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      Analysis of Sequence Variation and Risk Association of Human Papillomavirus 52 Variants Circulating in Korea

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          Abstract

          Introduction

          Human papillomavirus (HPV) 52 is a carcinogenic, high-risk genotype frequently detected in cervical cancer cases from East Asia, including Korea.

          Materials and Methods

          Sequences of HPV52 detected in 91 cervical samples collected from women attending Seoul St. Mary’s Hospital were analyzed. HPV52 genomic sequences were obtained by polymerase chain reaction (PCR)-based sequencing and analyzed using Seq-Scape software, and phylogenetic trees were constructed using MEGA6 software.

          Results

          Of the 91 cervical samples, 40 were normal, 22 were low-grade lesions, 21 were high-grade lesions and 7 were squamous cell carcinomas. Four HPV52 variant lineages (A, B, C and D) were identified. Lineage B was the most frequently detected lineage, followed by lineage C. By analyzing the two most frequently detected lineages (B and C), we found that distinct variations existed in each lineage. We also found that a lineage B-specific mutation K93R (A379G) was associated with an increased risk of cervical neoplasia.

          Conclusions

          To our knowledge, we are the first to reveal the predominance of the HPV52 lineages, B and C, in Korea. We also found these lineages harbored distinct genetic alterations that may affect oncogenicity. Our findings increase our understanding on the heterogeneity of HPV52 variants, and may be useful for the development of new diagnostic assays and therapeutic vaccines.

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          Most cited references24

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          Live or let die: the cell's response to p53.

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            Mechanisms of human papillomavirus-induced oncogenesis.

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              Epidemiology and natural history of human papillomavirus infections and type-specific implications in cervical neoplasia.

              Worldwide human papillomavirus (HPV) prevalence in women with normal cytology at any given point in time is approximately 10% indicating that HPV is one of the most common sexually transmitted infections. HPV-16 is consistently the most common type and HPV-18 the second with some minor regional differences. Furthermore, across the spectrum of cervical lesions, HPV-16 is consistently the most common HPV type contributing to 50-55% of invasive cervical cancer cases strongly suggesting that this viral type has a biological advantage for transmission, persistency and transformation. The same phenomenon is observed albeit at a lower level for HPV-18 and HPV-45. Sexual behavioral patterns across age groups and populations are central to the description of the HPV circulation and of the risk of infection. The concept of group sexual behavior (in addition to individual sexual behavior) is important in exploring HPV transmission and has implications for defining and monitoring HPV and cancer prevention strategies. In natural history studies, the pattern of HPV DNA prevalence by age groups is similar to the patterns of HPV incidence. Rates of exposure in young women are high and often include multiple types. There is a spontaneous and rapid decrease of the HPV DNA detection rates in the middle-age groups followed by a second rise in the post-menopausal years. This article reviews: 1) the evidence in relation to the burden of HPV infections in the world and the contributions of each HPV type to the spectrum of cervical cellular changes spanning from normal cytology to invasive cervical cancer; 2) the critical role of the patterns of sexual behavior in the populations; and 3) selected aspects of the technical and methodological complexity of natural history studies of HPV and cervical neoplasia.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                15 December 2016
                2016
                : 11
                : 12
                : e0168178
                Affiliations
                [1 ]Departments of Obstetrics and Gynecology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
                [2 ]Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Special Administrative Region, China
                Georgetown University, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: YJC PKC JSP.

                • Data curation: YJC CZ WCH.

                • Formal analysis: YJC.

                • Funding acquisition: JSP.

                • Investigation: YJC.

                • Methodology: CZ WCH.

                • Project administration: PKC JSP.

                • Resources: EYK JSP.

                • Software: CZ WCH.

                • Supervision: PKC JSP.

                • Validation: YJC CZ WCH.

                • Visualization: YJC CZ WCH.

                • Writing – original draft: YJC.

                • Writing – review & editing: YJC SJL MJJ PKC JSP.

                Author information
                http://orcid.org/0000-0003-4086-4885
                Article
                PONE-D-16-31501
                10.1371/journal.pone.0168178
                5158036
                27977741
                3d614827-9302-43ed-9378-a43f3c9dc617
                © 2016 Choi et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 6 August 2016
                : 25 November 2016
                Page count
                Figures: 1, Tables: 3, Pages: 10
                Funding
                The work was supported by Grants of National R&D Program for Cancer Control (0720510), Ministry of Health and Welfare, Republic of Korea and Statistical consultations were supported by a Korean Health Technology R&D Project grant from the Ministry of Health & Welfare, Republic of Korea (HI14C1731).
                Categories
                Research Article
                Biology and Life Sciences
                Molecular Biology
                Molecular Biology Techniques
                Artificial Gene Amplification and Extension
                Polymerase Chain Reaction
                Research and Analysis Methods
                Molecular Biology Techniques
                Artificial Gene Amplification and Extension
                Polymerase Chain Reaction
                Biology and Life Sciences
                Molecular Biology
                Molecular Biology Techniques
                Sequencing Techniques
                Nucleotide Sequencing
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                Molecular Biology Techniques
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                DNA viruses
                Papillomaviruses
                Human Papillomavirus
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                Phylogenetic Analysis
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                Phylogenetic Analysis
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Carcinomas
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                Oncology
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                Gynecological Tumors
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                Sequence Analysis
                Research and Analysis Methods
                Molecular Biology Techniques
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                Sequence Analysis
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