Analysis of HPV Integrations in Mexican Pre-Tumoral Cervical Lesions Reveal Centromere-Enriched Breakpoints and Abundant Unspecific HPV Regions.

Human papillomavirus (HPV) DNA integration is a crucial event in cervical carcinogenesis. However, scarce studies have focused on studying HPV integration (HPVint) in early-stage cervical lesions. Using HPV capture followed by sequencing, we investigated HPVint in pre-tumor cervical lesions. Employing a novel pipeline, we analyzed reads containing direct evidence of the integration breakpoint. We observed multiple HPV infections in most of the samples (92%) with a median integration rate of 0.06% relative to HPV mapped reads corresponding to two or more sequence breakages. Unlike cancer studies, most integrations events were unique (supported by one read), consistent with the lack of clonal selection. Congruent to other studies, we found that breakpoints could occur, practically, in any part of the viral genome. We noted that L1 had a higher frequency of rupture integration (25%). Based on host genome integration frequencies, we found previously reported integration sites in cancer for genes like FHIT, CSMD1, and LRP1B and putatively many new ones such as those exemplified in CSMD3, ROBO2, and SETD3. Similar host integrations regions and genes were observed in diverse HPV types within many genes and even equivalent integration positions in different samples and HPV types. Interestingly, we noted an enrichment of integrations in most centromeres, suggesting a possible mechanism where HPV exploits this structural machinery to facilitate integration. Supported by previous findings, overall, our analysis provides novel information and insights about HPVint.

High expression of Helicobacter pylori VapD in both the intracellular environment and biopsies from gastric patients with severity.

Helicobacter pylori is a Gram-negative bacterium that causes chronic atrophic gastritis and peptic ulcers and it has been associated with the development of gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT). One of the more remarkable characteristics of H. pylori is its ability to survive in the hostile environment of the stomach. H. pylori regulates the expression of specific sets of genes allowing it to survive high acidity levels and nutrient scarcity. In the present study, we determined the expression of virulence associated protein D (VapD) of H. pylori inside adenocarcinoma gastric (AGS) cells and in gastric biopsies. Using qRT-PCR, VapD expression was quantified in intracellular H. pylori-AGS cell cultures at different time points and in gastric mucosa biopsies from patients suffering from chronic atrophic gastritis, follicular gastritis, peptic ulcers, gastritis precancerous intestinal metaplasia and adenocarcinoma. Our results show that vapD of H. pylori presented high transcription levels inside AGS cells, which increased up to two-fold above basal values across all assays over time. Inside AGS cells, H. pylori acquired a coccoid form that is metabolically active in expressing VapD as a protection mechanism, thereby maintaining its permanence in a viable non-cultivable state. VapD of H. pylori was expressed in all gastric biopsies, however, higher expression levels (p = 0.029) were observed in gastric antrum biopsies from patients with follicular gastritis. The highest VapD expression levels were found in both antrum and corpus gastric biopsies from older patients (>57 years old). We observed that VapD in H. pylori is a protein that is only produced in response to interactions with eukaryotic cells. Our results suggest that VapD contributes to the persistence of H. pylori inside the gastric epithelial cells, protecting the microorganism from the intracellular environment, reducing its growth rate, enabling long-term infection and treatment resistance.

Accuracy of Anal Cytology for Diagnostic of Precursor Lesions of Anal Cancer: Systematic Review and Meta-analysis.

BACKGROUND: Anal canal carcinoma is relevant because it commonly occurs in high-risk groups, and its incidence has been increasing. OBJECTIVE: This study evaluated the accuracy of anal cytology in the screening of precursor lesions of anal cancer, compared with histopathologic examination as the reference, in all subjects and in men who have sex with men, HIV-infected men and women, and men who have sex with men and HIV-infected subgroups. DATA SOURCES: The data included studies identified in the MEDLINE, Latin American and Caribbean Health Sciences, Cochrane Library, and Embase electronic databases, as well as in the grey literature. The search terms included anal cancer, anal dysplasia, anal intraepithelial neoplasia, screening, and anal cytology. STUDY SELECTION: After excluding studies with no histopathological data and those with duplicate and missing data, 34 primary studies were included. INTERVENTION: Cytology of anal smears was studied. MAIN OUTCOME MEASURES: Sensitivity, specificity, diagnostic OR, and area under the curve were measured. RESULTS: A total of 5093 patients were included. The pooled sensitivity of anal cytology was 85.0% (95% CI, 82.0%-87.0%) and pooled specificity was 43.2% (95% CI, 41.4%-45.1%) for the detection of anal intraepithelial neoplasia grade 2 or worse versus anal intraepithelial neoplasia grade 1 and normal when measuring all subjects. The accuracy of anal cytology was higher in the men who have sex with men and HIV-infected and men who have sex with men only subgroups. LIMITATIONS: This study was limited by its specificity. CONCLUSIONS: The study results support the hypothesis that cytology is a good test for the screening of anal cancer.

