The Colombian Zika Virus Isolate (COL345Si) Replicates in Prostate Adenocarcinoma Cells and Modulates the Antiviral Response.

Zika virus (ZIKV), a flavivirus that is mainly transmitted by A. aegypti and A. albopictus and sexual transmission, has been documented and described. The ZIKV RNA detection in the semen of vasectomized men indicates that accessory glands such as the prostate could be a site of virus replication. In this study, we characterized the ZIKV infection, evaluated the antiviral profile, and demonstrated the AXL and TIM-1 expression on the PC3 prostate cell line. It was also determined that PC3 cells are susceptible and permissive to ZIKV infection without altering the cell viability or causing a cytopathic effect. The antiviral profile suggests that the PC3 cells modulate the antiviral response through the suppressor molecule expression, SOCS-1, during a ZIKV infection.

Virus de la hepatitis E

Resumen El virus de la hepatitis E (VHE) es uno de los principales agentes etiológicos de hepatitis entérica en el mundo. En países en vía de desarrollo, la seroprevalencia oscila entre 20 y 50% y en países desarrollados entre 4,4 y 21%. Clínicamente los casos de infección por VHE en individuos inmunocompetentes cursan como una hepatitis viral aguda auto limitada; por el contrario, en mujeres embarazadas, individuos receptores de trasplantes de órganos e individuos que conviven con el virus de la inmunodeficiencia humana (VIH), la infección puede manifestarse como una hepatitis crónica y grave. En América Latina, sólo Brasil y Argentina reportan cifras en individuos que conviven con el VIH. Se requieren más estudios en nuestra región que permitan determinar la prevalencia del VHE en individuos inmunosuprimidos, donantes de sangre y población general para adoptar medidas que garanticen un diagnóstico oportuno, acceso a la atención y el control de la transmisión.

Abstract The hepatitis E virus (HEV) is one of the main etiological agents of enteric hepatitis in the world. In developing countries its sero-prevalence ranges from 20 to 50% and in developed countries from 4.4% to 21%. Clinically, cases of HEV infection in immunocompetent individuals present as self-limited acute viral hepatitis; conversely, in pregnant women, transplanted individuals, and individuals living with the human immunodeficiency virus (HIV), the infection can manifest as chronic and severe hepatitis. In Latin America, only Brazil and Argentina report figures for individuals living with HIV. More studies are required in our region to determine the prevalence of HEV in immunosuppressed individuals, blood donors, and the general population to adopt measures that guarantee timely diagnosis, access to care, and control of transmission.

Comparison of immediate colposcopy, repeat conventional cytology and hrHPV testing for the clinical management of ASC-US cytology in routine health services of Medellin, Colombia: The ASCUS-COL Trial.

In the context of opportunistic cervical cancer screening settings of low-and-middle-income countries, little is known about the benefits of high-risk human papillomavirus (hrHPV) testing on high-grade cervical abnormality detection among women with atypical squamous cells of undetermined significance (ASC-US) cytology in routine clinical practice. We compared the effectiveness of immediate colposcopy (IC), conventional cytology at 6 and 12 months (colposcopy if ≥ASC-US) (RC), and hrHPV testing (colposcopy if hrHPV-positive) (HPV) to detect cervical intraepithelial neoplasia grade 2 or more severe diagnoses (CIN2+) among women aged 20-69 years with ASC-US in routine care. Participants (n=2,661) were evenly randomized into three arms (n=882 IC, n=890 RC, n=889 HPV) to receive services by routine healthcare providers and invited to an exit visit 24 months after recruitment. Histopathology was blindly reviewed by a quality-control external panel (QC). The primary endpoint was the first QC-diagnosed CIN2+ or CIN3+ detected during three periods: enrolment (≤6 months for IC and HPV, ≤12 months for RC), follow-up (between enrolment and exit visit), and exit visit. The trial is completed. Colposcopy was done on 88%, 42%, and 52% of participants in IC, RC, and HPV. Overall, 212 CIN2+ and 52 CIN3+ cases were diagnosed. No differences were observed for CIN2+ detection (p=0.821). However, compared to IC, only HPV significantly reduced CIN3+ cases that providers were unable to detect during the 2-year routine follow-up (relative proportion 0.35, 95% CI 0.09-0.87). In this context, hrHPV testing was the most effective and efficient management strategy for women with ASC-US cytology.

