ABSTRACT
As a middle-income country, Brazil has one of the largest public health systems worldwide, which deals with free and universal access to health care. Regarding cervical cancer, the country possesses a large infrastructure for the screening of premalignant and malignant lesions, but yet based on old technology, having Papanicolaou as the major screening method, followed by colposcopy and treatment. Also, large disparities in access are present, which makes effectiveness of screening and treatment in different regions of the country highly unequal. In this review, we describe and evaluate the current screening, treatment and prophylactic (HPV vaccination) strategies to combat cervical cancer in Brazil, and discuss potential incorporation of more recent technologies in these areas in the country to pave its way toward cervical cancer elimination.
ABSTRACT
INTRODUCTION: The use of e-cigarettes has been the subject of a public health debate on their possibility of undermining efforts for tobacco control. The aim of this study was to synthesize the risk of smoking relapse with the use of e-cigarettes by former smokers. METHODS: MEDLINE, EMBASE, PsycInfo and LILACS were searched without restriction to language or date of publication. Longitudinal observational studies evaluating the association between e-cigarette use and smoking relapse were selected by two independent reviewers, and disagreements solved by discussion with a third researcher. Data extraction and risk of bias assessment were also carried out by two independent reviewers. The meta-analysis was performed using the random effect Mantel-Haenszel model. RESULTS: From 632 retrieved records, six studies were eligible and described, while three were included in the quantitative synthesis. The studies were conducted in the USA, UK and France, with final sample size varying from 374 to 4094 former smokers. Risk of relapse was 2.03 (95% CI: 1.39-2.96) among former smoker users than non-users of e-cigarettes, and 1.38 (95% CI: 1.11-1.65) when pooling the adjusted association measures. Long-term former smokers were the main contributors for the higher relapse risk, while the impact of frequency of exposure to e-cigarettes (past, non-daily, daily) was uncertain. CONCLUSIONS: Considering the growing popularity of e-cigarettes among former smokers, our results point to the great potential for an increase in the frequency of relapse to conventional smoking and vaping for those who move to regular use of e-cigarettes.
ABSTRACT
HPV73 is classified as possibly oncogenic. It is neither routinely evaluated in HPV screening, nor covered by any of the prophylactic vaccines. We sought to investigate the carcinogenic characteristics of HPV73. Molecular studies were performed on eight cervix cancer biopsy specimens containing HPV73 from a cross-sectional cancer cohort of 590 women referred to the National Cancer Institute in Rio de Janeiro, Brazil. Transcriptional activity of HPV73 was evaluated by detection of spliced transcripts of E6/E6* and E1^E4 in cDNA created from RNA isolated from fresh tissue. Disruption of viral E1 and E2 genes in the tumor DNA was assessed by overlapping PCR amplification. Evaluation of viral integration was performed using a customized capture panel and next-generation sequencing, and an in-house bioinformatic pipeline. HPV73 E6/E6* transcripts were found in 7/7 specimens with available RNA, and three also had HPV73 E1^E4 transcripts. Disruption of E1 and E2 genes was observed in 4/8 specimens. Integration of HPV73 sequences into the cancer cell genomes was identified in all cervix cancer tissues. These results provide evidence that HPV73 is an oncogenic virus that can cause invasive cervix cancer. With current molecular screening and HPV vaccination, not all cervix cancers will be prevented.
Subject(s)
Papillomavirus Infections/complications , Uterine Cervical Neoplasms/etiology , Uterine Cervical Neoplasms/virology , Adult , Aged , Brazil , Cross-Sectional Studies , DNA, Neoplasm/genetics , Female , Humans , Middle Aged , Oncogene Proteins, Viral/genetics , Papillomaviridae/genetics , Polymerase Chain Reaction/methods , RNA, Viral/genetics , Virus Integration/geneticsABSTRACT
Scarce data are available on the expression of papillomavirus genome and the frequency of alternatively spliced E6E7 mRNAs in invasive cervical cancer. We carried out a comprehensive characterization of HPV expression by RNA-Seq analysis in 22 invasive cervical cancer with HPV16 or HPV18, characterizing the presence of integrated/episomal viral DNA, the integration sites in human genome and the proportion of alternative splicing products of E6 and E7 genes. The expression patterns suggested the presence of episomal and/or integrated viral DNA, with integration detected in most tumors, frequently occurring within human genes in HPV18+ and in intergenic regions in HPV16+ tumors. Alternative splicing of E6E7 transcripts showed E6*I as the most frequent isoform for both viral types, followed by E6*II and E6/E7 (unspliced) transcripts in HPV16+, and by E6/E7 in HPV18+ tumors. Previously described E6*VI and E6*V transcript isoforms for HPV16, and E6*X for HPV18, were rare or not detected.
Subject(s)
DNA-Binding Proteins , Gene Expression Regulation, Neoplastic , Gene Expression Regulation, Viral , Human papillomavirus 16 , Human papillomavirus 18 , Oncogene Proteins, Viral , Papillomavirus E7 Proteins , RNA-Seq , Repressor Proteins , Uterine Cervical Neoplasms , Virus Integration , Alternative Splicing , DNA-Binding Proteins/biosynthesis , DNA-Binding Proteins/genetics , Female , Human papillomavirus 16/genetics , Human papillomavirus 16/metabolism , Human papillomavirus 18/genetics , Human papillomavirus 18/metabolism , Humans , Oncogene Proteins, Viral/biosynthesis , Oncogene Proteins, Viral/genetics , Papillomavirus E7 Proteins/biosynthesis , Papillomavirus E7 Proteins/genetics , Repressor Proteins/biosynthesis , Repressor Proteins/genetics , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/virologyABSTRACT
To evaluate the impact of HPV immunization and possible changes in virus type-specific prevalence associated with cervical cancer, it is important to obtain baseline information based on socioeconomic, educational, and environmental characteristics in human populations. We describe these characteristics and the type-specific HPV distribution in 1,183 women diagnosed with cervical cancer in two Brazilian healthcare institutions located at the Southeastern (Rio de Janeiro/RJ) and the Amazonian (Belém/PA) regions. Large differences were observed between women in these regions regarding economic, educational, and reproductive characteristics. The eight most frequent HPV types found in tumor samples were the following: 16, 18, 31, 33, 35, 45, 52, and 58. Some HPV types classified as unknown or low risk were found in tumor samples with single infections, HPV 83 in RJ and HPV 11, 61, and 69 in PA. The proportion of squamous cervical cancer was lower in RJ than in PA (76.3% versus 87.3%, p < 0.001). Adenocarcinoma was more frequent in RJ than in PA (13.5% versus 6.9%, p < 0.001). The frequency of HPV 16 in PA was higher in younger women (p < 0.05). The success of a cervical cancer control program should consider HPV types, local health system organization, and sociodemographic diversity of Brazilian regions.
