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WHO cervical cancer elimination goals comprise 70% of highly-sensitive screening coverage and 90% treatment of precancerous lesions. Triage for HPV-positive women may challenge sensitivity of screening algorithms and women's follow-up, particularly in low- and middle-income countries (LMIC) where screening quality and protocol adherence are frequently deficient. We aimed to determine the accuracy of triage for HPV positive women in routine screening services from Colombia by a prospective cross-sectional study. Consecutively, HPV DNA-positive women underwent six triage strategies (conventional cytology, two methods of visual inspection, HPV16/18/45-genotyping, telomerase, and HPV mRNA). Positive triage results underwent regular colposcopy/biopsy in public hospitals. Adjusted sensitivity, specificity, and predictive values for CIN2+/CIN3+ were estimated for stand-alone and combined tests. We explored the impact of triage strategies on referral rates and the complete screening algorithm (screening plus triage). Overall 16,242 women underwent HPV screening and 1789 (11.0%) were HPV-positive. In total, 20.1% of women were lost to follow-up. mRNA showed the highest positivity rate (0.64 among HPV-positive and 0.05 among the total screened cohort), the highest sensitivity (0.94 95%CI 0.75-0.96), and the lowest specificity (0.36 95%CI 0.29-0.43). Parallel testing with HPV-mRNA revealed the highest increase in sensitivity for all triage strategies. Accuracy of cytology and visual inspection differ between screening units but parallel testing with HPV16/18/45 genotyping significantly increased their sensitivity (over 0.80). Morphology-based triage for HPV-positive women remains a suitable alternative for routine practice in LMIC if combined with HPV16/18/45-genotyping; however, point-of-care triage would be preferable to reduce losses to follow-up. HPV-mRNA triage deserves cost-benefit analyses.
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Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Colômbia , Colposcopia , Estudos Transversais , Detecção Precoce de Câncer/métodos , Feminino , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Programas de Rastreamento/métodos , Infecções por Papillomavirus/patologia , Gravidez , Estudos Prospectivos , Triagem , Esfregaço Vaginal/métodos , Displasia do Colo do Útero/patologiaRESUMO
BACKGROUND: Few studies have analyzed the association between human telomerase reverse transcriptase (hTERT) protein expression (nuclear and cytoplasmic localization), hTERT methylation status, and human papillomavirus (HPV) genotype infection in cervical cancer. PATIENTS AND METHODS: One hundred seventy-three patients with cervical cancer were analyzed. hTERT protein expression was detected by immunohistochemistry. hTERT DNA methylation analysis was performed using a PCR-RLB-hTERT assay, targeting two regions of the hTERT promoter. Type specific HPV infection was detected by using GP5+/GP6+PCR-RLB. RESULTS: hTERT protein expression was found in both cytoplasm and nucleus (78.0% of the samples showed a cytoplasmic localization and 79.8% had a nuclear localization). A statistically significant association was found between alpha 9 and 7 HPV species with a non-methylation pattern of the hTERT promoter and between these species and high expression of hTERT protein with nuclear localization. CONCLUSION: hTERT protein is found in both the nucleus and cytoplasm of patients with cervical cancer and confirm the relationship between the non-methylated status of hTERT promoter and some HPV species as well as the relationship between these species and hTERT protein expression.
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Metilação de DNA , Infecções por Papillomavirus/genética , Telomerase/metabolismo , Neoplasias do Colo do Útero/genética , Adulto , Idoso , Núcleo Celular/patologia , Colo do Útero/citologia , Colo do Útero/patologia , Colo do Útero/virologia , Quimiorradioterapia/métodos , Estudos Transversais , Citoplasma/patologia , DNA Viral/isolamento & purificação , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/terapia , Infecções por Papillomavirus/virologia , Regiões Promotoras Genéticas/genética , Telomerase/análise , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/virologia , Adulto JovemRESUMO
This article is a preliminary investigational study that is aimed at giving hints about the interesting biomarkers involved in the transition process from low-grade cervix lesion to invasive cervical cancer. Our study focuses on the risk factors and tumour molecular changes in one patient. First in 1986, she was diagnosed a preinvasive cervix lesion. Then, 16 years later, she was diagnosed an invasive cervical cancer. The 2002 diagnosis was a squamous cell carcinoma of the cervix, stage IIIB (FIGO), whereas in 1986, she had been diagnosed a high-grade squamous intraepithelial cervical lesion. Retrospectively, the analysis of samples of preneoplastic lesions and invasive cervical cancer confirmed the histopathological diagnoses and detected the presence of HPV type and HPV-16 variants, as well as the overexpression of proteins such as hTERT, IGF1Rα, IGF1Rß, CAIX, and GLUT1. Finally, the Arg72Pro polymorphism was detected in TP53. The role of high-risk HPV and HPV-16 variants and of hTERT, IGF1Rα, IGF1Rß, CAIX, and GLUT1 variations seemed confirmed in the development and progression of cervical cancer. As a result, analyzing the molecular changes in one and same tumour that progresses from a low-grade cervix lesion to invasive cervical cancer could provide valuable information in order to improve detection, diagnosis, and treatment in the future.