Meta-analyses of the validity and performance of screening tests for Hepatitis C Virus in the blood banks, 2000-2018 / Metaanálisis de la validez y el desempeño de las pruebas de tamización del virus de la hepatitis c en bancos de sangre, 2000-2018

RESUMEN Este estudio evaluó la validez y desempeño del inmunodiagnóstico del virus de la hepatitis C (VHC), con base en estudios publicados en la literatura científica mundial. Se diseñó y validó un protocolo de búsqueda y selección de investigaciones en las fases de la guía PRISMA, se analizaron los parámetros de sensibilidad, especificidad, cocientes de probabilidad, razón de odds y curva ROC, en MetaDisc. Se tamizaron 4602 estudios, de los cuales sólo 545 se realizaron en bancos de sangre y 18 evaluaron la validez diagnóstica de las pruebas para el VHC. La mayoría de los estudios fueron de Europa y Asia, con un 78 % basados en determinación de anticuerpos. Los estudios con detección de anticuerpos se realizaron en 21 483 donantes sanos y 3 145 infectados en quienes se halló una sensibilidad de 97,8 % (IC 95 % = 97,3 - 98,2), especificidad 99,0 % (IC 95 % = 98,9 - 99,2), cociente de probabilidad positivo 75,4 (IC 95 % = 27,2 - 209,2) y negativo de 0,02 (IC 95 % = 0,01 - 0,07) y área bajo la curva de 99,8 %. Se concluye que la detección de anticuerpos presenta excelente validez, desempeño y utilidad diagnóstica para la detección del VHC en donantes de sangre y población general.

ABSTRACT This study evaluated the validity and performance of the immunodiagnosis of the Hepatitis C Virus (HCV), based on studies published in the worldwide scientific literature. A search and selection research protocol was designed and validated in the phases of the PRISMA guide, the parameters of sensitivity, specificity, likelihood ratios, odds ratio, and ROC curve were analyzed in MetaDisc. 4602 studies were screened, of which only 545 were performed in blood banks and 18 evaluated the diagnostic validity of the tests for HCV. Most studies were from Europe and Asia, with 78 % based on antibody determination. Studies with antibody detection were carried out in 21483 healthy donors and 3145 infected patients in whom a sensitivity of 97.8 % (95 % CI = 97.3 - 98.2) was found, 99.0 % specificity (95 % CI = 98.9 - 99.2), positive likelihood ratio 75.4 (95 % CI = 27.2 - 209.2) and negative of 0.02 (95% CI = 0.01 - 0.07) and area under the curve 99.8 %. It is concluded that the detection of antibodies presents excellent validity, performance, and diagnostic utility for the detection of HCV in blood donors and the general population.

Factores de riesgo para el cáncer de mama / Risk Factors for Breast Cancer

Introducción: El cáncer de mama es el más común entre las mujeres, sus factores de riesgo no han sido sistematizados desde un enfoque amplio de las revisiones publicadas. Objetivo: Sistematizar los factores de riesgo del cáncer de mama a partir de publicaciones de estudios de casos y controles en el período 2008-2018. Métodos: Revisión sistemática de la literatura con base en la aplicación de un protocolo exhaustivo y reproducible, siguiendo las fases de identificación, tamización, elección e inclusión de la guía PRISMA. Se realizó síntesis cualitativa con proporciones e intervalos de confianza del 95 por ciento. Resultados: Se analizaron 298 estudios, en 2 927 342 mujeres, la mayoría de México (2 000 835). Los países con mayor frecuencia de publicación fueron EE.UU. (20,9 por ciento) y China (10,8 por ciento). El grupo de factores de riesgo más estudiado fue la dieta (26,6 por ciento), los factores reproductivos (14,8 por ciento) y el estilo de vida (9,1 por ciento). Los menos estudiados son los biológicos, solo uno abordó este tipo de factor reportando una fuerte asociación de la seroconversión IgG en citomegalovirus con el desarrollo de cáncer de mama. Los tres factores que registraron mayor fuerza de asociación fueron la obesidad, los factores psicosociales y el citomegalovirus. Conclusiones: Se halló una amplia diversidad de factores de riesgo, algunos estudios con diseños rigurosos para establecer asociaciones etiológicas sólidas y otros con un desarrollo investigativo incipiente o problemas metodológicos que impiden consolidar hipótesis causales y por tanto la posibilidad de intervenir en los principales desencadenantes de la aparición de la enfermedad(AU)

