Cell-cycle and suppressor proteins expression in uterine cervix in HIV/HPV co-infection: comparative study by tissue micro-array (TMA)

<p>Abstract</p> <p>Background</p> <p>The oncoproteins of human papillomavirus (HPVs) directly effect cell-cycle control. We hypothesize that regulatory and cell cycle protein expression might be additionally modified in the cervix of HIV/HPV co-infected women.</p> <p>Methods</p> <p>We analyzed the expression of Rb, p27, VEGF and Elf-1 transcriptor factor by immunohistochemistry in 163 paraffin-embeded cervical samples using Tissue Micro-Array (TMA) and correlated this to HIV-1 and HPV infection.</p> <p>Results</p> <p>HIV/HPV co-infection was associated with a significant increase in expression (p < 0.001) of VEGF and p27 in both low and high grade CIN when compared to the cervices of women infected by HPV alone. Decreased Rb expression was evident with increased CIN grade in the cervices of women infected with HPV alone (p = 0.003 average of cells/mm²in CIN I: 17.9, CIN II/III: 4.8, and tumor 3.9). Rb expression increased 3-fold for both low and high grade CIN with HPV/HIV-1 co-infection compared to HPV infection alone but did not reach statistical significance. There was a significant increase in Elf-1 expression in HPV+/HIV- women with CIN II/III and tumor (average of cells/mm²in CIN I: 63.8; CIN II/III: 115.7 and tumor: 112.0, p = 0.005), in comparison to controls.</p> <p>Conclusion</p> <p>Co-infection of HPV and HIV leads to significant increase in the VEGF and p27 expression when compared to HPV+/HIV-negative infection that could facilitate viral persistence and invasive tumor development.</p

Evaluation of MCM-2 Expression in TMA Cervical Specimens

Background:Minichromosome maintenance proteins (MCM) are highly expressed in actively replicating cells. The need for biological markers for cervical carcinoma and its precursor lesions is emerging. Our main aim was to determine the immunohistochemical expression of MCM-2 in HIV-positive and -negative dysplastic cervical specimens. Methods:Immunohistochemical analysis of MCM-2 was performed in a total of 352 cervical TMA specimens of normal control, low-grade CIN, high-grade CIN and invasive tumor. 38 specimens were from HIV-positive women. A receiver operating characteristic (ROC) curve was constructed to determine the best cutoff to diagnose high-grade CIN and invasive cervical cancer. Results:In the progression from normal epithelium to high-grade CIN and invasive tumor we found significant differences in the MCM-2 expression (p,0.05). Based on the ROC curve of 80% with an area under the curve (AUC) of 0.78, expression of MCM-2 to diagnose high-grade CIN and invasive tumor resulted in sensitivity of 81%, specificity of 66%, a positive predictive value (PPV) of 86% and a negative predictive value (NPV) of 57%. HIV-positive cervices revealed a decreasing expression of MCM-2 in both LGCIN and HGCIN compared with HIV-negative specimens (p,0.0001). Conclusions:The present study suggests that immunohistochemical MCM-2 may not be a promising biomarker for diagnosing high-grade CIN and invasive cance

A summary of the 25th International Papillomavirus Conference 2009: Vaccines, screening, epidemiology and therapeutics

The 25th International Papillomavirus Conference was held in Malmo, Sweden, on May 8-14, 2009. The conference encompassed all areas of papillomavirus (PV) research, from clinical vaccinology to molecular biology. This review highlights some of the 237 presentations and 887 abstracts which were presented and summarizes sessions on prophylactic vaccines, screening, epidemiology and therapeutics. Important advances included identification of variants in four genes associated with HPV persistence, new HPV detection are likely new infections and not latency reactivation, and development of effective DNA vaccines that targets E6/E7 genes of HPV11. Also, many studies from different countries demonstrated that HPV vaccination provided sustained protection and substantial reduction of disease burden in both women and men, and in HIV-infected neonates. All the references cited are from the abstract book of the IPV Conference. See http://www.hpv2009.org/. (C) 2009 Elsevier B.V. All rights reserved

Sexually transmitted infections among HIV-infected and HIV-uninfected women in the Tapajós region, Amazon, Brazil: Self-collected vs. clinician-collected samples.