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Certain variants of human papillomavirus (HPV)type 58 are associated with an increased risk of high grade squamous intraepithelial lesions and cervical cancer. However, little is known about the persistence of HPV58 E6/E7 variants in women with incident HPV58 infections. The aim of the present study was to evaluate the presence and persistence of HPV58 E6/E7 variants in 71 women with incident HPV58 infection throughout their follow-up. These women belonged to a cohort examined in a longitudinal study of 1,610 Colombian women, who were HPV-negative and had normal baseline cytology. E6/E7 DNA regions of HPV58-positive samples were amplified and sequenced using automated direct sequencing. A total of 639 samples were analyzed from the 71 women, and 117 samples (18.3%) were HPV58-positive. HPV58 E6/E7 variants were detected in 85.5% of the samples. The T307/A694/G744/A761 variant was identified in 88% of the samples, the T307/G744 variant was identified in 9% of samples and the T187/T307/A367/G744/G793/T798/A801/T840/C852 was identified in 3% of the samples. Overall, 50% of the HPV58 infections were present after 1 year of follow-up and all infections were cleared after 7 years. Women who had first sexual intercourse at >15 years of age had a lower clearance rate than those who had sexual intercourse for the first time at ≤15 years of age [hazard ratio (HR)=0.29; 95% confidence interval (CI)=0.09-0.92]. Likewise, parous women had a higher clearance rate than nulliparous women (HR=3.43, 95% CI=1.23-9.60). There was no difference in clearance rates between HPV58 E6/E7 variants. In conclusion, HPV58 variants were not associated with persistence of the infection in this group of women.
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BACKGROUND: There exists limited information on the role of hTERT methylation, and its association with type-specific HPV infections in cervical cancer. MATERIALS AND METHODS: Eighty-seven frozen samples were analyzed for type-specific HPV infection using a GP5+/GP6+ PCR-RLB assay (RLB). hTERT DNA methylation analysis was performed using a newly developed PCR-RLB-hTERT. RESULTS: Ninety-three percent of samples were HPV-positive and fifteen different types were detected. hTERT methylation analysis of region 1 revealed no methylation in 78.8% of the samples and partial methylation in 21.2%. In region two, 68.2% showed no methylation and 31.8% showed a pattern of partial methylation. An association between the alpha 9 and alpha 7 species with a pattern of no methylation of hTERT in the region 1 was established (p=0.02 and p=0.03, respectively). CONCLUSION: Differences in patterns of methylation of the hTERT core promoter [region 1 (nt -208 to -1) and region 2 (nt +1 to +104) relative to first ATG] are related to the HPV species present.
Assuntos
Metilação de DNA/genética , Infecções por Papillomavirus/genética , Telomerase/genética , Neoplasias do Colo do Útero/genética , Feminino , Células HeLa , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/patogenicidade , Papillomavirus Humano 18/genética , Papillomavirus Humano 18/patogenicidade , Humanos , Invasividade Neoplásica/genética , Infecções por Papillomavirus/classificação , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologiaRESUMO
High hypoxic, glycolytic and acidosis metabolisms characterize cervical cancer tumors and have been described to be involved in chemoradioresistance mechanisms. Based on these observations, the present study assessed four selected novel biomarkers on the prognosis of locally advanced cervical carcinoma. A total of 66 patients with stage IIB/IIIB cervical cancer were retrospectively included. The protein expression levels of glucose transporter 1 (GLUT1), carbonic anhydrase 9 (CAIX) and hexokinase 1 (HKII) were investigated by immunohistochemistry on tumor biopsies, hemoglobin was measured and the disease outcome was monitored. A total of 53 patients (80.3%) presented a complete response. For these patients, the protein expression levels of GLUT1, CAIX and HKII were overexpressed. A significant difference was observed (P=0.0127) for hemoglobin levels (≤11 g/dl) in responsive compared with non-responsive patients. The expression of GLUT1 is associated with a lower rate of both overall and disease-free survival, with a trend of decreased risk of 1.1x and 1.5x, respectively. Co-expression of GLUT1 and HKII is associated with a decreased trend risk of 1.6x for overall survival. Patients with hemoglobin levels ≤11 g/dl had a 4.3-fold risk (P=0.02) in decreasing both to the rate of overall and disease-free survival. The presence of anemic hypoxia (hemoglobin ≤11 g/dl) and the expression of GLUT1 and/or HKII influence treatment response and are associated with a lower overall and disease-free survival. The present results demonstrated that these biomarkers may be used as predictive markers and suggested that these metabolic pathways can be used as potential novel therapeutic targets.
