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      Role of HPV 16 variants among cervical carcinoma samples from Northeastern Brazil

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          Abstract

          Background

          Cervical cancer is the fourth most common type of cancer affecting women globally. In Brazil, it is the third most frequent type of cancer in women and HPV is present in approximately 90% of cases. Evidence suggests that variants of HPV 16 can interfere biologically and etiologically during the development of cervical cancer.

          Methods

          Cervix tumor fragments were collected, their DNA was extracted, and nested PCR was used to detect HPV. Positive samples were sequenced to determine the viral genotype. To characterize the HPV 16 strains, positive samples PCR was used to amplify the LCR and E6 regions of the HPV 16 virus.

          Results

          Data from 120 patients with cervical cancer were analyzed. Most women were between 41 and 54 years of age, had schooling until primary school, a family income between 1 and 2 times the minimum wage and were married/in a consensual union. There was no statistically significant association between HPV or socio-demographic variables and risk factors for cervical cancer ( P <  0.05). HPV was present in 88 women (73%). The most prevalent types were HPV 16 (53.4%), HPV 18 (13.8%), HPV 35 (6.9%) and HPV 45 (5.7%). Of the 47 HPV 16 positive cases, variant A (49%) was present in 23 samples, followed by variant D in 20 cases (43%), and variants B and C in 2 cases each (4%). The most prevalent histological type of HPV 16 tumors was squamous cell carcinoma, followed by adenocarcinoma. There was a statistically significant association between HPV 16 variants and the tumors’ histological types ( P <  0.001).

          Conclusions

          Knowledge of HPV 16 variants will provide data on their influence on the pathological and oncogenic aspects of cervical lesions.

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          Most cited references25

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          Human papillomavirus molecular biology and disease association

          Summary Human papillomaviruses (HPVs) have evolved over millions of years to propagate themselves in a range of different animal species including humans. Viruses that have co‐evolved slowly in this way typically cause chronic inapparent infections, with virion production in the absence of apparent disease. This is the case for many Beta and Gamma HPV types. The Alpha papillomavirus types have however evolved immunoevasion strategies that allow them to cause persistent visible papillomas. These viruses activate the cell cycle as the infected epithelial cell differentiates in order to create a replication competent environment that allows viral genome amplification and packaging into infectious particles. This is mediated by the viral E6, E7, and E5 proteins. High‐risk E6 and E7 proteins differ from their low‐risk counterparts however in being able to drive cell cycle entry in the upper epithelial layers and also to stimulate cell proliferation in the basal and parabasal layers. Deregulated expression of these cell cycle regulators underlies neoplasia and the eventual progression to cancer in individuals who cannot resolve high‐risk HPV infection. Most work to date has focused on the study of high‐risk HPV types such as HPV 16 and 18, which has led to an understanding of the molecular pathways subverted by these viruses. Such approaches will lead to the development of better strategies for disease treatment, including targeted antivirals and immunotherapeutics. Priorities are now focused toward understanding HPV neoplasias at sites other than the cervix (e.g. tonsils, other transformation zones) and toward understanding the mechanisms by which low‐risk HPV types can sometimes give rise to papillomatosis and under certain situations even cancers. Copyright © 2015 John Wiley & Sons, Ltd.
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            Human papillomavirus genome variants.

            Amongst the human papillomaviruses (HPVs), the genus Alphapapillomavirus contains HPV types that are uniquely pathogenic. They can be classified into species and types based on genetic distances between viral genomes. Current circulating infectious HPVs constitute a set of viral genomes that have evolved with the rapid expansion of the human population. Viral variants were initially identified through restriction enzyme polymorphisms and more recently through sequence determination of viral fragments. Using partial sequence information, the history of variants, and the association of HPV variants with disease will be discussed with the main focus on the recent utilization of full genome sequence information for variant analyses. The use of multiple sequence alignments of complete viral genomes and phylogenetic analyses have begun to define variant lineages and sublineages using empirically defined differences of 1.0-10.0% and 0.5-1.0%, respectively. These studies provide the basis to define the genetics of HPV pathogenesis. © 2013 Elsevier Inc. All rights reserved.
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              Molecular variants of human papillomavirus types 16 and 18 preferentially associated with cervical neoplasia.

