The repertoire of mutational signatures in tobacco- and non-tobacco-induced oral cancer

The use of tobacco products is one of the established contributors toward the development and spread of oral cancer. Additionally, recent research has indicated oral microbiome, infections with Human papilloma virus (HPV), Epstein–Barr virus (EBV), Candida as significant contributing factors to this disease along with lifestyle habits. Deregulation of cellular pathways envisaging metabolism, transcription, translation, and epigenetics caused by these risk factors either individually or in unison is manifold, resulting in the increased risk of oral cancer. Globally, this cancer continues to exist as one of the major causes of cancer-related mortalities; the numbers in the developing South Asian countries clearly indicate yearly escalation. This review encompasses the variety of genetic modifications, including adduct formation, mutation (duplication, deletion, and translocation), and epigenetic changes evident in oral squamous cell carcinoma (OSCC). In addition, it highlights the interference caused by tobacco products in Wnt signaling, PI3K/Akt/mTOR, JAK-STAT, and other important pathways. The information provided also ensures a comprehensive and critical revisit to non-tobacco-induced OSCC. Extensive literature survey and analysis has been conducted to generate the chromosome maps specifically highlighting OSCC-related mutations with the potential to act as spectacles for the early diagnosis and targeted treatment of this disease cancer (AU)

Exploration and analysis of differentially expressed genes in Epstein–Barr virus negative and positive plasmablastic lymphoma

Objectives Plasmablastic lymphoma (PBL) is a subtype of diffuse large B-cell lymphoma (DLBCL) often associated with Epstein–Barr virus (EBV) infection. Despite recent advances in treatment, PBL still has a poor prognosis. EBV is listed as one of the human tumor viruses that may cause cancer, and is closely related to the occurrence of some nasopharyngeal carcinoma (NPC), lymphoma and 10% of gastric cancer (GC). It is very important to explore the differentially expressed genes (DEGs) between EBV-positive and EBV-negative PBL. Through bioinformatics analysis of DEGs between EBV-positive PBL and EBV-negative PBL, we gain a deeper understanding of the pathogenesis of EBV-positive PBL. Methods We selected the GSE102203 data set, and screened the DEGs between EBV-positive PBL and EBV-negative PBL. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied. The protein–protein interaction (PPI) network was constructed, and screened for the hub genes. Finally, Gene Set Enrichment Analysis (GSEA) was performed. Results In EBV-positive PBL, the immune-related pathway is upregulated and Cluster of differentiation 27 (CD27) and programmed cell death-ligand 1 (PD-L1) are hub genes. Conclusions In EBV-positive PBL, EBV may affect tumorigenesis through activation of immune-related pathways and upregulation of CD27, PD-L1. Immune checkpoint blockers of CD70/CD27 and programmed cell death 1 (PD-1)/PD-L1 pathways may be one of the effective strategies for the treatment of EBV-positive PBL (AU)

Enfermedad linfoproliferativa difusa postrasplante renal: estudio longitudinal de 21.546 receptores durante 2 décadas en España / Lymphoproliferative disorders after renal transplantation along 2 decades: A large longitudinal study of 21.546 recipients

Introducción: La enfermedad linfoproliferativa difusa postrasplante (ELPD) es un grupo heterogéneo de enfermedades que se caracteriza por una proliferación de linfocitos después de un trasplante de órgano sólido y que presenta un espectro que comprende desde hiperplasias a agresivos linfomas. Material y métodos: Hemos evaluado, en un estudio observacional multicéntrico retrospectivo que incluye 21.546 receptores adultos de trasplante renal simple trasplantados en España de 1990 al 2009, la incidencia de ELPD durante un periodo de 22 años, su relación con el virus de Epstein-Barr, los factores de riesgo clásico y su pronóstico. Resultados: Un total de 275 receptores desarrollaron ELPD durante el seguimiento (1,2%), siendo 195 varones (70,9%) y 80 mujeres (29,1%), con una mediana de edad al diagnóstico de 59,2 (p25 44,7; p75 68) años. Doscientos cuarenta y cinco (89,0%) eran primeros trasplantes y 269 (97,8%) fueron de donante cadáver. Se objetivó virus de Epstein-Barr en el tejido proliferativo de 94 de los 155 casos estudiados (60,6%) y el 86,0% de las proliferaciones eran linfocitos B. La mediana del tiempo de desarrollo después del trasplante fue de 42 (p25 12; p75 77,5) meses. Un total de 188 receptores de 275 (68,3%) tenían algún factor de riesgo clásico. La incidencia anual fue de 0,14% el primer año y de 0,98% la acumulada en 10 años postrasplante. El periodo de seguimiento postrasplante de los receptores fue de 3 a 22 años. Durante el seguimiento 172 pacientes murieron (62,5%) y 103 (37,5%) tuvieron remisión completa. La causa de muerte más frecuente fue la progresión (n=91, 52,9%), seguida de la sepsis (n=24, 13,9%). La supervivencia del paciente después del diagnóstico fue del 51% al año, del 44% al segundo año y del 39% al quinto año. La supervivencia del injerto fue de 48, 39 y 33%, respectivamente. (AU)

