Hostname: page-component-848d4c4894-75dct Total loading time: 0 Render date: 2024-05-16T21:03:27.440Z Has data issue: false hasContentIssue false
  • English
  • Français

Genetic variability of the HPV16 early genes and LCR. Present and future perspectives

Published online by Cambridge University Press:  01 December 2021

G. Bletsa ,
F. Zagouri ,
G. D. Amoutzias ,
M. Nikolaidis ,
E. Zografos ,
P. Markoulatos  and
D. Tsakogiannis Open the ORCID record for D. Tsakogiannis [Opens in a new window]
G. Bletsa
Affiliation:
Research Center, Hellenic Anticancer Institute, Athens, Greece
F. Zagouri
Affiliation:
Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
G. D. Amoutzias
Affiliation:
Bioinformatics Laboratory, Department of Biochemistry & Biotechnology, School of Health Sciences, University of Thessaly, Biopolis, Larissa, Greece
M. Nikolaidis
Affiliation:
Bioinformatics Laboratory, Department of Biochemistry & Biotechnology, School of Health Sciences, University of Thessaly, Biopolis, Larissa, Greece
E. Zografos
Affiliation:
Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
P. Markoulatos
Affiliation:
Research Center, Hellenic Anticancer Institute, Athens, Greece
D. Tsakogiannis*
Affiliation:
Research Center, Hellenic Anticancer Institute, Athens, Greece
*
Author for correspondence: D. Tsakogiannis, E-mail: dtsakogiannis@gmail.com, rdc@antikarkiniko.gr
Get access Rights & Permissions [Opens in a new window]

Abstract

Human papillomavirus 16 (HPV16) infection is the aetiologic factor for the development of cervical dysplasia and is regarded as highly carcinogen, because it is implicated in more than 50% of cervical cancer cases, worldwide. The tumourigenic potential of HPV16 has triggered the extensive sequence analysis of viral genome in order to identify nucleotide variations and amino acid substitutions that influence viral oncogenicity and subsequently the initiation and progression of cervical cancer. Nowadays, specific mutations of HPV16 DNA have been associated with an increased risk of high-grade squamous intraepithelial lesions and invasive cervical cancer (ICC) development, including E6: Q14H, H78Y, L83V, Ε7: N29S, S63F, E2: H35Q, P219S, T310K, E5: I65V, whereas highly conserved regions of viral DNA have been extensively characterised. In addition, numerous novel HPV16 mutations are observed among the studied populations from various geographic regions, hence advocating that different HPV16 strains seem to emerge with different tumourigenic capacities. The present review focuses on the variability of the early genes and the long control region, emphasising on the association of specific mutations with the development of severe dysplasia. Finally, it evaluates whether specific regions of HPV16 DNA are able to serve as valuable biomarkers for cervical cancer risk.

Keywords

Amino-acid mutationscervical cancerearly genesHPV16LCRmolecular biomarkersnucleotide variationsoncogenesoncogenicityoncoproteins
Type
Review
Information
Expert Reviews in Molecular Medicine , Volume 23 , 2021 , e19
Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Van Doorslaer, K et al. (2018) ICTV virus taxonomy profile: Papillomaviridae. Journal of General Virology 99, 989–990.CrossRefGoogle ScholarPubMed
Bernard, HU et al. (2010) Classification of papillomaviruses (PVs) based on 189 PV types and proposal of taxonomic amendments. Virology 401, 70–79.CrossRefGoogle ScholarPubMed
Bernard, HU, Calleja-Macias, IE and Dunn, ST (2006) Genome variation of human papillomavirus types: phylogenetic and medical implications. International Journal of Cancer 118, 1071–1076.CrossRefGoogle ScholarPubMed
de Villiers, EM et al. (2004) Classification of papillomaviruses. Virology 324, 17–27.CrossRefGoogle ScholarPubMed
Bzhalava, D, Eklund, C and Dillner, J (2015) International standardization and classification of human papillomavirus types. Virology 476, 341–344.CrossRefGoogle ScholarPubMed