Introduction: Breast cancer is most common among women; its risk factors have not been outlined from a broad approach of published reviews. Objective: To outline the risk factors of breast cancer from publications of case-control studies from 2008 to 2018. Methods: A systematic review of the literature based on the application of comprehensive and reproducible protocol, following identification, screening, selection and inclusion phases of PRISMA guide. Qualitative synthesis was performed with proportions and 95 percent confidence intervals. Results: 298 studies were analyzed in 2,927,342 women, mostly from Mexico (2 000 835). The countries with highest frequency of publication were USA. (20.9 percent) and China (10.8 percent). The most studied groups of risk factors were diet (26.6 percent), reproductive factors (14.8 percent) and lifestyle (9.1 percent). The least studied are the biological ones. Only one approached this type of factor, reporting a strong association of IgG seroconversion in cytomegalovirus with the appearance of breast cancer. The three factors that registered the greatest strength of association were obesity, psychosocial factors and cytomegalovirus. Conclusions: We found a wide diversity of risk factors, some rigorous-design studies to establish solid etiological associations and others with initial research development or methodological problems that prevent consolidating causal hypotheses and therefore the possibility of intervening in the main triggers for the appearance of the disease(AU)

Descripción de pruebas moleculares en el diagnóstico del virus Zika en el periodo 2008-Febrero 2018. Revisión sistemática / Description of molecular tests in the diagnosis of Zika virus in the period 2008-February 2018

Resumen Objetivo. Describir las pruebas moleculares usadas desde 2008 para la detección del virus Zika reportadas en artículos indexados en 3 bases de datos. Métodos. Se realizó la búsqueda de literatura científica utilizando el método PRISMA durante el periodo 2008 - febrero de 2018, en las bases de datos Pubmed, Science Direct y Embase, usando como criterios de inclusión artículos originales publicados entre los años 2008 a 2018 que realicen investigación en humanos con sospecha de infección por ZIKV y que describan la prueba molecular utilizada. Resultados. A partir de una búsqueda inicial de 2617 artículos recolectados con las palabras clave y aplicar los criterios de inclusión y exclusión, se seleccionan 18 artículos, de los cuales 8 son de Science Direct, 4 de Embase y 6 de Pubmed. Se describe la RT-PCR como la técnica más utilizada, se hallaron 9 blancos moleculares diferentes utilizados en las pruebas y 7 muestras biológicas de las cuales se pudo amplificar el genoma viral. Conclusiones. Hasta el momento la RT-PCR es la técnica más utilizada para el diagnóstico de la infección por el virus Zika al ser la más estandarizada y presentar una alta sensibilidad y especificidad, sin embargo se sigue trabajando sobre otras técnicas que garanticen la detección oportuna del virus, usando diferentes genes como el gen E, NS5, NS1, NS2B NS3, NS4B y CPREM principalmente en suero y orina.