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Objective: To analyze whether the immune response to HPV-16, -18, -31, -45 and -58 capsids in women vaccinated with the quadrivalent vaccine induces cross-reactivity against other HPV virus-like particles (VLPs). Methods: A total of 88 women aged between 18 and 27 years attending the HPV clinic at the Instituto Nacional de Cancerología were enrolled and vaccinated against HPV. Follow-up visits were scheduled at months 7, 12, and 24. Samples were collected for cytology, HPV-DNA typing, and detection of HPV antibodies. IgG antibodies were measured by ELISA using HPV-16, -18, -31, -45, and -58 VLPs. HPV-DNA detection was done by GP5+/GP6+PCR-ELISA and HPV typing was performed by Reverse Line-Blot assay. Results: Pre-vaccination, the seroprevalence of HPV-16, -18, -31, -45, and -58 was 39%, 31.7%, 15.9%, 31.7%, and 23.2%, respectively. One month post-vaccination, the seroprevalence increased close to 100% for all types. At month 24, this response was maintained only for HPV-16 and -18. For HPV-31, -45 and -58, the seroprevalence decreased to below 50%. The prevalence of HPV DNA types 16, 18 and 58 before vaccination was little changed 1 month after vaccination. No new infections were observed at 24 months. For HPV-16 and -18 related types, no differences were observed before vaccination and at month 24. For other high-risk HPV types, the prevalence increased 18 months post-vaccination (15.5%) compared with pre-vaccination (9.8%). Conclusion: Immune response to all HPV types increased after vaccination, but this increase was maintained only for HPV-16 and -18. These results suggest a possible cross-reactivity against HPV types 31, 45 and 58, but this cross-reactivity wanes with time. © 2012 Instituto Nacional de Cancerología. Publicado por Elsevier España, S.L. Todos los derechos reservados.
Objetivo: Analizar si la respuesta inmune hacia las cápsides del VPH tipos 16, 18, 31, 45 y 58 en mujeres que recibieron la vacuna tetravalente induce reactividad cruzada hacia otros tipos virales. Métodos: Ochenta y ocho mujeres entre 18 y 27 años, asistentes al Grupo VPH del Instituto Nacional de Cancerología, recibieron la vacuna de VPH. Visitas de seguimiento en los meses 7, 12 y 24. Se tomaron muestras para prueba de Papanicolaou, tipificación de VPH y detección de anticuerpos. Los anticuerpos se detectaron por ELISA, usando VLP-VPH. La detección del ADN-VPH se realizó por Reverse Line Blot. Resultados: Prevacunación, la seroprevalencia de VPH tipos 16, 18, 31, 45 y 58 fue de 39, 31,7, 15,9, 31,7 y 23,2%, respectivamente. Al mes 7 aumentó cerca del 100% para todos los tipos. Al mes 24 esta respuesta se mantuvo para VPH tipos 16 y 18. Para VPH tipos 31, 45 y 58 disminuyó por debajo del 50%. La prevalencia de ADN-VPH tipos 16, 18 y 58 tuvo poca variación antes y un mes después de la vacunación. Al mes 24, no se observaron nuevas infecciones. Para VPH tipos 16 y 18, no se observaron diferencias antes ni al mes 24. En otros tipos de HR-VPH aumentó la prevalencia al mes 24 (15,5%), comparada con la prevacunación (9,8%). Conclusión: Se observó un aumento de la respuesta inmune a todos los tipos de VPH después de la vacunación, pero esta se mantuvo solamente para los VPH tipos 16 y 18. Los resultados sugieren una posible reactividad cruzada contra VPH tipos 31, 45 y 58. Sin embargo, esta reactividad cruzada disminuye con el tiempo.
Assuntos
Humanos , Feminino , Adolescente , Adulto , Papiloma , Estudos Soroepidemiológicos , Prevalência , Vacinação , Ensaio de Imunoadsorção Enzimática , Papillomavirus Humano 16 , Papillomavirus Humano 31RESUMO
Objetivo: Describir las barreras para la implementación de un programa de tamización para cáncer de cuello uterino basado en la prueba de virus del papiloma humano (VPH) en Colombia. Métodos: Se aplicó el modelo de planeación Precede-Procede en cuatro municipios de Cundinamarca y dos de Boyacá; se realizó análisis de fuentes secundarias y primarias obtenidas de 74 encuestas a instituciones de salud, 18 grupos focales (GF), con líderes comunitarios, gerentes y profesionales de la salud y 12 entrevistas (autoridades locales). Resultados: Se identificaron las siguientes barreras: 1) la infección por VPH se asocia a una enfermedad venérea; 2) barreras epidemiológicas: la ausencia de un adecuado registro de diagnóstico definitivo de lesiones preneoplásicas; 3) barreras del comportamiento del sistema, tales como la no centralización de la lectura de citologías, laboratorios no habilitados que prestan servicios y la no estandarización de la colposcopia ni el tratamiento; 4) barreras educacionales: los profesionales de la salud sobreestiman la sensibilidad de la citología y les preocupa demasiado la infección por VPH en mujeres menores de 30 años, y 5) barreras administrativas de acceso a la colposcopia y a la biopsia de lesiones preneoplásicas. Conclusiones: Colombia presenta barreras que impiden el funcionamiento de un programa organizado de tamización, las cuales hacen difícil lograr los objetivos esperados con el cambio tecnológico de citología a pruebas moleculares.
