Human papillomavirus genome variants.

doi:10.1016/J.VIROL.2013.07.018

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Human papillomavirus genome variants.

Journal Article•DOI•

Human papillomavirus genome variants.

Robert D. Burk¹, Ariana Harari¹, Zigui Chen¹•Institutions (1)

Albert Einstein College of Medicine¹

01 Oct 2013-Virology (NIH Public Access)-Vol. 445, Iss: 1, pp 232-243

TL;DR: These studies provide the basis to define the genetics of HPV pathogenesis and 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.

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About: This article is published in Virology.The article was published on 2013-10-01 and is currently open access. It has received 346 citations till now. The article focuses on the topics: Genome & Population.

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Journal Article•DOI•

Genome-wide profiling of HPV integration in cervical cancer identifies clustered genomic hot spots and a potential microhomology-mediated integration mechanism

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Zheng Hu¹, Da Zhu¹, Wei Wang², Weiyang Li³, Wenlong Jia⁴, Xi Zeng⁵, Wencheng Ding¹, Lan Yu¹, Xiaoli Wang¹, Liming Wang¹, Hui Shen¹, Changlin Zhang¹, Hongjie Liu⁵, Xiao Liu⁵, Yi Zhao⁵, Xiaodong Fang⁵, Shuai Cheng Li⁴, Wei Chen⁵, Tang Tang, Aisi Fu, Zou Wang, Gang Chen¹, Qinglei Gao¹, Shuang Li¹, Ling Xi¹, Changyu Wang¹, Shujie Liao¹, Xiangyi Ma¹, Peng Wu¹, Kezhen Li¹, Shixuan Wang¹, Jianfeng Zhou¹, Wang Jun³, Xun Xu⁵, Hui Wang¹, Ding Ma¹ - Show less +32 more•Institutions (5)

Huazhong University of Science and Technology¹, Southern Medical University², South China University of Technology³, City University of Hong Kong⁴, Beijing Genomics Institute⁵

01 Feb 2015-Nature Genetics

TL;DR: Microhomologous sequence between the human and HPV genomes was significantly enriched near integration breakpoints, indicating that fusion between viral and human DNA may have occurred by microhomology-mediated DNA repair pathways.

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Abstract: Human papillomavirus (HPV) integration is a key genetic event in cervical carcinogenesis. By conducting whole-genome sequencing and high-throughput viral integration detection, we identified 3,667 HPV integration breakpoints in 26 cervical intraepithelial neoplasias, 104 cervical carcinomas and five cell lines. Beyond recalculating frequencies for the previously reported frequent integration sites POU5F1B (9.7%), FHIT (8.7%), KLF12 (7.8%), KLF5 (6.8%), LRP1B (5.8%) and LEPREL1 (4.9%), we discovered new hot spots HMGA2 (7.8%), DLG2 (4.9%) and SEMA3D (4.9%). Protein expression from FHIT and LRP1B was downregulated when HPV integrated in their introns. Protein expression from MYC and HMGA2 was elevated when HPV integrated into flanking regions. Moreover, microhomologous sequence between the human and HPV genomes was significantly enriched near integration breakpoints, indicating that fusion between viral and human DNA may have occurred by microhomology-mediated DNA repair pathways. Our data provide insights into HPV integration-driven cervical carcinogenesis.

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374 citations

Journal Article•DOI•

The natural history of human papillomavirus infection.

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Silvia de Sanjosé, Maria Brotons, Miguel Angel Pavón

06 Sep 2017-Best Practice & Research in Clinical Obstetrics & Gynaecology

TL;DR: Viral load and viral type are the main cofactors for progression from infection to cervical intraepithelial lesions and cancer and the adverse health effects of HPV infections can be largely controlled through vaccination and screening.