Abstract Objective. To describe the molecular tests used since 2008 for detection of Zika virus reported in indexed articles in 3 databases. Methods. A search of scientific literature was made using the PRISMA method during 2008 period - February 2018, in the databases Pubmed, Science Direct and Embase, using as inclusion criteria original articles published between 2008 to 2018 that make researches in humans with suspicion of ZIKV infection and that describes the use of molecular test. Results. From an initial search of 2617 articles recollected with the keywords and after applying inclusion and exclusion criteria, 18 articles were selected, of which 8 are from Science Direct, 4 from Embase and 6 from Pubmed. The RT- PCR was described as the most used technique, it was found 9 different molecular targets used in the tests and 7 biological samples of which the viral genome can be amplified. Conclusions. Until now the RT-PCR test is the most used technique for the diagnosis of infection for Zika virus, being the most standardized test and due it presents a high sensi-tivity and specificity, however there is still working about other techniques that guarantee opportune detection of the virus, using different genes like E, NS5, NS1, NS2B, NS3, NS4B y CPREM mainly in serum and urine.

Unexpected inverse correlation between Native American ancestry and Asian American variants of HPV16 in admixed Colombian cervical cancer cases.

BACKGROUND: European (E) variants of HPV 16 are evenly distributed among world regions, meanwhile Non-European variants such as European-Asian (EAs), Asian American (AA) and African (Af) are mostly confined to Eastern Asia, The Americas and African regions respectively. Several studies have shown that genetic variation of HPV 16 is associated with the risk of cervical cancer, which also seems to be dependent on the population. This relationship between ethnicity and variants have led to the suggestion that there is co-evolution of variants with humankind. Our aim was to evaluate the relationship between the individual ancestry proportion and infection with HPV 16 variants in cervical cancer. METHODS: We examined the association between ancestry and HPV 16 variants in samples of 82 cervical cancer cases from different regions of Colombia. Individual ancestry proportions (European, African and Native American) were estimated by genotyping 106 ancestry informative markers. Variants were identified by PCR amplification of the E6 gene, followed by reverse line blot hybridization (RLB) with variants specific probes. RESULTS: Overall European (E) and Asian American (AA) variants frequency was 66.5% and 33.5% respectively. Similar distribution was observed in cases with higher proportions of European or African ancestry. A higher Native American ancestry was significantly associated with higher frequency of E variants (median ancestry>23.6%, Age and place of birth adjusted OR: 3.55, 95% CI: 1.26-10.03, p=0.01). Even further, an inverse geographic correlation between Native American ancestry and frequency of infections with AA variants was observed (ρ=-0.825, p=0.008). Regions with higher proportion of Native American ancestry had a lower frequency of AA variants of HPV 16. CONCLUSIONS: This study suggests replacement of AA variants by E variants of human papillomavirus 16 in cervical cancer cases with high Native American ancestry.

Immunosuppression in cervical cancer with special reference to arginase activity.

INTRODUCTION: Cervical cancer is characterized by an immunosuppressive microenvironment and a Th2-type cytokine profile. Expression of arginase (ASE), the enzyme that converts L-arginine into L-ornithine and urea, is stimulated by Th2-type cytokines. OBJECTIVE: To assess the association of ASE activity and L-Arg metabolism products with cervical cancer. METHODS: Sera of 87 and 41 women with histologically confirmed by colposcopy-directed biopsy SCC and CIN3 respectively and 79 with normal cytology or Low-Grade Squamous Intraepithelial Lesion (LSIL), were evaluated. Cytokines were measured using Milliplex Human cytokine/chemokine kit. Arginase (ASE) activity was determined using an enzymatic assay. Levels of L-arginine, L-ornithine, putrescine and spermine were determined by HPLC. RESULTS: Significantly higher levels of ASE activity were observed in women with CIN3 (age-adjusted OR: 24.3; 95%CI: 3.82-155) and SCC (AOR: 9.8; 95%CI: 2.34-40.8). As expected, possibly due to high levels of ASE activity, higher levels of l-Arg were negatively associated with CIN3 (AOR: 0.03; 95%CI: 0.004-0.19) and SSC (AOR: 0.06; 95%CI: 0.02-0.24). Consistent with the role of ASE in the conversion of L-arginine to L-ornithine and polyamine production therefrom, women with cervical cancer had higher levels of spermine and putrescine. A correlation analysis revealed a significant albeit weak relationship between high levels of IL-10 and high levels of ASE (Pearson r=0.32, p-value=0.003) in women with cervical cancer. CONCLUSION: This study indicates that ASE activity and L-Arg degradation mechanisms of immunosuppression are present in cervical cancer. The results foster research in the design of possible strategies to inhibit ASE activity for therapy of cervical cancer.

