Th17 response in patients with cervical cancer.

Persistent infection by high-risk human papillomavirus (HR-HPV) is the main risk factor for uterine cervical cancer (UCC). However, viral infection alone is not sufficient for the development and progression of premalignant cervical lesions for cancer. In previous years it has been suggested that the adaptive immune response triggered by the differentiation of naïve helper T cells in Th17 cells may serve an important role in disease development. It has been hypothesized that Th17 cells may be involved in the promotion of UCC, as high levels of interleukin 17 (IL17) expression have been detected in the mucosa of the uterine cervix of patients affected by the disease. However, the role of Th17 cells in the tumor development and progression remains unclear. It is believed that the immune response of the Th17 type during persistent infection of the genital tract with HR-HPV triggers chronic inflammation with a long duration with the production of IL17 and other pro-inflammatory cytokines, creating a favorable environment for tumor development. These cytokines are produced by immune system cells in addition to tumor cells and appear to function by modulating the host immune system, resulting in an immunosuppressive response as opposed to inducing an effective protective immune response, thus contributing to the growth and progression of the tumor. In the present review, the latest advances are presented about the function of Th17 cells and the cytokines produced by them in the development and progression of UCC.

Immune Response to Human Papillomavirus One Year after Prophylactic Vaccination with AS04-Adjuvanted HPV-16/18 Vaccine: HPV-Specific IgG and IgA Antibodies in the Circulation and the Cervix

Objective: This study was designed to describe the course of IgG/IgA responses in cervical secretions and in serum one year after the first dose of intramuscular administration of the HPV16/18 AS04-adjuvant vaccine. Methods: Blood and cervical mucus samples were collected for immunologic assays, 7 months after the first doses and 1 year following the last boost vaccination (month 7) by enzyme linked immunosorbent assay (ELISA). The detection of IgG and IgA anti-HPV/VLP was developed for this purpose. Result: A total of 100% of serum samples were IgG antibody positive at a titer of 1:100 at both time periods and decreased according to the serum dilution. For serum IgA antibody, 95% were positive one month after vaccination and 79% were positive 1 year later. Similar results were observed with the cervical samples positive for both IgG and IgA antibodies at one month and decreasing after 1 year to 33% and 29%. The median absorbance in serum and the cervix for IgG and IgA anti-HPV-VLP antibodies was significantly higher at one month after vaccination when compared to 1 year post-vaccination (P<0.0001). Conclusion: Immune responses were significant one year after immunization, however it decreased in cervical and serum samples when compared to levels observed one month after the last dose. This suggests that a vaccine booster may be necessary to increase antibody titers.

Correlação entre vaginose bacteriana e desfechos obstétricos desfavoráveis em mulheres brasileiras / Correlation between bacterial vaginosis and adverse obstetric outcomes in Brazilian women

Infecções vaginais e mudanças na flora vaginal são prevalentes durante a gravidez e têm sido associadas com desfechos obstétricos adversos, tais como trabalho de parto prematuro, amniorrexe prematura e baixo peso ao nascer. Objetivos: Correlacionar a presença de vaginose bacteriana (VB) com desfecho obstétrico desfavorável em mulheres brasileiras com gravidez no terceiro trimestre. Métodos: O estudo prospectivo observacional foi conduzido avaliando microbiota vaginal por bacterioscopia (a fresco e Gram) usando swab vaginal obtido de mulheres grávidas entre a 26 e a 32a semanas de gestação. As mulheres foram monitoradas até o parto, e os dados de seu seguimento e os demográficos foram coletados por meio de um questionário autoaplicável. Resultados: Foi diagnosticada VB, com base nos critérios de Amsel e de Nugent, em 77 mulheres entre as 190, demonstrando prevalência de 42.5%. VB foi significativamente associada com maior risco de parto prematuro (risk ratio [RR], 2.89; 95% intervalo de confiança [IC], 2.35­3.56) e de baixo peso ao nascer (RR, 2.17; 95%IC, 1.61­2.92). A rotura prematura das membranas não foi associada com VB. Conclusão: Foi constatada alta frequência de VB entre as mulheres brasileiras grávidas no terceiro trimestre, e a BV correlacionou-se com piores prognósticos da gravidez. O rastreio rotineiro de mulheres grávidas pode permitir um tratamento precoce e a prevenção de algumas complicações obstétricas

