Caracterización molecular de la microbiota bacteriana cervical y del virus de papiloma humano (VPH) en muestras de mujeres provenientes de dos regiones de Colombia
El cáncer cervical (CC) es una de las principales preocupaciones de salud pública en países en desarrollo, ocupando el cuarto lugar entre los tipos más comunes de cáncer que afectan a mujeres. El factor de riesgo predominante en el desarrollo de CC es la infección por el Virus del Papiloma Humano de...
- Autores:
-
Arteaga Pautt, Heiser
- Tipo de recurso:
- Doctoral thesis
- Fecha de publicación:
- 0025
- Institución:
- Universidad de Córdoba
- Repositorio:
- Repositorio Institucional Unicórdoba
- Idioma:
- spa
- OAI Identifier:
- oai:repositorio.unicordoba.edu.co:ucordoba/9223
- Acceso en línea:
- https://repositorio.unicordoba.edu.co/handle/ucordoba/9223
https://repositorio.unicordoba.edu.co
- Palabra clave:
- Organización Mundial de la Salud
Infección de transmisión sexual
Enfermedad Pélvica Inflamatoria VPH
Virus de Papiloma Humano ADN
Ácido desoxirribonucleico ARN
Ácido Ribonucleico
Cancer cervical
Virus de Papiloma humano de alto riesgo
Reacción en cadena de la polimerasa
Lesión escamosa intraepitelial de bajo grado
Lesión escamosa intraepitelial de alto grado
Pares de bases
Región reguladora corriente arriba
Origen de replicación
Región Larga de control
Promotor región tardía
Promotor región temprana
Neoplasia intraepitelial cervical intraepitelial
Células escamosas atípicas de significado indeterminado
Carcinoma de células escamosas
Adenocarcinoma
Virus de Papiloma Humano de alto riesgo
Virus de Papiloma Humano de bajo riesgo
World Health Organization
Sexually transmitted infection
Pelvic inflammatory disease HPV
Human papillomavirus DNA
Deoxyribonucleic acid RNA
Ribonucleic acid
Cervical cancer
High-risk human papillomavirus
Polymerase chain reaction
Low-grade squamous intraepithelial lesion
High-grade squamous intraepithelial lesion
Base pairs, Upstream regulatory region
Origin of replication
Long control region
Late promoter
Early promoter
Cervical intraepithelial neoplasia
Atypical squamous cells of undetermined significance
Squamous cell carcinoma
Adenocarcinoma
High-risk human papillomavirus
Low-risk human papillomavirus
- Rights
- openAccess
- License
- Copyright Universidad de Córdoba, 2025
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dc.title.none.fl_str_mv |
Caracterización molecular de la microbiota bacteriana cervical y del virus de papiloma humano (VPH) en muestras de mujeres provenientes de dos regiones de Colombia |
title |
Caracterización molecular de la microbiota bacteriana cervical y del virus de papiloma humano (VPH) en muestras de mujeres provenientes de dos regiones de Colombia |
spellingShingle |
Caracterización molecular de la microbiota bacteriana cervical y del virus de papiloma humano (VPH) en muestras de mujeres provenientes de dos regiones de Colombia Organización Mundial de la Salud Infección de transmisión sexual Enfermedad Pélvica Inflamatoria VPH Virus de Papiloma Humano ADN Ácido desoxirribonucleico ARN Ácido Ribonucleico Cancer cervical Virus de Papiloma humano de alto riesgo Reacción en cadena de la polimerasa Lesión escamosa intraepitelial de bajo grado Lesión escamosa intraepitelial de alto grado Pares de bases Región reguladora corriente arriba Origen de replicación Región Larga de control Promotor región tardía Promotor región temprana Neoplasia intraepitelial cervical intraepitelial Células escamosas atípicas de significado indeterminado Carcinoma de células escamosas Adenocarcinoma Virus de Papiloma Humano de alto riesgo Virus de Papiloma Humano de bajo riesgo World Health Organization Sexually transmitted infection Pelvic inflammatory disease HPV Human papillomavirus DNA Deoxyribonucleic acid RNA Ribonucleic acid Cervical cancer High-risk human papillomavirus Polymerase chain reaction Low-grade squamous intraepithelial lesion High-grade squamous intraepithelial lesion Base pairs, Upstream regulatory region Origin of replication Long control region Late promoter Early promoter Cervical intraepithelial neoplasia Atypical squamous cells of undetermined significance Squamous cell carcinoma Adenocarcinoma High-risk human papillomavirus Low-risk human papillomavirus |