Location and Density of Immune Cells in Precursor Lesions and Cervical Cancer.

Only a small proportion of women infected with Human Papillomavirus (HPV) develop cervical cancer. Host immune response seems to play a role eliminating the viral infection and preventing progression to cancer. Characterization of tumor infiltrating lymphocytes (TILs) in cervical pre-neoplastic lesions and cervical cancer may be helpful to understand the mechanisms that mediate this protection. The aim of this study was to determine if there are differences in the localization and density (cells/mm(2)) of CD8+ T-cells, CD4+ T-cells and Tregs (CD25 + Foxp3+) in cervical pre-neoplastic lesions and cervical cancer. Immunohistochemical analysis of sections of 96 (26 CIN1, 21 CIN2, 25 CIN3, and 24 SCC) samples revealed that regardless of CIN grades, CD8+ T-cells are more abundant than CD4+, CD25+ and Foxp3+ cells in both the stroma and epithelium. There was a higher density of CD8+ cells in the stroma of cervical cancer compared to CIN3 (OR = 4.20, 95% CI 1.2-15), CIN2 (OR = 7.86, 95% CI 1.7-36.4) and CIN1 (OR = 4.25, 95% CI 1.1-17). Studies evaluating whether these cells are recruited before or after cancer progression will be helpful to understand the role of these cells in the natural history of HPV-induced lesions.

Distribución de variantes del virus del papiloma humano 16 (VPH 16) en mujeres con y sin neoplasia intraepitelial cervical grado 3 y cáncer cervical / Distribution of variants of the human papilloma virus 16 (HPV 16) in Women with and without grade 3 cervical intraepithelial neoplasia and cervical cancer

Objetivos: Describir la distribución de variantes del virus del papiloma humano 16 en mujeres con y sin neoplasia intraepitelial cervical grado 3 y cáncer cervical. Métodos: Se determinaron las variantes moleculares en casos de carcinoma escamocelular, adenocarcinoma cervical y en mujeres sin anormalidades citológicas de alto grado y positivas para el virus del papiloma humano 16. Para la detección de las variantes moleculares se amplificó el marco abierto de lectura del gen E6 del virus del papiloma humano 16 y se utilizó una técnica de hibridación reversa para la detección de los principales cambios de nucleótidos que identifican las ramas filogenéticas y las clases de variantes. Resultados:Hubo diferencias estadísticamente significativas en la distribución de variantes de virus del papiloma humano 16. Los controles no presentaron infecciones con variantes no europeas, mientras que ellas estuvieron presentes en el 30% de los casos de carcinoma escamocelular o neoplasia intraepitelial cervical grado tres. En adenocarcinoma, el 65% de las infecciones fueron del tipo no europeo. Conclusiones: La prevalencia de variantes no europeas de virus de papiloma humano 16 fue de 31,2% en neoplasia intraepitelial cervical grado 3 y cáncer escamocelular, y de 64,1% en adenocarcinoma de cérvix, mientras que estas no se observaron en mujeres sin cáncer.

Objectives: To describe the distribution of the variants of the human papilloma virus 16 in women with and without grade 3 cervical intraepithelial neoplasia and cervical cancer. Methods: Molecular variants were established in cases of squamous cell carcinoma, cervical adenocarcinoma and in women with high grade Pap smear abnormalities who tested positive for human papilloma virus 16. For the detection of molecular variants the open reading framework for the E6 gene of the human papilloma virus 16 was amplified and a reverse hybridization technique was utilized for the detection of major changes in the nucleotides which identify the phylogenetic branches and classes of variants. Results: There were statistically significant results in the distribution of the variants of the human papilloma virus 16. Control cases showed no infections with non European variants, but they were present in 30% of squamous cell carcinoma or grade three cervical intraepithelial neoplasia. For adenocarcinoma, 65% of infections were of non European type. Conclusions: The prevalence of non European variants of the human papilloma virus 16 was 31.2% in grade 3 cervical intraepithelial neoplasia and squamous cell cancer, and 64.1% in cervical adenocarcinoma; however, these were not observed among women without cancer.