Vaginal infections and modifications in the vaginal flora are very prevalent during pregnancy and have been associated with adverse obstetric outcomes, such as preterm labor, preterm premature rupture of membranes and low birth weight. Objective: To evaluate the prevalence and associations of bacterial vaginosis (BV) and pregnancy outcomes among Brazilian pregnant women in the third trimester. Methods: A prospective observational study was conducted assessing vaginal microbiota on bacterioscopy (wet mount and Gram stain), using vaginal swabs obtained from pregnant women between 26 and 32 weeks' gestation. The women were monitored until delivery, and their pregnancy outcome and demographic data were collected using an interviewer-administered questionnaire. Results: BV was assessed using both Amsel's criteria and Nugent's score in 77 of 190 women, resulting in the prevalence of 42.5%. BV was significantly associated with preterm labor (risk ratio [RR], 2.89; 95% confidence interval [CI], 2.35­3.56) and low birth weight (RR, 2.17; 95%CI, 1.61­2.92). Premature rupture of membranes was not associated with BV. Conclusion: BV was found to be very frequent among Brazilian pregnant women in the third trimester and correlated to unfortunate pregnancy outcomes. Regular screening of pregnant women may allow for early treatment and prevention of some obstetric complications.

Safety of Human Papillomavirus 9-Valent Vaccine: A Meta-Analysis of Randomized Trials.

Vaccination against human papillomavirus (HPV) has been progressively implemented in most developed countries for approximately 10 years. In order to increase the protection of the vaccines, a 9-valent vaccine (HPV9) was developed, which provides protection against nine types of the virus. Studies evaluating its safety are rare. Thus, we performed a meta-analysis of three clinical trials assessing adverse effects on women randomly vaccinated with HPV9 or tetravalent vaccine (HPV4), with the objective of analyzing whether the HPV9 is as safe as HPV4. An electronic data search was performed through the PubMed, Embase, Scopus, Web of Science, and SciELO databases. The studies selected 27,465 women who received one of the two vaccines. Pain (OR 1.72; 95% CI 1.62-1.82) and erythema (OR 1.29; 95% CI 1.21-1.36) occurred significantly more in the HPV9 group. However, there was no significant difference between the groups for the following adverse effects: headache (OR 1.07; 95% CI 0.99-1.15), dizziness (OR 1.09; 95% CI 0.93-1.27), and fatigue (OR 1.09; 95% CI 0.91-1.30), and the occurrence of serious events related to vaccination was similarly rare among those vaccinated. Therefore, our findings demonstrate that HPV9 in female patients is as safe as the tetravalent vaccine.

Macrophage Migration Inhibitory Factor (MIF): Biological Activities and Relation with Cancer.

Macrophage migration inhibitory factor (MIF) emerged in recent years as an important inflammation mediator, playing a prominent role in the pathogenesis of various types of malignant neoplasm. MIF is a glycoprotein that presents a wide spectrum of biological activities and exerts a complex interaction with various cellular signaling pathways, causing imbalance of homeostasis. Experimental and clinical studies show that high levels of MIF are found in almost all types of human cancers and are implicated in seemingly all stages of development of the tumors. The production of MIF is triggered through an autocrine signal emitted by tumor cells, and stimulates the production of cytokines, chemokines, and growth as well as angiogenic factors that lead to growth of the tumor, increasing its aggressiveness and metastatic potential. MIF is produced by virtually all types of human body cells, in response to stress caused by different factors, leading to pathological conditions such as chronic inflammation and immunomodulation with suppression of immune surveillance and of immune response against tumors, angiogenesis, and carcinogenesis. In this review, we present recent advances on the biological activity of MIF, the signaling pathways with which it is involved and their role in tumorigenesis.