Introduction: Posttransplant lymphoproliferative disorders (PTLD) are heterogeneous lymphoid proliferations in recipients of solid organs which seem to be related to Epstein-Barr virus. The use of antilymphocyte antibodies, Epstein-Barr virus seronegativity in the recipient, acute rejection and CMV infection have been identified as classical risk factors. Material and methods: We have studied, in a retrospective observational study, the incidence of PTLD in a period of 22 years, its relationship with Epstein-Barr virus, presence of classical risk factors and outcome in 21,546 simple adult renal transplant recipients from cadaveric and living donors, transplanted in 21 hospitals from 1990 to 2009. Results: A total of 275 recipients developed PTLD (1.2%), 195 males (70.9%), 80 females (29.1%), aged 59.2 (p25 44.7; p75 68) years. Two hundred forty-five (89.0%) were first transplant recipients and 269 (97.8%) from cadaveric donors. Epstein-Barr virus in the tissue was reported in 94 out of the 155 studied recipients (60.6%) and 86.0% of the proliferations were due to B lymphocytes. PTLD median appearance after transplant were 42 (p25 12; p75 77.5) months. One hundred eighty-eight recipients out of 275 patients (68.3%) had any classical risk factor and the use of antilymphocyte antibodies was the most frequent. During the follow-up, 172 patients died (62.5%) and 103 (37.5%) had a complete remission. The main cause of death was PTLD progression (n=91, 52,9%), followed by sepsis (n=24, 13.9%). The follow-up period post-transplant of the recipients was between 3 and 22 years. The incidence was 0.14% during the first year post-trasplant and 0.98% the cumulative incidence at 10 years. Patient survival after diagnosis was 51, 44 and 39% after one, 2 and 5 years, respectively. Finally, overall graft survival was 48, 39 and 33% at the same periods. (AU)

Factores asociados a la presencia del virus de Epstein-Barr en la cavidad oral de adolescentes de la ciudad de Cali (Colombia) / Factors associated with the presence of the Epstein-Barr virus in the oral cavity of high school students from the city of Cali (Colombia)

IntroducciónEl virus de Epstein-Barr (VEB) está clasificado como carcinógeno del grupo 1. Su principal vía de transmisión es la oral, a través de la saliva. Determinamos la frecuencia de detección del VEB en la cavidad oral en estudiantes de secundaria en Cali (Colombia).Materiales y métodosEstudio transversal analítico para estimar la frecuencia de detección del genoma del VEB en la cavidad oral, las razones de prevalencia y su asociación con diversos factores en 1.565 individuos. Las variables analizadas fueron factores sociodemográficos, de higiene y salud oral, comportamiento sexual, consumo de cigarrillos e ingesta de alcohol. La asociación entre la detección y las variables evaluadas se realizó mediante un modelo de regresión lineal generalizado con vínculo logarítmico y distribución de Poisson con varianza robusta.ResultadosLa exposición al VEB en la cavidad oral fue del 38,40% (IC 95%: 36,02-40,84). La frecuencia de presentar exposición al VEB fue un 22% mayor en los varones, y el riesgo se incrementó según el comportamiento sexual. Se encontró asociación inversa con el grado escolar: los participantes de undécimo grado tuvieron un 27% menos frecuencia de exposición al VEB que los de grados inferiores (sexto a octavo). Cuando se utilizó el modelo logístico para estudiar la asociación entre la detección del VEB y las variables independientes, se sobreestimó la asociación. El rango de sobreestimación fue entre el 27-47% según el tipo de variable.ConclusiónLa frecuencia de detección del VEB en la cavidad oral de estudiantes sanos fue similar a la previamente descrita. Factores asociados al comportamiento sexual incrementan el riesgo de oportunidad para la exposición al VEB.

