Contribution of HLA-G and FOXP3 genes and proteins in the severity of cervical intraepithelial neoplasia during HPV infection.

Human Papillomavirus (HPV) persistence leads to the chronification of cervical inflammation, where HLA-G and Foxp3; immunomodulatory molecules, may contribute to the aggravation of the lesion and cancerization. Here, we evaluated the synergic effect of these two molecules in the worsening of the lesion in presence of HPV infection. Hundred and eighty (180) women cervical cells and biopsies were collected for (i) HLAG Sanger sequencing and gene expression, and (ii) HLA-G and Foxp3 molecule expressions by immunohistochemistry. 53 women were HPV+ against 127 women HPV-. HPV+ women were more at risk of having cytological changes (p ≤ 0.0123), histological changes (p < 0.0011), and cervical lesion (p = 0.0004). The HLA-G + 3142CC genotype predisposed women to infection (p = 0.0190), while HLA-G + 3142C and +3035 T alleles were associated with HLA-G5 transcript expression. Both sHLA-G (p = 0.030) and Foxp3 (p = 0.0002) proteins were higher in cervical lesion as well as in high-grade lesion. In addition, sHLA-G+ cells were positively correlated to Foxp3+ cells in presence of HPV infection and in cervical grade II/III injuries. In conclusion, HPV may use HLA-G and Foxp3 as a way of host immune escape contributing to the persistence of infection and inflammation, leading to the cervical lesion and the worsening of lesions.

Hierarchical evaluation of histology and p16-labeling can improve the risk assessment on cervical intraepithelial neoplasia progression.

OBJECTIVE: High-grade cervical lesions (HSIL) are associated with the presence of high-risk HPV types, tissue expression of p16, and increased chance of malignant progression, requiring surgical intervention. To improve risk evaluation, we assessed the discriminatory power of the histological findings associated with p16 immunohistochemistry (IHC) staining to classify the low-grade cervical lesion (LSIL) and HSIL. METHODS: We collected cervical biopsies from colposcopy-visible lesions and non-affected tissue (adjacent to the lesions) of 62 Brazilian women and labeled them with anti-p16 antibodies. In addition to the observational pattern and labeling to define the latent classes (affected vs. non-affected), a computational tool was used for semi-quantitative analysis of p16 expression. The intensity of staining of the nucleus or cytoplasm was captured using the Gimp 2.10 software. ROC curves were used to determine cutoff values for p16 expression in patients classified as LSIL and HSIL by latent class statistics for each labeling stratum. RESULTS: p16 nuclear labeling showed the best sensitivity and specificity to discriminate LSIL with low p16 expression (62%) and HSIL with high p16 expression (37%). Many patients whose lesions had intermediate levels of p16 nuclear staining were subsequently stratified according to the expression of p16 in the cytoplasm, indicating that five of 21 LSIL were at risk of progression, and 13 of 41 HSIL at risk of regression. CONCLUSIONS: We suggest a hierarchical analysis, with histology at the first level, followed by a labeling analysis in the nucleus and then in the cytoplasm to increase the accuracy of the HPV cervical lesion stratification.

The antigen processing-associated transporter gene polymorphism: Role on gene and protein expression in HPV-infected pre-cancerous cervical lesion.

