José Veríssimo Fernandes

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.

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: Kaposis sarcoma (RR=0.30, 95% CI: 0.28-0.33) and non-Hodgkins 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.

Prevalence of HPV infection by cervical cytologic status in Brazil

To assess the prevalence of human papillomavirus (HPV) infection according to cervical cytologic status in northeastern Brazil; identify other risk factors for low‐ and high‐grade squamous intraepithelial lesions (LSILs and HSILs); and identify the most prevalent HPV genotypes associated with the lesions.

Prevalência de marcadores sorológicos do vírus da hepatite B em trabalhadores do serviço hospitalar

OBJETIVO: Determinar a prevalencia de marcadores sorologicos do virus da hepatite B (VHB) e identificar fatores de risco, de transmissao desse virus, no ambiente hospitalar. METODOS: Foram examinados 210 individuos de diversas profissoes que trabalham em hospital universitario. O metodo empregado foi o ELISA e utilizou-se, como grupo-controle, 45 doadores voluntarios de sangue. RESULTADOS: Constatou-se que 20,5% dos profissionais que trabalham no hospital apresentavam positividade para, pelo menos, um dos tres marcadores dos virus pesquisados, contra 6,6% do grupo-controle. Nos trabalhadores do hospital, a prevalencia de cada marcador isoladamente foi: anti-HBc 8,1%, anti-HBs 5,2% e AgHBs 2,9% , sendo que em 4,3% desses individuos foi detectada a presenca simultânea dos marcadores anti-HBc e anti-HBs. No grupo-controle, foi detectada apenas a presenca dos marcadores anti-HBc e anti-HBs, isoladamente, com prevalencias de 4,4 e 2,2%, respectivamente. Os maiores indices de positividade observados foram: pessoal de laboratorio, 24,0%; pessoal de enfermagem, 23,6%; medicos, 20,8%; e pessoal da limpeza, 18,2%. CONCLUSOES: Os achados indicam que os profissionais da saude estao mais expostos a infeccao pelo VHB, sugerindo que o contato com pacientes e a manipulacao de fluidos corporais sao fatores de risco de transmissao ocupacional desse virus, recomendando-se a vacinacao desses profissionais contra a hepatite B.OBJECTIVE To verify the prevalence of the anti-HBc, anti-HBs and HBsAg markers of hepatitis B virus, and to identify the risk factors determining occupational infection with this virus among hospital personnel. METHODS Samples of serum from 210 persons both male and female who work in different occupations at a hospital university, were analysed. The technique employed was the immunoenzymatic assay using commercial kits. RESULTS As a control group, samples of serum from 45 volunteer blood donors were utilized. It was verified that 20.5% of the hospital personnel presented a positive reaction to at least one of the markers songht, as against 6.6% of the control group. The prevalence of each marker separately was: anti-HBc 8.1%, anti-HBs 5.2%, and HBsAg 2.9% in the hospital personnel; and 4.4%, 2.2% and 0.0% in the control group. The simultaneous presence of the anti-HBc and anti-HBs markers was detected in 4.3% of the workers. In the control group, the presence of the anti-HBc and anti-HBs markers was detected, isolately, with respective prevalences of 4.4% and 2.2%. Those who presented the highest rates of positivite reaction were: laboratory technicians 24.0%, nurses 23.6%, physicians 20.8%, and cleaning personnel 18.2%. CONCLUSIONS The findings suggest that direct contact with patients and handling of blood and other body fluids are risk factors related to occupational infection with HBV. Therefore, it is recommended that hospital personnel be vaccinated against hepatitis B.

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.

Conhecimentos, atitudes e prática do exame de Papanicolaou por mulheres, Nordeste do Brasil