Chen, Z et al. (2011) Evolution and taxonomic classification of human papillomavirus 16 (HPV16)-related variant genomes: HPV31, HPV33, HPV35, HPV52, HPV58 and HPV67. PLoS ONE 6, e20183.Google ScholarPubMed
Burk, RD, Harari, A and Chen, Z (2013) Human papillomavirus genome variants. Virology 445, 232–243.CrossRefGoogle ScholarPubMed
Chen, Z et al. (2018) Niche adaptation and viral transmission of human papillomaviruses from archaic hominins to modern humans. PLoS Pathogens 14, e1007352.CrossRefGoogle ScholarPubMed
Mirabello, L et al. (2018) The intersection of HPV epidemiology, genomics and mechanistic studies of HPV-mediated carcinogenesis. Viruses 10, 80.CrossRefGoogle ScholarPubMed
Mirabello, L et al. (2017) HPV16 E7 genetic conservation is critical to carcinogenesis. Cell 170, 1164–1174 e6.CrossRefGoogle ScholarPubMed
Gheit, T (2019) Mucosal and cutaneous human papillomavirus infections and cancer biology. Frontiers in Oncology 9, 355.CrossRefGoogle ScholarPubMed
Zur Hausen, H (1996) Papillomavirus infections – a major cause of human cancers. Biochimica et Biophysica Acta 1288, F55–F78.Google Scholar
Tsakogiannis, D et al. (2017) Molecular approaches for HPV genotyping and HPV-DNA physical status. Expert Reviews in Molecular Medicine 19, e1.CrossRefGoogle ScholarPubMed
Munoz, N et al. (2003) Epidemiologic classification of human papillomavirus types associated with cervical cancer. New England Journal of Medicine 348, 518–527.CrossRefGoogle ScholarPubMed
Berman, TA and Schiller, JT (2017) Human papillomavirus in cervical cancer and oropharyngeal cancer: one cause, two diseases. Cancer 123, 2219–2229.CrossRefGoogle ScholarPubMed
Ferlay, J et al. (2019) Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. International Journal of Cancer 144, 1941–1953.CrossRefGoogle ScholarPubMed
Li, Y and Xu, C (2017) Human papillomavirus-related cancers. Advances in Experimental Medicine and Biology 1018, 23–34.CrossRefGoogle ScholarPubMed
Tsakogiannis, D et al. (2015) Multiplex PCR assay for the rapid identification of human papillomavirus genotypes 16, 18, 45, 35, 66, 33, 51, 58, and 31 in clinical samples. Archives of Virology 160, 207–214.CrossRefGoogle ScholarPubMed
Tsakogiannis, D et al. (2015) Duplex real-time PCR assay and SYBR green I melting curve analysis for molecular identification of HPV genotypes 16, 18, 31, 35, 51 and 66. Molecular and Cellular Probes 29, 13–18.CrossRefGoogle ScholarPubMed
Van Doorslaer, K et al. (2017) The papillomavirus episteme: a major update to the papillomavirus sequence database. Nucleic Acids Research 45, D499–D506.CrossRefGoogle Scholar
Togtema, M et al. (2015) The human papillomavirus 16 European-T350G E6 variant can immortalize but not transform keratinocytes in the absence of E7. Virology 485, 274–282.CrossRefGoogle Scholar
Graham, DA and Herrington, CS (2000) HPV-16 E2 gene disruption and sequence variation in CIN 3 lesions and invasive squamous cell carcinomas of the cervix: relation to numerical chromosome abnormalities. Molecular Pathology 53, 201–206.CrossRefGoogle ScholarPubMed
Chen, Z et al. (2009) Evolutionary dynamics of variant genomes of human papillomavirus types 18, 45, and 97. Journal of Virology 83, 1443–1455.CrossRefGoogle ScholarPubMed
Chen, Z et al. (2005) Diversifying selection in human papillomavirus type 16 lineages based on complete genome analyses. Journal of Virology 79, 7014–7023.CrossRefGoogle ScholarPubMed
Ho, L et al. (1993) The genetic drift of human papillomavirus type 16 is a means of reconstructing prehistoric viral spread and the movement of ancient human populations. Journal of Virology 67, 6413–6423.CrossRefGoogle ScholarPubMed
Schiffman, M et al. (2010) A population-based prospective study of carcinogenic human papillomavirus variant lineages, viral persistence, and cervical neoplasia. Cancer Research 70, 3159–3169.CrossRefGoogle ScholarPubMed