Age-specific seroprevalence of human papillomavirus 16, 18, 31, and 58 in women of a rural town of Colombia.

OBJECTIVE: The study's objective was to estimate human papillomavirus (HPV) genotype-specific seroprevalence to determine population HPV exposure and inform vaccine policy. METHODS: This study is a cross-sectional prevalence survey of 878 women of Pueblorrico, a rural town of Colombia. A standardized questionnaire was used to obtain information on demographic characteristics, sexual and reproductive history, and smoking habits. Seropositivity to HPV-16, -18, -31, and -58 was determined by virus-like particles in an enzyme-linked immunosorbent assay. RESULTS: Overall seropositivity to any HPV genotype was 27.9%. The combined seroprevalence of women 15 to 19 and 20 to 24 years old was 35.4% (95% confidence interval [CI], 25.9-46.2) and 36.0% (95% CI, 27.7-45.3), respectively. Seroprevalence for HPV-16 was 17% (95% CI, 14.6-19.6); for HPV-18, 9.8% (95% CI, 8.0-11.9); for HPV-31, 11.4% (95% CI, 9.5-13.7); and for HPV 58, 12.5% (95% CI, 10.5-14.9). Higher HPV seropositivity was associated with the lifetime number of occasional sexual partners (odds ratio, 3.05; 95% CI, 1.26-7.37) and having more than 2 regular sexual partners (odds ratio, 3.00; 95% CI, 1.21-7.45) in women younger than 44 and older than 45 years old, respectively. Use of oral contraceptives and tobacco/cigarettes was significantly associated with reduced HPV seropositivity in women older than 45 but not in women younger than 44 years old. CONCLUSIONS: Human papillomavirus seropositivity is associated with measures of sexual behavior, particularly a greater lifetime number of sexual partners. Hormonal and tobacco/cigarette use may be factors influencing the HPV seropositivity in women older than 45 years old.

Increased CD4+/CD8+ double-positive T cells in chronic Chagasic patients.

BACKGROUND: CD4+/CD8+ double positive (DP) T cells have been described in healthy individuals as well as in patients with autoimmune and chronic infectious diseases. In chronic viral infections, this cell subset has effector memory phenotype and displays antigen specificity. No previous studies of double positive T cells in parasite infections have been carried out. METHODOLOGY/PRINCIPAL FINDINGS: Seventeen chronic chagasic patients (7 asymptomatic and 10 symptomatic) and 24 non-infected donors, including 12 healthy and 12 with non-chagasic cardiomyopathy donors were analyzed. Peripheral blood was stained for CD3, CD4, CD8, HLA-DR and CD38, and lymphocytes for intracellular perforin. Antigen specificity was assessed using HLA*A2 tetramers loaded with T. cruzi K1 or influenza virus epitopes. Surface expression of CD107 and intracellular IFN-γ production were determined in K1-specific DP T cells from 11 chagasic donors. Heart tissue from a chronic chagasic patient was stained for both CD8 and CD4 by immunochemistry. Chagasic patients showed higher frequencies of DP T cells (2.1% ± 0.9) compared with healthy (1.1% ± 0.5) and non-chagasic cardiomyopathy (1.2% ± 0.4) donors. DP T cells from Chagasic patients also expressed more HLA-DR, CD38 and perforin and had higher frequencies of T. cruzi K1-specific cells. IFN-γ production in K1-specific cells was higher in asymptomatic patients after polyclonal stimulation, while these cells tended to degranulate more in symptomatic donors. Immunochemistry revealed that double positive T cells infiltrate the cardiac tissue of a chagasic donor. CONCLUSIONS: Chagasic patients have higher percentages of circulating double positive T cells expressing activation markers, potential effector molecules and greater class I antigenic specificity against T. cruzi. Although K1 tetramer positive DP T cell produced little IFN-γ, they displayed degranulation activity that was increased in symptomatic patients. Moreover, K1-specific DP T cells can migrate to the heart tissue.

