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

Factors Associated with Colposcopy-Histopathology Confirmed Cervical Intraepithelial Neoplasia among HIV-Infected Women from Rio De Janeiro, Brazil

Introduction: Despite the availability of preventive strategies (screening tests and vaccines), cervical cancer continues to impose a significant health burden in low- and medium-resourced countries. HIV-infected women are at increased risk for infection with human papillomavirus (HPV) and thus development of cervical squamous intraepithelial neoplasia (CIN). Methods:Study participants included HIV-infected women enrolling the prospective open cohort of Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation (IPEC/FIOCRUZ). At cohort entry, women were subjected to conventional Papanicolaou test, HPV-DNA test and colposcopy; lesions suspicious for CIN were biopsied. Histopathology report was based on directed biopsy or on specimens obtained by excision of the transformation zone or cervical conization. Poisson regression modeling was used to assess factors associated with CIN2+diagnosis. Results:The median age of the 366 HIV-infected women included in the study was 34 years (interquartile range: 28–41 years). The prevalence of CIN1, CIN2 and CIN3 were 20.0%, 3.5%, and 2.2%, respectively. One woman was found to have cervical cancer. The prevalence of CIN2+was 6.0%. Factors associated with CIN2+diagnosis in the multivariate model were age,years compared to$35 years (aPR = 3.22 95CD4 T-cell count,350 cells/mm3 when compared to$350 cells/mm3 (aPR = 6.03 95%CI 1.50–24.3) and concomitant diagnosis of vulvar and/or vaginal intraepithelial lesion (aPR = 2.68 95%CI 0.99–7.24). Discussion:Increased survival through wide-spread use of highly active antiretroviral therapy might allow for the development of cervical cancer. In Brazil, limited cytology screening and gynecological care adds further complexity to the HIV-HPV co-infection problem. Integrated HIV care and cervical cancer prevention programs are needed for the prevention of cervical cancer mortality in this group of wome

[Performance by cytology and hybrid capture II in screening for high-grade squamous intraepithelial lesions in women with HIV].

HIV-infected women are at increased risk of developing high-grade squamous intraepithelial lesions (HSIL), the precursor lesions for cervical cancer. This study estimated and compared the performance of cytology and hybrid capture II in screening for precursor lesions of cervical cancer among HIV-infected women. The study population consisted of women from the open prospective cohort at the Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation (IPEC/Fiocruz). Colposcopy and histology were considered jointly in defining the gold standard. Cytology showed 31.8% sensitivity and 95.5% specificity, while hybrid capture II showed higher sensitivity (100%) and lower specificity (52%). The positive likelihood ratio was 7.1 for cytology and 2.1 for hybrid capture II, while the negative likelihood ratio was 0.7 for cytology and 0.0 for hybrid capture II

Time trend analysis of cervical high-risk human papillomavirus (HPV) in HIV-infected women in an urban cohort from Rio de Janeiro, Brazil: the rise of non-16/18 HPV

Submitted by Fábio Marques ([email protected]) on 2018-10-18T16:00:10Z No. of bitstreams: 1 Time trend analysis of cervical high-risk human_Beatriz_Grinsztejn_etal_INI_Lapclin-AIDS_2015.pdf: 284898 bytes, checksum: 851b34477496d8830755104ac0c14044 (MD5)Approved for entry into archive by Regina Costa ([email protected]) on 2018-10-18T19:24:56Z (GMT) No. of bitstreams: 1 Time trend analysis of cervical high-risk human_Beatriz_Grinsztejn_etal_INI_Lapclin-AIDS_2015.pdf: 284898 bytes, checksum: 851b34477496d8830755104ac0c14044 (MD5)Made available in DSpace on 2018-10-18T19:24:56Z (GMT). No. of bitstreams: 1 Time trend analysis of cervical high-risk human_Beatriz_Grinsztejn_etal_INI_Lapclin-AIDS_2015.pdf: 284898 bytes, checksum: 851b34477496d8830755104ac0c14044 (MD5) Previous issue date: 2015UCLA David Geffen School of Medicine. Department of Medicine. Division of Infectious Diseases. Program in Global Health. Los Angeles, CA, USA./ Montefiore University Hospital of Albert Einstein College of Medicine. Department of Internal Medicine. Bronx, New York, USA.Universidade de São Paulo. Instituto de Medicina Tropical. Laboratório de Virologia. São Paulo, SP, Brasil.UCLA David Geffen School of Medicine. Department of Medicine. Division of Infectious Diseases. Program in Global Health. Los Angeles, CA, USA./ Montefiore University Hospital of Albert Einstein College of Medicine. Department of Internal Medicine. Bronx, New York, USA.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.HIV-infected women are at increased risk of human papillomavirus (HPV) infection. Time trends in annual prevalences of cervical high-risk human papillomavirus (HR-HPV) genotypes among a non-vaccinated, HIV-infected female cohort in urban Brazil were assessed for the period 2006-2012