Objective: To identify the barriers for the implementation of a cervical cancer-screening program based on human papillomavirus (HPV) testing in Colombia. Methods: The Precede-Proceed model was applied in four municipalities of Cundinamarca and two of Boyacá. Secondary and primary data were analyzed from 74 institutional surveys, 18 focus groups (with community leaders and health professionals), and 12 interviews (health authorities). Results: The most relevant barriers were identifi ed as follows: 1) Social barriers: in Duitama, the municipality with a religious tradition, HPV infection is represented as a venereal disease. 2) Epidemiological barrier: the absence of a register for defi nitive diagnosis of pre-neoplasic lesions. 3) Behavioral barriers: Pap smear laboratories are not centralized, some are not accredited and colposcopies are not standardized. 4) Health professionals overestimate Papsmear sensitivity and they are over worried about HPV infection among women younger than 30 years. 5) Administrative barriers: positive screened women need to have an authorization from Health Insurance Enterprises in order to access the diagnosis and treatment of cervical lesions. Conclusions: Colombia presents barriers to the operation of an organized screening program that make it diffi cult to achieve the expected objectives with the technological change from the use of cytology to molecular testing.
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Humanos , Feminino , Terapêutica , Neoplasias do Colo do Útero , Infecções por Papillomavirus , Métodos , Programas de Rastreamento , Seguro SaúdeRESUMO
Objetivo: Analizar la presencia y persistencia de variantes en E6/E7/VPH 58 en muestras de mujeres con infecciones prevalentes por VPH 58, con citología normal, que pertenecen a la cohorte de Bogotá, Colombia. Métodos: Se utilizaron cepillados cervicales de 34 mujeres VPH 58, con citología normal, pertenecientes a la línea de base de la cohorte, con su respectivo seguimiento. Se amplificó la región E6/E7 del VPH 58 usando los iniciadores E6F1-E7R1 y los iniciadores E7P1-E7P2. Para el análisis de las variantes se utilizó la técnica de secuencia automática directa. La secuencia referencia del VPH 58 se utilizó para comparar las secuencias obtenidas. Resultados: En 27/34 muestras se lograron detectar variantes de E6/E7 de VPH 58. En total, se detectaron cinco variantes diferentes, dos de ellas nunca antes reportadas (A169/T307/A694/G744/A761 y T307/A694/G744/A761/G763). Los análisis de eliminación mostraron que el 75% de las variantes se habían eliminado antes de los dos años de seguimiento, y todas las variantes ya se habían eliminado a los seis años de seguimiento. Conclusiones: Dos nuevas variantes se reportaron a escala mundial de gran relevancia en los ámbitos filogenético y epidemiológico.
Objective: To analyze the presence and persistence of E6/E7 HPV58 variations in women with prevalent HPV 58 infection, with normal cytology, who belong to the Bogotá, Colombia cohort. Methods: Cervical cytobrush was used on 34 HPV58 women, with normal cytology, who are part of the cohort base line; respective follow was performed. The HPV58 E67/E7 region was broadened by using E6F1-E7R1 and E7P1-E7P2 indicators. Variation analysis was carried out with automatic direct sequencing. HPV58 sequence reference was used to compare the sequences that had been obtained. Results: In 27/34 samples, E6/E7 variations of HPV58 were successfully detected. A total of five different variations were detected, two of which had never been reported before (A169/T307/A694/G744/A761 and T307/A694/G744/A761/G763). Elimination analysis revealed that 75% of variations had been eliminated within two years of follow up, and that all variation had been eliminated at the end of six years of follow up. Conclusions: Two new variations of universal phylogenetic and epidemiologic noteworthiness were reported.
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Humanos , Feminino , Adolescente , Adulto , Idoso , Estudos de Coortes , Colo do Útero/citologia , Estudos Epidemiológicos , Estudos Transversais/classificação , Estudos Transversais/estatística & dados numéricos , Estudos Transversais/métodos , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/genética , Neoplasias do Colo do Útero/classificação , Neoplasias do Colo do Útero/epidemiologia , Colômbia/epidemiologiaRESUMO
Objetivo: Describir la AT y la infección por VPH en el seguimiento de mujeres que pertenecen a la cohorte de Bogotá. Métodos: Se analizaron 79 muestras del seguimiento de 25 mujeres que desarrollaron LEI-AG y 149 muestras del seguimiento de 34 mujeres con citología normal. La detección del VPH se realizó usando PCR-EIA GP5+/GP6+ y RLB. La AT se midió mediante TRAP-ELISA. Resultados: El análisis mostró que de los 25 casos, 8 fueron casos prevalentes (ingresaron al estudio con la LEI-AG) y los 17 casos restantes fueron incidentes (la lesión se detectó durante el seguimiento). De estas 17 mujeres, 12 (70,5%) presentaron AT y VPH al momento del diagnóstico o en una visita previa, con VPH de alto riesgo (VPH-AR), principalmente de la especie α-9. Tres mujeres (17,7%) mostraron infecciones transitorias por VPH y 2 (11,8%) no tuvieron VPH o AT al diagnóstico. El seguimiento de la mujeres con citología normal mostró que solo ocho mujeres tuvieron VPH y AT al mismo tiempo (23,5%), 21/34 mujeres (61,8%) tuvieron eventos transitorios de VPH durante el seguimiento y 5 (14,7%) no tuvieron VPH durante todo el seguimiento. Conclusiones: Detectar AT e infección por VPH-AR al mismo tiempo parecen predecir el riesgo de LEI-AG.