Boulet, G et al. (2007) Human papillomavirus: E6 and E7 oncogenes. International Journal of Biochemistry & Cell Biology 39, 2006–2011.CrossRefGoogle ScholarPubMed
Jabbar, B et al. (2018) Antigenic peptide prediction from E6 and E7 oncoproteins of HPV types 16 and 18 for therapeutic vaccine design using immunoinformatics and MD simulation analysis. Frontiers in Immunology 9, 3000.CrossRefGoogle ScholarPubMed
Martinez-Zapien, D et al. (2016) Structure of the E6/E6AP/p53 complex required for HPV-mediated degradation of p53. Nature 529, 541–545.CrossRefGoogle ScholarPubMed
Olmedo-Nieva, L et al. (2018) The role of E6 spliced isoforms (E6*) in human papillomavirus-induced carcinogenesis. Viruses 10, 45.CrossRefGoogle Scholar
Aarthy, M et al. (2018) E7 oncoprotein of human papillomavirus: structural dynamics and inhibitor screening study. Gene 658, 159–177.CrossRefGoogle ScholarPubMed
Dick, FA et al. (2018) Non-canonical functions of the RB protein in cancer. Nature Reviews Cancer 18, 442–451.CrossRefGoogle ScholarPubMed
Shimada, M et al. (2020) The human papillomavirus E6 protein targets apoptosis-inducing factor (AIF) for degradation. Scientific Reports 10, 14195.CrossRefGoogle ScholarPubMed
Tsakogiannis, D et al. (2018) Polymorphic variability in the exon 19 of the RB1 gene and its flanking intronic sequences in HPV16-associated precancerous lesions in the Greek population. Journal of Medical Microbiology 67, 1638–1644.CrossRefGoogle Scholar
Wu, Y et al. (2006) Analysis of mutations in the E6/E7 oncogenes and L1 gene of human papillomavirus 16 cervical cancer isolates from China. Journal of General Virology 87, 1181–1188.CrossRefGoogle ScholarPubMed
Swan, DC et al. (2005) Human papillomavirus type 16 E2 and E6/E7 variants. Gynecologic Oncology 96, 695–700.CrossRefGoogle ScholarPubMed
Yamada, T et al. (1995) Human papillomavirus type 16 variant lineages in United States populations characterized by nucleotide sequence analysis of the E6, L2, and L1 coding segments. Journal of Virology 69, 7743–7753.CrossRefGoogle ScholarPubMed
Zhang, L et al. (2016) Association between human papillomavirus type 16 E6 and E7 variants with subsequent persistent infection and recurrence of cervical high-grade squamous intraepithelial lesion after conization. Journal of Medical Virology 88, 1982–1988.CrossRefGoogle ScholarPubMed
Tsakogiannis, D et al. (2013) Molecular and evolutionary analysis of HPV16 E6 and E7 genes in Greek women. Journal of Medical Microbiology 62, 1688–1696.CrossRefGoogle ScholarPubMed
Moschonas, GD et al. (2017) Association of codon 72 polymorphism of p53 with the severity of cervical dysplasia, E6–T350G and HPV16 variant lineages in HPV16-infected women. Journal of Medical Microbiology 66, 1358–1365.CrossRefGoogle ScholarPubMed
Zehbe, I et al. (2001) Human papillomavirus 16 E6 polymorphisms in cervical lesions from different European populations and their correlation with human leukocyte antigen class II haplotypes. International Journal of Cancer 94, 711–716.CrossRefGoogle ScholarPubMed
Sichero, L and Villa, LL (2006) Epidemiological and functional implications of molecular variants of human papillomavirus. Brazilian Journal of Medical and Biological Research 39, 707–717.CrossRefGoogle ScholarPubMed
Zacapala-Gomez, AE et al. (2016) Changes in global gene expression profiles induced by HPV 16 E6 oncoprotein variants in cervical carcinoma C33-A cells. Virology 488, 187–195.CrossRefGoogle ScholarPubMed
Grodzki, M et al. (2006) Increased risk for cervical disease progression of French women infected with the human papillomavirus type 16 E6–350G variant. Cancer Epidemiology, Biomarkers & Prevention 15, 820–822.CrossRefGoogle ScholarPubMed
Niccoli, S et al. (2012) The Asian-American E6 variant protein of human papillomavirus 16 alone is sufficient to promote immortalization, transformation, and migration of primary human foreskin keratinocytes. Journal of Virology 86, 12384–12396.CrossRefGoogle ScholarPubMed