Human papillomavirus (HPV) is the major pathogen for cervical lesions. The evasion mechanism of the immune response and persistence of HPV infection can be influenced by polymorphisms (SNPs) in genes associated with transporter associated with antigen processing (TAP), which may change the peptide binding affinity or the TAP expression impacting the efficiency of peptide transport in the secretory pathway, and the presentation of peptides to cytotoxic T lymphocytes. This study aimed to evaluate the role of the TAP1 and TAP2 polymorphisms, TAP1, and TAP2 genes expressions, and protein levels in cervical cells presenting different degrees of pre-cancerous lesions in 296 immunocompetent women infected or not by HPV. TAP SNPs were genotyped by Sanger sequencing, and gene expression by real-time PCR. Aneuploidy was determined by DNA index using flow cytometry. TAP-1 and TAP-2 tissue expressions were evaluated by immunohistochemistry. The Asp697Gly SNP of TAP1 presented a risk for cellular aneuploidy (P=0.0244). HPV+ women had higher TAP-2 mRNA (P=0.0212) and protein (P<0.0001) levels. The TAP2D and TAP2E haplotypes were associated with the risk for aneuploidy and pre-cancerous lesions. In conclusion, nucleotide variability at the peptide binding region of peptide transporter genes, particularly of the TAP2 gene, may influence the HPV-peptide transportation from the cytosol to the endoplasmic reticulum, increasing the susceptibility to the development of high-grade cervical lesions.

Increased PD-1 Level in Severe Cervical Injury Is Associated With the Rare Programmed Cell Death 1 (PDCD1) rs36084323 A Allele in a Dominant Model.

The high-risk oncogenic human papillomavirus (HPV) has developed mechanisms for evasion of the immune system, favoring the persistence of the infection. The chronic inflammation further contributes to the progression of tissue injury to cervical cancer. The programmed cell death protein (PD-1) after contacting with its ligands (PD-L1 and PD-L2) exerts an inhibitory effect on the cellular immune response, maintaining the balance between activation, tolerance, and immune cell-dependent lesion. We evaluated 295 patients exhibiting or not HPV infection, stratified according to the location (injured and adjacent non-injured areas) and severity of the lesion (benign, pre-malignant lesions). Additionally, we investigated the role of the promoter region PDCD1 -606G>A polymorphism (rs36084323) on the studied variables. PD-1 and PDCD1 expression were evaluated by immunohistochemistry and qPCR, respectively, and the PDCD1 polymorphism was evaluated by nucleotide sequencing. Irrespective of the severity of the lesion, PD-1 levels were increased compared to adjacent uninjured areas. Additionally, in cervical intraepithelial neoplasia (CIN) I, the presence of HPV was associated with increased (P = 0.0649), whereas in CIN III was associated with decreased (P = 0.0148) PD-1 levels, compared to the uninjured area in absence of HPV infection. The PDCD1 -606A allele was rare in our population (8.7%) and was not associated with the risk for development of HPV infection, cytological and histological features, and aneuploidy. In contrast, irrespective of the severity of the lesion, patients exhibiting the mutant PDCD1 -606A allele at single or double doses exhibited increased protein and gene expression when compared to the PDCD1 -606GG wild type genotype. Besides, the presence of HPV was associated with the decrease in PDCD1 expression and PD-1 levels in carriers of the -606 A allele presenting severe lesions, suggesting that other mediators induced during the HPV infection progression may play an additional role. This study showed that increased PD-1 levels are influenced by the -606G>A nucleotide variation, particularly in low-grade lesions, in which the A allele favors increased PDCD1 expression, contributing to HPV immune system evasion, and in the high-grade lesion, by decreasing tissue PD-1 levels.

Variation sites at the HLA-G 3' untranslated region confer differential susceptibility to HIV/HPV co-infection and aneuploidy in cervical cell.