Assessment of Gastritis and Gastric Cancer Risk in the Chilean Population Using the OLGA System.

Gastric cancer (GC) is the first cancer-related cause of death in Chile; however, no plan for GC early detection has been implemented in this country. The OLGA system characterizes gastritis from stages 0 to IV according to the risk of developing GC based on H. pylori infection, atrophy, metaplasia and GC. In this study, the performance of the OLGA system was evaluated in 485 Chilean patients receiving routine endoscopy to improve the detection of early GC or preneoplastic lesions. The results showed that OLGA scores, atrophy, metaplasia and GC increased significantly with age (p < 0.001). Conversely, H. pylori infection was higher in younger groups (p < 0.05). All gastric lesions were more frequent in men than women. The majority of patients with atrophy also had metaplasia (99%, p < 0.0001). Patients with H. pylori infection had more gastric atrophy and metaplasia than those without infection (p < 0.05). Of the 485 patients, 21 (4.3%) had GC, being 2.3 times more frequent among men than women and about 2/3 (14) were in OLGA stage ≥2. In addition, 19 (90%) GC patients had atrophy and 18 (85%) had metaplasia (p < 0.001). In conclusion, the OLGA system facilitated the evaluation of GC precursor lesions particularly in patients with an OLGA score > 2 between 45 and 56 years old, because this group showed atrophy and intestinal metaplasia more frequently. Therefore, biennial endoscopic surveillance of patients with an OLGA >2 can be an important health policy in Chile for diagnosing GC in its early stages and reducing mortality over the next two decades.

Loss of ZNF516 protein expression is related with HR-HPV infection and cervical preneoplastic lesions.

PURPOSE: Cervical cancer is an important health issue among women worldwide. Cervical smear and human papillomavirus detection are the most used screening methods to detect preneoplastic and neoplastic lesions. However, as neither can predict cervical development, new markers are needed for this disease. ZNF516, a potential tumor suppressor gene, has been found altered in cervical cancer. The objective of this study was to determine ZNF516 immunohistochemistry frequency in cervical biopsies and its association with clinicopathological parameters, to evaluate its potential as marker in cervical lesions. METHODS: A retrospective series of 452 formalin-fixed, paraffin-embedded (FFPE) cervical biopsies, obtained between 2002 and 2007, were selected for immunohistochemistry of ZNF516, p16 and Ki-67 markers. Human papillomavirus genotyping was performed on 272 of these samples through reverse line blot assay. RESULTS: An inverse relation between ZNF516 expression and cervical lesions grade (P < 0.001) was observed, given this protein was found mainly expressed in normal tissues, while was decreased in cervical lesions. As expected, the proliferation markers p16 and Ki-67 were found highly expressed in cervical cancer compared to normal tissues, and inversely correlated to ZNF516 expression (P < 0.01). High oncogenic risk-Human papillomavirus presence also was related to the lack of ZNF516 expression in cervical lesions (P < 0.05), and the detection of these two parameters showed a high sensitivity (70.9%) for preneoplastic lesions detection. CONCLUSIONS: The loss of ZNF516 expression was found in cervical lesions, and its detection potentially could be used as a complementary marker of early diagnosis in cervical lesions.