IntroductionThe Epstein-Barr virus (EBV) is classified as a group 1 carcinogen. The main route of EBV transmission is oral, through saliva. The present study aimed to determine the frequency of EBV detection in the oral cavity in high school students in the city of Cali (Colombia).Materials and methodsAnalytical cross-sectional study in order to determine the frequency of EBV detection in the oral cavity, the reasons for its prevalence and its association with several factors, in 1,565 individuals. The variables analyzed were sociodemographic factors, oral hygiene, oral health, sexual behavior, cigarrete smoking and alcohol intake. The association between the EBV detection and the variables evaluated was done through a generalized linear regression model with logarithmic linkage and Poisson distribution with robust variance.ResultsThe percentage of exposure to EBV in the oral cavity was 38.40% (CI 95%: 36.02-40.84). The frequency of presenting EBV exposure was 22% higher in men and the risk increased according to sexual behaviour. An inverse association with the school grade was found: the eleventh-grade participants had 27% less frequency of exposure to EBV than the lower grades (sixth to eighth). When analyzing the logistic model to study the association between EBV detection and independent variables, the association was overestimated. The overestimation ranged from 27 to 47% depending on the type of variable.ConclusionsThe frequency of EBV detection in the oral cavity of healthy students was similar to that previously described. Factors associated to sexual behavior increased the risk of opportunity to be exposed to EBV.

Altres tests de diagnòstic ràpid respiratori: VRS, adenovirus, pneumococ, Mycoplasma pneumoniae I mononucleosi infecciosa / No disponible

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Neuroimagen en la encefalitis por virus Epstein-Barr / Neuroimaging of Epstein-Barr virus-associated encephalitis

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Immunosuppression for inflammatory bowel disease does not influence Epstein-Barr viral load in the short-term / La inmunosupresión no modifica la carga viral del virus de Epstein-Barr a corto plazo en los pacientes con enfermedad inflamatoria intestinal

Introduction: Immunomodulators and biologics are two of the main drugs used for the treatment of inflammatory bowel disease (IBD). Some of these agents have been associated with certain infections and lymphoproliferative disorders, including Epstein-Barr virus (EBV) infection. Our aim was to determine the influence of immunosuppression in the EBV viral load in patients with IBD. Materials and methods: We prospectively included naïve patients with IBD who were starting immunosuppressive therapy in four IBD Units. All patients were assessed at baseline and four months after starting immunosuppression for clinical disease activity, biomarkers, EBV serology (IgM VCA, IgG VCA and IgG EBNA) and viral load. Results: Thirty-two patients were included. At baseline, all patients showed positive results for IgG VCA or IgG EBNA with undetectable EBV viral load. No patient showed detectable EBV viral load after starting the immunosuppressive therapy. Conclusion: Immunosuppression did not influence on EBV viral load in the short-term in naïve IBD patients

Introducción: Los fármacos inmunomoduladores y biológicos son algunos de los tratamientos usados con más frecuencia en la enfermedad inflamatoria intestinal (EII). Algunos de ellos se han relacionado con un mayor riesgo de infecciones o síndromes linfoproliferativos, entre los que se encuentra el virus de Epstein-Barr (VEB). Nuestro objetivo era determinar la influencia a corto plazo de la inmunosupresión sobre la carga viral en pacientes con EII. Material y métodos: Incluimos de forma prospectiva pacientes con EII en los que se iniciaba algún tratamiento inmunosupresor en 4 hospitales. Todos los pacientes fueron evaluados en el momento de iniciar el tratamiento y 4 meses después de iniciarlo, mediante la actividad clínica, los biomarcadores, la serología del VEB (IgM VCA, IgG VCA e IgG EBNA) y su carga viral. Resultados: Se incluyeron 32 pacientes, observando en todos ellos una serología positiva para IgG VCA o IgG EBNA, con una carga viral indetectable. No se observó ninguna muestra con carga viral detectable durante el seguimiento. Conclusión: La inmunosupresión no influye sobre la carga viral del VEB a corto plazo en pacientes con EII

