RESUMO
In Colombia, the human papillomavirus (HPV) vaccine was launched in 2012 in the context of a school-based national vaccination program targeting girls ages 9 to 14 and offering catch-up vaccination for girls ages 14 to 17. In this study, we evaluated the program's impact on type-specific HPV infection by comparing HPV cervical prevalence among vaccinated and nonvaccinated women. This is a comparative cross-sectional study conducted 5 years after the quadrivalent HPV vaccination implementation in a sentinel Colombian City. This study included young women (18-25 years old) who had been vaccinated in the catch-up group and were attending universities and technical institutions, and women who attended primary health care facilities for Pap smear screening. The HPV prevalence of 1,287 unvaccinated women was compared with the prevalence of 1,986 vaccinated women. The prevalence of HPV16/18 infections was significantly lower in vaccinated compared with unvaccinated women (6.5% vs. 15.4%; P < 0.001), whereas for HPV6/11 infections, a decrease of 63.7% in vaccinated women (1.02% vs. 2.81%) was observed. The adjusted effectiveness to HPV16/18 was 61.4%; 95% CI, 54.3%-67.6%. However, the effectiveness against HPV16/18 was significantly higher among women vaccinated before their sexual debut 91.5%; 95% CI, 86.8-94.5, compared with effectiveness for vaccination after their sexual debut, 36.2%; 95% CI, 23.6-46.7. Five years after the introduction of HPV vaccines in Colombia, high effectiveness of HPV to prevent HPV16/18 infections is observed in the catch-up cohorts including virgin and sexually active women. PREVENTION RELEVANCE: Monitoring HPV vaccines post-licensure plays an important role in assessing the progress of immunization programs, demonstrating the impact of vaccines on the population, and providing data for policy needs. In Colombia, HPV vaccines showed effectiveness when administered before start of sexual activity, and two doses are sufficient to achieve good protection.
Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Mulheres , Adolescente , Adulto , Criança , Colômbia/epidemiologia , Estudos Transversais , Feminino , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/uso terapêutico , Prevalência , Vacinação , Adulto JovemRESUMO
BACKGROUND: Hispanic/Latino populations are a genetically admixed and heterogeneous group, with variable fractions of European, Indigenous American and African ancestries. The molecular profile of breast cancer has been widely described in non-Hispanic Whites but equivalent knowledge is lacking in Hispanic/Latinas. We have previously reported that the most prevalent breast cancer intrinsic subtype in Colombian women was Luminal B as defined by St. Gallen 2013 criteria. In this study we explored ancestry-associated differences in molecular profiles of Luminal B tumors among these highly admixed women. METHODS: We performed whole-transcriptome RNA-seq analysis in 42 Luminal tumors (21 Luminal A and 21 Luminal B) from Colombian women. Genetic ancestry was estimated from a panel of 80 ancestry-informative markers (AIM). We categorized patients according to Luminal subtype and to the proportion of European and Indigenous American ancestry and performed differential expression analysis comparing Luminal B against Luminal A tumors according to the assigned ancestry groups. RESULTS: We found 5 genes potentially modulated by genetic ancestry: ERBB2 (log2FC = 2.367, padj<0.01), GRB7 (log2FC = 2.327, padj<0.01), GSDMB (log2FC = 1.723, padj<0.01, MIEN1 (log2FC = 2.195, padj<0.01 and ONECUT2 (log2FC = 2.204, padj<0.01). In the replication set we found a statistical significant association between ERBB2 expression with Indigenous American ancestry (p = 0.02, B = 3.11). This association was not biased by the distribution of HER2+ tumors among the groups analyzed. CONCLUSIONS: Our results suggest that genetic ancestry in Hispanic/Latina women might modify ERBB2 gene expression in Luminal tumors. Further analyses are needed to confirm these findings and explore their prognostic value.
Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença , Colômbia , Feminino , HumanosRESUMO
Single-nucleotide polymorphisms (SNPs) in cytokine genes can affect gene expression and thereby modulate inflammation and carcinogenesis. However, the data on the association between SNPs in the interleukin 1 beta gene (IL1B) and colorectal cancer (CRC) are conflicting. We found an association between a 4-SNP haplotype block of the IL1B (-3737C/-1464G/-511T/-31C) and CRC risk, and this association was exclusively observed in individuals with a higher proportion of African ancestry, such as individuals from the Coastal Colombian region (odds ratio, OR 2.06; 95% CI 1.31-3.25; p < 0.01). Moreover, a significant interaction between this CRC risk haplotype and local African ancestry dosage was identified in locus 2q14 (p = 0.03). We conclude that Colombian individuals with high African ancestry proportions at locus 2q14 harbour more IL1B-CGTC copies and are consequently at an increased risk of CRC. This haplotype has been previously found to increase the IL1B promoter activity and is the most frequent haplotype in African Americans. Despite of limitations in the number of samples and the lack of functional analysis to examine the effect of these haplotypes on CRC cell lines, our results suggest that inflammation and ethnicity play a major role in the modulation of CRC risk.