Expresión de E-cadherina y factor de crecimiento epidérmico en leucoplasias orales / Expression of E-cadherin and epidermal growth factor in oral leukoplakia

Introducción: se define a las leucoplasias orales como una placa blancaque no puede desprenderse por raspado y que no puede clasifi carse comoninguna otra lesión. Son lesiones con potencial maligno, relacionadascon la presencia de displasia epitelial. Estos cambios preneoplásicospueden ser evidenciados histológicamente como también a travésde técnicas que pongan en evidencia los diferentes cambios a nivelmolecular. La E-cadherina es una glicoproteína membranosa quedesempeña papeles importantes en el mantenimiento de la adhesióncélula-célula, la preservación de la polaridad del tejido epitelial y laintegridad estructural. Los factores de crecimiento epidérmico son unconjunto de moléculas de naturaleza proteica, biorreguladores, cuyafuncionalidad fundamental radica en el control del ciclo celular. Elobjetivo del presente trabajo es identifi car y comparar parámetros histológicosy moleculares predictores de riesgo de transformación malignaen leucoplasias orales. Material y métodos: El estudio correspondea un diseño observacional descriptivo. Se seleccionaron muestras de26 biopsias de leucoplasias orales, las cuales fueron evaluadas contécnica histológica de rutina y tinción con hematoxilina y eosina, luegosometidas a inmunomarcación con factor de crecimiento epidérmico yE-cadherina, donde se evaluó la intensidad de tinción y cambios en laexpresión de cada marcador, así como la localización en los diferentessubtipos celulares. Resultados: De las 26 leucoplasias observadas,16 mostraron histología con cambios hiperplásicos y 10 con cambiosdisplásicos leves a moderados. La expresión de E-cadherina no mostróalteraciones signifi cativas en leucoplasias sin displasia, sólo hubopérdida de expresión en aquellas leucoplasias con cambios displásicosde alto grado, en concordancia a los hallazgos histológicos...

Introduction: oral leukoplakia is defined as a white plaque thatcannot be removed by scraping and cannot be classifi ed as any otherdisease entity. They are potentially malignant lesions related to thepresence of epithelial dysplasia. These preneoplastic changes can bedetected histologically, as well as through techniques that demonstratediff erent changes at the molecular level. E-cadherin is a membraneglycoprotein that plays a major role in maintaining cell-cell adhesion,preserving structural integrity and the polarity of epithelial tissue.Epidermal growth factors are a group of bio-regulatory proteins,whose primary function is to control the cell cycle. The aim of thisstudy is to identify and compare the parameters for histological andmolecular markers for malignant transformation in oral leukoplakia.Material and methods: The study was observational and descriptive indesign. Samples were selected from 26 oral leukoplakia biopsies, whichwere routinely evaluated for histology and stained with hematoxylinand eosin, then subjected to immunostaining with epidermal growthfactor and E-cadherin, with the intensity of staining and changes inthe expression of each marker being evaluated. Results: Of the 26leukoplakia examined, 16 showed hyperplastic changes and 10 mildto moderate dysplastic changes. The expression of E-cadherin showedno signifi cant changes in non-dysplastic leukoplakia, while a lossof expression was found in only those leukoplakias with high-gradedysplastic changes, which was consistent with the histological fi ndings...

Recurrent acute thermal lesion induces esophageal hyperproliferative premalignant lesions in mice esophagus.

Hot beverage consumption is a risk factor for esophageal squamous cell carcinoma, but the underlying mechanisms are still unknown. We developed an experimental mouse model to understand the mechanism of thermal lesion to esophageal carcinogenesis. Female BALB/c mice were treated by gavage with water at different temperatures three times a week and nitrosamines in the drinking water. Water at 70°C, but not at lower temperatures, initially induced an esophageal necrosis that healed and became resistant to necrosis after further administrations. However, when 70°C water was associated with N-nitrosodiethylamine at doses above 1 ppm, there was interference in epithelial regeneration, allowing recurrent thermal injury and inflammation. Recurrent thermal injury resulted in hyper proliferative premalignant lesions being induced earlier (at 4 weeks) and at a higher frequency (4-fold increase at 16 weeks) when compared to mice treated with NDEA only. Ki-67 immunostaining revealed that recurrent thermal injury induced basal cell proliferation resulting in the expansion of epithelial basal cells, confirmed by the increase in cytokeratin 14 positive cells with concomitant reduction of differentiated cytokeratin 5 positive cells. We conclude that recurrent thermal lesion may act as a tumor promoter though a strong proliferation stimulus of esophageal epithelial basal cells.