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Abstract: Human papillomavirus (HPV) is a small double-stranded DNA virus that commonly infects humans. The oncogenic characteristics of HPV derive from the oncoproteins E6 and E7 that act inhibiting p53 and pRB tumor suppressors. About 5% of all cancers worldwide are attributable mainly to those known as high-risk, including HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59. Infection with HPV is common after sexual initiation, but the majority of HPV infections do not cause symptoms or disease and are cleared within 12-24 months post-infection. Only a small fraction of those infections that persist or progress to a preneoplastic lesion result in cancer. Persistence of HPV infection is needed to start the oncogenic process. Clearance of infection is common in young adults. Viral load and viral type are the main cofactors for progression from infection to cervical intraepithelial lesions and cancer. Smoking, hormonal exposure, and HIV are additional exposures that increase the risk of progression to cancer. The adverse health effects of HPV infections can be largely controlled through vaccination and screening.

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253 citations

Cites background from "Human papillomavirus genome variant..."

...4 %) of the squamous cell carcinomas of the cervix [27,28]....
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...Papillomaviruses are classified into types based on L1 sequencing, defining a new type when its genome differs by at least 10% from that of all other classified types [27]....
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Journal Article•DOI•

HPV16 E7 Genetic Conservation Is Critical to Carcinogenesis

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Lisa Mirabello¹, Meredith Yeager¹, Kai Yu¹, Gary M. Clifford², Yanzi Xiao¹, Bin Zhu¹, Michael Cullen¹, Michael Cullen³, Joseph Boland¹, Joseph Boland³, Nicolas Wentzensen¹, Chase W. Nelson⁴, Tina Raine-Bennett⁵, Zigui Chen⁶, Sara Bass¹, Sara Bass³, Lei Song³, Lei Song¹, Qi Yang³, Qi Yang¹, Mia Steinberg¹, Mia Steinberg³, Laurie Burdett³, Laurie Burdett¹, Michael Dean¹, David Roberson³, David Roberson¹, Jason Mitchell¹, Jason Mitchell³, Thomas Lorey⁵, Silvia Franceschi², Philip E. Castle⁷, Joan L. Walker⁸, Rosemary E. Zuna⁸, Aimée R. Kreimer¹, Daniel C. Beachler¹, Allan Hildesheim¹, Paula Gonzalez, Carolina Porras, Robert D. Burk⁷, Mark Schiffman¹ - Show less +37 more•Institutions (8)

National Institutes of Health¹, International Agency for Research on Cancer², Leidos³, American Museum of Natural History⁴, Kaiser Permanente⁵, The Chinese University of Hong Kong⁶, Albert Einstein College of Medicine⁷, University of Oklahoma Health Sciences Center⁸

07 Sep 2017-Cell

TL;DR: Strict conservation of the 98 amino acids of E7, which disrupts Rb function, is critical for HPV16 carcinogenesis, presenting a highly specific target for etiologic and therapeutic research.

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201 citations

Cites background from "Human papillomavirus genome variant..."

...HPV types including HPV16 are comprised, in turn, of phylogenetic variant lineage and sublineage evolutionary clades that differ from each other by 1%–9% of the 8,000 bp HPV genome (Burk et al., 2013)....
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...It is already well established that although all the HR-HPV types are genetically related, they differ profoundly in prevalence, a measure of evolutionary fitness, and risk of causing precancer and cancer (Burk et al., 2013; Guan et al., 2012)....
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...HPV16 can be divided into four main variant lineages (A, B, C, D) and at least ten sublineages (A1, A2, A3, A4, B1, C1, D1, D2, D3, D4) (Burk et al., 2013)....
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Journal Article•DOI•

Human Papillomavirus Infection and Cervical Cancer: Epidemiology, Screening, and Vaccination—Review of Current Perspectives

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Chee Kai Chan¹, Gulzhanat Aimagambetova¹, Talshyn Ukybassova, Kuralay Kongrtay¹, Azliyati Azizan¹ - Show less +1 more•Institutions (1)

Nazarbayev University¹

10 Oct 2019-Journal of Oncology

TL;DR: In spite of the successful implementation of the HPV vaccination program in many countries all over the world, problems related to HPV prevention and treatment of the related diseases will continue to persist in developing and underdeveloped countries.