Objective: To describe telomerase activity (TA) and HPV infection in follow up of women in the Bogotá cohort. Methods: Analysis was carried out on 79 follow up samples from 25 women who developed LEI-AG, and 149 follow up samples from 34 women with normal cytology. HPV detection was made with PCR-EIA GP5+/GP6+ and RLB. TA was measured with TRAP-ELISA. Results: Analysis revealed that out of the 25 cases, 8 were prevalent (enrolled in the study with LEI-AG), and the remaining 17 incidental (lesion was detected during follow up). Among these 17 women, 12 (70.5%) had, at diagnosis or during a previous checkup, TA and high-risk HPV (HPV-AR), primarily type α-9. Three women (17.7%) had transitory HPV infections, and 2 (11.8%) had neither HPV nor TA at diagnosis. Follow up on women with normal cytology revealed that only eight women (23.5%) had HPV and TA at the same time, 21/34 women (61.8%) had transitory HPV event during follow up, and 5 (14.7%) had no HPV during entirety of follow up. Conclusions: Detection of TA and simultaneous HPV-AR infection apparently predicts LEI-AR risk.
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Humanos , Feminino , Adolescente , Adulto Jovem , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos de Coortes , Seguimentos , Infecções por Papillomavirus/classificação , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/genética , Telomerase , Biologia Celular/instrumentação , Colômbia/epidemiologia , Ensaio de Imunoadsorção Enzimática/classificação , Ensaio de Imunoadsorção Enzimática/métodosRESUMO
Reports on taxonomic identification of E6/HPV 16 variants, don't have a worldwide, updated and unified criterion for clustering and nomenclature. Our aim was to update the existing criterion and propose a new one for clustering and nomenclature for E6/HPV 16 molecular variants based on the descriptive and comparative analyses of nucleotide sequences. A systematic search of the publications between 1991 and 2010 was carried out in PUBMED and manually. 240 E6/HPV 16 variants were identified. 157 were classified as European (E), 24 as Asian (As), 14 as Asian American (AA), 11 as North American 1 (NA 1), 19 as African 1 (Af 1) and 15 as African 2 (Af 2). Three classes were determined for the E, 3 each for the As, Af 2 and AA branches, 4 classes for the NA 1 and 6 for the Af 1 branch. This study reports our results and proposes an updated criterion for clustering and nomenclature that will be useful for E6 variant identification.
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Variação Genética , Papillomavirus Humano 16/classificação , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Terminologia como Assunto , Sequência de Bases , Análise por Conglomerados , Feminino , Regulação Viral da Expressão Gênica/fisiologia , Saúde Global , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/metabolismo , Humanos , Dados de Sequência Molecular , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologiaRESUMO
Objective: To analyze the role of Human Papillomavirus (HPV) and other risk factors in the regression of cervical lesions in women from the Bogotá Cohort. Methods: 200 HPV positive women with abnormal cytology were included for regression analysis. The time of lesion regression was modeled using methods for interval censored survival time data. Median duration of total follow-up was 9 years. Results: 80 (40%) women were diagnosed with Atypical Squamous Cells of Undetermined Significance (ASCUS) or Atypical Glandular Cells of Undetermined Significance (AGUS) while 120 (60%) were diagnosed with Low Grade Squamous Intra-epithelial Lesions (LSIL). Globally, 40% of the lesions were still present at first year of follow up, while 1.5% was still present at 5 year check-up. The multivariate model showed similar regression rates for lesions in women with ASCUS/AGUS and women with LSIL (HR= 0.82, 95% CI 0.59-1.12). Women infected with HR HPV types and those with mixed infections had lower regression rates for lesions than did women infected with LR types (HR=0.526, 95% CI 0.33-0.84, for HR types and HR=0.378, 95% CI 0.20-0.69, for mixed infections). Furthermore, women over 30 years had a higher lesion regression rate than did women under 30 years (HR= 1.53, 95% CI 1.03-2.27). The study showed that the median time for lesion regression was 9 months while the median time for HPV clearance was 12 months. Conclusions: In the studied population, the type of infection and the age of the women are critical factors for the regression of cervical lesions.
Objetivo: Analizar el papel del virus del papiloma humano (VPH) y otros factores en la regresión de lesiones del cuello del útero en mujeres de la cohorte de Bogotá, Colombia. Métodos: El tiempo medio de seguimiento fue nueve años. Se incluyeron 200 mujeres VPH positivas con citología anormal. El tiempo de regresión de lesión fue modelado mediante análisis de supervivencia censurando por intervalos. Resultados: 80 mujeres (40%) tuvieron células escamosas atípicas de significado indeterminado (ASCUS) o células glandulares atípicas de significado indeterminado (AGUS) y 120 (60%) tuvieron lesiones escamosas intraepiteliales de bajo grado (LEI-BG). El 40% de las lesiones estaban presentes en el primer año de seguimiento, mientras que el 1,5% aún estaba a los cinco años. Se observaron tasas similares de regresión para ASCUS/AGUS y LEI-BG (HR=0,82, IC 95% 0,59-1,12). Mujeres infectadas con VPH de alto riesgo y aquéllas con infecciones mixtas tuvieron tasas inferiores de regresión de las lesiones que las mujeres con VPH de bajo riesgo (HR=0,526, IC 95% 0,33-0,84, para los VPH de alto riesgo, y HR=0,378, IC 95% 0,20-0,69, para las infecciones mixtas). Las mujeres mayores de 30 años tuvieron una mayor tasa de regresión de lesiones que las menores de 30 (HR= 1,53, IC 95% 1,03-2,27). El tiempo medio de regresión de las lesiones fue 9 meses, y el tiempo medio para la eliminación del VPH fue 12 meses. Conclusiones: En la población estudiada, el tipo de infección y la edad de las mujeres son factores críticos para la regresión de lesiones cervicales.