Assuntos
Neoplasias Colorretais/genética , Interleucina-1beta/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , População Negra/genética , Estudos de Casos e Controles , Cromossomos Humanos Par 2/genética , Colômbia , Neoplasias Colorretais/etnologia , Feminino , Loci Gênicos , Haplótipos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
DNA methylation (DNAm) measured in lymphoblastoid cell lines has been repeatedly demonstrated to differ between various human populations. Due to the role that DNAm plays in controlling gene expression, these differences could significantly contribute to ethnic phenotypic differences. However, because previous studies have compared distinct ethnic groups where genetic and environmental context are confounded, their relative contribution to phenotypic differences between ethnicities remains unclear. Using DNAm assayed in whole blood and colorectal tissue of 132 admixed individuals from Colombia, we identified sites where differential DNAm levels were associated with the local ancestral genetic context. Our results are consistent with population specific DNAm being primarily driven by between population genetic differences in cis, with little environmental contribution, and with consistent effects across tissues. The findings offer new insights into a possible mechanism driving phenotypic differences among different ethnic groups, and could help explain ethnic differences in colorectal cancer incidence.
Assuntos
Neoplasias Colorretais/genética , Metilação de DNA/genética , Epigenômica , Genética Populacional , Colômbia/epidemiologia , Neoplasias Colorretais/epidemiologia , Ilhas de CpG/genética , Feminino , Genótipo , Hispânico ou Latino , Humanos , MasculinoRESUMO
Urine sampling for HPV DNA detection has been proposed as an effective method for monitoring the impact of HPV vaccination programs; however, conflicting results have been reported. The goal of this study was to evaluate the performance of optimized urine HPV DNA testing in women aged 19 to 25 years. Optimization process included the use of first void urine, immediate mixing of urine with DNA preservative, and the concentration of all HPV DNA, including cell-free DNA fragments. Urine and cervical samples were collected from 535 young women attending cervical screening at health centers from two Colombian cities. HPV DNA detection and genotyping was performed using an HPV type-specific multiplex genotyping assay, which combines multiplex polymerase chain reaction with bead-based Luminex technology. Concordance between HPV DNA detection in urine and cervical samples was determined using kappa statistics and McNemar tests. The accuracy of HPV DNA testing in urine samples was evaluated measuring sensitivity and specificity using as reference the results obtained from cervical samples. Statistical analysis was performed using STATA11.2 software. The findings revealed an overall HPV prevalence of 60.00% in cervical samples and 64.72% in urine samples, HPV-16 being the most frequent HPV type detected in both specimens. Moreover, our results indicate that detection of HPV DNA in first void urine provides similar results to those obtained with cervical samples and can be used to monitor HPV vaccination trials and programs as evidenced by the substantial concordance found for the detection of the four vaccine types. Cancer Prev Res; 9(9); 766-71. ©2016 AACR.
Assuntos
Colo do Útero/virologia , DNA Viral/análise , Programas de Rastreamento/métodos , Infecções por Papillomavirus/diagnóstico , Urina/virologia , Adulto , Colômbia , Feminino , Humanos , Papillomaviridae , Infecções por Papillomavirus/virologia , Sensibilidade e Especificidade , Esfregaço Vaginal , Adulto JovemRESUMO
Breast cancer is the most frequent malignancy in women worldwide. Distinct intrinsic subtypes of breast cancer have different prognoses, and their relative prevalence varies significantly among ethnic groups. Little is known about the prevalence of breast cancer intrinsic subtypes and their association with clinicopathological data and genetic ancestry in Latin Americans. Immunohistochemistry surrogates from the 2013 St. Gallen International Expert Consensus were used to classify breast cancers in 301 patients from Colombia into intrinsic subtypes. We analyzed the distribution of subtypes by clinicopathological variables. Genetic ancestry was estimated from a panel of 80 ancestry informative markers. Luminal B breast cancer subtype was the most prevalent in our population (37.2%) followed by luminal A (26.3%), non-basal triple negative (NBTN) (11.6%), basal like (9%), human epidermal growth factor receptor 2 (HER2) enriched (8.6%) and unknown (7.3%). We found statistical significant differences in distribution between Colombian region (P = 0.007), age at diagnosis (P = 0.0139), grade (P < 0.001) and recurrence (P < 0.001) according to intrinsic subtype. Patients diagnosed with HER2-enriched, basal-like and NBTN breast cancer had the highest African ancestry. Future studies analyzing the molecular profiles of breast cancer in Colombian women will help us understand the molecular basis of this subtype distribution and compare the molecular characteristics of the different intrinsic subtypes in Colombian patients.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/epidemiologia , Recidiva Local de Neoplasia/epidemiologia , Prognóstico , Adulto , Idoso , População Negra/genética , Neoplasias da Mama/classificação , Neoplasias da Mama/genética , Colômbia/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/classificação , Recidiva Local de Neoplasia/genética , Receptor ErbB-2/genética , Receptores de Estrogênio/genética , Receptores de Progesterona/genéticaRESUMO
DNA methylation (DNAm) has been linked to changes in chromatin structure, gene expression and disease. The DNAm level can be affected by genetic variation; although, how this differs by CpG dinucleotide density and genic location of the DNAm site is not well understood. Moreover, the effect of disease causing variants on the DNAm level in a tissue relevant to disease has yet to be fully elucidated. To this end, we investigated the phenotypic profiles, genetic effects and regional genomic heritability for 196080 DNAm sites in healthy colorectum tissue from 132 unrelated Colombian individuals. DNAm sites in regions of low-CpG density were more variable, on average more methylated and were more likely to be significantly heritable when compared with DNAm sites in regions of high-CpG density. DNAm sites located in intergenic regions had a higher mean DNAm level and were more likely to be heritable when compared with DNAm sites in the transcription start site (TSS) of a gene expressed in colon tissue. Within CpG-dense regions, the propensity of the DNAm level to be heritable was lower in the TSS of genes expressed in colon tissue than in the TSS of genes not expressed in colon tissue. In addition, regional genetic variation was associated with variation in local DNAm level no more frequently for DNAm sites within colorectal cancer risk regions than it was for DNAm sites outside such regions. Overall, DNAm sites located in different genomic contexts exhibited distinguishable profiles and may have a different biological function.