Prevalencia y características clínicas y anatomopatológicas de los pacientes con diagnóstico de linfoma difuso de células B grandes y positivo al virus Epstein-Barr en un hospital de alta complejidad en Cali (Colombia) / Prevalence and clinico-pathological characteristics in patients with Epstein-Barr virus-positive diffuse large B-cell lymphoma in a high complexity hospital in Cali, Columbia

INTRODUCCIÓN: El linfoma difuso de células B grandes (LDCBG) constituye el 35% de los linfomas no Hodgkin y su incidencia aumenta con la edad. El virus Epstein-Barr (VEB) está ampliamente distribuido a nivel mundial. La asociación entre el LDCBG y VEB está cerca del 10% en pacientes inmunocompetentes; este tipo de linfoma tiene alta prevalencia en países de Latinoamérica. OBJETIVO: Conocer la frecuencia del LDCBG asociado al VEB y describir sus características demográficas, clínicas, inmunofenotípicas y desenlace de los pacientes en un centro de alta complejidad en Cali (Colombia). MATERIALES Y MÉTODOS: Estudio observacional descriptivo de una cohorte histórica. Se revisaron los registros clínicos y de anatomía patológica de pacientes con diagnóstico de LDCBG y se realizó la hibridación in situ para la detección del VEB (EBER). Se realizó un análisis descriptivo. RESULTADOS: Entre 2011 y 2017 se revisó la historia clínica de 55 pacientes con diagnóstico de LDCBG. El 16% fueron VEB positivos, los cuales fueron en su mayoría del subtipo no centro germinal (89%), con presentación nodal (56%); hubo mayor prevalencia en hombres (68%), menor edad de presentación (mediana 48 años) y muerte en el 56% de los casos. CONCLUSIONES: Los pacientes con LDCBG y VEB positivo presentan con mayor frecuencia el subtipo no centro germinal, el cual, según nuestros hallazgos, se presenta en pacientes más jóvenes y se asocia a peor pronóstico. El EBER no es un examen que se hace de rutina, por lo cual se recomienda realizar pruebas para la detección del VEB en pacientes con diagnóstico de LDCBG

INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) accounts for 35% of non-Hodgkin lymphoma and its incidence increases with age. Epstein Barr virus (EBV) is widely spread worldwide. There is a 10% association between EBV and DLBCL in immunocompetent patients; this type of malignancy has a high prevalence in Latin American countries. OBJECTIVE: Estimate the percentage of association between DLBCL and EBV patients, describing demographics, clinical and immunological features, as well as phenotype and clinical outcome in a high complexity healthcare institution in Colombia. MATERIALS AND METHODS: This is an analytic observational study from an historical cohort. Clinical and pathological records were revised among DLBCL patients and subsequent in-situ hybridization was performed for EBV detection. A descriptive analysis of the data was carried out. RESULTS: From 2011 to 2017, 55 DLBCL patients were identified.16% were positive on ISH for EBV, most of which belonged to the non-germinal center B-cell immunophenotype (89%), with a nodal presentation (56%). DLBCL EBV positive was more prevalent among males (67%) and in younger patients (median of 48 years) where the mortality rate was 56%. CONCLUSIONS: DLBCL patients positive for EBV are more prone to belong to the non-germinal center B-cell immunophenotype which, according to our findings, is associated with a younger age and worse prognosis. Presently, EBER in-situ hybridization is not a part of routine tests, but we recommend its inclusion in the pathology package for DLBCL patients, as it can influence clinical outcomes

Síndrome de Alicia en el País de las Maravillas e infección por virus de Epstein-Barr / Alice in Wonderland syndrome and Epstein-Barr virus infection

La infección por el virus de Epstein-Barr (VEB) es habitual y generalmente ocurre en la infancia o en la adultez temprana. El VEB es la etiología de la mononucleosis infecciosa, generalmente asociada con fiebre, dolor de garganta, inflamación de los ganglios linfáticos en el cuello y en ocasiones esplenomegalia. El síndrome de Alicia en el País de las Maravillas (SAPM) o síndrome de Todd es una afección rara, que principalmente afecta la integración visual y somatoestética. El SAPM sigue siendo un síndrome poco conocido y probablemente mal diagnosticado, puede ocurrir a cualquier edad, pero sobre todo en los niños en los que se asocia principalmente con la migraña y la infección por VEB. Presentamos a una paciente de diez años que acudió al servicio de urgencias con distorsión visual de la forma corporal y comportamiento extraño, sospechado inicialmente como una patología psiquiátrica pero posteriormente diagnosticado con mononucleosis infecciosa e infección por VEB confirmada serológicamente. Este caso refleja la importancia de reconocer este síndrome por parte de los médicos de urgencias y evitar derivaciones inadecuadas al servicio psiquiátrico