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Humanos , Adulto , Feminino , Idoso , Estudos de Coortes , Infecções por Papillomavirus , Análise de Sobrevida , Técnicas Citológicas/métodos , Carcinoma de Células Escamosas , ColômbiaRESUMO
Objetivo: Caracterizar la respuesta IgG e IgA hacia VLP (partículas semejantes a virus) del virus del papiloma humano (VPH) 16, 31 y 58 y determinar su asociación con la eliminación de la infección. Métodos: Se incluyeron 186 mujeres con citología normal participantes en un estudio de cohorte sobre la historia natural de la infección por VPH. Se evaluaron tres grupos: control (negativas para ADN VPH, n=146), eliminación (positivas al ingreso y negativas durante el seguimiento, n=25) y persistencia (positivas durante el seguimiento, n=15). Los anticuerpos IgG e IgA hacia VLP VPH 16, 31 y 58 se analizaron mediante ELISA. Resultados: En la primera visita, se observó en el grupo de eliminación una mayor seroprevalencia de anticuerpos IgG hacia VLP VPH 16. Esta prevalencia estuvo acompañada de mayores niveles de anticuerpos en este grupo, en comparación con los niveles observados en el grupo de persistencia (media DO405 nm 0,665 vs. 0,290, respectivamente). En contraste, en la quinta visita, se observó una mayor seroprevalencia de anticuerpos IgG hacia VLP VPH 16 y 58 en el grupo de persistencia (p=0,001 y p=0,003, respectivamente). Esta respuesta se correlacionó con mayores niveles de anticuerpos en esta visita (media DO405 nm 0,653 y 0,532, respectivamente), en comparación con los niveles de anticuerpos observados en la primera visita (media DO405 nm 0,290 y 0,362, respectivamente). Conclusiones: La presencia de altos niveles de anticuerpos IgG hacia VPH 16 y 58 durante la infección podría estar asociada con la eliminación de la infección.
Objective: To profile IgG and IgA response to the VLP ( virus-like particles) of the human papillomaviruses (HPV) 16, 31 and 58 and to assess the possibility that they may be related to eliminating infection. Methods: A group of 186 women with normal cytology, participants in a cohort study on the natural history of HPV infection, were selected. Three groups were evaluated: control (DNA HPV, n=146 negative), elimination (positive at outset and negative during follow-up, n=25), and persistance (positive during follow-up, n=15). The IgG and IgA antibodies against HPV-VLP 16, 31, and 58 were submitted to ELISA analysis. Results: During the initial visit greater IgG antibody seroprevalence against HPV16-VLP was observed among the elimination group. This prevalence was combined with greater antibody levels in this group in comparison with the levels found among members of the persistence (mean DO405 nm 0.665 vs. 0.290, respectively). In contrast, during the fifth visit, there was greater IgG antibody seroprevalence against HPV-PLV 16 and 58 among the persistance group (p=0.001 and p=0.003, respectively). This response correlated with greater anitbody levels on this visit (mean DO 405 nm 0.653 and 0.532, respectively) in comparison with the antibody levels observed on the first visit (mean DO 405 nm 0.290 and0.362, respectively). Conclusion: High levels of IgG antibodies working against HPV 16 and 58 during infection phase may be associated with elimination of infection.
Assuntos
Humanos , Adulto , Feminino , Idoso , Estudos de Casos e Controles , Antígenos HLA-D , Imunoglobulina A , Imunoglobulina G , Controle de Infecções , Neoplasias do Colo do Útero , Colômbia , Ensaio de Imunoadsorção Enzimática/métodos , Reação em Cadeia da Polimerase/métodosRESUMO
BACKGROUND: The aim of the present study was to estimate the prevalence of Kaposi sarcoma-associated herpesvirus (KSHV) in the female general population, to define geographic variation in and heterosexual transmission of the virus. METHODS: The study included 10,963 women from 9 countries for whom information on sociodemographic characteristics and reproductive, sexual, and smoking behaviors were available. Antibodies against KSHV that encoded lytic antigen K8.1 and latent antigen ORF73 were determined. RESULTS: The range of prevalence of KSHV (defined as detection of any antigen) was 3.81%-46.02%, with significant geographic variation noted. In Nigeria, the prevalence was 46.02%; in Colombia, 13.32%; in Costa Rica, 9.81%; in Argentina, 6.40%; in Ho Chi Minh City, Vietnam, 15.50%; in Hanoi, Vietnam, 11.26%; in Songkla, Thailand, 10%; in Lampang, Thailand, 8.63%; in Korea, 4.93%; and in Spain, 3.65%. The prevalence of KSHV slightly increased with increasing age among subjects in geographic areas where the prevalence of KSHV was high, such as Nigeria and Colombia, and it significantly decreased with increases in the educational level attained by subjects in those areas. KSHV was not statistically associated with age at first sexual intercourse, number of sex partners, number of children, patterns of oral contraceptive use, presence of cervical human papillomavirus DNA, or smoking status. CONCLUSIONS: The study provides comparable estimates of KSHV prevalence in diverse cultural settings across 4 continents and provides evidence that sexual transmission of KSHV is not a major source of infection in the general population.