Assuntos
Colo/metabolismo , Metilação de DNA/genética , Epigênese Genética , Reto/metabolismo , Pólipos do Colo/genética , Pólipos do Colo/metabolismo , Ilhas de CpG/genética , Feminino , Regulação da Expressão Gênica , Genoma Humano , Genômica , Humanos , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Regiões Promotoras GenéticasRESUMO
BACKGROUND: Invasive penile cancer is a rare disease with an approximately 22 000 cases per year. The incidence is higher in less developed countries, where penile cancer can account for up to 10% of cancers among men in some parts of Africa, South America, and Asia. OBJECTIVE: To describe the human papillomavirus (HPV) DNA prevalence, HPV type distribution, and detection of markers of viral activity (ie, E6*I mRNA and p16(INK4a)) in a series of invasive penile cancers and penile high-grade squamous intraepithelial lesions (HGSILs) from 25 countries. A total of 85 penile HGSILs and 1010 penile invasive cancers diagnosed from 1983 to 2011 were included. DESIGN, SETTING, AND PARTICIPANTS: After histopathologic evaluation of formalin-fixed paraffin-embedded samples, HPV DNA detection and genotyping were performed using the SPF-10/DEIA/LiPA25 system, v.1 (Laboratory Biomedical Products, Rijswijk, The Netherlands). HPV DNA-positive cases were additionally tested for oncogene E6*I mRNA and all cases for p16(INK4a) expression, a surrogate marker of oncogenic HPV activity. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: HPV DNA prevalence and type distributions were estimated. RESULTS AND LIMITATIONS: HPV DNA was detected in 33.1% of penile cancers (95% confidence interval [CI], 30.2-36.1) and in 87.1% of HGSILs (95% CI, 78.0-93.4). The warty-basaloid histologic subtype showed the highest HPV DNA prevalence. Among cancers, statistically significant differences in prevalence were observed only by geographic region and not by period or by age at diagnosis. HPV16 was the most frequent HPV type detected in both HPV-positive cancers (68.7%) and HGSILs (79.6%). HPV6 was the second most common type in invasive cancers (3.7%). The p16(INK4a) upregulation and mRNA detection in addition to HPV DNA positivity were observed in 69.3% of HGSILs, and at least one of these HPV activity markers was detected in 85.3% of cases. In penile cancers, these figures were 22.0% and 27.1%, respectively. CONCLUSIONS: About a third to a fourth of penile cancers were related to HPV when considering HPV DNA detection alone or adding an HPV activity marker, respectively. The observed HPV type distribution reinforces the potential benefit of current and new HPV vaccines in the reduction of HPV-related penile neoplastic lesions. PATIENT SUMMARY: About one-third to one-quarter of penile cancers were related to human papillomavirus (HPV). The observed HPV type distribution reinforces the potential benefit of current and new HPV vaccines to prevent HPV-related penile neoplastic lesions.