title_short |
Caracterización molecular de la microbiota bacteriana cervical y del virus de papiloma humano (VPH) en muestras de mujeres provenientes de dos regiones de Colombia |
title_full |
Caracterización molecular de la microbiota bacteriana cervical y del virus de papiloma humano (VPH) en muestras de mujeres provenientes de dos regiones de Colombia |
title_fullStr |
Caracterización molecular de la microbiota bacteriana cervical y del virus de papiloma humano (VPH) en muestras de mujeres provenientes de dos regiones de Colombia |
title_full_unstemmed |
Caracterización molecular de la microbiota bacteriana cervical y del virus de papiloma humano (VPH) en muestras de mujeres provenientes de dos regiones de Colombia |
title_sort |
Caracterización molecular de la microbiota bacteriana cervical y del virus de papiloma humano (VPH) en muestras de mujeres provenientes de dos regiones de Colombia |
dc.creator.fl_str_mv |
Arteaga Pautt, Heiser |
dc.contributor.advisor.none.fl_str_mv |
Soto De León, Sara Cecilia |
dc.contributor.author.none.fl_str_mv |
Arteaga Pautt, Heiser |
dc.contributor.jury.none.fl_str_mv |
Alvarez Aldana, Adalucy Sierra Verbel, Álvaro Arroyo Salgado, Bárbara |
dc.subject.proposal.none.fl_str_mv |
Organización Mundial de la Salud Infección de transmisión sexual Enfermedad Pélvica Inflamatoria VPH Virus de Papiloma Humano ADN Ácido desoxirribonucleico ARN Ácido Ribonucleico Cancer cervical Virus de Papiloma humano de alto riesgo Reacción en cadena de la polimerasa Lesión escamosa intraepitelial de bajo grado Lesión escamosa intraepitelial de alto grado Pares de bases Región reguladora corriente arriba Origen de replicación Región Larga de control Promotor región tardía Promotor región temprana Neoplasia intraepitelial cervical intraepitelial Células escamosas atípicas de significado indeterminado Carcinoma de células escamosas Adenocarcinoma Virus de Papiloma Humano de alto riesgo Virus de Papiloma Humano de bajo riesgo |
topic |
Organización Mundial de la Salud Infección de transmisión sexual Enfermedad Pélvica Inflamatoria VPH Virus de Papiloma Humano ADN Ácido desoxirribonucleico ARN Ácido Ribonucleico Cancer cervical Virus de Papiloma humano de alto riesgo Reacción en cadena de la polimerasa Lesión escamosa intraepitelial de bajo grado Lesión escamosa intraepitelial de alto grado Pares de bases Región reguladora corriente arriba Origen de replicación Región Larga de control Promotor región tardía Promotor región temprana Neoplasia intraepitelial cervical intraepitelial Células escamosas atípicas de significado indeterminado Carcinoma de células escamosas Adenocarcinoma Virus de Papiloma Humano de alto riesgo Virus de Papiloma Humano de bajo riesgo World Health Organization Sexually transmitted infection Pelvic inflammatory disease HPV Human papillomavirus DNA Deoxyribonucleic acid RNA Ribonucleic acid Cervical cancer High-risk human papillomavirus Polymerase chain reaction Low-grade squamous intraepithelial lesion High-grade squamous intraepithelial lesion Base pairs, Upstream regulatory region Origin of replication Long control region Late promoter Early promoter Cervical intraepithelial neoplasia Atypical squamous cells of undetermined significance Squamous cell carcinoma Adenocarcinoma High-risk human papillomavirus Low-risk human papillomavirus |