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Abstract: Viral infections contribute as a cause of 15–20% of all human cancers. Infection by oncogenic viruses can promote different stages of carcinogenesis. Among many types of HPV, around 15 are linked to cancer. In spite of effective screening methods, cervical cancer continues to be a major public health problem. There are wide differences in cervical cancer incidence and mortality by geographic region. In addition, the age-specific HPV prevalence varies widely across different populations and showed two peaks of HPV positivity in younger and older women. There have been many studies worldwide on the epidemiology of HPV infection and oncogenic properties due to different HPV genotypes. However, there are still many countries where the population-based prevalence has not yet been identified. Moreover, cervical cancer screening strategies are different between countries. Organized cervical screening programs are potentially more effective than opportunistic screening programs. Nevertheless, screening programs have consistently been associated with a reduction in cervical cancer incidence and mortality. Developed countries have achieved such reduced incidence and mortality from cervical cancer over the past 40 years. This is largely due to the implementation of organized cytological screening and vaccination programs. HPV vaccines are very effective at preventing infection and diseases related to the vaccine-specific genotypes in women with no evidence of past or current HPV infection. In spite of the successful implementation of the HPV vaccination program in many countries all over the world, problems related to HPV prevention and treatment of the related diseases will continue to persist in developing and underdeveloped countries.

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183 citations

Cites background from "Human papillomavirus genome variant..."

...Furthermore, alpha-PV can be classified into nine groups: alpha-5 (HPV23, 51, 69, and 82), alpha-6 (HPV30, 53, 56, and 66), alpha-7 (HPV18, 39, 45, 59, 68, 70, 85, and 97), and alpha-9 (HPV16, 31, 33, 35, 52, 58, and 67), which include mostly the oncogenic high-risk types [7]....
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...With the development of highly sensitive HPV DNA testing, studies have confirmed that most cervical cancer specimens have detectable HPV DNA, and greater than 90% contain DNA for HPV16, 18, 31, 33, 39, 45, 52, or 58 [7]....
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Journal Article•DOI•

The precision prevention and therapy of HPV-related cervical cancer: new concepts and clinical implications.

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Zheng Hu¹, Zheng Hu², Ding Ma²•Institutions (2)

Sun Yat-sen University¹, Huazhong University of Science and Technology²

14 Sep 2018-Cancer Medicine

TL;DR: The fundament here is to elucidate the carcinogenic pattern and applicable targets during HPV‐host interaction, and more urgently, how these concepts and technologies might lead to clinical precision medicine which could provide prediction, prevention, and early treatment for patients.

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Abstract: Cervical cancer is the third most common cancer in women worldwide, with concepts and knowledge about its prevention and treatment evolving rapidly. Human papillomavirus (HPV) has been identified as a major factor that leads to cervical cancer, although HPV infection alone cannot cause the disease. In fact, HPV-driven cancer is a small probability event because most infections are transient and could be cleared spontaneously by host immune system. With persistent HPV infection, decades are required for progression to cervical cancer. Therefore, this long time window provides golden opportunity for clinical intervention, and the fundament here is to elucidate the carcinogenic pattern and applicable targets during HPV-host interaction. In this review, we discuss the key factors that contribute to the persistence of HPV and cervical carcinogenesis, emerging new concepts and technologies for cancer interventions, and more urgently, how these concepts and technologies might lead to clinical precision medicine which could provide prediction, prevention, and early treatment for patients.

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167 citations

Cites background from "Human papillomavirus genome variant..."