Post-transcriptional regulatory elements associated with transcript degradation or transcript instability have been described at the 3' untranslated region (3'UTR) of the HLA-G gene. Considering that HPV infection and aneuploidy, which causes gene instability, are associated with cervical cell malignancy, as well as the fact that HIV infection and HLA-G may modulate the immune response, the present study aimed to compare the frequencies of HLA-G 3'UTR polymorphic sites (14-base pair insertion/deletion, +3142C/G, and +3187A/G) between 226 HIV+ women co-infected (n = 82) or not with HPV (n = 144) and 138 healthy women. We also evaluated the relationship between those HLA-G 3'UTR variants and aneuploidy in cervical cells. HPV types and HLA-G polymorphisms were determined by PCR and sequencing of cervical samples DNA. Aneuploidy in cervical cell was measured by flow cytometry. The HLA-G 3'UTR 14-bp ins/del was not associated with either HIV nor HIV/HPV co-infection. The +3142G allele (p = 0.049) and +3142GG genotype (p = 0.047) were overrepresented in all HIV-infected women. On the other hand, the +3187G allele (p = 0.028) and the +3187GG genotype (p = 0.026) predominated among healthy women. The +3142G (p = 0.023) and +3187A (p = 0.003) alleles were associated with predisposition to HIV infection, irrespective of the presence or not of HIV/HPV co-infection. The diplotype formed by the combination of the +3142CX (CC or CG) and +3187AA genotype conferred the highest risk for aneuploidy in cervical cell induced by HPV. The HLA-G 3'UTR +3142 and +3187 variants conferred distinct susceptibility to HIV infection and aneuploidy.

Prevalence of human papillomavirus infection, distribution of viral types and risk factors in cervical samples from human immunodeficiency virus-positive women attending three human immunodeficiency virus-acquired immune deficiency syndrome reference centres in northeastern Brazil.

Human immunodeficiency virus (HIV)-positive patients have a greater prevalence of coinfection with human papillomavirus (HPV) is of high oncogenic risk. Indeed, the presence of the virus favours intraepithelial squamous cell lesion progression and may induce cancer. The aim of this study was to evaluate the prevalence of HPV infection, distribution of HPV types and risk factors among HIV-positive patients. Cervical samples from 450 HIV-positive patients were analysed with regard to oncotic cytology, colposcopy and HPV presence and type by means of polymerase chain reaction and sequencing. The results were analysed by comparing demographic data and data relating to HPV and HIV infection. The prevalence of HPV was 47.5%. Among the HPV-positive samples, 59% included viral types of high oncogenic risk. Multivariate analysis showed an association between HPV infection and the presence of cytological alterations (p = 0.003), age greater than or equal to 35 years (p = 0.002), number of partners greater than three (p = 0.002), CD4⁺ lymphocyte count < 200/mm³ (p = 0.041) and alcohol abuse (p = 0.004). Although high-risk HPV was present in the majority of the lesions studied, the low frequency of HPV 16 (3.3%), low occurrence of cervical lesions and preserved immunological state in most of the HIV-positive patients were factors that may explain the low occurrence of precancerous cervical lesions in this population.

Prevalence of human papillomavirus infection, distribution of viral types and risk factors in cervical samples from human immunodeficiency virus-positive women attending three human immunodeficiency virus-acquired immune deficiency syndrome reference centres in northeastern Brazil

Human immunodeficiency virus (HIV)-positive patients have a greater prevalence of coinfection with human papillomavirus (HPV) is of high oncogenic risk. Indeed, the presence of the virus favours intraepithelial squamous cell lesion progression and may induce cancer. The aim of this study was to evaluate the prevalence of HPV infection, distribution of HPV types and risk factors among HIV-positive patients. Cervical samples from 450 HIV-positive patients were analysed with regard to oncotic cytology, colposcopy and HPV presence and type by means of polymerase chain reaction and sequencing. The results were analysed by comparing demographic data and data relating to HPV and HIV infection. The prevalence of HPV was 47.5%. Among the HPV-positive samples, 59% included viral types of high oncogenic risk. Multivariate analysis showed an association between HPV infection and the presence of cytological alterations (p = 0.003), age greater than or equal to 35 years (p = 0.002), number of partners greater than three (p = 0.002), CD4+ lymphocyte count < 200/mm3 (p = 0.041) and alcohol abuse (p = 0.004). Although high-risk HPV was present in the majority of the lesions studied, the low frequency of HPV 16 (3.3%), low occurrence of cervical lesions and preserved immunological state in most of the HIV-positive patients were factors that may explain the low occurrence of precancerous cervical lesions in this population.

Prognostic evaluation of DNA index in HIV-HPV co-infected women cervical samples attending in reference centers for HIV-AIDS in Recife.