dc.subject.keywords.none.fl_str_mv |
World Health Organization Sexually transmitted infection Pelvic inflammatory disease HPV Human papillomavirus DNA Deoxyribonucleic acid RNA Ribonucleic acid Cervical cancer High-risk human papillomavirus Polymerase chain reaction Low-grade squamous intraepithelial lesion High-grade squamous intraepithelial lesion Base pairs, Upstream regulatory region Origin of replication Long control region Late promoter Early promoter Cervical intraepithelial neoplasia Atypical squamous cells of undetermined significance Squamous cell carcinoma Adenocarcinoma High-risk human papillomavirus Low-risk human papillomavirus |
description |
El cáncer cervical (CC) es una de las principales preocupaciones de salud pública en países en desarrollo, ocupando el cuarto lugar entre los tipos más comunes de cáncer que afectan a mujeres. El factor de riesgo predominante en el desarrollo de CC es la infección por el Virus del Papiloma Humano de alto riesgo (VPH-AR). Esta infección se caracteriza por variables intrínsecas del virus como el genotipo infectante, la carga viral y la presencia de múltiples genotipos. Además, factores individuales, ambientales y conductuales como el consumo de alcohol, tabaquismo y el uso de anticonceptivos hormonales también influyen significativamente. Recientemente, la microbiota cervical ha ganado atención debido a su potencial influencia en la susceptibilidad y progresión del VPH. En la región Caribe de Colombia, hay una falta de estudios sobre la frecuencia específica de los tipos de VPH-AR. Este estudio se enfocó en determinar la frecuencia de VPH-AR y su asociación con variables sociodemográficas en mujeres que asisten a controles de citología cervical en la IPS Liga Cordobesa Contra el Cáncer. También se investigó la composición del microbiota cervical en mujeres infectadas con VPH-AR, diferenciando entre infecciones únicas y múltiples. Participaron voluntariamente 450 mujeres, quienes, tras firmar un consentimiento informado, completaron una encuesta que recopiló datos sociodemográficos, clínicos y de comportamiento sexual. Se les realizaron pruebas de citología cervical y análisis molecular mediante PCR. De las muestras positivas, se tipificaron los VPH con el kit de Optiplex HPV Genotyping. Para el análisis de la microbiota cervical, se seleccionaron 60 muestras con cantidad óptima de ADN y se procesaron con la técnica de Ilumina. |
publishDate |
0025 |
dc.date.issued.none.fl_str_mv |
0025-06-27 |
dc.date.accessioned.none.fl_str_mv |
2025-06-27T20:16:26Z |
dc.date.available.none.fl_str_mv |
2025-06-27T20:16:26Z |
dc.type.none.fl_str_mv |
Trabajo de grado - Doctorado |
dc.type.driver.none.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
dc.type.coar.none.fl_str_mv |
http://purl.org/coar/resource_type/c_db06 |
dc.type.version.none.fl_str_mv |
info:eu-repo/semantics/acceptedVersion |
dc.type.content.none.fl_str_mv |
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dc.type.redcol.none.fl_str_mv |
http://purl.org/redcol/resource_type/TD |
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http://purl.org/coar/resource_type/c_db06 |
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acceptedVersion |
dc.identifier.uri.none.fl_str_mv |
https://repositorio.unicordoba.edu.co/handle/ucordoba/9223 |
dc.identifier.instname.none.fl_str_mv |
Universidad de Córdoba |
dc.identifier.reponame.none.fl_str_mv |
Repositorio Institucional Unicórdoba |
dc.identifier.repourl.none.fl_str_mv |
https://repositorio.unicordoba.edu.co |