Neoplasia yield and colonoscopic workload of surveillance regimes for colorectal cancer in colitis patients: a retrospective study comparing the performance of the updated AGA and BSG guidelines.

BACKGROUND: Due to the increased risk of colorectal cancer, colonoscopic surveillance is recommended for patients with ulcerative and Crohn's colitis. Because surveillance intervals differ considerably between the recently updated American Gastroenterological Association (AGA) and British Society of Gastroenterology (BSG) guidelines, we compared the neoplasia yield and colonoscopic workload of these guidelines. METHODS: Patients with inflammatory bowel disease undergoing surveillance were identified using medical records. Patients were stratified according to the BSG and AGA guidelines, and corresponding colonoscopic workload was calculated based on the risk factors present during follow-up. The incidence of colitis-associated neoplasia (CAN), defined as a low-grade dysplasia in flat mucosa or a non-adenoma-like mass, high-grade dysplasia, or colorectal cancer was compared between the risk groups of either guidelines. RESULTS: In total, 1018 patients with inflammatory bowel disease who underwent surveillance were identified. Using the AGA surveillance intervals, 64 patients (6%) were assigned to annual and 954 patients (94%) to biannual surveillance, resulting in 541 colonoscopies per year. The yield of CAN was 5.3% and 20.3% in the low- and high-risk groups, respectively (P = 0.02). Using the BSG surveillance intervals, 204 patients received surveillance annually (20%), 393 patients every 3 years (39%), and 421 patients every 5 years (41%), resulting in 420 colonoscopies per year, which is 22% lower than the AGA guidelines. The yield of CAN was 3.6%, 6.9%, and 10.8%, for the low-, intermediate-, and high-risk groups, respectively (P = 0.26). CONCLUSIONS: Although the BSG surveillance intervals offer the advantage of a lower colonoscopic workload, the risk stratification of the AGA seems superior in distinguishing patients at higher risk of CAN.

Hepatic repercussions of azoxymethane-induced colorectal carcinogenesis.

OBJECTIVE: To evaluate the hepatic effects of colonic carcinogenesis induced by azoxymethane at different doses and times of exposure in rats. METHODS: Forty-four Wistar rats were divided into four groups. The animals were eight weeks at the beginning of the experiment. group 1 received 1.0 ml of saline intraperitoneally once a week for two weeks. Group 2 received 15 mg/kg of azoxymethane intraperitoneally once a week for two weeks. These animals were killed at the 15th week of the experiment. The animals of group 3 received saline intraperitoneally once a week for two weeks. Group 4 animals received 20mg/kg of azoxymethane intraperitoneally once a week for two weeks. These animals were killed at the 26th week of the experiment. The fragments of liver tissue were stained with hematoxylin and eosin and evaluated microscopically. RESULTS: Groups 1 and 2 differed significantly in relation to steatosis, no difference having been found between group 3 and group 4. However, in group 4 we observed pre-neoplastic lesions (foci of altered, clear, vacuolated, basophilic, amphophilic tigroid, oncocytic, small or acidophilus cells, spongiosis and peliosis) and neoplastic lesions (adenomas and colangiomas) containing atypical hepatocytes in between, not identified in group 3. CONCLUSION: In the model of colorectal carcinogenesis, preneoplastic and neoplastic hepatic lesions appear and evolve in proportion to the time of exposure and dose of azoxymethane.

Repercussão hepática da carcinogênese colorretal induzida pelo azoximetano / Hepatic repercussions of azoxymethane-induced colorectal carcinogenesis