Assuntos
Carcinoma/virologia , DNA Viral/análise , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 6/isolamento & purificação , Infecções por Papillomavirus/complicações , Neoplasias Penianas/virologia , África , Idoso , Ásia , Estudos Transversais , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Europa (Continente) , Genótipo , Papillomavirus Humano 16/genética , Papillomavirus Humano 6/genética , Humanos , América Latina , Masculino , Pessoa de Meia-Idade , América do Norte , Oceania , Infecções por Papillomavirus/virologia , Neoplasias Penianas/patologia , RNA Viral/análise , Estudos RetrospectivosRESUMO
UNLABELLED: Aim To estimate relative contribution and time trends of HPV types in cervical cancer in Cali, Colombia over a 50 years' period. METHODS: Paraffin blocks of 736 cervical cancer histological confirmed cases were retrieved from the pathology laboratory at Hospital Universitario del Valle (Cali, Colombia) and HPV genotyped using SPF10-PCR/DEIA/LiPA25 (version 1) assay. Marginal effect of age and year of diagnosis in secular trends of HPV type prevalence among HPV+ cases were assessed by robust Poisson regression analysis. RESULTS: 64.7% (95%CI: 59.9-69.2) of squamous cell carcinomas (SCCs) were attributed to HPV 16 and 18, 78.2% (95%CI: 74-82) to HPV 16, 18, 31, 33 and 45 and 84.8% (95%CI: 81-88.1) to HPV 16, 18, 31, 33, 45, 52 and 58 while ninety-three percent of adenocarcinomas (ADCs) were attributed to HPV 16, 18 and 45 only. The prevalence of specific HPV types did not change over the 50-year period. A significant downward trend of prevalence ratios of HPV16 (âP=0.017) and α7 but HPV 18 (i.e., HPV 39, 45, 68, 70, âP=0.024) with increasing age at diagnosis was observed. In contrast, the prevalence ratio to other HPV genotypes of α9 but HPV 16 genotypes (i.e., HPV 31, 33, 35, 52, 58, 67, âP=0.002) increased with increasing age at diagnosis. CONCLUSION: No changes were observed in the relative contribution of HPV types in cervical cancer in Cali, Colombia during the 50 years. In this population, an HPV vaccine including the HPV 16, 18, 31, 33, 45, 52 and 58 genotypes may have the potential to prevent â¼85% and 93% of SCC and ADC cases respectively.
Assuntos
Adenocarcinoma/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Papillomaviridae/genética , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Adenocarcinoma/virologia , Adulto , Idoso , Carcinoma de Células Escamosas/virologia , Colômbia/epidemiologia , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Papillomaviridae/classificação , Infecções por Papillomavirus/virologia , Reação em Cadeia da Polimerase , Prevalência , Fatores de Tempo , Neoplasias do Colo do Útero/virologiaRESUMO
Knowledge about human papillomaviruses (HPV) types involved in anal cancers in some world regions is scanty. Here, we describe the HPV DNA prevalence and type distribution in a series of invasive anal cancers and anal intraepithelial neoplasias (AIN) grades 2/3 from 24 countries. We analyzed 43 AIN 2/3 cases and 496 anal cancers diagnosed from 1986 to 2011. After histopathological evaluation of formalin-fixed paraffin-embedded samples, HPV DNA detection and genotyping was performed using SPF-10/DEIA/LiPA25 system (version 1). A subset of 116 cancers was further tested for p16(INK4a) expression, a cellular surrogate marker for HPV-associated transformation. Prevalence ratios were estimated using multivariate Poisson regression with robust variance in the anal cancer data set. HPV DNA was detected in 88.3% of anal cancers (95% confidence interval [CI]: 85.1-91.0%) and in 95.3% of AIN 2/3 (95% CI: 84.2-99.4%). Among cancers, the highest prevalence was observed in warty-basaloid subtype of squamous cell carcinomas, in younger patients and in North American geographical region. There were no statistically significant differences in prevalence by gender. HPV16 was the most frequent HPV type detected in both cancers (80.7%) and AIN 2/3 lesions (75.4%). HPV18 was the second most common type in invasive cancers (3.6%). p16(INK4a) overexpression was found in 95% of HPV DNA-positive anal cancers. In view of the results of HPV DNA and high proportion of p16(INK4a) overexpression, infection by HPV is most likely to be a necessary cause for anal cancers in both men and women. The large contribution of HPV16 reinforces the potential impact of HPV vaccines in the prevention of these lesions.
Assuntos
Neoplasias do Ânus/virologia , Carcinoma de Células Escamosas/virologia , DNA Viral/genética , Papillomavirus Humano 16/genética , Infecções por Papillomavirus/virologia , Idoso , Neoplasias do Ânus/epidemiologia , Neoplasias do Ânus/metabolismo , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/metabolismo , Estudos Transversais , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/metabolismo , Distribuição de Poisson , Prevalência , Estudos RetrospectivosRESUMO
Colorectal cancer rates in Latin American countries are less than half of those observed in the United States. Latin Americans are the resultant of generations of an admixture of Native American, European, and African individuals. The potential role of genetic admixture in colorectal carcinogenesis has not been examined. We evaluate the association of genetic ancestry with colorectal neoplasms in 190 adenocarcinomas, 113 sporadic adenomas and 243 age- and sex-matched controls enrolled in a multicentric case-control study in Colombia. Individual ancestral genetic fractions were estimated using the STRUCTURE software, based on allele frequencies and assuming three distinct population origins. We used the Illumina Cancer Panel to genotype 1,421 sparse single-nucleotide polymorphisms (SNPs), and Northern and Western European ancestry, LWJ and Han Chinese in Beijing, China populations from the HapMap project as references. A total of 678 autosomal SNPs overlapped with the HapMap data set SNPs and were used for ancestry estimations. African mean ancestry fraction was higher in adenomas (0.13, 95% confidence interval (95% CI)=0.11-0.15) and cancer cases (0.14, 95% CI=0.12-0.16) compared with controls (0.11, 95% CI=0.10-0.12). Conditional logistic regression analysis, controlling for known risk factors, showed a positive association of African ancestry per 10% increase with both colorectal adenoma (odds ratio (OR)=1.12, 95% CI=0.97-1.30) and adenocarcinoma (OR=1.19, 95% CI=1.05-1.35). In conclusion, increased African ancestry (or variants linked to it) contributes to the increased susceptibility of colorectal cancer in admixed Latin American population.