The role of the mediators of inflammation in cancer development.

Epigenetic disorders such as point mutations in cellular tumor suppressor genes, DNA methylation and post-translational modifications are needed to transformation of normal cells into cancer cells. These events result in alterations in critical pathways responsible for maintaining the normal cellular homeostasis, triggering to an inflammatory response which can lead the development of cancer. The inflammatory response is a universal defense mechanism activated in response to an injury tissue, of any nature, that involves both innate and adaptive immune responses, through the collective action of a variety of soluble mediators. Many inflammatory signaling pathways are activated in several types of cancer, linking chronic inflammation to tumorigenesis process. Thus, Inflammatory responses play decisive roles at different stages of tumor development, including initiation, promotion, growth, invasion, and metastasis, affecting also the immune surveillance. Immune cells that infiltrate tumors engage in an extensive and dynamic crosstalk with cancer cells, and some of the molecular events that mediate this dialog have been revealed. A range of inflammation mediators, including cytokines, chemokines, free radicals, prostaglandins, growth and transcription factors, microRNAs, and enzymes as, cyclooxygenase and matrix metalloproteinase, collectively acts to create a favorable microenvironment for the development of tumors. In this review are presented the main mediators of the inflammatory response and discussed the likely mechanisms through which, they interact with each other to create a condition favorable to development of cancer.

Link between chronic inflammation and human papillomavirus-induced carcinogenesis (Review).

Inflammation is a defense strategy against invading agents and harmful molecules that is activated immediately following a stimulus, and involves the release of cytokines and chemokines, which activate the innate immune response. These mediators act together to increase blood flow and vascular permeability, facilitating recruitment of effector cells to the site of injury. Following resolution of the injury and removal of the stimulus, inflammation is disabled, but if the stimulus persists, inflammation becomes chronic and is strongly associated with cancer. This is likely to be due to the fact that the inflammation leads to a wound that does not heal, requiring a constant renewal of cells, which increases the risk of neoplastic transformation. Debris from phagocytosis, including the reactive species of oxygen and nitrogen that cause damage to DNA already damaged by the leukotrienes and prostaglandins, has an impact on inflammation and various carcinogenic routes. There is an association between chronic inflammation, persistent infection and cancer, where oncogenic action is mediated by autocrine and paracrine signals, causing changes in somatic cells under the influence of the microbial genome or of epigenetic factors. Among the infectious agents associated with cancer, certain genotypes of human papillomavirus (HPV) stand out. HPV is responsible for virtually all cases of cervical cancer and a lower proportion of cancers of the vagina, vulva, anus, penis and a number of extragenital cancers. In the present review, recent advances in the mechanisms involved in the inflammatory response are presented with their participation in the process of carcinogenesis, emphasizing the role of chronic inflammation in the development of HPV-induced cervical cancer.

Efeitos adversos em usuárias de implante contraceptivo / Adverse effects on contraceptive implant users

A gravidez indesejada continua a ser um grave problema de saúde pública em todo o mundo. Uma das explicações para a manutenção de altas taxas de gestações não planejadas relaciona-se com os efeitos adversos provocados por grande parte dos métodos contraceptivos disponíveis que levam as usuárias a descontinuar seu uso. Nos últimos anos, tem se visto um aumento nas opções de contracepção para garantir métodos mais eficazes, com maiores taxas de continuação e níveis elevados de satisfação da paciente. Entre os métodos contraceptivos de longa ação e com rápida reversibilidade, o implante é considerado um dos mais eficazes e mais seguros. Dentre os efeitos adversos relacionados com esse tipo de contracepção, estão incluídos: alterações no padrão do sangramento, cefaleia, aumento do peso, acne, mastalgia, labilidade emocional e dor abdominal. Portanto, no presente estudo, fez-se uma atualização sobre os possíveis efeitos colaterais desse contraceptivo, visando a um melhor aconselhamento pelos profissionais de saúde antes da inserção desse método, a fim de garantir melhor adesão a ele. Estudos demonstram que um aconselhamento claro antes de iniciar um método de longa duração como o implante subdérmico é imprescindível para melhorar a satisfação e a adesão ao método contraceptivo.