Infection with Epstein-Barr virus (EBV) is common and usually occurs in childhood or early adulthood. EBV is the cause of infectious mononucleosis, usually associated with fever, sore throat, swollen lymph nodes in the neck, and sometimes an enlarged spleen. Alice in Wonderland Syndrome (AIWS), also called Todd's syndrome, is a rare condition, principally involving visual and somesthetic integration. AIWS remains a poorly known and probably misdiagnosed syndrome, can occur at any age but mostly in children is mostly associated with migraine and EBV infection. We present a 10-year-old patient who went to the emergency department with visual distortion of corporal form and bizarre behaviour, initially suspected as a psychiatric pathology but subsequently diagnosed with infectious mononucleosis and serologically confirmed Epstein-Barr virus (EBV) infection. This case reflects the importance of recognizing this syndrome by emergency physicians in order to avoid inadequate referrals to the psychiatric service

Acrodermatitis papulosa infantil tras infección por virus de Epstein-Barr / Papular acrodermatitis of childhood after Epstein-Barr virus infection

La acrodermatitis papulosa infantil se considera una dermatosis paraviral secundaria a diversas infecciones y antígenos vacunales. El diagnóstico es clínico y el tratamiento sintomático, con pronóstico excelente, ya que el cuadro es autolimitado y se resuelve sin lesiones residuales. Presentamos el caso de un niño que desarrolló una acrodermatitis papulosa infantil tras una infección por el virus de Epstein-Barr

Papular acrodermatitis of childhood is considered a paraviral dermatosis due to various infections and vaccines. The diagnosis is based on clinical features and treatment is symptomatic. The prognosis is excellent, because the syndrome is self-limited. We describe the case of a boy who presented a papular acrodermatitis of childhood after an Epstein-Barr virus infection

Parotiditis recurrente y déficit de células natural killer: ¿coincidencia o patogenia? / Juvenile recurrent parotitis and natural killer cells deficiency, coincidence or pathogenesis?

La parotiditis recurrente juvenil puede tener multitud de causas, es importante tener en cuenta, dentro de la etiología, el estudio de las subpoblaciones linfocitarias, ya que puede haber una relación patogénica con la deficiencia de células natural killer. Se presenta el caso clínico de una paciente de diez años con parotiditis recurrente secundaria a dicho proceso

Juvenile recurrent parotitis may have many causative factors. It is important to make an study of lymphocyte subsets, due to natural killer cells deficiency could be pathogenic. The clinical case of a 10-year-old patient with recurrent parotitis secondary to this process is presented

Epstein-Barr virus is not detected in mucosal lichen planus

BACKGROUND: Lichen planus (LP) is a chronic inflammatory, immunological, mucocutaneous disease can affect skin, genital and oral mucosa. Oral lichen planus (OLP) is the most common noninfectious, chronic inflammatory oral disease affecting 1-2% of the general adult population. World Health Organization (WHO) classifies OLP as a potentially malignant disorder. Epstein Barr virus or human herpesvirus-4, is a member of the herpes virus family and one of the most ubiquitous viruses known to human, infecting approximately 90% of the world's adult population. The virus often infects B lymphocytes resulting in a wide spectrum of mucocutaneous and systemic diseases, ranging from mild lesions to aggressive malignancies. The aim of this study was to investigate expression of the EBV encoded RNAs EBER1 and EBER2 in oral and genital lichen planus and compare results with normal tissues in situ hybridization which is considered the golden standard for detection of EBER. MATERIAL AND METHODS: A total of 68 biopsies, 25 oral LP, 26 genital LP, 10 oral controls and finally 7 genital controls were analysed using situ hybridization. RESULT: All samples had RNA as shown by the control slide, whereas no case contained neither EBER1 nor EBER2. CONCLUSIONS: Based on results from our study EBV is not involved in aetiology of lichen planus

Infección diseminada por Propionibacterium acnes en un varón de 42 años con infección por el VIH / Disseminated Propionibacterium acnes infection in a 42-year-old HIV-positive man

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