The anogenital prevalence of sexually transmitted infections (STIs) and the use of cervico-vaginal self-collected vs. clinician-collected samples were evaluated for the diagnosis of human immunodeficiency virus (HIV)-infected and HIV-uninfected women in the Tapajós region, Amazon, Brazil. We recruited 153 women for a cross-sectional study (112 HIV-uninfected and 41 HIV-infected) who sought health services. Anal and cervical scrapings and cervico-vaginal self-collection samples were collected. Real-time polymerase chain reaction methods were used for Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis and Mycoplasma genitalium. A syphilis test was also performed. Risk factors for STIs were identified by multivariate analysis. The overall prevalence of STIs was 30.4% (34/112) in HIV-uninfected women and 24.4% (10/41) in HIV-infected women. Anogenital Chlamydia trachomatis infection was the most prevalent in both groups of women (20.5% vs 19.5%). There was significant agreement for each STI between self-collected and clinician-collected samples: 91.7%, kappa 0.67, 95% confidence interval (CI) 0.49-0.85 for Chlamydia trachomatis; 99.2%, kappa 0.85, 95% CI 0.57-1.00 for Neisseria gonorrhoeae; 97.7%, kappa 0.39, 95% CI -0.16-0.94 for Trichomonas vaginalis; and 94.7%, kappa 0.51, 95% CI 0.20-0.82 for Mycoplasma genitalium. Women with human papillomavirus had coinfection or multiple infections with other STIs. Risk factors for STIs were being ≤ 25 years old, being employed or a student, reporting a history of STI and having a positive HPV test. A high prevalence of STIs in women in the Tapajós region was found. Cervico-vaginal self-collection is a useful tool for STI screening and can be used in prevention control programs in low-resource settings, such as in northern Brazil

Claudin-1 expression in HIV/HPV co-infected anal intra-epithelial neoplasia

Submitted by Alcina Frederica Nicol ([email protected]) on 2017-11-12T20:40:33Z No. of bitstreams: 1 CLAUDIN-2017-ijcep0041268.pdf: 1039575 bytes, checksum: 1ba1845ab78d47b6a5b46a310ead62f5 (MD5)Approved for entry into archive by Raphael Rodrigues ([email protected]) on 2017-11-13T14:05:08Z (GMT) No. of bitstreams: 1 CLAUDIN-2017-ijcep0041268.pdf: 1039575 bytes, checksum: 1ba1845ab78d47b6a5b46a310ead62f5 (MD5)Made available in DSpace on 2017-11-13T14:05:08Z (GMT). No. of bitstreams: 1 CLAUDIN-2017-ijcep0041268.pdf: 1039575 bytes, checksum: 1ba1845ab78d47b6a5b46a310ead62f5 (MD5) Previous issue date: 2017Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisas Médicas. Rio de Janeiro, RJ, Brasil.University of California. Department of Medicine. San Francisco, CA, USA.University of California. Department of Medicine. San Francisco, CA, USA.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ. Brasil.University of California. Department of Medicine. San Francisco, CA, USA.University of California. Department of Medicine. San Francisco, CA, USA.University of California. Department of Medicine. San Francisco, CA, USA.University of California. Department of Medicine. San Francisco, CA, USA.Background: Claudin-1 expression is poorly characterized in anal intraepithelial neoplasia (AIN) from HIVpositive individuals. Aim: To investigate claudin-1 in situ expression in HPV-positive AIN lesions from HIV-positive individuals compared with non-dysplastic anal tissues. Materials and Methods: By means of immunofluorescence microscopy, claudin-1 was analyzed in 46 anal tissues: 18 AIN1; 14 AIN2/3 and 14 non-dysplastic specimens. Results: A higher proportion of cells with overexpression of claudin-1 were found in HIV-positive AIN lesions compared with controls. Overexpression of claudin-1 was most evident in AIN 2/3 lesions. HPV16 was detected in 21.8% anal specimens and HPV18 in 3.1%. A great diversity of 18 low-risk HPV types were detected, 40% of AIN specimens had multiple HPV types. Conclusions: Our data show that there is an over-expression of claudin-1 in HIV-positive AIN lesions compared with non-dysplastic anal biopsies. A high prevalence of HPV16 and diversity of HPV types was detected. The overexpression of claudin-1 in HIV-positive AIN specimens may play a role on the development of anal cancer, however further studies should be performed to better understand the role of claudin-1 in AIN and anal cancer development in the HIV-positive individuals

A comparative analysis of clinical and molecular factors with the stage of cervical cancer in a brazilian cohort