Lesões intra-epiteliais vulvares em pacientes infectadas pelo HIV Vulval intraepithelial lesions in HIV-infected patients

OBJETIVOS: avaliar a prevalência de lesões escamosas intra-epiteliais vulvares em pacientes infectadas pelo HIV atendidas em rede pública na cidade do Rio de Janeiro e estudar os fatores associados a essas lesões. MÉTODO: 374 pacientes infectadas pelo HIV e atendidas em serviços públicos na cidade do Rio de Janeiro foram submetidas a exame ginecológico, colheita de citologia e exame colposcópico do colo uterino e vulva. A associação do diagnóstico de HIV com lesão intra-epitelial da vulva foi analisada de acordo com de variáveis clínicas (idade e presença de lesões cervicais), laboratoriais (contagem de CD4) e comportamentais (número de parceiros e hábito de fumar). Consideraram-se como variáveis de estudo (independente) os dados epidemiológicos, o status imunológico e o resultado da propedêutica ginecológica. Assim foram selecionados: idade, hábito de fumar, número de parceiros, contagem de linfócitos T CD4 e lesão intra-epitelial cervical. Uma análise bivariada foi inicialmente efetuada, objetivando avaliar a associação entre a presença de lesões intra-epiteliais vulvares (variável de desfecho) e as variáveis independentes (idade, tabagismo, número de parceiros, citologia, colposcopia e contagem de CD4). Em seguida, os resultados de significância estatística (pPURPOSE: to evaluate the prevalence of vulval squamous intraepithelial lesions and associated factors in HIV-infected patients attended at the public health services of Rio de Janeiro city. METHOD: a total of 374 HIV-infected patients were attended at public services in Rio de Janeiro city and submitted to gynecological examination, Pap smear and colposcopic examination of the cervix and vulva. The association of vulval intraepithelial lesion was analyzed according to the results of clinical (age and cervical lesions), laboratorial (CD4 count) and behavioral (number of partners and smoking habit) variables. The study (independent) variables were the epidemiological data, the immunologic status and the results of gynecological propaedeutic. Thus, age, the smoking habit, number of sexual partners, count of T CD4 lymphocites, and cervical intraepithelial lesion were selected. In the beginning, a bivariate analysis was performed, aiming at assessing the association between the presence of vulval intraepithelial lesion (ultimate variable) and the independent variables (age, smoking habits, number of sexual partners, cytology, colposcopy and CD4 count). Thereafter, the results with statistical significance (p<0.05) were submitted to a multiple logistic regression, and the probability ratio with the respective 95% confidence interval was established. RESULTS: the prevalence of vulval intraepithelial lesions was 40%. In the multivariate analysis CD4 count below 500 cells/mm³ OR=2.69 [IC 95%: 1.61-4.52], abnormal colposcopy OR=1.64 [IC 95%: 1.01-2.67] and age under 26 OR=1.98 [IC 95%: 1.18-3.30] were significant. In the vulval and cervical simultaneous lesion subgroup, age under 26 OR=3.30 [IC 95%: 1.65-6.59] and CD4 count below 500 cells/mm³ OR=4.15 [IC 95%: 1.92-8.96], were significant on analysis. CONCLUSIONS: the prevalence of vulval squamous intraepithelial lesions in HIV-infected patients is high. Immunodeficiency, presence of cervical intraepithelial lesions and age under 26 were associated with the presence of vulval intraepithelial lesions