Cuninghame, S et al. (2017) Two common variants of human papillomavirus type 16 E6 differentially deregulate sugar metabolism and hypoxia signalling in permissive human keratinocytes. Journal of General Virology 98, 2310–2319.CrossRefGoogle ScholarPubMed
Tornesello, ML et al. (2011) Human papillomavirus (HPV) genotypes and HPV16 variants and risk of adenocarcinoma and squamous cell carcinoma of the cervix. Gynecologic Oncology 121, 32–42.CrossRefGoogle ScholarPubMed
Vander Heiden, MG, Cantley, LC and Thompson, CB (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324, 1029–1033.CrossRefGoogle ScholarPubMed
Richard, C et al. (2010) The immortalizing and transforming ability of two common human papillomavirus 16 E6 variants with different prevalences in cervical cancer. Oncogene 29, 3435–3445.CrossRefGoogle ScholarPubMed
Liberti, MV and Locasale, JW (2016) The Warburg effect: how does it benefit cancer cells? Trends in Biochemical Sciences 41, 211–218.CrossRefGoogle ScholarPubMed
Cornet, I et al. (2013) HPV16 genetic variation and the development of cervical cancer worldwide. British Journal of Cancer 108, 240–244.CrossRefGoogle ScholarPubMed
Tsakogiannis, D et al. (2013) Identification of novel E6-E7 sequence variants of human papillomavirus 16. Archives of Virology 158, 821–828.CrossRefGoogle ScholarPubMed
Gheit, T et al. (2011) Risks for persistence and progression by human papillomavirus type 16 variant lineages among a population-based sample of Danish women. Cancer Epidemiology, Biomarkers & Prevention 20, 1315–1321.CrossRefGoogle ScholarPubMed
Nicolas-Parraga, S et al. (2016) HPV16 variants distribution in invasive cancers of the cervix, vulva, vagina, penis, and anus. Cancer Medicine 5, 2909–2919.CrossRefGoogle ScholarPubMed
Yamada, T et al. (1997) Human papillomavirus type 16 sequence variation in cervical cancers: a worldwide perspective. Journal of Virology 71, 2463–2472.CrossRefGoogle ScholarPubMed
Clifford, GM et al. (2019) Human papillomavirus 16 sub-lineage dispersal and cervical cancer risk worldwide: whole viral genome sequences from 7116 HPV16-positive women. Papillomavirus Research (Amsterdam, Netherlands) 7, 67–74.CrossRefGoogle ScholarPubMed
Burroni, E et al. (2013) Codon 72 polymorphism of p53 and HPV type 16 E6 variants as risk factors for patients with squamous epithelial lesion of the uterine cervix. Journal of Medical Virology 85, 83–90.CrossRefGoogle ScholarPubMed
Hu, Y et al. (2017) Association of HLA-DRB1, HLA-DQB1 polymorphisms with HPV 16 E6 variants among young cervical cancer patients in China. Journal of Cancer 8, 2401–2409.CrossRefGoogle ScholarPubMed
Bao, X et al. (2018) HLA and KIR associations of cervical neoplasia. Journal of Infectious Diseases 218, 2006–2015.CrossRefGoogle ScholarPubMed
Shang, Q et al. (2011) Human papillomavirus type 16 variant analysis of E6, E7, and L1 [corrected] genes and long control region in [corrected] cervical carcinomas in patients in northeast China. Journal of Clinical Microbiology 49, 2656–2663.CrossRefGoogle ScholarPubMed
Zhe, X et al. (2019) Genetic variations in E6, E7 and the long control region of human papillomavirus type 16 among patients with cervical lesions in Xinjiang, China. Cancer Cell International 19, 65.CrossRefGoogle Scholar
Pande, S et al. (2008) Human papillomavirus type 16 variant analysis of E6, E7, and L1 genes and long control region in biopsy samples from cervical cancer patients in north India. Journal of Clinical Microbiology 46, 1060–1066.CrossRefGoogle ScholarPubMed
Plesa, A et al. (2014) Molecular variants of human papilloma virus 16 E2, E4, E5, E6 and E7 genes associated with cervical neoplasia in Romanian patients. Archives of Virology 159, 3305–3320.CrossRefGoogle ScholarPubMed
Szostek, S et al. (2017) HPV16 E6 polymorphism and physical state of viral genome in relation to the risk of cervical cancer in women from the south of Poland. Acta Biochimica Polonica 64, 143–149.CrossRefGoogle ScholarPubMed