OBJECTIVE To assess the knowledge, attitudes and practices of women related to the Pap test and the association between these behaviors and sociodemographic characteristics. METHODS A household survey with quantitative approach was conducted. A total of 267 women aged 15 to 69 years, randomly selected in a stratified manner, living in the city of São José de Mipibu, Northeastern Brazil, were interviewed in 2007. A questionnaire consisting of pre-coded open questions was administered and answers were described and analyzed, as for adequacy of knowledge, attitudes, and practices of women regarding the Pap test. Tests of association were carried out between sociodemographic characteristics and behaviors studied at a 5% significance level. RESULTS Although 46.1% of the women interviewed showed adequate knowledge about the Pap test, a significantly higher proportion of adequacy was seen regarding attitudes and practices, 63.3% and 64.4%, respectively. Higher schooling was associated with adequacy of knowledge, attitudes, and practices. The main barriers to the Pap test were negligence, non-requesting by their physicians, and shame. CONCLUSIONS The physician is the main source of information about the Pap test. However, women who more often attend medical visits, despite their good practice, show low adequacy of knowledge and attitudes related to the Pap test, which indicates that they are not receiving appropriate information on the tests purpose, advantages and benefits to womens health.OBJETIVO: Analisar conhecimentos, atitudes e praticas das mulheres em relacao ao exame citologico de Papanicolaou e a associacao entre esses comportamentos e caracteristicas sociodemograficas METODOS: Inquerito domiciliar com abordagem quantitativa. Foram entrevistadas 267 mulheres com idade de 15 a 69 anos, selecionadas de forma estratificada aleatoria, residentes no municipio de Sao Jose do Mipibu, RN, em 2007. Utilizou-se questionario com perguntas pre-codificadas e abertas, cujas respostas foram descritas e analisadas quanto a adequacao dos conhecimentos, atitudes e pratica das mulheres em relacao ao exame preventivo de Papanicolaou. Foram realizados testes de associacao entre as caracteristicas sociodemograficas e os comportamentos estudados, com nivel de significância de 5%. RESULTADOS: Apesar de 46,1% das mulheres entrevistadas terem mostrado conhecimento adequado, proporcoes de adequacao significativamente maiores foram observadas em relacao as atitudes e pratica quanto ao exame: 63,3% e 64,4%, respectivamente. O maior grau de escolaridade apresentou associacao com adequacao dos conhecimentos, atitudes e pratica, enquanto as principais barreiras para a realizacao do exame relatadas foram descuido, falta de solicitacao do exame pelo medico e vergonha. CONCLUSOES: O medico e a principal fonte de informacao sobre o exame de Papanicolau. Entretanto, mulheres que vao a consultas com maior frequencia, embora apresentem pratica mais adequada do exame, possuem baixa adequacao de conhecimento e atitude frente ao procedimento, sugerindo que nao estejam recebendo as informacoes adequadas sobre o objetivo do exame, suas vantagens e beneficios para sua saude.OBJETIVO: Analizar conocimientos, actitudes y practicas de las mujeres con relacion al examen citologico de Papanicolaou y su asociacion entre comportamientos y caracteristicas sociodemograficas. METODOS: Pesquisa domiciliar con abordaje cuantitativo. Fueron entrevistadas 267 mujeres con edad de 15 a 69 anos, seleccionadas de forma estratificada aleatoria, residentes en el municipio de Sao Jose do Mipibu, Noreste de Brasil, en 2007. Se utilizo cuestionario con preguntas pre-codificadas y abiertas, cuyas respuestas fueron descritas y analizadas con relacion a la adecuacion de los conocimientos, actitudes y practica de las mujeres con relacion al examen preventivo de Papanicolaou. Fueron realizadas examenes de asociacion entre las caracteristicas sociodemograficas y los comportamientos estudiados, con nivel de significancia de 5%. RESULTADOS: A pesar de 46,1% de las mujeres entrevistadas haber mostrado conocimiento adecuado, proporciones de adecuacion significativamente mayores fueron observadas con relacion a las actitudes y practica con respecto al examen: 63,3% y 64,4%, respectivamente. El mayor grado de escolaridad presento asociacion con adecuacion de los conocimientos, actitudes y practica, con relacion a las principales barreras para la realizacion del examen relatadas fueron descuido, falta de solicitud del examen por el medico y verguenza. CONCLUSIONES: El medico es la principal fuente de informacion sobre el examen de Papanicolaou. Mientras tanto, mujeres que van a consultas con mayor frecuencia, a pesar de presentar practica mas adecuada del examen, poseen baja adecuacion del conocimiento y actitud frente al procedimiento, sugiriendo que no estan recibiendo las informaciones adecuadas sobre el objetivo del examen, sus ventajas y beneficios para su salud.

Herpes simplex virus type 1 is the main cause of genital herpes in women of Natal, Brazil

OBJECTIVES The purpose of this study was to assess the prevalence of HSV-1 and HSV-2 in sexually active women who participated in the cervical cancer screening program in Natal, Brazil. STUDY DESIGN The study included 261 sexually active women resident in the metropolitan area of Natal, Brazil and attending a public clinic for cervical screening. From each participant, a sample of exfoliated uterine cervical cells was collected, using a cytobrush which was conditioned in a tube containing a preserving solution (PBS+vancomycin+nystatin) and sent to a laboratory where it was processed for DNA extraction. The samples were analyzed for the presence of HSV-1 and HSV-2 DNA in separate reactions by PCRs using specific primers. RESULTS HSV-1 in genital infection is four times more prevalent than HSV-2 in the population analyzed. The highest prevalence rates for both viruses were found in women aged 31-39years. We did not observe any association between the presence of both virus serotypes and socio-demographic characteristics in the population studied, nor with some classical risk factors for sexually transmitted diseases. CONCLUSIONS HSV-1 was the major cause of genital infection by Herpes simplex virus in the women included in this study. No association was found between HSV infection and the socio-demographic characteristics or some classical risk factors for sexually transmitted diseases.