Assuntos
Adenocarcinoma/genética , Neoplasias Colorretais/genética , Hispânico ou Latino/genética , Negro ou Afro-Americano/genética , Índice de Massa Corporal , Estudos de Casos e Controles , China , Ingestão de Energia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genética Populacional , Genótipo , Técnicas de Genotipagem , Projeto HapMap , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco , População Branca/genéticaRESUMO
Low-risk human papillomaviruses (LR-HPVs) have been associated occasionally with clinically and pathologically unusual anogenital malignancies. The relation between clinicopathologic features and any pathogenetic role of LR-HPV remains unclear. From a global study of 13,328 anogenital carcinomas, we identified 57 cases in which whole-tissue polymerase chain reaction using SPF10-LiPA25 showed single LR-HPV infection. In 43/46 (93.5%) available carcinomas, multiple polymerase chain reaction assays confirmed single detection of HPV6, 11, 42, 44, or 70 DNA. In 75% (n=32) of these, LR-HPV DNA was confirmed in tumor cells by laser capture microdissection. In 2 cases, including 1 adenocarcinoma, viral DNA was only found outside the tumor. All anogenital tumors with confirmed HPV6/11 showed a distinctive range of papillary, warty or warty-basaloid, squamous, or transitional histology with patchy or negative p16 expression. HPV6-associated cervical tumors occurred at a low median age. HPV42/70 was associated with typical squamous cell carcinoma showing diffuse p16 staining like high-risk HPV-related malignancies. HPV44 was found in malignant cells in 1 case. Viral taxonomy and theoretical analysis show that HPV6/11 belong to a different genus from HPV42/70 with E6/E7 gene products that would not bind pRb or p53, whereas HPV42/70 could bind pRb. Our data support the causal involvement of LR-HPVs in the carcinogenesis of <2% of anogenital malignancies of 2 distinct clinicopathologic patterns related to the genetic structure of the HPV types 6/11 and 70/42. HPV42/70 was associated with typical squamous carcinomas. Importantly all carcinomas associated with HPV6/11 globally showed verruco-papillary, well-differentiated, squamous, or transitional histology without p16 expression.
Assuntos
Neoplasias do Ânus/virologia , Carcinoma/virologia , DNA Viral/análise , Neoplasias dos Genitais Femininos/virologia , Neoplasias dos Genitais Masculinos/virologia , Testes de DNA para Papilomavírus Humano/métodos , Papillomavirus Humano 11/genética , Papillomavirus Humano 6/genética , Microdissecção e Captura a Laser , Infecções por Papillomavirus/virologia , Reação em Cadeia da Polimerase , Adulto , Idoso , Neoplasias do Ânus/química , Neoplasias do Ânus/patologia , Biomarcadores Tumorais/análise , Biópsia , Carcinoma/química , Carcinoma/patologia , Inibidor p16 de Quinase Dependente de Ciclina/análise , Sondas de DNA de HPV , Feminino , Neoplasias dos Genitais Femininos/química , Neoplasias dos Genitais Femininos/patologia , Neoplasias dos Genitais Masculinos/química , Neoplasias dos Genitais Masculinos/patologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/patologia , Valor Preditivo dos Testes , Prognóstico , Fatores de RiscoRESUMO
BACKGROUND: Human papillomavirus (HPV) contribution in vulvar intraepithelial lesions (VIN) and invasive vulvar cancer (IVC) is not clearly established. This study provides novel data on HPV markers in a large series of VIN and IVC lesions. METHODS: Histologically confirmed VIN and IVC from 39 countries were assembled at the Catalan Institute of Oncology (ICO). HPV-DNA detection was done by polymerase chain reaction using SPF-10 broad-spectrum primers and genotyping by reverse hybridisation line probe assay (LiPA25) (version 1). IVC cases were tested for p16(INK4a) by immunohistochemistry (CINtec histology kit, ROCHE). An IVC was considered HPV driven if both HPV-DNA and p16(INK4a) overexpression were observed simultaneously. Data analyses included algorithms allocating multiple infections to calculate type-specific contribution and logistic regression models to estimate adjusted prevalence (AP) and its 95% confidence intervals (CI). RESULTS: Of 2296 cases, 587 were VIN and 1709 IVC. HPV-DNA was detected in 86.7% and 28.6% of the cases respectively. Amongst IVC cases, 25.1% were both HPV-DNA and p16(INK4a) positive. IVC cases were largely keratinising squamous cell carcinoma (KSCC) (N=1234). Overall prevalence of HPV related IVC cases was highest in younger women for any histological subtype. SCC with warty or basaloid features (SCC_WB) (N=326) were more likely to be HPV and p16(INK4a) positive (AP=69.5%, CI=63.6-74.8) versus KSCC (AP=11.5%, CI=9.7-13.5). HPV 16 was the commonest type (72.5%) followed by HPV 33 (6.5%) and HPV 18 (4.6%). Enrichment from VIN to IVC was significantly high for HPV 45 (8.5-fold). CONCLUSION: Combined data from HPV-DNA and p16(INK4a) testing are likely to represent a closer estimate of the real fraction of IVC induced by HPV. Our results indicate that HPV contribution in invasive vulvar cancer has probably been overestimated. HPV 16 remains the major player worldwide.