de Boer, MA et al. (2004) Human papillomavirus type 16 E6, E7, and L1 variants in cervical cancer in Indonesia, Suriname, and The Netherlands. Gynecologic Oncology 94, 488–494.CrossRefGoogle ScholarPubMed
Zhou, Z et al. (2019) Human papillomavirus type 16 E6 and E7 gene variations associated with cervical cancer in a Han Chinese population. Infection Genetics and Evolution 73, 13–20.CrossRefGoogle Scholar
Zhao, J et al. (2019) Phylogeny and polymorphism in the E6 and E7 of human papillomavirus: alpha-9 (HPV16, 31, 33, 52, 58), alpha-5 (HPV51), alpha-6 (HPV53, 66), alpha-7 (HPV18, 39, 59, 68) and alpha-10 (HPV6, 44) in women from Shanghai. Infectious Agents and Cancer 14, 38.CrossRefGoogle ScholarPubMed
Song, YS et al. (1997) Major sequence variants in E7 gene of human papillomavirus type 16 from cervical cancerous and noncancerous lesions of Korean women. Gynecologic Oncology 66, 275–281.CrossRefGoogle ScholarPubMed
Fujinaga, Y et al. (1994) Sequence variation of human papillomavirus type 16 E7 in preinvasive and invasive cervical neoplasias. Virus Genes 9, 85–92.CrossRefGoogle ScholarPubMed
Stephen, AL et al. (2000) Analysis of mutations in the URR and E6/E7 oncogenes of HPV 16 cervical cancer isolates from central China. International Journal of Cancer 86, 695–701.3.0.CO;2-C>CrossRefGoogle ScholarPubMed
Carvajal-Rodriguez, A (2008) Detecting recombination and diversifying selection in human alpha-papillomavirus. Infection Genetics and Evolution 8, 689–692.CrossRefGoogle ScholarPubMed
DeFilippis, VR, Ayala, FJ and Villarreal, LP (2002) Evidence of diversifying selection in human papillomavirus type 16 E6 but not E7 oncogenes. Journal of Molecular Evolution 55, 491–499.CrossRefGoogle Scholar
Chan, PK et al. (2002) Human papillomavirus type 16 intratypic variant infection and risk for cervical neoplasia in southern China. Journal of Infectious Diseases 186, 696–700.CrossRefGoogle ScholarPubMed
Nindl, I et al. (1999) Uniform distribution of HPV 16 E6 and E7 variants in patients with normal histology, cervical intra-epithelial neoplasia and cervical cancer. International Journal of Cancer 82, 203–207.3.0.CO;2-9>CrossRefGoogle ScholarPubMed
Eschle, D et al. (1992) Geographical dependence of sequence variation in the E7 gene of human papillomavirus type 16. Journal of General Virology 73, 1829–1832.CrossRefGoogle ScholarPubMed
Todorovic, B et al. (2012) Conserved region 3 of human papillomavirus 16 E7 contributes to deregulation of the retinoblastoma tumor suppressor. Journal of Virology 86, 13313–13323.CrossRefGoogle ScholarPubMed
Bergvall, M, Melendy, T and Archambault, J (2013) The E1 proteins. Virology 445, 35–56.CrossRefGoogle ScholarPubMed
Cote-Martin, A et al. (2008) Human papillomavirus E1 helicase interacts with the WD repeat protein p80 to promote maintenance of the viral genome in keratinocytes. Journal of Virology 82, 1271–1283.CrossRefGoogle ScholarPubMed
Garcia-Vallve, S, Alonso, A and Bravo, IG (2005) Papillomaviruses: different genes have different histories. Trends in Microbiology 13, 514–521.CrossRefGoogle ScholarPubMed
Stenlund, A (2003) E1 initiator DNA binding specificity is unmasked by selective inhibition of non-specific DNA binding. EMBO Journal 22, 954–963.CrossRefGoogle ScholarPubMed
Egawa, N et al. (2017) HPV16 and 18 genome amplification show different E4-dependence, with 16E4 enhancing E1 nuclear accumulation and replicative efficiency via its cell cycle arrest and kinase activation functions. PLoS Pathogens 13, e1006282.CrossRefGoogle ScholarPubMed
Castro-Munoz, LJ et al. (2019) The human papillomavirus (HPV) E1 protein regulates the expression of cellular genes involved in immune response. Scientific Reports 9, 13620.CrossRefGoogle ScholarPubMed
Clower, RV, Hu, Y and Melendy, T (2006) Papillomavirus E2 protein interacts with and stimulates human topoisomerase I. Virology 348, 13–18.CrossRefGoogle ScholarPubMed