Submitted by Luis Guilherme Macena ([email protected]) on 2013-07-31T16:33:15Z No. of bitstreams: 1 A Comparative Analysis of Clinical and Molecular Factors.pdf: 1117978 bytes, checksum: 9363a0174c2fd7de506f55cbf0020692 (MD5)Made available in DSpace on 2013-07-31T16:33:15Z (GMT). No. of bitstreams: 1 A Comparative Analysis of Clinical and Molecular Factors.pdf: 1117978 bytes, checksum: 9363a0174c2fd7de506f55cbf0020692 (MD5) Previous issue date: 2013Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisa Médica. Rio de Janeiro, RJ, Brasil.Johns Hopkins Bloomberg School of Public Health. Department of Epidemiology Infectious Diseases. Baltimore, Maryland, USA.Ohio State University. Comprehensive Cancer Center. Columbus, Ohio, USA.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Universidade de São Paulo. Instituto de Medicina Tropical Laboratório de Virologia. São Paulo, SP, Brasil.Hospital Alemão Oswaldo Cruz. São Paulo, SP, Brasil.Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Rio de Janeiro, RJ, Brasil.Universidade Federal Fluminense. Niterói, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisa Médica. Rio de Janeiro, RJ, Brasil.Cell cycle protein expression plays an important role in the pathophysiology of cervical cancer. However, few studies have attempted to correlate the use of these biomarkers with the clinical progression of the tumor. Objectives:1) To analyze the expression of Ki-67, p53 and p16 INK4a in cervical cancer, 2) to correlate the relative expression of these proteins as well as clinical parameters with the stage of disease, and 3) to determine the HPV DNA prevalence and subtype distribution. Methods:Tissue Micro-Arrays (TMA) from patients with invasive cervical cancer (ICC) and controls were analyzed. HPV DNA detection was done by PCR and in situ hybridization. Ki-67, p53 and p16 INK4a were analyzed by immunohistochemistry; clinical data was derived from the chart review. Results:Advanced tumor stage (III and IV) was strongly associated (p,0.005) with advanced age (.55 years old), with more than four pregnancies and with the lack of formal education. HPV DNA was found in 94.3% of cases with the most prevalent types being HPV16 (67.5%), followed by HPV33 (12.0%) and HPV35 (3.6%). High expression of Ki-67 and p16 was more common in the advanced FIGO stages (p = 0.023). Women with HPV16 tended to be younger (50.9 years; SE 1.9) compared to women with other types (59.9 years; SE 2.8). Conclusion:We found that Ki-67 and p16 expression were independently associated with the tumor stage. We also noted that about 1/3 of the cervical cancers in this Brazilian cohort were not associated with HPV types directly targeted by the current HPV vaccines

HIV-1, HBV, HCV, HTLV, HPV-16/18, and Treponema pallidum Infections in a Sample of Brazilian Men Who Have Sex with Men

Made available in DSpace on 2015-05-15T13:16:42Z (GMT). No. of bitstreams: 2 license.txt: 1914 bytes, checksum: 7d48279ffeed55da8dfe2f8e81f3b81f (MD5) adriana_pinhoetal_IOC_2014.pdf: 592143 bytes, checksum: 5a4d1bb30fc740f1e38596328e1da952 (MD5) Previous issue date: 2014Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisas de Estudos Contábeis. Laboratório de Análises Clínicas. Seção Imunodiagnóstico. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Referência Nacional para Hepatites Virais. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Referência Nacional para Hepatites Virais. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisas Médicas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Educação em Ambiente e Saúde. Rio de Janeiro, RJ, Brasil.Laboratório Municipal de Patologia Clínica de Campinas.São Paulo, SP, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genética Molecular e Microrganismos. Rio de Janeiro, RJ, Brasil.Johns Hopkins University School of Medicine. Department of Pediatrics. Baltimore, Maryland, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil.Background: Men who have sex with men (MSM) are more vulnerable to blood-borne infections and/or sexuallytransmitted infections (STI). This study was conducted to estimate the prevalences of mono and co-infections of HIV-1 and other blood-borne/STIs in a sample of MSM in Campinas, Brazil. Methods: Responding Driven Sampling (RDS) was used for recruitment of MSM. Serum samples collected from 558 MSM were analyzed for the presence of serological markers for HIV-1, HBV, HCV, HTLV, HPV-16/18, and T. pallidum infections. Results: The highest prevalences of infection in serum samples were found for HPV-16 and 18 (31.9% and 20.3%, respectively). Approximately 8% of the study population showed infection with HIV-1, and within that group, 27.5% had recently become infected with HIV-1. HBV infection and syphilis were detected in 11.4% and 10% of the study population, respectively, and the rates of HTLV and HCV infection were 1.5% and 1%, respectively. With the exception of HTLV, all other studied infections were usually found as co-infections rather then mono-infections. The rates of co-infection for HCV, HPV- 18, and HIV-1 were the highest among the studied infections (100%, 83%, and 85%, respectively). Interestingly, HTLV infection was usually found as a mono-infection in the study group, whereas HCV was found only as a co-infection. Conclusions: The present findings highlight the need to educate the MSM population concerning their risk for STIs infections and methods of prevention. Campaigns to encourage vaccination against HBV and HPV could decrease the rates of these infections in MSM