Assuntos
Carcinoma in Situ/virologia , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Neoplasias Vulvares/virologia , Adulto , Algoritmos , Biomarcadores Tumorais/análise , Carcinoma in Situ/química , Carcinoma in Situ/patologia , Estudos Transversais , Inibidor p16 de Quinase Dependente de Ciclina/análise , Sondas de DNA de HPV , Feminino , Genótipo , Testes de DNA para Papilomavírus Humano , Humanos , Imuno-Histoquímica , Modelos Logísticos , Pessoa de Meia-Idade , Invasividade Neoplásica , Papillomaviridae/classificação , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Estudos Retrospectivos , Regulação para Cima , Neoplasias Vulvares/química , Neoplasias Vulvares/patologiaRESUMO
BACKGROUND: Cancer has become increasingly acknowledged as a public health issue in Colombia. Rates of the most common malignancies have been generally increasing. We update an evaluation of mortality trends in the major cancers in Colombia one decade ago, discussing the trends in the context of cancer control. METHODS: We calculated the annual age-standardized mortality rates for the major cancer sites by sex between 1984 and 2008; we also present the estimated annual percentage change (EAPC) for the entire period and for the last decade. RESULTS: There was an average of 32,000 cancer deaths annually in Colombia in the period studied. Overall cancer mortality rates decreased slightly in both men and women. The four most common sites of cancer death among men were stomach (17.6%), prostate (15.0%), lung (14.8%) and colorectum (6.5%). In women, the most common cancer sites were breast (12.3%), cervix (12.1%), stomach (11.5%) and lung (9.2%). Colorectal and CNS cancers exhibited the greatest increases (EAPC of 2.0% and 3.4% respectively) while the largest declines were seen for cancers of the larynx, stomach and oesophagus (EAPC between -3% and -4%). In the last decade, the greatest declines were seen in cervical cancer mortality rates (EAPC = -3.2). CONCLUSIONS: The slight decrease in mortality trends from all cancers combined is partially driven by the strong declines in mortality of stomach and cervical cancer. It may be still too early to properly evaluate trends in mortality due to other cancers and the relative impact of changing access to health care in Colombia.
Assuntos
Neoplasias/mortalidade , Colômbia/epidemiologia , Feminino , Humanos , Masculino , Mortalidade/tendências , Fatores de Risco , Fatores Sexuais , Análise de SobrevidaRESUMO
BACKGROUND: Information on HPV knowledge in patients with genital warts is scarse as is the information on factors related to the impact on self-esteem and sex life among them. METHODS: We conducted a cross-sectional study in adult patients with a clinical diagnosis of genital warts (GW) attending a major private out-patient clinic in Bogotá, Colombia. Patients underwent biopsy for pathological diagnosis, HPV-DNA testing and completed a questionnaire assessing HPV knowledge, and the consequences of GW on self-esteem and sexual life. Differences in proportions were assessed with a chi2 test. RESULTS: 106 men and 155 women had pathologic confirmation of GW. 51% of subjects had heard of HPV before consultation coming mainly from the media (82%). Less than half of the participants knew that HPV could be transmitted through non-penetrant sexual intercourse and only two thirds acknowledged HPV vaccine as a preventive measure against HPV infection. Impact on self-esteem was higher among women than men (90.3% vs 60.4%, [p < 0.01]). In men, factors related to a higher impact on sexual life were HPV awareness and age; in women they were higher education and anatomic location; external GW had a higher impact on sexual life in women (83% vs. 66%; [p = 0.05]). CONCLUSIONS: We found a low awareness of HPV and low knowledge on the vaccine as a preventive measure for associated diseases even in patients suffering from genital warts, highlighting the need for communication and education on HPV. Greater impact on self-esteem in women might reflect higher health consciousness among Latin American women.