...Human papillomaviruses are a big family with the systematic classification of five genera (α, β, γ, μ, and ν), 48 species, and 206 types [47]....
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...In the same way, HPV18 variants have been defined into three major lineages (A, B, and C) and additional sublineages (A1 to A5 and B1 to B3) with translation [A1 and A2 = AA (Asian Amerindian), A3 to A5 = E (European), and B/C = AFR (African)][47]....
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Journal Article•DOI•

Global cancer statistics

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Ahmedin Jemal¹, Freddie Bray², Jacques Ferlay², Elizabeth Ward¹, David Forman² - Show less +1 more•Institutions (2)

American Cancer Society¹, International Agency for Research on Cancer²

01 Jan 1999-CA: A Cancer Journal for Clinicians

TL;DR: A substantial proportion of the worldwide burden of cancer could be prevented through the application of existing cancer control knowledge and by implementing programs for tobacco control, vaccination, and early detection and treatment, as well as public health campaigns promoting physical activity and a healthier dietary intake.

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Abstract: The global burden of cancer continues to increase largely because of the aging and growth of the world population alongside an increasing adoption of cancer-causing behaviors, particularly smoking, in economically developing countries. Based on the GLOBOCAN 2008 estimates, about 12.7 million cancer cases and 7.6 million cancer deaths are estimated to have occurred in 2008; of these, 56% of the cases and 64% of the deaths occurred in the economically developing world. Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females, accounting for 23% of the total cancer cases and 14% of the cancer deaths. Lung cancer is the leading cancer site in males, comprising 17% of the total new cancer cases and 23% of the total cancer deaths. Breast cancer is now also the leading cause of cancer death among females in economically developing countries, a shift from the previous decade during which the most common cause of cancer death was cervical cancer. Further, the mortality burden for lung cancer among females in developing countries is as high as the burden for cervical cancer, with each accounting for 11% of the total female cancer deaths. Although overall cancer incidence rates in the developing world are half those seen in the developed world in both sexes, the overall cancer mortality rates are generally similar. Cancer survival tends to be poorer in developing countries, most likely because of a combination of a late stage at diagnosis and limited access to timely and standard treatment. A substantial proportion of the worldwide burden of cancer could be prevented through the application of existing cancer control knowledge and by implementing programs for tobacco control, vaccination (for liver and cervical cancers), and early detection and treatment, as well as public health campaigns promoting physical activity and a healthier dietary intake. Clinicians, public health professionals, and policy makers can play an active role in accelerating the application of such interventions globally.

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52,293 citations

Journal Article•DOI•

MEGA5: Molecular Evolutionary Genetics Analysis using Maximum Likelihood, Evolutionary Distance, and Maximum Parsimony Methods

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Koichiro Tamura¹, Daniel S. Peterson², Nicholas Peterson², Glen Stecher², Masatoshi Nei³, Sudhir Kumar² - Show less +2 more•Institutions (3)

Tokyo Metropolitan University¹, Arizona State University², Pennsylvania State University³

01 Oct 2011-Molecular Biology and Evolution

TL;DR: The newest addition in MEGA5 is a collection of maximum likelihood (ML) analyses for inferring evolutionary trees, selecting best-fit substitution models, inferring ancestral states and sequences, and estimating evolutionary rates site-by-site.

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Abstract: Comparative analysis of molecular sequence data is essential for reconstructing the evolutionary histories of species and inferring the nature and extent of selective forces shaping the evolution of genes and species. Here, we announce the release of Molecular Evolutionary Genetics Analysis version 5 (MEGA5), which is a user-friendly software for mining online databases, building sequence alignments and phylogenetic trees, and using methods of evolutionary bioinformatics in basic biology, biomedicine, and evolution. The newest addition in MEGA5 is a collection of maximum likelihood (ML) analyses for inferring evolutionary trees, selecting best-fit substitution models (nucleotide or amino acid), inferring ancestral states and sequences (along with probabilities), and estimating evolutionary rates site-by-site. In computer simulation analyses, ML tree inference algorithms in MEGA5 compared favorably with other software packages in terms of computational efficiency and the accuracy of the estimates of phylogenetic trees, substitution parameters, and rate variation among sites. The MEGA user interface has now been enhanced to be activity driven to make it easier for the use of both beginners and experienced scientists. This version of MEGA is intended for the Windows platform, and it has been configured for effective use on Mac OS X and Linux desktops. It is available free of charge from http://www.megasoftware.net.