An evaluation of p16INK4a expression in cervical intraepithelial neoplasia specimens, including women with HIV-1

Although several studies have evaluated the role of p16INK4a as a diagnostic marker of cervical intraepithelial neoplasia (CIN) and its association with disease progression, studies regarding the role of p16INK4a in human immunodeficiency virus (HIV)-infected patients remain scarce. The present study was designed to determine the potential utility of p16INK4a as a diagnostic marker for CIN and invasive cervical cancer in HIV-positive and negative cervical specimens. An immunohistochemical analysis of p16INK4a was performed in 326 cervical tissue microarray specimens. Performance indicators were calculated and compared using receiving operating characteristics curve (ROC)/area under the curve. In HIV-1-negative women, the percentage of cells that was positive for p16INK4a expression was significantly correlated with the severity of CIN (p < 0.0001). A ROC curve with a cut-off value of 55.28% resulted in a sensitivity of 89%, a specificity of 81%, a positive predictive value of 91% and a negative predictive value of 78%. HIV-seropositive women exhibited decreased expression of p16INK4a in CIN2-3 specimens compared with HIV-negative specimens (p = 0.031). The ROC data underscore the potential utility of p16INK4a under defined conditions as a diagnostic marker for CIN 2-3 staging and invasive cervical cancer. HIV-1 infection, however, is associated with relatively reduced p16INK4a expression in CIN 2-3

In situ FoxP3+ and IL-10 over-expression is associated with high grade anal lesions in HIV infected patients

Submitted by Alcina Frederica Nicol ([email protected]) on 2017-11-12T20:43:42Z No. of bitstreams: 1 FOX-ijcep0019868.pdf: 1341261 bytes, checksum: 188a212005045eeaaae4280385a30d59 (MD5)Approved for entry into archive by Raphael Rodrigues ([email protected]) on 2017-11-13T14:43:39Z (GMT) No. of bitstreams: 1 FOX-ijcep0019868.pdf: 1341261 bytes, checksum: 188a212005045eeaaae4280385a30d59 (MD5)Made available in DSpace on 2017-11-13T14:43:39Z (GMT). No. of bitstreams: 1 FOX-ijcep0019868.pdf: 1341261 bytes, checksum: 188a212005045eeaaae4280385a30d59 (MD5) Previous issue date: 2016Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisas Médicas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira. Departamento de Patologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ. Brasil.Universidade Estácio de Sá. Departamento de Endodontia. Programa de pós graduação em odontologia. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisas Médicas. Rio de Janeiro, RJ, Brasil.Instituto Nacional do Cancer. Divisão de Genética. Rio de Janeiro, RJ. Brasil.Comprehensive Cancer Center, Ohio State University, Columbus, Ohio, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisas Médicas. Rio de Janeiro, RJ, Brasil.Human papillomavirus (HPV) is the main etiologic agent of lower genital tract cancers. The natural history of HPV infection and the immune response to HIV/HPV co-infection, particularly in the anal mucosa, is poorly understood. The aim was evaluate the in situ immune response in anorectal biopsies from HIV-infected patients. A total of 114 biopsies were analyzed by Tissue Micro-Array: 15 were from HIV-negative individuals with normal squamous epithelium and 99 from HIV-positive individuals (21 normal squamous epithelium, 39 with anal intra-epithelial lesion grade 1 and 39 with anal intra-epithelial lesion grade 2/3). PCR and sequencing were used to identify HPV DNA. Staining for CD4, CD8, Foxp3+, T-bet and IL-10 were analyzed via immunohistochemistry. HIV-positive patients with AIN 2/3 showed a lower number of CD4+ cells (< 50 cells/mm3) compared to HIV negative subjects (P = 0.01). HIV infected individuals showed a higher expression of FoxP3+ and IL-10 that correlated with the severity of the lesion (P = 0.002). A positive coefficient correlation was found between FoxP3+ and IL-10 (r = 0.34; P = 0.027). HPV DNA was detected in 93.4% (101/107) of the samples and the most common types were HPV 16 (26.9%), followed by HPV 6 (15.7%), HPV 59 (13%) and HPV 18 (10.2%). Our results showed a strong association between the increased T-reg cells and IL-10 expression in HIV-positive patients with AIN 2/3. HPV 16 was the most prevalent type. Our study suggests that the immune regulatory in situ profile may favor HPV persistence in HIV-positive individuals. Further in situ studies should be done in order to elucidate the development of anal cancer in HPV/HIV co-infected individuals