Prevalence of specific herpes simplex virus-2 antibodies and associated factors in women of a rural town of Colombia.

There is lack of age-specific seroprevalence surveys and identification of factors associated with herpes simplex virus type-2 seropositivity (HSV-2) in rural populations in Colombia. A random sample of 869 women was interviewed about socio-demographic aspects, sexual and reproductive history. Antibodies to HSV-2 were determined by a specific type immunoenzymatic technique (ELISA). Participants had a mean age of 38±16.1 years, 67% were married, 60% monogamous and 47% reported use of condoms. HSV-2 seroprevalence was 19.1% (95% CI: 16.6-21.9) and it was strongly associated with increasing age (Ptrend<0.001). In the logistic regression analysis, women who reported between two or three lifetime sexual partners (OR=2.4; 95% CI: 1.5-3.7), >31 years of sexual activity with regular or occasional sexual partners (OR=4.3; 95% CI: 1.2-15.7) and not using condoms with regular sexual partners (OR=2.1; 95% CI: 1.4-3.3) were more likely to be HSV-2 seropositive. The overall seroprevalence rate of women of Pueblorrico, Colombia, is lower than that reported in other Latin American countries especially in women>45 years. The difference may be explained by higher prevalence of condom use in this population or lower exposure to herpes infection in male as well as females in the past.

Variantes del Papilomavirus Humano 16 y su asociación con el HLA en cáncer cervical / Variants of Human Papillomavirus 16 and its association with HLA in cervical cancer

El cáncer cervical es el segundo cáncer más común en mujeres en el mundo y es el principal cáncer en mujeres en países en desarrollo. La infección persistente por los genotipos oncogénicos del Virus del Papiloma Humano (VPH) es la causa necesaria para el desarrollo del cáncer cervical, siendo el VPH-16 el genotipo responsable del 50-60% de los casos. Las variantes No Europeas del VPH-16 han sido asociadas con infección persistente, lesiones de alto grado y cáncer. Los polimorfismos del Antígeno Leucocitario Humano (HLA) están también asociados con la susceptibilidad al cáncer cervical y se ha postulado una relación entre variantes del VPH y ciertos alelos del HLA. La presente revisión hace referencia a la relación entre los polimorfismos de HLA y el desarrollo de cáncer cervical y la evidencia que documenta la interrelación de este factor con la variabilidad del VPH-16.

Cervical cancer is the second most common cancer in women worldwide and the most frequent cancer in women of the majority of developing countries. Persistent infection with Human Papillomavirus (HPV) oncogenic types of HPV is necessary to develop cervical, cancer, with HPV-16 responsible for 50-60% of cases. Non-European variants of HPV-16 have been associated with persistant infection and high degree cervical cancer. Human Leucocyte Antigen (HLA) polymorphisms are also associated with susceptibility to cervical cancer. It has been suggested relationship between HPV-16 variability and some HLA Alleles. , This revision refers to the relation between HLA polymorphisms and cervical cancer development, and present evidence that may explain its relation with HPV-16 variability.

Conocimiento de los estudiantes y docentes de la Escuela de Microbiología de la Universidad de Antioquia sobre la infección por el virus del papiloma humano / Knowledge about infection with human papilomavirus among students and teachers from the School of Microbiology at the University of Antioquia, Colombia