Assuntos
Glicoproteínas/genética , Sarcoma de Kaposi/genética , Proteínas Virais/genética , Adulto , Antígenos Virais/genética , Colômbia/epidemiologia , Comparação Transcultural , Feminino , Glicoproteínas/isolamento & purificação , Infecções por Herpesviridae/epidemiologia , Infecções por Herpesviridae/genética , Infecções por Herpesviridae/transmissão , Herpesvirus Humano 8 , Humanos , Pessoa de Meia-Idade , Nigéria/epidemiologia , Razão de Chances , Prevalência , Fatores de Risco , Sarcoma de Kaposi/epidemiologia , Comportamento Sexual , Tailândia/epidemiologia , Proteínas Virais/isolamento & purificaçãoRESUMO
Human Papillomavirus (HPV) vaccines have been considered potentially cost-effective for the reduction of cervical cancer burden in developing countries; their effectiveness in a public health setting continues to be researched. We conducted an HPV prevalence survey among Colombian women with invasive cancer. Paraffin-embedded biopsies were obtained from one high-risk and one low-middle-risk regions. GP5+/GP6+ L1 primers, RLB assays, and E7 type specific PCR were used for HPV-DNA detection. 217 cases were analyzed with 97.7% HPV detection rate. HPV-16/18 prevalence was 63.1%; HPV-18 had lower occurrence in the high-risk population (13.8% versus 9.6%) allowing for the participation of less common HPV types; HPV-45 was present mainly in women under 50 and age-specific HPV type prevalence revealed significant differences. Multiple high-risk infections appeared in 16.6% of cases and represent a chance of replacement. Age-specific HPV prevalence and multiple high-risk infections might influence vaccine impact. Both factors highlight the role of HPVs other than 16/18, which should be considered in cost-effectiveness analyses for potential vaccine impact.
Assuntos
Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/imunologia , Infecções por Papillomavirus/epidemiologia , Vacinas contra Papillomavirus/administração & dosagem , Neoplasias do Colo do Útero/epidemiologia , Adulto , Idoso , Distribuição de Qui-Quadrado , Colômbia , Estudos Transversais , Feminino , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/virologia , Prevalência , Estatísticas não Paramétricas , Neoplasias do Colo do Útero/etiologia , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologiaRESUMO
UNLABELLED: Human Papillomavirus type 16 (HPV 16) DNA is regularly found in around 50% of all cervical carcinomas. Variants of this type have been found associated with different risks for cervical cancer development. Presence of HPV 16 variants in Colombia has not been previously reported. The aims of this study were to assess the feasibility of non-radioactive PCR-SSCP (polymerase chain reaction single-strand conformation polymorphism) analysis for determination of variability of ORF of E6, variability in the enhancer sequence of the LCR, and for establishment of the distribution of HPV 16 variants in invasive squamous cell carcinoma of the uterine cervix in Colombian women. Biopsies from 59 patients at the Instituto Nacional de Cancerología (INC) in Bogotá (Colombia) were collected. HPV detection was performed using universal primers. HPV 16 variants were detected by non-radioactive single-stranded conformational polymorphism (SSCP) analysis and direct sequencing. HPV 16 was detected in 57.6% of the tumors. The European branch was identified in 88.2% of the samples with the E-G350 class being the most prevalent variant (41.1%). The Asian-American branch was identified in 8.8% of the samples. Within this group it was possible to distinguish between c and a classes. It was not possible to determine the branch in 2.9% of the cases. A nucleotide transition (G to A) at position 7521 was the most prevalent variation (80%) found in the enhancer sequence of the LCR region. CONCLUSION: A non-radioactive PCR-SSCP analysis allowed us to distinguish between European and Asian-American branches of HPV 16, and to distinguish among classes in squamous cell carcinomas of the uterine cervix in Colombia. This method is an excellent alternative that can be used as a screening tool for identification of HPV 16 variants.