OBJETIVO: Avaliar as repercussões hepáticas da carcinogênese colônica induzida por diferentes doses e tempos de exposição ao azoximetano em ratos Wistar. MÉTODOS: Quarenta e quatro ratos foram distribuídos em quatro grupos. Os animais tinham oito semanas no início do experimento. No grupo 1, receberam 1.0mL de solução salina intraperitonealmente uma vez por semana por duas semanas. No grupo 2, receberam 15 mg/kg de azoximetano intraperitonealmente uma vez por semana por duas semanas. Esses animais foram mortos na 15ª semana do experimento. Os animais do grupo 3 receberam solução salina intraperitonealmente uma vez por semana por duas semanas. Os animais do grupo 4 receberam 20mg/kg de azoximetano intraperitonealmente uma vez por semana por duas semanas. Esses animais foram mortos na 26ª semana do experimento. Os fragmentos de tecido hepático foram corados pela hematoxilina e eosina e avaliadas microscopicamente. RESULTADOS: Grupo 1 e grupo 2 diferiram significantemente em relação a esteatose, mas não houve diferença entre o grupo 3 e o grupo 4. No entanto, no grupo 4 foram observadas lesões pré-neoplásicas (focos de células alteradas, claras, vacuoladas, basofílicas, anfofílicas, tigróides, oncocíticas, pequenas ou acidófilas, espongioses e pelioses) e lesões neoplásicas (colangiomas e adenomas) contendo hepatócitos atípicos de permeio, não identificados no grupo 3. CONCLUSÃO: No modelo de carcinogênese colorretal, lesões hepáticas pré-neoplásicas e neoplásicas aparecem e evoluem na proporção do tempo e dose de exposição ao azoximetano.

OBJECTIVE: To evaluate the hepatic effects of colonic carcinogenesis induced by azoxymethane at different doses and times of exposure in rats. METHODS: Forty-four Wistar rats were divided into four groups. The animals were eight weeks at the beginning of the experiment. group 1 received 1.0ml of saline intraperitoneally once a week for two weeks. Group 2 received 15 mg/kg of azoxymethane intraperitoneally once a week for two weeks. These animals were killed at the 15th week of the experiment. The animals of group 3 received saline intraperitoneally once a week for two weeks. Group 4 animals received 20mg/kg of azoxymethane intraperitoneally once a week for two weeks. These animals were killed at the 26th week of the experiment. The fragments of liver tissue were stained with hematoxylin and eosin and evaluated microscopically. RESULTS: Groups 1 and 2 differed significantly in relation to steatosis, no difference having been found between group 3 and group 4. However, in group 4 we observed pre-neoplastic lesions (foci of altered, clear, vacuolated, basophilic, amphophilic tigroid, oncocytic, small or acidophilus cells, spongiosis and peliosis) and neoplastic lesions (adenomas and colangiomas) containing atypical hepatocytes in between, not identified in group 3. CONCLUSION: In the model of colorectal carcinogenesis, preneoplastic and neoplastic hepatic lesions appear and evolve in proportion to the time of exposure and dose of azoxymethane.

Comparative study of the behavior of p53 immunoexpression in smoking associated lesions: Reinke's edema and laryngeal carcinoma.

OBJECTIVE: To assess the behavior of the immunoexpression of protein p53 in Reinke's edema and laryngeal squamous cell carcinoma. STUDY DESIGN: retrospective. METHODS: we recovered the histological paraffin blocks of patients who were subjected to Reinke's edema and laryngeal squamous cell carcinoma surgery in 2000-2011. The paraffin blocks were cut into 3-µm sections; the specimens were prepared in silanized slides (one slide for each paraffin block) and subjected to immunohistochemical reaction according to the Avidin Biotin Peroxidase method. Monoclonal primary anti-p53 antibodies were used at 1:50 dilution. Slides were examined under a light microscope at different magnitudes and results were interpreted based on the degree of brown staining in the nuclei of epithelial cells and in the extent of the fragment by using a semi-quantitative score from 0 to 3. RESULTS: 67 slides of Reinke's edema and 60 slides of laryngeal squamous cell carcinoma were included. Scores 2 and 3 for staining of the nuclei of epithelial cells were recorded for 46 slides of Reinke's edema (68.65%) and for 57 slides of laryngeal squamous cell carcinoma (95%). As to the extent of the fragment, scores 2 and 3 were recorded for 74% slides of Reinke's edema and for 95% slides of carcinomas. CONCLUSION: the positive immunoexpression for protein p53, positive in 95% carcinomas and 74% Reinke's edemas, makes us aware of the possible preneoplastic condition of the latter lesion. Further studies are needed to identify and reveal the genetic changes that lead to these results.

Coffee and caffeine protect against liver injury induced by thioacetamide in male Wistar rats.