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39,110 citations

"Human papillomavirus genome variant..." refers methods in this paper

...The p-distance method in MEGA5 (Tamura et al., 2011) was used to...
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Journal Article•DOI•

RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models

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Alexandros Stamatakis¹•Institutions (1)

École Polytechnique Fédérale de Lausanne¹

01 Oct 2006-Bioinformatics

TL;DR: UNLABELLED RAxML-VI-HPC (randomized axelerated maximum likelihood for high performance computing) is a sequential and parallel program for inference of large phylogenies with maximum likelihood (ML) that has been used to compute ML trees on two of the largest alignments to date.

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Abstract: Summary: RAxML-VI-HPC (randomized axelerated maximum likelihood for high performance computing) is a sequential and parallel program for inference of large phylogenies with maximum likelihood (ML). Low-level technical optimizations, a modification of the search algorithm, and the use of the GTR+CAT approximation as replacement for GTR+Γ yield a program that is between 2.7 and 52 times faster than the previous version of RAxML. A large-scale performance comparison with GARLI, PHYML, IQPNNI and MrBayes on real data containing 1000 up to 6722 taxa shows that RAxML requires at least 5.6 times less main memory and yields better trees in similar times than the best competing program (GARLI) on datasets up to 2500 taxa. On datasets ≥4000 taxa it also runs 2--3 times faster than GARLI. RAxML has been parallelized with MPI to conduct parallel multiple bootstraps and inferences on distinct starting trees. The program has been used to compute ML trees on two of the largest alignments to date containing 25 057 (1463 bp) and 2182 (51 089 bp) taxa, respectively. Availability: icwww.epfl.ch/~stamatak Contact: Alexandros.Stamatakis@epfl.ch Supplementary information: Supplementary data are available at Bioinformatics online.

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14,847 citations

"Human papillomavirus genome variant..." refers methods in this paper

...(Stamatakis, 2006) inferred from the global alignment of complete genome nucleotide sequences using the program MUSCLE (Edgar, 2004) linearized at the first ATG of the...
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Journal Article•DOI•

MUSCLE: a multiple sequence alignment method with reduced time and space complexity

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Robert C. Edgar¹•Institutions (1)

University of California, Berkeley¹

19 Aug 2004-BMC Bioinformatics

TL;DR: MUSCLE offers a range of options that provide improved speed and / or alignment accuracy compared with currently available programs, and a new option, MUSCLE-fast, designed for high-throughput applications.

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Abstract: In a previous paper, we introduced MUSCLE, a new program for creating multiple alignments of protein sequences, giving a brief summary of the algorithm and showing MUSCLE to achieve the highest scores reported to date on four alignment accuracy benchmarks. Here we present a more complete discussion of the algorithm, describing several previously unpublished techniques that improve biological accuracy and / or computational complexity. We introduce a new option, MUSCLE-fast, designed for high-throughput applications. We also describe a new protocol for evaluating objective functions that align two profiles. We compare the speed and accuracy of MUSCLE with CLUSTALW, Progressive POA and the MAFFT script FFTNS1, the fastest previously published program known to the author. Accuracy is measured using four benchmarks: BAliBASE, PREFAB, SABmark and SMART. We test three variants that offer highest accuracy (MUSCLE with default settings), highest speed (MUSCLE-fast), and a carefully chosen compromise between the two (MUSCLE-prog). We find MUSCLE-fast to be the fastest algorithm on all test sets, achieving average alignment accuracy similar to CLUSTALW in times that are typically two to three orders of magnitude less. MUSCLE-fast is able to align 1,000 sequences of average length 282 in 21 seconds on a current desktop computer. MUSCLE offers a range of options that provide improved speed and / or alignment accuracy compared with currently available programs. MUSCLE is freely available at http://www.drive5.com/muscle .