Objetivo: estimar el nivel de conocimiento de los estudiantes y docentes de la Escuela de Microbiología de la Universidad de Antioquia sobre el virus del papiloma humano (VPH). Metodología: estudio descriptivo de corte transversal. 220 estudiantes y 35 docentes fueron encuestados. Los estudiantes fueron seleccionados mediante un muestreo aleatorio. El conocimiento se midió a través de un cuestionario previamente validado. Un análisis de varianza permitió identificar factores relacionados con el conocimiento. Resultados: 70% de los estudiantes tuvieron conocimiento bajo sobre el vph; 46% conocían las formas de transmisión y 9% conocían sobre los factores de riesgo. El programa y nivel académico se relacionó con el conocimiento de los estudiantes. El 34,3% de los docentes tuvieron conocimiento bajo. Discusión: hay desconocimiento global tanto en estudiantes como en profesores sobre el vph. A la luz de los beneficios de la prevención, se hace necesarias campañas de educación para mejorar el conocimiento de la población sobre este virus.

Objective: to estimate the level of knowledge on human papillomavirus (hpv) among students and teachers of the School of Microbiology of the University of Antioquia. Methodology: cross-sectional descriptive study. A total amount of 220 students and 35 professors were surveyed. The students were selected by random sampling. Knowledge was measured through a previously validated questionnaire. An analysis of variance identified factors related to level of knowledge. Results: 70% of students showed a low awareness on hvp, 46% knew its modes of transmission and 9% knew about risk factors. The academic curriculum and the academic level were both related to the level of knowledge of students. A total percentage of 34,3% of professors showed low knowledge. Discussion: there is a global lack of knowledge among both students and professors about the modes of transmission, the prevention and the causes for hpv. In pursuit of the benefits of primary prevention of this virus, it is necessary to implement educational campaigns to raise awareness of people about it.

Estructura moleuular y antigénica de la vacuna ontra el virus del papiloma hummano 16 (vph 16) / Antigenic and Molecular Structure of Human Papillomavirus (HPV) 16 Vaccine

La proteína L1 del Virus del Papiloma Humano (VPH) constituye el 80% de la cápside viral. Las vacunas profilácticas contra el VPH son sintetizadas a partir de la proteína L1 ensamblada en Partículas similares al Virus (del inglés VLP), las cuales son altamente inmunogénicas generando anticuerpos específicos de tipo y en algunos casos pueden presentar reacción cruzada entre tipos de VPH filogenéticamente próximos. La estructura de la proteína L1 del VPH es importante porque confiere estabilidad a la cápside mediante el establecimiento de interacciones intra e intercapsoméricas lo que asegura la integridad viral y antigénicamente porque contiene los epítopes que inducen la respuesta inmune protectora. En estudios en los que se evaluó la antigenicidad de la proteína L1 se determinó que los epítopes inmunodominantes de la cápside viral se encuentran en los bucles B-C, D-E, F-G, H-I y en el extremo C-terminal. Estos bucles son poco conservados entre los diferentes genotipos y se encuentran en segmentos de la proteína expuestos en la superficie de la cápside. Los aminoácidos situados en los bucles B-C, F-G y H-I son primordiales para el reconocimiento por los anticuerpos neutralizantes. Los diferentes subtipos y variantes presentan cambios en estos aminoácidos o en residuos que conforman otros epítopes. En esta revisión se presentará un estado del arte de la proteína L1 del VPH genotipo 16, la estructura y su importancia en el desarrollo de vacunas contra la infección producida por este virus.

Human Papillomavirus L1 protein makes up 80% of the viral capsid and self assembles in Virus-like Particles (VLP); these particles are immunogenic, generate type-specific antibodies and can induce very limited cross-reactivity among highly homologous HPV types. In addition to its structural function, it confers the stability to the capsid by establishing disulfide bonds and other intra and intercapsomeric interactions, and also contains the epitopes that induce the protective immune response of prophylactic vaccines. Immunological studies of this protein have concluded that the main epitopes of the HPV viral capsid are found in the loops B-C, D-E, F-G, H-I and the C-terminal arm. These loops are exposed on the surface of the viral capsid and have a low degree of conservation among the different genotypes. Specifically, amino acid 50 located on loop B-C and aminoacids 266, 271 and 288 located on loop F-G are important for the recognition on neutralizing antibodies. The different genotypes and variants exhibit mutations on these residues.