Prevalence of Human Papillomavirus types in women attending at University hospital in southern Brazil

Study design: cross-sectional. Objective: To determine the HPV prevalence and genotypes in women treated at University Hospital in southern Brazil. Methodology: Cervical cells samples from 200 women were collected. HPV was detected by nested polymerase chain reaction and genotypes were determined by sequencing. Variables were analyzed by the Fisher Exact Test and Chi-squared test of Pearson (X²) with a significance level of ≤ 5%. The strength of association was calculated by the prevalence ratio, with their confidence intervals at 95%. Multivariate analysis was calculated by Binary Logistic Regression for variables with P <0.20 Results: HPV DNA was detected in 55 women (27.5%). HPV prevalence was associate with income (P =0.01), early initiation of sexual life (P <0.001), pregnant (P = 0. 002), HIV- 1 infection (P = 0. 001) and koilocytosis presence in cytological test (P =0.006). Were found an association between serological status for HIV-1 and the genotypes HPV–33 (P =0.001) and HPV–68 (P <0.001). Multivariate analysis showed that HPV prevalence was associated with patients who had early initiation of sexual life (P =0.001), was infected by HIV–1 (P = 0.01), was pregnant (P = 0.02), and women with koilocytosis in cytological test (P =0.01). Genotypes were 90.4% higher-risk oncogenic (18 HPV–18, 14 HPV–16, four HPV–53, three HPV–31, two HPV–58, two HPV–59, two HPV–68, one HPV–33 and one HPV–52) and 9.6% low-risk (two HPV–11, two HPV–16 and one HPV–70). Conclusions: This study had the HPV prevalence similar to prevalence described in this region. The high-risk HPV genotypes were the most prevalent, being HPV–18 the main viral type found.Modelo do estudo: Transversal. Objetivo do estudo: Determinar a prevalência e os genótipos do HPV em mulheres atendidas em um Hospital Universitário no Sul do Brasil. Metodologia: Foram coletadas amostras de secreções cérvico-vaginal de 200 mulheres. O HPV foi detectado pela Reação em Cadeia da Polimerase aninhada e os genótipos por sequenciamento. As variáveis foram analisadas pelo Teste Exato de Fisher e pelo Chi-quadrado de Pearson com o nível de significância < 5%. A força de associação foi calculada pela razão de prevalência e os seus intervalos de confiança a 95%. A análise Multivariada foi calculada pela Regressão Logística Binária para as variáveis com P <0,20. Resultados: O DNA do HPV foi detectado em 55 mulheres (27,5%). A prevalência do HPV foi associada a baixa renda (P =0,01), o início sexual precoce (P <0,001), a gestação (P = 0, 002), a infecção pelo HIV–1 (P = 0, 001) e a coilocitose no exame citopatológico (P =0,006). Houve associação entre o status sorológico para o HIV–1 e os genótipos HPV–33 (P =0,001) e HPV–68 (P <0,001). Na análise multivariada, a prevalência do HPV foi associada ao início sexual precoce (P =0,001), a infecção pelo HIV–1 (P =0,01), a gestação (P =0,02) e a coilocitose no citopatológico (P =0,01). Sobre os genótipos, 90,4% eram de alto risco oncogênico (18 HPV–18, 14 HPV–16, quatro HPV–53, três HPV–31, dois HPV–58, dois HPV–59, dois HPV–68, um HPV–33 e um HPV–52) e 9,6% de baixo risco (dois HPV–11, dois HPV–16 e um HPV– 70). Conclusões: Esse estudo teve a prevalência do HPV semelhante à prevalência descrita para esta região. Os genótipos do HPV de alto risco foram os mais prevalentes, sendo o HPV–18 o principal tipo viral encontrad

Human Papillomavirus E6 Triggers Upregulation of the Antiviral and Cancer Genomic DNA Deaminase APOBEC3B

ABSTRACT Several recent studies have converged upon the innate immune DNA cytosine deaminase APOBEC3B (A3B) as a significant source of genomic uracil lesions and mutagenesis in multiple human cancers, including those of the breast, head/neck, cervix, bladder, lung, ovary, and other tissues. A3B is upregulated in these tumor types relative to normal tissues, but the mechanism is unclear. Because A3B also has antiviral activity in multiple systems and is a member of the broader innate immune response, we tested the hypothesis that human papillomavirus (HPV) infection causes A3B upregulation. We found that A3B mRNA expression and enzymatic activity were upregulated following transfection of a high-risk HPV genome and that this effect was abrogated by inactivation of E6. Transduction experiments showed that the E6 oncoprotein alone was sufficient to cause A3B upregulation, and a panel of high-risk E6 proteins triggered higher A3B levels than did a panel of low-risk or noncancer E6 proteins. Knockdown experiments in HPV-positive cell lines showed that endogenous E6 is required for A3B upregulation. Analyses of publicly available head/neck cancer data further support this relationship, as A3B levels are higher in HPV-positive cancers than in HPV-negative cancers. Taken together with the established role for high-risk E6 in functional inactivation of TP53 and published positive correlations in breast cancer between A3B upregulation and genetic inactivation of TP53, our studies suggest a model in which high-risk HPV E6, possibly through functional inactivation of TP53, causes derepression of A3B gene transcription. This would lead to a mutator phenotype that explains the observed cytosine mutation biases in HPV-positive head/neck and cervical cancers

Characterisation of complete high- and low-risk human papillomavirus genomes isolated from cervical specimens in southern Brazil

The classification of human papillomavirus (HPV) intratypic lineages by complete genome sequencing is a determinant in understanding biological differences in association with this disease. In this work, we have characterised complete HPV genomes from southern Brazil. Fifteen cervicovaginal Pap smear negative samples previously categorised as HPV-positive were sequenced using ultradeep sequencing, and 18 complete genomes from 13 different HPV types were assembled. Phylogenetic and genetic distance analyses were performed to classify the HPV genomes into lineages and sublineages. This is the first report describing the distribution of HPV intratype lineages of high and low oncogenic risk in asymptomatic women from southern Brazil

Effect of combined polymorphims in chemokines and chemokine receptors on the clinical course of HIV-1 infection in a brazilian population

Polymorphisms in genes that encode chemokines or their receptors can modulate susceptibility to human immunodeficiency virus (HIV) infection and disease progression. The objective of this study was to assess the frequency of polymorphisms CCR5-Δ32, CCR2-64I, CCR5-59029A and SDF1-3’A and their role in the course of HIV infection in a southern Brazilian population. Clinical data were obtained from 249 patients for an average period of 6.4 years and genotypes were determined by standard polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism. Survival analyses were conducted for three outcomes: CD4+ T-cell counts below 200 cells/ μl, acquired immune deficiency syndrome (AIDS) or death. The frequency of the polymorphisms CCR5-Δ32, CCR2- 64I, CCR5-59029A and SDF1-3’A were 0.024, 0.113, 0.487 and 0.207, respectively. CCR5-Δ32 was associated with a reduction in the risk for CD4+ T-cell depletion and with an increased risk for death after AIDS diagnosis. CCR2-64I was associated with a reduction in the risk for developing AIDS. SDF1-3’A was also associated with decreased risk for AIDS, but its effect was only evident when CCR2-64I was present as well. These results highlight the possibility of using these markers as indicators for the prognosis of disease progression and provide evidence for the importance of analysing the effects of gene polymorphisms in a combined fashion