RESUMO
The persistence of the human papillomavirus type 16 (HPV16) infection on the cervical epithelium contributes to the progression of cervical cancer. Studies have demonstrated that HPV16 genetic variants may be associated with different risks of developing cervical cancer. However, the E5 oncoprotein of HPV16, which is related to several cellular mechanisms in the initial phases of the infection and thus contributes to carcinogenesis, is still little studied. Here we investigate the HPV16 E5 oncogene variants to assess the effects of different mutations on the biological function of the E5 protein. We detected and analyzed the HPV16 E5 oncogene polymorphisms and their phylogenetic relationships. After that, we proposed a tertiary structure analysis of the protein variants, preferential codon usage, and functional activity of the HPV16 E5 protein. Intra-type variants were grouped in the lineages A and D using in silico analysis. The mutations in E5 were located in the T-cell epitopes region. We therefore analyzed the interference of the HPV16 E5 protein in the NF-kB pathway. Our results showed that the variants HPV16E5_49PE and HPV16E5_85PE did not increase the potential of the pathway activation capacity. This study provides additional knowledge about the mechanisms of dispersion of the HPV16 E5 variants, providing evidence that these variants may be relevant to the modulation of the NF-κB signaling pathway.
RESUMO
Breast cancer risk factors include lifestyle, genetic-hormonal influences, and viral infections. Human papillomavirus (HPV), known primarily as the etiological agent of cervical cancer, also appears active in breast carcinogenesis, as evidenced in our study of 56 patients from northeastern Brazil. We assessed the clinical and sociodemographic characteristics, correlating them with various breast cancer tumor types. HPV detection involved amplifying the L1 region, with viral load measured using the E2/E6 ratio and viral activity indicated by E5 oncogene expression. Predominantly, patients over 56 years of age with healthy lifestyles showed a high incidence of invasive ductal carcinoma and triple-negative breast cancer. HPV was detected in 35.7% of cases, mostly HPV16, which is associated with high viral loads (80 copies per cell) and significant E5 expression. These results hint at a possible link between HPV and breast carcinogenesis, necessitating further studies to explore this association and the underlying viral mechanisms.
Assuntos
Neoplasias da Mama , Infecções por Papillomavirus , Humanos , Brasil/epidemiologia , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Neoplasias da Mama/virologia , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Adulto , Idoso , Papillomaviridae , Carga ViralRESUMO
PURPOSE: Evaluate the presence of human papillomavirus (HPV) in biopsies of Brazilian patients with lung cancer and also the expression of the E6 and E7 oncoproteins. HPV is widely known as an important condition for cervical cancer although evidence today shows it is associated with several other types of cancer and may also be involved in lung cancer development. However, there are some divergences regarding the presence and activity of HPV in lung carcinogenesis. METHODS: The detection of HPV was performed by PCR, followed by genotype and immunohistochemical evaluation of E6 and E7 HPV type specific, from 63 patients. RESULTS: HPV was found to be present in 33 of the 63 samples, and types 16 and 18 were detected with frequencies of 81% (27/33) and 19% (6/33), respectively. About the presence of the virus in different histological types of tumors, HPV was detected in squamous cell carcinoma (39.39%), followed by adenocarcinoma (33.33%) and small cell carcinoma (18.18%) and large cell carcinoma (9.1%). The presence of the E6 (antibody anti-HPV 16 and anti-HPV 18) and E7 (antibody anti-HPV 16 and anti-HPV 18) oncoproteins was detected by immunohistochemical stain technique in 28/33 samples and 25/33 samples, respectively. CONCLUSIONS: Our results suggest that the lung tumor patients have high prevalence of HPV and the virus is not only present but also active in tumor cells. Therefore, the HPV is probably playing a role in lung carcinogenesis.
Assuntos
Neoplasias Pulmonares/etiologia , Papillomaviridae , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/metabolismo , Papillomaviridae/classificação , Papillomaviridae/genética , Proteínas E7 de Papillomavirus/genética , Proteínas E7 de Papillomavirus/metabolismo , Adulto JovemRESUMO
This study showed the prevalence of human papillomavirus (HPV) variants as well as nucleotide changes within L1 gene and LCR of the HPV16, HPV31, and HPV58 found in cervical lesions of women from North-East Brazil.