI 95%: 2.3 - 6.2), low risk of 3.5% (CI 95%: 1.4 - 5.6) and for indeterminate genotype of 1.9%. HPV-59 was the most common high-risk genotype and HPV-62/81 was a low-risk genotype. There was coinfection with high risk / low risk genotypes in five women and coinfection with two low risk genotypes in a woman. Conclusion: The prevalence of infection by Human Papilloma Virus in women living in vulnerable areas of Bucaramanga is lower than that reported in Bogotá and Cali (14.9% and 13%, respectively). No predominance of any particular high-risk genotype was found.

Revisión sistemática: estrategias virales para la inducción de cáncer "virus de Epstein-Barr: latencia y mecanismos asociados a la oncogénesis viral" / Viral strategies for cancer induction "Epstein-Barr virus: latency and mechanisms associated with viral oncogenesis"

Resumen La infección crónica con virus oncogénicos es responsable de aproximadamente el 20% de todos los cánceres reportados en humanos, este proceso de oncogénesis viral presenta una naturaleza compleja, multietapa y multifactorial. Un ejemplo de ello es el Virus de Epstein- Barr (EBV), un herpesvirus que infecta de manera latente a más del 90% de la población. Aunque la infección a menudo cursa de manera asintomática, el EBV es capaz de modificar su expresión genómica estableciendo diferentes fases de latencia, alterando así el metabolismo de sus células blanco, como son los linfocitos B y las células epiteliales, proceso que resulta determinante en la aparición y desarrollo de diferentes patologías que van desde la mononucleosis infecciosa hasta procesos oncológicos como el linfoma de Burkitt, el cáncer gástrico o el cáncer nasofaríngeo.

Abstract Chronic infection with oncogenic viruses is responsible for approximately 20% of all cancers worldwide in humans, this viral transformation represents a complex, multistage and multifactorial process. An example is the Epstein-Barr virus (EBV), a herpesvirus that latently infects over 90% of the population. Although the infection often courses asymptomatically, EBV is able to modify its genomic expression by establishing different latency phases, thus altering the B lymphocytes and epithelial cells metabolism, a determinant process in the appearance and development of different pathologies ranging from infectious mononucleosis to oncological processes such as Burkitt's lymphoma, gastric cancer and nasopharyngeal cancer.

Modernas metodologías diagnosticas para la detección del Virus del Papiloma Humano y prevención del cáncer de cuello uterino / Modern diagnostic methods for detection of Human Papillomavirus and cervical cancer prevention

RESUMEN Los Virus del Papiloma Humano (VPH) presentes en mucosa clasificados como de "alto riesgo" son agentes etiológicos de patologías oncológicas como cáncer de cuello uterino, ano, pene, vulva y cáncer orofaríngeo. Actualmente el principal método de tamizaje utilizado en Colombia para detección de cáncer de cuello uterino es la citología cervical, presentando una moderada cobertura en la población femenina y una sensibilidad cercana al 50%. El objetivo de este trabajo es describir las técnicas modernas utilizadas para la detección del VPH y prevención de los cánceres producidos por estos virus. Se llevó a cabo una revisión de literatura de las ultimas metodologías diagnosticas en la infección viral por VPH y marcadores de malignidad en muestras cervicales. La citología cervical es un recurso altamente específico y de bajo costo, pero poco sensible para la detección y prevención de cáncer de cuello uterino, que puede ser complementado con las tecnologías modernas revisadas con el objetivo de obtener un diagnóstico temprano del VPH como agente etiológico de estas enfermedades malignas.

ABSTRACT Human Papilloma Viruses (HPVs) types present in mucosa and classified as "high risk" are etiologic agents of several oncological diseases as cervical cancer, anus, penis, vulva, and oropharyngeal cancer. Currently the principal method of screening used in Colombia for detecting cervical cancer is cervical cytology, which presents a moderate coverage in the population and sensitivity close to 50%. The objetive of this work is to describe new techniques for detection of Human Papillomavirus and cancer prevention for these viruses. We carried out a literature review of the cutting edge diagnostic methods for HPV viral infection. Cervical cytology is a highly specific resource, low-cost but low sensitivity for preventing cervical cancer, which can be supplemented with the modern technologies checked in order to obtain an early diagnosis of HPV as an etiologic agent of those malignancies.

Systems-level effects of ectopic galectin-7 reconstitution in cervical cancer and its microenvironment.