INTRODUCTION: Persistence of cervical infection caused by human papillomavirus (HPV) types with high oncogenic risk may lead to cervical intraepithelial neoplasia (CIN). The aim of the present study was to evaluate whether, in HIV-positive women, the presence of aneuploidy in cervical cell samples is associated with presence and evolution of CIN. METHODS: The present study had two stages. In the first stage, comprising a cross-sectional study, the association between the presence of aneuploidy seen via flow cytometry and sociodemographic characteristics, habits and characteristics relating to HPV and HIV infection was analyzed. In the second stage, comprising a cohort study, it was investigated whether aneuploidy was predictive of CIN evolution. RESULTS: No association was observed between the presence of aneuploidy and HPV infection, or between its presence and alterations seen in oncotic cytological analysis. On the other hand, aneuploidy was associated with the presence of CIN (p = 0.030) in histological analysis and with nonuse of antiretroviral therapy (p = 0.001). Most of the HIV-positive women (234/272) presented normal CD4+ T lymphocyte counts (greater than 350 cells/mm3) and showed a greater aneuploidy regression rate (77.5%) than a progression rate (23.9%) over a follow-up of up to two years. CONCLUSION: Although there was an association between the presence of cervical tissue lesions and the DNA index, the latter was not predictive of progression of the cervical lesion. This suggests that progression of the cervical lesion to cancer in HIV-positive women may also be changed through improvement of the immunological state enabled by using antiretroviral therapy.

Misoprostol sublingual versus vaginal para indução do parto a termo / Sublingual versus vaginal misoprostol for labor induction of term pregnancies

OBJETIVO: comparar efetividade e segurança de uso de comprimido sublingual de 25 æg de misoprostol com o comprimido vaginal de 25 æg do misoprostol na indução do parto com idade gestacional e > 37 semanas e colo uterino desfavorável. MÉTODOS: realizou-se ensaio clínico controlado e aleatorizado, não cego, na Maternidade Monteiro de Morais (CISAM-UPE), em Recife, no período de outubro de 2003 a fevereiro de 2004. Participaram do estudo 123 gestantes com idade gestacional e > 37 semanas, índice de Bishop <8 e fora de trabalho de parto, que apresentavam indicação para interrupção da gravidez. As gestantes aleatoriamente receberam 25 æg de misoprostol sublingual ou 25 æg de misoprostol vaginal a cada seis horas, até uma dose máxima de oito comprimidos (200 µg). Para verificar diferenças entre os grupos foram utilizados média, desvio padrão, teste t de Student, c² para tendência e teste de Mann-Whitney. O valor de significação estatística adotado foi de 5 por cento. RESULTADOS: não houve diferença significativa entre o número de mulheres que tiveram parto por via vaginal no grupo do misoprostol sublingual e no vaginal (65,5 por cento vs 75,8 por cento, p=0,22). Também não foi significativa a diferença do intervalo de tempo entre o início da indução e o parto (24 horas e 42 minutos vs 20 horas e 37 minutos, respectivamente, p=0,11) entre os grupos. Os grupos, sublingual e vaginal, não mostraram também diferenças significativas em relação à síndrome de hiperestimulação (1,7 por cento vs 3,2 por cento, p=0,95), às incidências de mecônio (5,2 por cento vs 4,8 por cento, p=0,74), ao índice de Apgar <7 no quinto minuto (3,4 por cento vs 4,8 por cento, p=0,98) e a outros efeitos adversos. CONCLUSAO: o misoprostol na dose de 25 mg por via sublingual apresentou a mesma efetividade e segurança quando comparado com a mesma dose vaginal para indução do parto. O misoprostol por via sublingual parece representar mais uma opção a ser considerada na indução do parto

Gêmeos acolados: relato de caso / Conjoined twins: a case report

Trata-se de um caso de gêmeos acolados que teve lugar na Maternidade da Encruzilhada, Recife, em 1( de agosto de 1994. O diagnóstico de gêmeos acolados nao foi feito antes do parto, porém o diagnóstico de gravidez gemelar foi formulado através da ultra-sonografia. A operaçao cesariana resultou em gêmeos acolados cujo peso foi 3.340 gramas. Ambos pereceram cinco dias após o nascimento.