Unwanted pregnancy remains a serious public health problem worldwide. An explanation for keeping high rates of unplanned pregnancies is related to the adverse effects caused by most of the available contraceptive methods that lead users to discontinue its use. In recent years, it has been seen an increase in contraceptive options to ensure the most effective methods with higher continuation rates and high levels of patient satisfaction. Among the long-acting contraceptive methods with rapid reversibility, the implant is considered one of the most effective and safest ways. Among the adverse effects associated with the drug are included: changes in the pattern of bleeding, headache, weight gain, acne, breast pain, emotional lability and abdominal pain. Therefore, in our study it was made an update review on possible side effects of contraception, seeking a better counseling by health professionals before insertion in order to ensure better adherence to the method. Studies show that clear advice before starting long duration method as subdermal implant is essential to improve the satisfaction and adherence to contraception.

Genital tract infection with Chlamydia trachomatis in women attended at a cervical cancer screening program in Northeastern from Brazil.

PURPOSE: This cross-sectional study aimed to estimate the prevalence of Chlamydia trachomatis (CT) infection alone and in combination with human papillomavirus (HPV). Furthermore, the study investigates whether the CT infection increases the risk of contracting HPV and whether the presence of both pathogens is associated with a higher prevalence of cervical lesions. METHODS: Cervical samples of 1,134 asymptomatic women enrolled in a screening program for cervical cancer were analyzed. Two cervical specimens were collected from each patient, one for cytologic examination and the other for detection of CT by polymerase chain reaction (PCR), using a primer pair which amplifies a specific sequence of the DNA plasmid. RESULTS: The overall prevalence rate infection was 10.9%, being 10% in the women with normal cytology, 13.8% in those with atypical squamous cells of undetermined significance (ASC-US), and 25% with low-grade squamous intraepithelial lesion (LSIL). The infection by CT did not increase the risk of acquiring HPV infection. The higher prevalence of LSIL in women co-infected with HPV and CT is possibly due to HPV. CONCLUSION: CT infection was more prevalent in younger women aged up to 32 years, who had an early onset of reproductive activity and a history of having had multiple sexual partners lifelong may be at a greater risk of acquiring infection of the genital tract by C. trachomatis.

Assessing the impact of HAART on the incidence of defining and non-defining AIDS cancers among patients with HIV/AIDS: a systematic review.

After highly active antiretroviral therapy (HAART) became widespread, several studies demonstrated changes in the incidence of defining and non-defining AIDS cancers among HIV/AIDS patients. We conducted a systematic review of observational studies evaluating the incidence of malignancies before and after the introduction of HAART in people with HIV/AIDS. Eligible studies were searched up to December 2012 in the following databases: Pubmed, Embase, Scielo, Cancerlit and Google Scholar. In this study, we determined the cancer risk ratio by comparing the pre- and post-HAART eras. Twenty-one relevant articles were found, involving more than 600,000 people with HIV/AIDS and 10,891 new cases of cancers. The risk for the development of an AIDS-defining cancer decreased after the introduction of HAART: Kaposi's sarcoma (RR=0.30, 95% CI: 0.28-0.33) and non-Hodgkin's lymphoma (RR=0.52, 95% CI: 0.48-0.56), in contrast to invasive cervical cancer (RR=1.46, 95% CI: 1.09-1.94). Among the non-AIDS-defining cancers, the overall risk increased after the introduction of HAART (RR=2.00, 95% CI: 1.79-2.23). The incidence of AIDS-defining cancers decreased and the incidence of non-AIDS-defining cancers increased after the early use of HAART, probably due to better control of viral replication, increased immunity and increased survival provided by new drugs.

Genital infection with herpes simplex virus types 1 and 2 in women from natal, Brazil.