Assuntos
Coito/psicologia , Condiloma Acuminado/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Infecções por Papillomavirus/psicologia , Autoimagem , Adulto , Colômbia/epidemiologia , Condiloma Acuminado/epidemiologia , Condiloma Acuminado/etiologia , Estudos Transversais , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Pacientes , Distribuição por Sexo , Fatores Socioeconômicos , Inquéritos e QuestionáriosRESUMO
In Latin America, gastric cancer is a leading cancer, and countries in the region have some of the highest mortality rates worldwide, including Chile, Costa Rica, and Colombia. Geographic variation in mortality rates is observed both between neighboring countries and within nations. We discuss epidemiological observations suggesting an association between altitude and gastric cancer risk in Latin America. In the Americas, the burden of gastric cancer mortality is concentrated in the mountainous areas along the Pacific rim, following the geography of the Andes sierra, from Venezuela to Chile, and the Sierra Madre and Cordillera de Centroamérica, from southern Mexico to Costa Rica. Altitude is probably a surrogate for host genetic, bacterial, dietary, and environmental factors that may cluster in the mountainous regions. For example, H. pylori strains from patients of the Andean Nariño region of Colombia display European ancestral haplotypes, whereas strains from the Pacific coast are predominantly of African origin. The observation of higher gastric cancer rates in the mountainous areas is not universal: the association is absent in Chile, where risk is more strongly associated with the age of H. pylori acquisition and socio-economic determinants. The dramatic global and regional variations in gastric cancer incidence and mortality rates offer the opportunity for scientific discovery and focused prevention programs.
Assuntos
Altitude , Neoplasias Gástricas/epidemiologia , Feminino , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/mortalidade , Helicobacter pylori/isolamento & purificação , Humanos , Incidência , América Latina/epidemiologia , Masculino , Fatores Sexuais , Fatores Socioeconômicos , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/mortalidadeRESUMO
Background: There is an association of interleukin (IL)1B polymorphism with gastric cancer risk. However systematic reviews of the existing evidence have shown that such association varies across populations with different genetic ancestry. Aim: To evaluate the association of IL-1B-511 and IL-1RN polymorphism and Helicobacter pylori IgG antibodies CagA, with gastric cancer in two Colombian cities located in a high risk area for gastric cancer. Material and Methods: A case-control study including 46 gastric cancer cases and 99 controls with non-atrophic gastritis from a high risk zone for gastric cancer. Polymorphism genotyping was carried out by polymerase chain reaction (PCR) and IgG CagA status by ELISA. Results: IgG CagA seropositive individuals had an increased gastric cancer risk (odds ratio (OR) = 11.56; 95 percent confidence intervals (CI) 2.62-50.91 in Tunja and OR = 19.66, 95 percentCI 0.98-395 in Bogotá). IL-1B-511TT carriers in Tunja had increased risk of gastric cancer (OR = 11.31; 95 percentCI 1.20-106.54)), while IL-1RN*2 alelle carriers in Bogotá showed an inverse association with gastric cancer risk (OR = 0.03; 95 percentCI 0.01-0.65). Conclusions: This study adds evidence to the positive association of Helicobacter pylori CagA positive strains with non-cardial gastric cancer etiology. There is a possible heterogeneity in the association of IL-1B gene polymorphism with cancer, in populations of similar ethnic background and settled in the same risk area.
Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Infecções por Helicobacter/genética , Helicobacter pylori/imunologia , Proteína Antagonista do Receptor de Interleucina 1/genética , Interleucina-1beta/genética , Polimorfismo Genético/genética , Neoplasias Gástricas , Estudos de Casos e Controles , Colômbia/etnologia , Infecções por Helicobacter/imunologia , Helicobacter pylori/genética , Imunoglobulina G/sangue , Fatores de Risco , Neoplasias Gástricas/genética , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/microbiologiaRESUMO
BACKGROUND: There is an association of interleukin (IL)1B polymorphism with gastric cancer risk. However systematic reviews of the existing evidence have shown that such association varies across populations with different genetic ancestry. AIM: To evaluate the association of IL-1B-511 and IL-1RN polymorphism and Helicobacter pylori IgG antibodies CagA, with gastric cancer in two Colombian cities located in a high risk area for gastric cancer. MATERIAL AND METHODS: A case-control study including 46 gastric cancer cases and 99 controls with non-atrophic gastritis from a high risk zone for gastric cancer. Polymorphism genotyping was carried out by polymerase chain reaction (PCR) and IgG CagA status by ELISA. RESULTS: IgG CagA seropositive individuals had an increased gastric cancer risk (odds ratio (OR) = 11.56; 95% confidence intervals (CI) 2.62-50.91 in Tunja and OR = 19.66, 95%CI 0.98-395 in Bogotá). IL-1B-511TT carriers in Tunja had increased risk of gastric cancer (OR = 11.31; 95%CI 1.20-106.54)), while IL-1RN*2 alelle carriers in Bogotá showed an inverse association with gastric cancer risk (OR = 0.03; 95%CI 0.01-0.65). CONCLUSIONS: This study adds evidence to the positive association of Helicobacter pylori CagA positive strains with non-cardial gastric cancer etiology. There is a possible heterogeneity in the association of IL-1B gene polymorphism with cancer, in populations of similar ethnic background and settled in the same risk area.