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7,617 citations

"Human papillomavirus genome variant..." refers methods in this paper

...(Stamatakis, 2006) inferred from the global alignment of complete genome nucleotide sequences using the program MUSCLE (Edgar, 2004) linearized at the first ATG of the...
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...2006) inferred from the global alignment of complete genome nucleotide sequences using the program MUSCLE (Edgar, 2004) linearized at the first ATG of the E1 ORF....
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Journal Article•DOI•

Epidemiologic Classification of Human Papillomavirus Types Associated with Cervical Cancer

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Nubia Muñoz¹, F. Xavier Bosch, Silvia de Sanjosé, Rolando Herrero, Xavier Castellsagué, Keerti V. Shah², Peter J.F. Snijders, Chris J.L.M. Meijer - Show less +4 more•Institutions (2)

International Agency for Research on Cancer¹, Johns Hopkins University²

06 Feb 2003-The New England Journal of Medicine

TL;DR: In addition to HPV types 16 and 18, types 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82Should be considered carcinogenic, or high-risk, types, and types 26, 53, and 66 should be considered probably carcinogenic.

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Abstract: Background Infection with human papilloma virus (HPV) is the main cause of cervical cancer, but the risk associated with the various HPV types has not been adequately assessed. Methods We pooled data from 11 case–control studies from nine countries involving 1918 women with histologically confirmed squamous-cell cervical cancer and 1928 control women. A common protocol and questionnaire were used. Information on risk factors was obtained by personal interviews, and cervical cells were collected for detection of HPV DNA and typing in a central laboratory by polymerase-chain-reaction–based assays (with MY09/MY11 and GP5+/6+ primers). Results HPV DNA was detected in 1739 of the 1918 patients with cervical cancer (90.7 percent) and in 259 of the 1928 control women (13.4 percent). With the GP5+/6+ primer, HPV DNA was detected in 96.6 percent of the patients and 15.6 percent of the controls. The most common HPV types in patients, in descending order of frequency, were types 16, 18, 45, 31, 33, 52, 58, and 35. A...

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5,979 citations

"Human papillomavirus genome variant..." refers background in this paper

...In this review, we update knowledge of variant lineages and sublineages using currently available complete genome sequences of human Alphapapillomavirus from species groups: alpha-3 (HPV61), alpha-5 (HPV26, 51, 69 and 82), alpha-6 (HPV30, 53, 56, 66), alpha-7 (HPV18, 39, 45, 59, 68, 70, 85 and 97), alpha-9 (HPV16, 31, 33, 35, 52, 58 and 67), alpha-10 (HPV6 and 11), alpha11 (HPV34 and 73) and alpha-13 (HPV54)....
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...…et al., 2012; Ho et al., 1993; Smith et al., 2011; Yamada et al., 1995), as can other names for HPV18 (Arias-Pulido et al., 2005; Chen et al., 2009; Ong et al., 1993), previous assignments for lineages for HPV33/53/56/68/69 variants analyzed in Schiffman et al. (2010) that have changed are also…...
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...In fact, there is a lack of compelling evidence for HPV18 variants role in different stages of the pathogenesis....
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...* Other common names for HPV16 are shown and can be found in the following references (Cornet et al., 2012; Ho et al., 1993; Smith et al., 2011; Yamada et al., 1995), as can other names for HPV18 (Arias-Pulido et al., 2005; Chen et al., 2009; Ong et al., 1993), previous assignments for lineages for HPV33/53/56/68/69 variants analyzed in Schiffman et al. (2010) that have changed are also listed above....
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...Although the co-evolution of human populations and HPV16 and HPV18 variants is well supported, the geographic associations for variants of other types remains unresolved (Calleja-Macias et al., 2004, 2005; Chan et al., 1997; Heinzel et al., 1995; Matos et al., 2013; Prado et al., 2005)....
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