Objective. To evaluate the prevalence of HSV-1 and HSV-2 in pregnant and nonpregnant women, testing the correlation between DNA of the viruses with colposcopic and/or cytological changes, and evaluate association with sociodemographic characteristics and sexual activity. Methods. Included in this study were 106 pregnant and 130 nonpregnant women treated at primary health care units of Natal, Brazil, in the period 2010-2011. The patients were examined by colposcopy, and two cervical specimens were collected: one for cytology examination and another for analysis by PCR for detection of HSV-1 and HSV-2. Results. HSV-1 alone was detected in 16.0% of pregnant and 30.0% of nonpregnant women. For HSV-2, these rates were 12.3% and 15.5%, respectively. HSV-2 had a higher correlation with cytology and/or colposcopy changes than HSV-1 did. Genital HSV-1 infection was not associated with any of the variables tested, whereas HSV-2 infection was associated with ethnicity, marital status, and number of sexual partners. Conclusions. The prevalence of HSV-1 was higher than that observed for HSV-2 in both pregnant and nonpregnant women. The genital infection by HSV-2 was higher in women with changed colposcopy and/or cytology, and it was associated with ethnicity, marital status, and number of sexual partners.

O papel da inflamação na carcinogênese induzida pelo HPV / The role of inflammation in HPV carcinogenesis

A inflamação é uma estratégia de defesa inata que evoluiu nos organismos superiores, contra agentes invasores externos e moléculas nocivas. Estudos recentes mostram que a inflamação opera como um sistema muito mais complexo do que se imaginava antes, em termos moleculares, envolvendo diversos processos na sua iniciação, regulação e resolução. Na última década, tornou-se evidente que a inflamação crônica está fortemente associada com câncer, desempenhando um papel importante na tumorigênese. Uma das causas de inflamação crônica são as infecções persistentes por agentes patogênicos virais, com destaque para o papilomavírus humano (HPV). A ligação entre a inflamação crônica decorrente da infecção persistente por agentes infecciosos e o câncer está atualmente sendo apontada como um dos mecanismos-chave para o controle do surgimento de novos casos de carcinomas. Por esse motivo, consultamos os bancos de dados eletrônicos PubMed/Medline, Lilacs, Embase e SciELO, sem restrição linguística, à procura de artigos que abordassem avanços recentes sobre os mecanismos envolvidos na inflamação, sua participação no processo de carcinogênese, com ênfase na correlação entre inflamação e o desenvolvimento do câncer associado ao HPV, os quais foram incluídos na presente revisão.(AU)

Inflammation is an innate defense strategy that evolved in higher organisms against external invaders and harmful molecules. Recent studies show that inflammation operates as a much more complex system than imagined before, in molecular terms, involving many processes in its initiation, regulation and resolution. In the very last decade, it has become evident that chronic inflammation is strongly associated with cancer and plays an important role in tumorigenesis. One of the causes of chronic inflammation are persistent infections by viral pathogens, particularly human papillomavirus (HPV). The link between chronic inflammation resulting from persistent infection by infectious agents and cancer is currently being suggested as a key mechanism for controlling the appearance of new cases of carcinoma. Therefore, we consult electronic databases such as PubMed/Medline, Lilacs, Embase and SciELO, without language restriction, looking for papers discussing recent advances on the mechanisms involved in inflammation, their participation in the process of carcinogenesis, with emphasis on the correlation between inflammation and the development of cancer associated with HPV, which were included in this review.(AU)

Prevalência das complicações pós-operatórias decorrentes da mastectomia radical modificada com linfadenectomia axilar / Prevalence of postoperative complications resulting from the modified radical mastectomy with axillary lymphadenectomy