url |
https://repositorio.unicordoba.edu.co/handle/ucordoba/9223 https://repositorio.unicordoba.edu.co |
identifier_str_mv |
Universidad de Córdoba Repositorio Institucional Unicórdoba |
dc.language.iso.none.fl_str_mv |
spa |
language |
spa |
dc.relation.references.none.fl_str_mv |
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Soto De León, Sara Cecilia7356aa40-3bf1-40d2-8597-5cb8e28c0a24-1Arteaga Pautt, Heiser441d2b85-c88d-4b2a-aa61-f855de96f2a6-1Alvarez Aldana, Adalucy7b2d485b-9839-4a14-bec0-872d61b9e669-1Sierra Verbel, Álvarobe6ec478-dd68-4b37-bcc6-6ae1e7d83d89-1Arroyo Salgado, Bárbara7bab0ce3-140a-4827-9194-678674efc1f9-12025-06-27T20:16:26Z2025-06-27T20:16:26Z0025-06-27https://repositorio.unicordoba.edu.co/handle/ucordoba/9223Universidad de CórdobaRepositorio Institucional Unicórdobahttps://repositorio.unicordoba.edu.coEl cáncer cervical (CC) es una de las principales preocupaciones de salud pública en países en desarrollo, ocupando el cuarto lugar entre los tipos más comunes de cáncer que afectan a mujeres. El factor de riesgo predominante en el desarrollo de CC es la infección por el Virus del Papiloma Humano de alto riesgo (VPH-AR). Esta infección se caracteriza por variables intrínsecas del virus como el genotipo infectante, la carga viral y la presencia de múltiples genotipos. Además, factores individuales, ambientales y conductuales como el consumo de alcohol, tabaquismo y el uso de anticonceptivos hormonales también influyen significativamente. Recientemente, la microbiota cervical ha ganado atención debido a su potencial influencia en la susceptibilidad y progresión del VPH. En la región Caribe de Colombia, hay una falta de estudios sobre la frecuencia específica de los tipos de VPH-AR. Este estudio se enfocó en determinar la frecuencia de VPH-AR y su asociación con variables sociodemográficas en mujeres que asisten a controles de citología cervical en la IPS Liga Cordobesa Contra el Cáncer. También se investigó la composición del microbiota cervical en mujeres infectadas con VPH-AR, diferenciando entre infecciones únicas y múltiples. Participaron voluntariamente 450 mujeres, quienes, tras firmar un consentimiento informado, completaron una encuesta que recopiló datos sociodemográficos, clínicos y de comportamiento sexual. Se les realizaron pruebas de citología cervical y análisis molecular mediante PCR. De las muestras positivas, se tipificaron los VPH con el kit de Optiplex HPV Genotyping. Para el análisis de la microbiota cervical, se seleccionaron 60 muestras con cantidad óptima de ADN y se procesaron con la técnica de Ilumina.Cervical cancer (CC) is a major public health concern in developing countries, ranking fourth among the most common cancers affecting women. The primary risk factor for developing CC is infection with high-risk types of Human Papillomavirus (HPV-AR). This infection is characterized by intrinsic viral variables such as the infecting genotype, viral load, and the presence of multiple genotypes. Additionally, individual, environmental, and behavioral factors like alcohol consumption, smoking, and the use of hormonal contraceptives significantly influence the risk. Recently, cervical microbiota has attracted attention for its potential role in influencing HPV susceptibility and progression. In the Colombian Caribbean region, there is a notable lack of studies on the specific frequency of high-risk HPV types (HPV-AR). This study aimed to determine the type-specific frequency of HPV-AR and its association with sociodemographic variables in women attending cervical cytology screening at the IPS Liga Cordobesa Contra el Cáncer. The study also explored the cervical microbiota composition in women