BACKGROUND: Galectin-7 (Gal-7) is negatively regulated in cervical cancer, and appears to be a link between the apoptotic response triggered by cancer and the anti-tumoral activity of the immune system. Our understanding of how cervical cancer cells and their molecular networks adapt in response to the expression of Gal-7 remains limited. METHODS: Meta-analysis of Gal-7 expression was conducted in three cervical cancer cohort studies and TCGA. In silico prediction and bisulfite sequencing were performed to inquire epigenetic alterations. To study the effect of Gal-7 on cervical cancer, we ectopically re-expressed it in the HeLa and SiHa cervical cancer cell lines, and analyzed their transcriptome and SILAC-based proteome. We also examined the tumor and microenvironment host cell transcriptomes after xenotransplantation into immunocompromised mice. Differences between samples were assessed with the Kruskall-Wallis, Dunn's Multiple Comparison and T tests. Kaplan-Meier and log-rank tests were used to determine overall survival. RESULTS: Gal-7 was constantly downregulated in our meta-analysis (p < 0.0001). Tumors with combined high Gal-7 and low galectin-1 expression (p = 0.0001) presented significantly better prognoses (p = 0.005). In silico and bisulfite sequencing assays showed de novo methylation in the Gal-7 promoter and first intron. Cells re-expressing Gal-7 showed a high apoptosis ratio (p < 0.05) and their xenografts displayed strong growth retardation (p < 0.001). Multiple gene modules and transcriptional regulators were modulated in response to Gal-7 reconstitution, both in cervical cancer cells and their microenvironments (FDR < 0.05 %). Most of these genes and modules were associated with tissue morphogenesis, metabolism, transport, chemokine activity, and immune response. These functional modules could exert the same effects in vitro and in vivo, even despite different compositions between HeLa and SiHa samples. CONCLUSIONS: Gal-7 re-expression affects the regulation of molecular networks in cervical cancer that are involved in diverse cancer hallmarks, such as metabolism, growth control, invasion and evasion of apoptosis. The effect of Gal-7 extends to the microenvironment, where networks involved in its configuration and in immune surveillance are particularly affected.

Avances en el desarrollo de nuevas vacunas profilácticas y terapéuticas contra el Virus del Papiloma Humano / Advances in the development of new prophylactic and therapeutic vaccines against Human Papillomavirus

El uso de vacunas profilácticas contra el Virus del Papiloma Humano (VPH) de alto riesgo ha adquirido gran importancia debido al alto potencial oncogénico, de estos virus, especialmente por su asociación con el cáncer de cuello uterino, uno de los canceres más comunes y de mayor mortalidad en mujeres a nivel mundial. El objetivo de este artículo es describir las vacunas profilácticas y terapéuticas disponibles actualmente contra el VPH, analizando las características, ventajas, desventajas y estudios científicos sobre su uso y seguridad en la población. Se llevó a cabo una revisión de literatura de los últimos avances en el desarrollo de vacunas profilácticas y terapéuticas contra el VPH. La vacunación profiláctica es efectiva y esencial para la prevención del cáncer de cuello uterino causadas por VPH-16 y -18, pero no genera protección cruzada contra otros VPH de alto riesgo, esto ha encaminado a la creación de nuevas vacunas nanovalentes que protegen contra un número mas amplio de VPHs de alto riesgo. Por otra parte, las vacunas terapéuticas han demostrado en sus fases de estudio iniciales ser promisorias en la regresión de lesiones premalignas o malignas in situ.

Prophylactic vaccines against high risk HPV has become important because of the high oncogenic potential of the virus and its association with cervical cancer development, one of the most common and fatal cancers among women worldwide. The objective of this article is describe the state of the art of the current prophylactic and therapeutic HPV vaccines, analyzing their characteristics, advantages, disadvantages and scientific reports on its use and safety in the population. A systematic revision of the latest advances in the development of prophylactic and therapeutic vaccines against HPV was performed. Prophylactic vaccination is effective and essential for the prevention of uterine cervical cancer; new therapeutic vaccines have been shown at the initial phases to be promising contributing in the regression of premalignant or malignant in situ lesions.

Expression of WNT genes in cervical cancer-derived cells: Implication of WNT7A in cell proliferation and migration.

According to the multifactorial model of cervical cancer (CC) causation, it is now recognized that other modifications, in addition to Human papillomavirus (HPV) infection, are necessary for the development of this neoplasia. Among these, it has been proposed that a dysregulation of the WNT pathway might favor malignant progression of HPV-immortalized keratinocytes. The aim of this study was to identify components of the WNT pathway differentially expressed in CC vs. non-tumorigenic, but immortalized human keratinocytes. Interestingly, WNT7A expression was found strongly downregulated in cell lines and biopsies derived from CC. Restoration of WNT7A in CC-derived cell lines using a lentiviral gene delivery system or after adding a recombinant human protein decreases cell proliferation. Likewise, WNT7A silencing in non-tumorigenic cells markedly accelerates proliferation. Decreased WNT7A expression was due to hypermethylation at particular CpG sites. To our knowledge, this is the first study reporting reduced WNT7A levels in CC-derived cells and that ectopic WNT7A restoration negatively affects cell proliferation and migration.