Disjunçäo de sínfise púbica: relato de 2 casos / Pelvic symphysis separation: review of two cases

Faz-se um relato breve da literatura com ênfase na incidência e a seguir, dois casos são descritos com abordagem da sintomatologia clínica e do diagnóstico firmado através da mesma e ratificado pela radiografia da pelve. Um dos casos associou-se a infecçäo que foi debelada de maneira adequada. O tratamento da disjunção foi empreendido e com resultados plenamente satisfatórios

Gravidez abdominal com feto vivo de 36 semanas / Abdominal pregnancy with live fetus of 36 weeks

The diagnosis of abdominal pregnancy with live fetus whose weight was 2O5Og at birth was made using sonography and clinic methods. The surgery took place without problems and the placenta was removed completely. The female newborn had abnormalities in the limbs and head. She died with hyaline membrane twelve hours later. There were no complícatíons in the postoperative and the patient left the hospital 5 days after surgery.

Mola Hidatiforme parcial e polidrâmnios / Partial hydatiform mole and polyhydramnios

A 22 years old, gravida 3, para 2 woman was admitted to the hospital with preterm labor which was a 23rd week pregnancy. The diagnosis of partial hydatiform mole and polydramnios was made after delivery and confirmed by histologic findings. The post-operative did not present any aspect worth registering. The patient was discharged two days after delivery in excellent conditions.

Ferimento penetrante do abdômen com lesäo do útero grávido / Penetrating abdominal wound with injury of pregnant uterus

This study is about a case of penetrating wound of the gravid uterus and large intestine in pregnancy of 32 weeks. It was performed laparotomy and suture of gravid uterus and colostomy. After eight weeks it took place normal delivery and it was delivered a female newborn in excellent conditions. The discharge was conceded 48 hours after delivery and bowel definitive sugery was performed thirty days later

Gemelidade Imperfeita: estudo de caso / Conjoined twinning: study of one case

The following describes a case of imperfect twinning consisting of twins joined by the thorax and by the head. the diagnosis was confirmed only after cesarean section was performed. Both newborns died during the first hous after delivery and weighed, jointly, 2500 grams

Corpo estranho na bexiga de paciente em trabalho de parto / Foreign body in the bladder in patient at labor

This paper is about a case of foreign body which was introduced in the bladder through the urethra when the patient was scratching herself with a hairpin. She was pregnant and the pregnancy was at term. The diagnosis was performed with radiology and ultrasonography and the hairpin was brought out through the laparoscope

Mola embrionada associada à pré-eclâmpsia grave e polidrâmnio / Mole with embryo combined to severe preeclampsia and polyhydramnios

O quadro típico de pré-eclâmpsia grave, instalado antes da 20ª semana gestacional, implicou na investigaçäo de corioma, que foi evidenciado através da ultra-sonografia. Havia polidramnia associada e a interrupçäo da gravidez foi empreendida através da operaçäo cesariana, que resultou em feto vivo, feminino, de 400 gramas, que sucumbiu logo depois. Após a interrupçäo da gravidez o quadro clínico de toxemia regrediu e 15 dias após a HCG plasmática tornou-se negativa

Miose estromal indolinfática: relato de um caso / Endolymphatic stromal myosis: a case report

Um caso de sarcoma endometrial de baixo grau de malignidade é relatado e a literatura relativa é revista. Os autores enfatizam a raridade da patologia e os poucos relatos na literatura mundial, e alertam para o fato de ser o diagnóstico histopatológico acurado para evitar terapêutica agressiva, uma vez que a patologia se comporta como benigna, com recorrência mínima. As pacientes deveräo ficar sob observaçäo rigorosa