Coffee intake has been inversely related to the incidence of liver diseases, although there are controversies on whether these beneficial effects on human health are because of caffeine or other specific components in this popular beverage. Thus, this study evaluated the protective effects of coffee or caffeine intake on liver injury induced by repeated thioacetamide (TAA) administration in male Wistar rats. Rats were randomized into five groups: one untreated group (G1) and four groups (G2-G5) treated with the hepatotoxicant TAA (200 mg/kg b.w., i.p.) twice a week for 8 weeks. Concomitantly, rats received tap water (G1 and G2), conventional coffee (G3), decaffeinated coffee (G4) or 0.1% caffeine (G5). After 8 weeks of treatment, rats were killed and blood and liver samples were collected. Conventional and decaffeinated coffee and caffeine intake significantly reduced serum levels of alanine aminotransferase (ALT) (p < 0.001) and oxidized glutathione (p < 0.05), fibrosis/inflammation scores (p < 0.001), collagen volume fraction (p < 0.01) and transforming growth factor ß-1 (TGF-ß1) protein expression (p ≤ 0.001) in the liver from TAA-treated groups. In addition, conventional coffee and caffeine intake significantly reduced proliferating cellular nuclear antigen (PCNA) S-phase indexes (p < 0.001), but only conventional coffee reduced cleaved caspase-3 indexes (p < 0.001), active metalloproteinase 2 (p ≤ 0.004) and the number of glutathione S-transferase placental form (GST-P)-positive preneoplastic lesions (p < 0.05) in the liver from TAA-treated groups. In conclusion, conventional coffee and 0.1% caffeine intake presented better beneficial effects than decaffeinated coffee against liver injury induced by TAA in male Wistar rats.

Single nucleotide polymorphisms in the PRDX3 and RPS19 and risk of HPV persistence and cervical precancer/cancer.

BACKGROUND: Host genetic factors might affect the risk of progression from infection with carcinogenic human papillomavirus (HPV), the etiologic agent for cervical cancer, to persistent HPV infection, and hence to cervical precancer and cancer. METHODOLOGY/PRINCIPAL FINDINGS: We assessed 18,310 tag single nucleotide polymorphisms (SNPs) from 1113 genes in 416 cervical intraepithelial neoplasia 3 (CIN3)/cancer cases, 356 women with persistent carcinogenic HPV infection (median persistence of 25 months) and 425 randomly selected women (non-cases and non-HPV persistent) from the 10,049 women from the Guanacaste, Costa Rica HPV natural history cohort. For gene and SNP associations, we computed age-adjusted odds ratio and p-trend. Three comparisons were made: 1) association with CIN3/cancer (compared CIN3/cancer cases to random controls), 2) association with persistence (compared HPV persistence to random controls), and 3) progression (compared CIN3/cancers with HPV-persistent group). Regions statistically significantly associated with CIN3/cancer included genes for peroxiredoxin 3 PRDX3, and ribosomal protein S19 RPS19. The single most significant SNPs from each gene associated with CIN3/cancer were PRDX3 rs7082598 (P(trend)<0.0001), and RPS19 rs2305809 (P(trend)=0.0007), respectively. Both SNPs were also associated with progression. CONCLUSIONS/SIGNIFICANCE: These data suggest involvement of two genes, RSP19 and PRDX3, or other SNPs in linkage disequilibrium, with cervical cancer risk. Further investigation showed that they may be involved in both the persistence and progression transition stages. Our results require replication but, if true, suggest a role for ribosomal dysfunction, mitochondrial processes, and/or oxidative stress, or other unknown function of these genes in cervical carcinogenesis.

[Barrett's esophagus: an update]. / Esófago de Barrett: actualización del tema.

Barrett's esophagus is an acquired condition that results in a serious injury of the esophageal mucosa and whose importance lies in the possible progression to esophageal adenocarcinoma. The incidence of esophageal adenocarcinoma continues to rise in the Western world, being survival rate very grim when diagnosis is made in later stages. For this reason the current strategies to improve survival in patients with esophageal adenocarcinoma focus on cancer detection at an early and potentially curable stage. This purpose could be achieved either by screening patients most likely to have Barrett's esophagus or by endoscopic surveillance in patients with known Barrett's esophagus. However, the detection and monitoring strategies are currently invasive, expensive and with not really proven benefit. However, new techniques have been and are developed to improve the diagnosis and treatment in order to change the current reality. The aim of this paper is to update the reader on this pathology in terms of pathophysiological and epidemiological aspects, but especially in relation to advances in diagnosis and endoscopic treatment. We also propose a guideline for monitoring and clinical management in this group of patients.