Assuntos
Asiático , Carcinoma de Células Escamosas/virologia , Papillomavirus Humano 16/classificação , Infecções por Papillomavirus/virologia , Reação em Cadeia da Polimerase/métodos , Polimorfismo Conformacional de Fita Simples , Neoplasias do Colo do Útero/virologia , População Branca , Adulto , Idoso , Asiático/estatística & dados numéricos , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/etnologia , Colômbia/epidemiologia , Elementos Facilitadores Genéticos , Feminino , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/isolamento & purificação , Humanos , Pessoa de Meia-Idade , Proteínas Oncogênicas Virais/genética , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/etnologia , Mutação Puntual , Proteínas Repressoras/genética , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/etnologia , População Branca/estatística & dados numéricosRESUMO
INTRODUCTION: high risk HPV infections and variants presence has been associated to increase the risk of cervical cancer. However, there are few studies that analyze the presence of them in patients with cervical cancer before and alter radiotherapy treatment. OBJECTIVES: to analyse the human papilloma virus presence and E7/HPV16 variants in 60 women with cervical cancer before and after radiotherapy. MATERIALS AND METHODS: HPV detection and typing were based on a GP5+/GP6+ PCR Enzyme immune assay. E7/HPV16 variants were detected by PCR -Single strand conformation polymorphism (SSCP) and confirmed by direct sequence. RESULTS: before radiotherapy, 50/60 patients (83.3 percent) were HPV positive and HPV16 (53.3 percent) was the most prevalent type. After 3 months of radiotherapy, 55 patients attended to consult; of them, 19 (34.6 percent) were HPV positive, this decrease in the HPV detection was significant (p<0.0005). The E7/HPV16 analysis showed that 20 samples (62.5 percent) amplified before radiotherapy, 18 of them (90 percent) had identical SSCP pattern to the prototype and 2 showed a different SSCP pattern. The sequence of these two samples showed silent mutations at nt. 732 (T-to-C), 789 (T-to-C) and 795 (T-to-G). After radiotherapy, the was not detection of new mutations, 6 patients showed persistent HPV16 infection with the same SSCP pattern to the prototype, and samples that initially showed a different SSCP pattern were negative to E7/ HPV16 after radiotherapy. CONCLUSION: few E7/HPV16 variants were detected before radiotherapy and it seems that the treatment did not cause mutations in this gene
Assuntos
Humanos , Sondas de DNA de HPV , Mutação , Papiloma , Reação em Cadeia da Polimerase , Radioterapia , Neoplasias do Colo do Útero , Vírus , ColômbiaRESUMO
Objetivo: Describir la prevalencia, incidencia y persistencia de infecciones cervicales por virus del papiloma humano (VPH), C. trachomatis y sus factores de riesgo en mujeres de una cohorte en Bogotá, Colombia. Materiales y métodos: Se revisaron 6 artículos publicados de una cohorte de 1.845 mujeres bogotanas con edades entre 13 y 85 años, con citología normal y seguimiento de 5 años.Resultados: La prevalencia de infección por VPH fue 14,9por ciento. Los virus de alto riesgo fueron tres veces más comunes que los de bajo riesgo (9,0por ciento/3,2por ciento). La mayor prevalencia se observó en menores de 20 años (26 por ciento). Para tipos de bajo riesgo, la mayor prevalencia fue en mayores de 55 años (7,6por ciento). La incidencia de infección por VPH fue de 6,2 por 100 mujeres-año, 5,0 para los de alto riesgo y 2,0 para los de bajo riesgo. Siete por ciento de las infecciones prevalentes e incidentes aún estaban presentes a los 5 años de seguimiento.La eliminación de la infección por VPH16 fue más lenta que la de tipos de bajo riesgo (RR=0,47; IC95por ciento, 0,32 a 0,72) e infecciones por uno o múltiples tipos virales tuvieron tasas de eliminación similares.La prevalencia de infección por C. trachomatis fue 5,5por ciento, con un pico en mujeres menores de 20 años (8,1por ciento). Su principal factor de riesgo fueron infecciones múltiples por VPH (OR=2,8; IC95por ciento, 1,2 a 6,0). 94por ciento de las mujeres habían eliminado la infección a los 4 años de seguimiento. Las serovariantes del grupo B y el C tuvieron tasas de eliminación más lentas que el grupo intermedio (RR=0,4; IC95por ciento, 0,1 a 0,9). Conclusión: El estudio de la historia natural de la infección por VPH y C. trachomatis en un país en desarrollo contribuye significativamente al conocimiento biológico, clínico y epidemiológico de estos agentes. La prevalencia y la incidencia de VPH por tipos específicos y por edad es información necesaria para plantear nuevas estrategias de prevención del cá...
Assuntos
Chlamydia trachomatis , Estudos de Coortes , Seguimentos , Infecções por Papillomavirus/epidemiologia , História Natural , Neoplasias do Colo do Útero/prevenção & controle , ColômbiaRESUMO
Coinfection with multiple types of human papillomavirus (HPV) and its implications for the development of efficacious HPV vaccines is a subject of great interest. To describe the occurrence of concurrent infection with multiple HPV types and to determine whether genital HPV infection modifies the risk of acquiring a new HPV infection with another HPV type, 1610 subjects were monitored for an average of 4.1 years in Bogota, Colombia. Information on risk factors for HPV infection and cervical cells was collected for detection of HPV DNA of 36 types at study entry and at 6 consecutive 6-month follow-up visits. Clustering or the concurrent acquisition of multiple types occurred more often than would be expected by chance. Subjects with incident HPV-16 or -18 infection had 5-7 times higher odds of acquiring a subsequent HPV-58 infection than subjects not infected with HPV-16 or -18. This might affect the protection conferred by effective HPV vaccines.