Biology and natural history of human papillomavirus infection

Human papillomavirus (HPV) is one of the most common causes of sexually trans- mitted diseases worldwide. It has been proposed that the great majority of women and men have been infected with HPV at least once during their lifetime. HPV infection is associated with a variety of clinical conditions, ranging from benign lesions to cervical cancer. In most cases, the infection is transient, where most of the individuals are healing, eliminating the virus without the presence of any clinical manifestation. Actually, more than 120 HPV types have been cataloged, of which approximately 40 can infect the mucosa of the anogenital tract and are collectively known as mucosal HPV, which are classified based on their oncogenic potential as either low- or high-risk HPV types. The low-risk HPV type causes benign hyperproliferative lesions or genital warts, with a very limited tendency for malignant progression, while the high-risk HPV type is strongly associated with premalignant and malignant cervical lesions. The HPV cycle initiates when the virus gains access to undifferentiated cells of the basement membrane of the squamous columnar junction epithelium of the ectocervix, after these regions are exposed to mechanical or chemical trauma. The basal cells in the transformation zone retain the ability to differentiate, a property required for virion production. Cervical infection with high-risk HPV typically lasts from 12 to 18 months and in most cases is cleared spontaneously. However, in some women the immune response is insufficient to eliminate the virus, resulting in a persistent, long-term infection that may progress to a malignant lesion. In this review, we discuss the biology and natural history of HPV infection and its association with cervical cancer.

Prevalence of human papillomavirus in archival samples obtained from patients with cervical pre-malignant and malignant lesions from Northeast Brazil.

BackgroundHuman Papillomavirus (HPV) is considered as a necessary, but not sufficient, cause of cervical cancer. In this study, we aimed to assess the prevalence of HPV in a series of pre-malignant and malignant cervical lesion cases, to identify the virus genotypes, and to assess their distribution pattern according to lesion type, age range, and other considered variables. The samples were submitted to histopathological revision examination and analysed by polymerase chain reaction (PCR) for the presence of HPV DNA, followed by HPV typing by dot blot hybridisation.FindingsOf the analysed samples, 53.7% showed pre-malignant cervical lesions, and 46.3% presented with cervical cancer. Most cancer samples (84.1%) were classified as invasive carcinoma. The mean age of these cancer patients was 47.3 years. The overall HPV prevalence was 82.4% in patients with pre-malignant lesions and 92.0% in the cancer patients. HPV 16 was the most prevalent type, followed by HPV 18 and 58, including both single and double infections. Double infection was detected in 11.6% of the samples, and the most common combination was HPV 16+18.ConclusionsCervical cancer appears to occur in women in a lower age range in the studied area, compared to the situation in other Brazilian regions. Furthermore, among the patients with CIN 3 and those with cancer, we observed a higher proportion of married women, women with more than one sexual partner, smokers, and individuals with less than an elementary education, relative to their counterparts.FindingsThe overall HPV prevalence was 82.4% in patients with pre-malignant lesions and 92.0% in the cervical cancer patients from Northeast Brazil. HPV 16 was the most prevalent type, followed by HPV 18 and 58. The most common double infection was HPV 16+18. Cervical cancer appears to occur in women in a lower age range in the Northeast Brazil. Among the patients with CIN 3 and those with cancer, we observed a higher proportion of married women, women with more than one sexual partner, smokers, and individuals with less than an elementary education, relative to their counterparts.

Human papillomavirus infection in women attended at a cervical cancer screening service in Natal, Brazil

We analyzed cervical specimens of 202 women, aged 15 to 64 years, attended at Luis Antonio Hospital, Natal, Brazil, to determine the prevalence of HPV and identify the more frequent genotypes and risk factors for HPV infection in women attended at a cervical cancer screening service. Two specimens were collected from each patient: one for cytological examination and the other to detect HPV DNA by PCR, and typing by dot blot hybridization. A total of 54.5% of the sample had normal cytology and 45.5% had cytological alterations. HPV was detected in 24.5% of the cytologically normal women and in 59.8% of those with altered cytology. Both single and double HPV infection increased the likelihood of cytological alterations. Thirteen types of HPV were identified, most of which were high risk. HPV 16 was the most prevalent single-type infection, followed by HPV 58. The most frequent double infection was the association between HPV 56 and 57. The prevalence of HPV in cytologically normal women was greater than that reported for countries on all the continents except Africa. The inverse was observed in women with cytological alterations. The distribution of HPV types was similar to that described for the Americas, with some differences. Multiple sexual partners was the only risk factor showing an association with the presence of HPV infection.