Analysis of cagA in Helicobacter pylori strains from Colombian populations with contrasting gastric cancer risk reveals a biomarker for disease severity.

BACKGROUND: Helicobacter pylori infection is a risk factor for the development of gastric cancer, and the bacterial oncoprotein CagA contributes to gastric carcinogenesis. METHODS: We analyzed H. pylori isolates from persons in Colombia and observed that there was marked variation among strains in levels of CagA expression. To elucidate the basis for this variation, we analyzed sequences upstream from the CagA translational initiation site in each strain. RESULTS: A DNA motif (AATAAGATA) upstream of the translational initiation site of CagA was associated with high levels of CagA expression. Experimental studies showed that this motif was necessary but not sufficient for high-level CagA expression. H. pylori strains from a region of Colombia with high gastric cancer rates expressed higher levels of CagA than did strains from a region with lower gastric cancer rates, and Colombian strains of European phylogeographic origin expressed higher levels of CagA than did strains of African origin. Histopathologic analysis of gastric biopsy specimens revealed that strains expressing high levels of CagA or containing the AATAAGATA motif were associated with more advanced precancerous lesions than those found in persons infected with strains expressing low levels of CagA or lacking the AATAAGATA motif. CONCLUSIONS: CagA expression varies greatly among H. pylori strains. The DNA motif identified in this study is associated with high levels of CagA expression, and may be a useful biomarker to predict gastric cancer risk. IMPACT: These findings help to explain why some persons infected with cagA-positive H. pylori develop gastric cancer and others do not.

Epidemiologia da infecção pelo HPV em mulheres infectadas pelo HIV / Epidemiology of HPV infection in women infected by HIV

A infecção pelo papilomavírus humano (HPV) é um importante fator de risco para o desenvolvimento de lesões pré-neoplásicas e neoplásicas do colo uterino, com maior chance de desenvolvimento em portadoras do HIV (vírus da imunodeficiência humana), em decorrência da imunossupressão. A alta prevalência de lesões intraepiteliais escamosas (SIL - squamous intraepithelial lesion) associadas ao HPV, em mulheres infectadas pelo HIV, sugere que a resposta imune do hospedeiro desempenha um papel importante no desenvolvimento do câncer cervical associado ao HPV. Mulheres HIV positivas apresentam alta prevalência de DNA do HPV, de câncer cervical e de SIL. A infecção pelo HIV resulta em uma progressiva perda de células TCD4+, a qual, por sua vez, está associada a um aumento na prevalência das infecções pelo HPV, levando a uma maior persistência da infecção e do risco aumentado para o desenvolvimento de câncer cervical. Nas mulheres infectadas pelo vírus HIV, as infecções são mais persistentes e geralmente apresentam múltiplos genótipos do HPV, sendo os tipos oncogênicos os mais prevalentes. O objetivo deste estudo foi revisar o corrente conhecimento sobre a associação existente entre a infecção pelo HPV nas mulheres infectadas pelo HIV, analisando os aspectos epidemiológicos da coinfecção HPV e HIV.

The human papillomavirus (HPV) infection is an important risk factor for the development of pre-neoplasics and neoplasics cervix lesions, with higher possibility of development in HIV (human immunodeficiency virus) carriers, as a result of the immunossupression. The high prevalence of squamous intraepithelial lesions (SIL) associated with HPV, in women infected by HIV, suggests that the immune response of the host plays an important role in the development of the cervical cancer associated with HPV. Women with HIV presents high DNA of the HPV, cervical cancer, and SIL. The HIV infection result in a gradual loss of TCD4+ cells, which, in turn, is associated with an increase in the prevalence of HPV infections, leading to a higher persistence of the infection and increased risk for the development of cervical cancer. In women infected by HIV, the infections are more persistent and generally presents multiple genotypes of the HPV, being most prevalent the oncogenics types. The aim of this study was to revise the current knowledge on the existing association between HPV infection in women infected by HIV, analyzing the epidemiologic aspects of the HPV and HIV coinfection.

[Prevalence of intestinal metaplasia of the gastric cardia and its relation with Helicobacter pylori strains cagA and vacA]. / Prevalencia de metaplasia intestinal en el cardias gástrico y su relación con cepas virulentas de Helicobacter pylori cagA y vacA.

