RESUMO
Lung cancer is the most common cause of cancer deaths worldwide. Although tobacco smoking is considered to be the main risk factor and the most well-established risk factor for lung cancer, a number of patients who do not smoke have developed this disease. This number varies between 15 % to over one-half of lung cancer cases, and the deaths from lung cancer in non-smokers are increasing every year. There are many other agents that are thought to be etiological, including diesel exhaust exposure, metals, radiation, radon, hormonal factors, cooking oil, air pollution and infectious diseases, such as human papillomavirus (HPV). Studies in various parts of the world have detected HPV DNA at different rates in lung tumors. However, the role of HPV in lung cancer is still unclear. Thus, in this review, we investigated some molecular mechanisms of HPV protein activity in host cells, the entry of HPV into lung tissue and the possible route used by the virus to reach the lung cells.
Assuntos
Transformação Celular Viral , Neoplasias Pulmonares/virologia , Papillomaviridae/fisiologia , Transformação Celular Viral/genética , Humanos , Pulmão/patologia , Pulmão/virologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Infecções por Papillomavirus/complicações , Internalização do VírusRESUMO
The aim of this study was to examine the prevalence and genetic variability of the capsid L1 gene of rare HPV genotypes that were found in the cervical lesions of women from North-East Brazil. A total number of 263 patients were included in this study. HPV detection was performed using PCR followed by direct sequencing of MY09/11, as well as type-specific PCR to detect the Alpha-9 species. Epitope prediction was performed to determine whether or not the genetic variants are inserted in B-cell and T-cell epitopes. The prevalence of rare HPV types in cervical lesions was found to be 9.47%. The rare HPV genotypes that were detected were HPV-53, 54, 56, 61, 62, 66, 70, and 81. The genetic variability in the L1 gene of rare HPV types involved thirty nucleotide changes, eight of which were detected for the first time in this study. Moreover, some of these variants are embedded in B-cell or T-cell epitope regions. The results of this research suggest that rare HPV types might be involved in cervical lesions and some of these variants can be found in B-cell and T-cell epitopes. Data on the prevalence and variability of rare HPV types will assist in clarifying the role of these viruses in carcinogenesis.
Assuntos
Proteínas do Capsídeo/genética , Variação Genética , Papillomaviridae/genética , Neoplasias do Colo do Útero/virologia , Adolescente , Adulto , Idoso , Sequência de Aminoácidos , Aminoácidos/genética , Sequência de Bases , Brasil/epidemiologia , Proteínas do Capsídeo/química , Epitopos de Linfócito B/química , Epitopos de Linfócito T/química , Feminino , Humanos , Pessoa de Meia-Idade , Dados de Sequência Molecular , Prevalência , Adulto Jovem , Displasia do Colo do Útero/virologiaRESUMO
HPV-31 has been widely described as an important oncogenic type, showing high incidence in worldwide and especially in Northeastern Brazil. We sought to identify the presence of specific mutations in HPV-31 E6 and E7 oncogenes in women with abnormal cervical smear. We enrolled 150 gynecological patients from Sergipe State, Northeastern Brazil. HPV screening was carried out by polymerase chain reaction (MY09/11). E6 and E7 oncogenes were amplified with specific primers and sequenced. The sequences obtained were aligned with the GenBank reference sequences in order to search for genetic variants. We identified genetic variants in E6 and E7 sequences from HPV-31. Two new nucleotide changes in E6 and E7 were described for the first time in this study. A novel mutation in E6 resulted in amino acid change in a site belonging to T-cell epitope with MHC II binding activity. There was no significant difference in the distribution of HPV-31 E6 and E7 variants when compared to all selected clinical/epidemiological characteristics. HPV-31 isolates have been clustered into three main groups called lineages A, B and C. We describe new HPV-31 variants in Brazil, contributing to better understand the genomic diversity of these viruses.
Assuntos
Papillomavirus Humano 31/genética , Proteínas Oncogênicas Virais/genética , Proteínas E7 de Papillomavirus/genética , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/virologia , Adolescente , Adulto , Brasil/epidemiologia , Feminino , Variação Genética , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/epidemiologia , Filogenia , Neoplasias do Colo do Útero/epidemiologiaRESUMO
Cervical cancer is the second most common cancer in females worldwide. It is well-established that Human Papillomavirus (HPV) infections play a critical role in the development of cervical cancer. However, a large number of women infected with oncogenic HPV types will never develop cervical cancer. Thus, there are several external environment and genetic factors involved in the progression of a precancerous lesion to invasive cancer. In this review article, we addressed possible susceptible phenotypes to cervical cancer, focusing on host genome and HPV DNA variability, multiple HPV infections, co-infection with other agents, circulating HPV DNA and lifestyle.