infected with HPV-AR, distinguishing between single and multiple infections. The study involved 450 voluntary participants who, after signing informed consent forms, completed a survey collecting sociodemographic, clinical, and sexual behavior information. Each woman underwent cervical cytology and molecular analysis through Polymerase Chain Reaction (PCR). Positive samples were genotyped using the Optiplex HPV Genotyping kit. For cervical microbiota analysis, 60 samples with optimal DNA quantities were selected and processed using Illumina sequencing techniques.ABREVIATURAS.. 8RESUMEN 9ABSTRACT 12ESTRUCTURA DEL TRABAJO 15INTRODUCCIÓN 17OBJETIVOS 29CAPITULO I 30CAPITULO 2 39CAPITULO 3 25CAPITULO 4 62CONCLUSIONES FINALES 76RECOMENDACIONES 78PERSPECTIVAS ........79CONSIDERACIONES ÉTICAS 80REFERENCIAS BIBLIOGRÁFICAS 81ANEXOS 93ANEXO 1: CONSENTIMIENTO INFORMADO 94ANEXO 2: FICHA EPIDEMIOLÓGICA 99ANEXO 3: ACTA DE COMITÉ ÉTICA 100ANEXO 4: ARTÍCULO CIENTÍFICO PUBLICADO 101DoctoradoDoctor(a) en Microbiología y Salud TropicalTrabajos de Investigación y/o Extensiónapplication/pdfspaCopyright Universidad de Córdoba, 2025https://creativecommons.org/licenses/by-nc-nd/4.0/Atribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0)info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Caracterización molecular de la microbiota bacteriana cervical y del virus de papiloma humano (VPH) en muestras de mujeres provenientes de dos regiones de ColombiaTrabajo de grado - Doctoradoinfo:eu-repo/semantics/doctoralThesishttp://purl.org/coar/resource_type/c_db06info:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TDAagaard, K., Riehle, K., Ma, J., Segata, N., Mistretta, T. 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ISME J, 1(2), 121-133. doi:10.1038/ismej.2007.12Organización Mundial de la SaludInfección de transmisión sexualEnfermedad Pélvica Inflamatoria VPHVirus de Papiloma Humano ADNÁcido desoxirribonucleico ARNÁcido RibonucleicoCancer cervicalVirus de Papiloma humano de alto riesgoReacción en cadena de la polimerasaLesión escamosa intraepitelial de bajo gradoLesión escamosa intraepitelial de alto gradoPares de basesRegión reguladora corriente arribaOrigen de replicaciónRegión Larga de controlPromotor región tardíaPromotor región tempranaNeoplasia intraepitelial cervical intraepitelialCélulas escamosas atípicas de significado indeterminadoCarcinoma de células escamosasAdenocarcinomaVirus de Papiloma Humano de alto riesgoVirus de Papiloma Humano de bajo riesgoWorld Health OrganizationSexually transmitted infectionPelvic inflammatory disease HPVHuman papillomavirus DNADeoxyribonucleic acid RNARibonucleic acidCervical cancerHigh-risk human papillomavirusPolymerase chain reactionLow-grade squamous intraepithelial lesionHigh-grade squamous intraepithelial lesionBase pairs, Upstream regulatory regionOrigin of replicationLong control regionLate promoterEarly promoterCervical intraepithelial neoplasiaAtypical squamous cells of undetermined significanceSquamous cell carcinomaAdenocarcinomaHigh-risk human papillomavirusLow-risk human papillomavirusFacultad de Medicina Veterinaria y ZootecniaMontería, Córdoba, ColombiaDoctorado en Microbiología y Salud TropicalPublicationORIGINALArteaga-Pautt.pdfArteaga-Pautt.pdfapplication/pdf12636373https://repositorio.unicordoba.edu.co/bitstreams/fa760c51-511b-4d5d-9993-344dde411459/downloaddcd24f4c499913c0d5dbfa0d90652c2aMD51Formato de autorización.pdfFormato de autorización.pdfapplication/pdf410752https://repositorio.unicordoba.edu.co/bitstreams/f8392536-f97d-4fc4-b951-4e80db7ea946/downloadbf2cdb71f0264fcb81384dffe6a8ff39MD53LICENSElicense.txtlicense.txttext/plain; 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