Assuntos
Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Infecções por Helicobacter/genética , Helicobacter pylori/imunologia , Proteína Antagonista do Receptor de Interleucina 1/genética , Interleucina-1beta/genética , Polimorfismo Genético/genética , Neoplasias Gástricas , Adulto , Idoso , Estudos de Casos e Controles , Colômbia/etnologia , Feminino , Infecções por Helicobacter/imunologia , Helicobacter pylori/genética , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Neoplasias Gástricas/genética , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/microbiologiaRESUMO
OBJECTIVE. To assess the risk of cervical intraepithelial neoplasia grades 2, 3 or higher (CIN 2/3+) for women with normal cytology and concurrent high-risk human papillomavirus infection (HR-HPV). MATERIAL AND METHODS. We examined 2 200 women every 6 months for an average of 9 years. Cervical smears and samples for HPV DNA were obtained at each visit. Absolute risk of subsequent CIN2/CIN3+ was estimated using the Kaplan-Meier method. RESULTS. The absolute risk of CIN2/CIN3+ among HR-HPV-positive women with normal Pap smear results was 1.06 percent (95 percentCI, 0.57-2.20), 5 times higher the risk among all women with normal Pap smears (0.20 percent; 95 percentCI, 0.12-0.32) but 7 times lower than that for women with HR-HPV infection and LSIL (7.24 percent; 95 percentCI, 3.78-15.2). CONCLUSION. Short-term absolute risk of CIN2/3+ after a normal Pap smear with concurrent HR-HPV infection is low (~1 percent), suggesting that the HR-HPV test has limited utility in short-term clinical decision-making for women with normal cytology.
OBJETIVO. Evaluar el riesgo a corto plazo de neoplasia intraepitelial cervical de alto grado (CIN2/CIN3+) en mujeres con citologí-a cervicouterina normal e infección por virus del papiloma humano de alto riesgo (HR-HPV). MATERIAL Y MÉTODOS. Cohorte prospectiva de 2200 mujeres evaluadas cada seis meses durante 9 años en promedio. En cada visita se tomó muestra cervical para extendido y detección de HPV DNA. El riesgo absoluto de CIN2/CIN3+ a la siguiente visita fue calculado utilizando el método de Kaplan-Meier. RESULTADOS. En mujeres con citologí-a normal e infección concomitante por HR-HPV el riesgo absoluto de presentar CIN2/CIN3+ fue de 1.06 por ciento (95 por cientoCI, 0.57-2.20). Este riesgo fue cinco veces mayor al observado en todas las mujeres con citologí-a normal (0.20 por ciento; 95 por cientoCI, 0.12-0.32) pero siete veces menor que el observado en mujeres con lesiones intraepiteliales escamosas de bajo grado con infección concomitante (7.24 por ciento; 95 por cientoCI, 3.78-15.2). CONCLUSIÓN. El riesgo absoluto de CIN2/3+ a corto plazo luego de una citologí-a normal e infección por HR-HPV es baja (~1 por ciento), sugiriendo que, a corto plazo, la prueba de HR-HPV tiene utilidad clí-nica muy limitada en mujeres con citologí-a normal.
Assuntos
Adolescente , Adulto , Feminino , Humanos , Adulto Jovem , Alphapapillomavirus/isolamento & purificação , Displasia do Colo do Útero/epidemiologia , Infecções por Papillomavirus/patologia , Lesões Pré-Cancerosas/patologia , Cervicite Uterina/patologia , Esfregaço Vaginal , Alphapapillomavirus/patogenicidade , Displasia do Colo do Útero/virologia , Estudos de Coortes , Colômbia/epidemiologia , Anticoncepcionais Orais Hormonais/efeitos adversos , DNA Viral/análise , Progressão da Doença , Estimativa de Kaplan-Meier , Razão de Chances , Lesões Pré-Cancerosas/virologia , Prognóstico , Estudos Prospectivos , Risco , Fumar/epidemiologia , Cervicite Uterina/virologiaRESUMO
OBJECTIVE: The aim was to evaluate the concordance in the diagnosis of precursor lesions of intestinal-type gastric carcinoma among observers with different levels of experience. MATERIAL AND METHODS: Gastric biopsies from 1 056 cases were studied: 341 from Colombia, 382 from Mexico, and 333 from Paraguay. Pathologists without experience (A) and with experience (B) in gastrointestinal pathology, as well as experts working in an international reference center (C) participated in the diagnosis of each case. RESULTS: The concordance (k) between pathologists with experience and those without was poor for the diagnosis of atrophic gastritis (k=0.04 to 0.12) and dysplasia (k=0.11 to 0.05), and good for the diagnosis of intestinal metaplasia (k=0.52 to 0.58). Supervision of pathologists without experience by those with experience remarkably improved the concordance in the diagnosis of atrophic gastritis (k=0.65) and intestinal metaplasia (k=0.91), and to a lesser degree, of dysplasia (k=0.28). The concordance among experts before and after the consensus meeting showed no variation in the diagnosis of atrophic gastritis (k=0.57); the concordance varied from good to excellent in the diagnosis of intestinal metaplasia (k=0.67 to 0.81) and from poor to good in that of dysplasia (k=0.18 to 0.66). CONCLUSION: The greatest differences arose in the diagnosis of chronic atrophic gastritis and dysplasia. The interobserver concordance depended on the experience of the observer and the consensus reading.