BACKGROUND: Esophageal metaplasia progression is a consequence of chronic gastroesophageal reflux (CGR). Patients with this condition are frequently infected by Helicobacter pylori and show several symptoms including gastritis as well as ulcer formation. In addition, they present an increased risk for the development of gastric adenocarcinoma. Several pathogenic markers for Helicobacter pylori such as ureC, vacA and cagA genes have been described. Evidence indicates that direct injury to the epithelial mucosa is caused by cytotoxins and enzymes codified by these genes. We undertook this study to establish a relationship between the presence of pathogenic Helicobacter pylori strains and the presence of metaplasia progression in patients with CGR. METHODS: We detected the presence of Helicobacter pylori cagA and vacA positive strains in patients with CGR. Using polymerase chain reaction, we analyzed 120 samples obtained from 60 patients with CGR and 60 control group patients, including samples from both anatomic areas: cardia and gastric antrum. RESULTS: We detected 56% of Helicobacter pylori positive patients; 57.5% of these patients were positive for either cagA(+) and/or vacA(+) Helicobacter pylori strains. Cardiac intestinal metaplasia was observed in 35% of the patients. A marked tendency was observed to develop cardiac intestinal metaplasia in those patients diagnosed with high-pathogenicity strains infected in both anatomic areas. CONCLUSIONS: These results suggest that infection with Helicobacter pylori can be considered a risk factor for developing gastric cardiac intestinal metaplasia.

Relationship between chronic trauma of the oral mucosa, oral potentially malignant disorders and oral cancer.

BACKGROUND: Oral cancer represents 2%-5% of all cancers, being one of the 10 most frequent ones. Apart from oral cancer risk factors already described in literature, such as tobacco and alcohol consumption, others emerging risk factors have been proposed, such as chronic irritation from dental factors. The aim of this work was to assess the influence of chronic trauma of the oral mucosa (CTOM) in patients with oral potentially malignant disorders (OPMD) and cancer. METHODS: A retrospective study of 406 patients (both sexes; aged between 18 and 80 years; with OPMD and cancer) who attended the Department of Clinical Stomatology A of the National University of Cordoba was performed by non-probabilistic sampling. The association of variables and outcome variable diagnosis, with levels control, OPMD, oral cancer, was evaluated by multinomial regression model. RESULTS: Population under study was represented by 72% of control patients, 16% patients with OPMD and 11% of patients with oral cancer. It was observed a significant association between diagnosis and CTOM (P = 0.000), after adjustment of confounding factors (smoking and drinking habits, sex, cancer inheritance and denture use). CONCLUSIONS: Our results suggest that CTOM is, together with other factors, an important risk factor in patients with oral cancer diagnosis, but not for patients with OPMD.

Actinic lesions in fishermen's lower lip: clinical, cytopathological and histopathologic analysis.

INTRODUCTION: Actinic cheilitis (AC) is considered to be a pre-malignant lesion or an incipient and superficial form of lip squamous cell carcinoma. It is commonly found in individuals whose occupational activities are related to chronic sun exposure and the definitive diagnosis is performed with biopsy. Although Exfoliative cytology has been used as a screening procedure to evaluate cancer of the oral cavity no studies have proposed the use of exfoliative cytologic analysis to evaluate and diagnose AC. OBJECTIVE: The purpose of this study was to evaluate lower lip lesions on fishermen related to chronic solar exposure using clinical, cytologic and histopathologic analyses. PATIENTS AND METHODS: Smears taken from the vermilion of the lower lips of 125 fishermen and 30 control individuals were subjected to cytologic analysis. RESULTS: The harvested cells were sufficient for cytologic analysis in 83.2% of the samples. Sixteen fishermen exhibited prominent lower lip lesions that justified biopsy and histological studies. In total, 4 specimens were malignant (3.2%), and 12 displayed epithelial dysplasia, demonstrating that the prevalence of epithelial dysplasia and malignant lesions was high among the fishermen population. These conditions were strongly associated with infiltration and blurring of the vermilion margin of the lower lip. CONCLUSION: The cytologic analysis was not useful for detecting epithelial dysplasia or malignant alterations.