              In order to determine geographically related intratypic variation in human papillomavirus (HPV) type 16 and 18 isolates that could be associated with lesion development, data were analysed from an ongoing cohort study of the natural course of infection of HPVs and cervical neoplasia. Testing for HPVs was carried out by PCR and molecular variants of these HPVs were characterized by sequence analysis of the long control region and by dot blot hybridization of the E6 and L1 genes. Tests for HPV were done in multiple first-year specimens from 1690 women enrolled in a cancer screening program from 1993 to 1997. Subjects were followed-up by cytology and cervicography for detection of cervical lesions. Seven variants of HPV-16 and four of HPV-18 were detected in one or more specimens from 65 subjects. The same variant was found in specimens taken on different visits from each case of persistent infection. Overall, non-European variants tended to persist more frequently [odds ratio (OR)=4.5; 95% confidence interval (CI), 1.6-12.4] than European (E) variants (OR=2.5; 95% CI, 1.3-4.9), relative to the risk of persistence for non-oncogenic HPVs. In addition, non-E variants were more strongly associated with risk of both prevalent (age- and race-adjusted OR=172.2; 95% CI, 47.1-630.1) and incident [relative risk (RR)=22.5; 95% CI, 6.0-83.9] high-grade lesions than E variants (prevalent lesions OR=46.3; 95% CI, 15.5-138.0 and incident lesons RR=6.1; 95% CI, 1.3-27.4), relative to the risk for HPV-negative women. Although consistent, the latter differences were not statistically significant. If confirmed in other populations, measurement of intratypic variation of HPV-16 and -18 has the potential to serve as an ancillary tool in cervical cancer screening.
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                Author and article information

                Contributors
                cnsd_ma@uol.com.br
                Journal
                BMC Womens Health
                BMC Womens Health
                BMC Women's Health
                BioMed Central (London )
                1472-6874
                1 August 2020
                1 August 2020
                2020
                : 20
                : 162
                Affiliations
                [1 ]GRID grid.411204.2, ISNI 0000 0001 2165 7632, Federal University of Maranhão (UFMA), ; São Luís, Maranhão Brazil
                [2 ]GRID grid.411204.2, ISNI 0000 0001 2165 7632, Faculty of Medicine, , Federal University of Maranhão (UFMA), ; São Luís, Maranhão Brazil
                [3 ]GRID grid.411087.b, ISNI 0000 0001 0723 2494, Faculty of Medical Sciences (FCM), , State University of Campinas (UNICAMP), ; Campinas, São Paulo Brazil
                [4 ]GRID grid.459974.2, ISNI 0000 0001 2176 7356, Center of Advanced Studies of Caxias (CESC), , State University of Maranhão (UEMA), ; Caxias, Maranhão Brazil
                [5 ]GRID grid.419166.d, Genetic Division, , National Institute of Cancer (INCA), ; Rio de Janeiro, Brazil
                Author information
                http://orcid.org/0000-0003-2783-362X
                Article
                1035
                10.1186/s12905-020-01035-0
                7395427
                32738888
                937bc159-f892-4895-b199-a01c18d6e9c5
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 19 January 2020
                : 26 July 2020
                Funding
                Funded by: Fundação de Amparo à Pesquisa e ao Desenvolvimento Científico e Tecnológico do Maranhão (BR)
                Award ID: 00668/15
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2020

                Obstetrics & Gynecology
                cervical cancer,human papillomavirus,hpv 16,variants
                Obstetrics & Gynecology
                cervical cancer, human papillomavirus, hpv 16, variants

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