Objetivo: verificar as complicações mais prevalentes em pacientes submetidas à mastectomia radical modificada com linfadenectomia axilar no período pós-operatório imediato até o 30º dia pós-cirurgia. Método: estudo de corte transversal com 18 mulheres susbmetidas à mastectomia radical modificada com linfadenectomia axilar. As avaliações ocorrem do pós-operatório imediato até o 30º dia após a mastectomia. Os critérios de avaliação usados foram, principalmente, presença dos sintomas subjetivos de edema e dor, a amplitude de movimento (ADM) dos ombros direito e esquerdo e a presença de complicações transoperatórias e imediatas. Resultados: a idade das participantes da pesquisa variou de 38 a 81 anos (60,7±12,6). Com relação às complicações pós-mastectomia, observou-se que os achados mais frequentes foram os sintomas subjetivos de edema (50%), os sintomas relacionados a alterações de nervo intercostobraquial (44,4%) e a limitação na ADM do ombro (50%). Conclusões: faz-se necessário que as alterações identificadas sejam conhecidas por profissionais da saúde, pois, assim, buscar-se-á prevenir ou minimizar possíveis complicações físico-funcionais que venham a dificultar a recuperação das mulheres no pós-operatório de câncer de mama.

Avaliação da incidência do câncer ginecológico e das lesões precursoras em pacientes portadoras de HIV / Evaluation of the incidence of gynaecological cancer and precursor lesions in HIV patients

Esta revisão sistemática tem como objetivo demonstrar a incidência do câncer ginecológico e de suas lesões precursoras em mulheres que vivem com HIV/AIDS. Foi realizada ampla pesquisa nas bases de dados, MedLine-PubmMed, Scielo-Lilacs e Embase. Após a aplicação dos critérios de elegibilidade, foram incluídos 15 estudos que pesquisaram a incidência de lesões intraepiteliais vulvares, vaginais e cervicais, bem como de carcinomas de mama, endométrio, ovário, vulva, vagina e colo uterino. Observou-se que mulheres infectadas por HIV têm maior risco de apresentarem lesões de vulva, vagina e colo, assim como câncer desses sítios. Por outro lado, essas mulheres apresentam menor incidência de carcinomas mamários, endometriais e ovarianos do que a população feminina geral.(AU)

The aim of this systematic review is to demonstrate the incidence of gynaecological cancer and intraepithelial lesions among women living with HIV/AIDS. A broad research has been done in MedLine-PubMed, Scielo-Lilacs and Embase databases. Fifteen studies that described the incidence of vulvar, vaginal and cervical intraepithelial lesions, as well as breast, ovary, endometrial, vulva, vagina and uterine cervical cancer met the inclusion criteria. Women living with HIV have a greater risk to develop vulvar, vaginal and cervical intraepithelial lesions, as well as cancer in these sites. However, they present a lower incidence of breast, endometrial and ovarian cancer than the general female population.(AU)

O papel do rastreamento e tratamento sistemático das infecções vaginaisna prevenção do parto pré-termo / The role of screening and systematic treatment of vaginal infections to prevent preterm birth

Esta revisão sistemática tem como objetivo demonstrar o valor do rastreamento e do tratamento das infecções vaginais na gravidez para prevenir o parto pré-termo. Foi realizada ampla pesquisa nas bases de dados Google Scholar, Medline-PubMed, Scielo-Lilacs e Central Cochrane. Após aplicação dos critérios de elegibilidade, foram incluídos no texto final dez estudos que descreviam nos resultados o rastreamento, o tratamento das infecções e a sua relação com o parto pré-termo. Nesta revisão não foi possível recomendar rastreamento e tratamento para Streptococcus, vaginose bacteriana e infecção por clamídia. O rastreamento e o tratamento para candidíase reduzem significativamente a ocorrência do parto pré-termo. A conduta nos casos de tricomoníase vaginal é não tratá-la durante a gravidez, pois seu tratamento representa fator de risco para prematuridade

The aim of this systematic review is to demonstrate the role of screening and treatment of vaginal infections to avoid preterm delivery. A broad research has been done in Google Scholar, Medline-PubMed, Scielo-Lilacs and Central Cochrane databases. Ten studies that described the role of screening and treatment of vaginal infections to prevent preterm birth met the inclusion criteria. In this review it was not possible to recommend the screening and treatment programs for Streptococcus, Vaginosis and Chlamydia in pregnant women may reduce preterm birth. The screening and treatment for Candidiasis significantly reduce the preterm birth. It is not recommended to treat trichomonas vaginalis during pregnancy, since its treatment represents a risk factor for prematurity