Loo, YM and Melendy, T (2004) Recruitment of replication protein A by the papillomavirus E1 protein and modulation by single-stranded DNA. Journal of Virology 78, 1605–1615.CrossRefGoogle ScholarPubMed
Parker, LM et al. (2000) The bovine papillomavirus E2 transactivator is stimulated by the E1 initiator through the E2 activation domain. Virology 270, 430–443.CrossRefGoogle ScholarPubMed
Swindle, CS and Engler, JA (1998) Association of the human papillomavirus type 11 E1 protein with histone H1. Journal of Virology 72, 1994–2001.CrossRefGoogle ScholarPubMed
Lee, D et al. (1999) Interaction of E1 and hSNF5 proteins stimulates replication of human papillomavirus DNA. Nature 399, 487–491.CrossRefGoogle ScholarPubMed
Tsakogiannis, D et al. (2014) Nucleotide polymorphisms of the human papillomavirus 16 E1 gene. Archives of Virology 159, 51–63.CrossRefGoogle ScholarPubMed
Yao, Y et al. (2019) Human papillomavirus type 16 E1 mutations associated with cervical cancer in a Han Chinese population. International Journal of Medical Sciences 16, 1042–1049.CrossRefGoogle Scholar
Dong, X, Zhou, W and Pfister, H (2000) Presence of genetic rearrangements in E1/E2 regions of episomal HPV 16 isolates from cervical carcinomas 5–8. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 14, 5–8.Google ScholarPubMed
Sabol, I et al. (2012) Characterization and whole genome analysis of human papillomavirus type 16 e1–1374^63nt variants. PLoS ONE 7, e41045.CrossRefGoogle ScholarPubMed
Bogovac, Z et al. (2011) Prevalence of HPV 16 genomic variant carrying a 63 bp duplicated sequence within the E1 gene in Slovenian women. Acta Dermatovenerologica Alpina, Pannonica, Et Adriatica 20, 135–139.Google ScholarPubMed
Tsakogiannis, D et al. (2014) Prevalence of HPV16 E1–1374^63nt variants in Greek women. Journal of Medical Virology 86, 778–784.CrossRefGoogle ScholarPubMed
McPhillips, MG, Ozato, K and McBride, AA (2005) Interaction of bovine papillomavirus E2 protein with Brd4 stabilizes its association with chromatin. Journal of Virology 79, 8920–8932.CrossRefGoogle ScholarPubMed
McBride, AA (2013) The papillomavirus E2 proteins. Virology 445, 57–79.CrossRefGoogle ScholarPubMed
D'Abramo, CM and Archambault, J (2011) Small molecule inhibitors of human papillomavirus protein–protein interactions. The Open Virology Journal 5, 80–95.CrossRefGoogle ScholarPubMed
Gauson, EJ et al. (2015) Evidence supporting a role for TopBP1 and Brd4 in the initiation but not continuation of human papillomavirus 16 E1/E2-mediated DNA replication. Journal of Virology 89, 4980–4991.CrossRefGoogle Scholar
Tsakogiannis, D et al. (2012) Sequence variation analysis of the E2 gene of human papilloma virus type 16 in cervical lesions from women in Greece. Archives of Virology 157, 825–832.CrossRefGoogle Scholar
Kahla, S et al. (2014) Sequence variation in the E2-binding domain of HPV16 and biological function evaluation in Tunisian cervical cancers. Biomed Research International 2014, 639321.CrossRefGoogle ScholarPubMed
Eriksson, A et al. (1999) Human papillomavirus type 16 variant lineages characterized by nucleotide sequence analysis of the E5 coding segment and the E2 hinge region. Journal of General Virology 80, 595–600.CrossRefGoogle ScholarPubMed
Dai, S et al. (2018) The association of human papillomavirus type 16 E2 variations with cervical cancer in a Han Chinese population. Infection Genetics and Evolution 64, 241–248.CrossRefGoogle Scholar
Doorbar, J (2013) The E4 protein; structure, function and patterns of expression. Virology 445, 80–98.CrossRefGoogle ScholarPubMed
Biryukov, J et al. (2017) Mutations in HPV18 E1^E4 impact virus capsid assembly, infectivity competence, and maturation. Viruses 9, 385.CrossRefGoogle ScholarPubMed
Shiraz, A et al. (2020) The early detection of cervical cancer. The current and changing landscape of cervical disease detection. Cytopathology 31, 258–270.CrossRefGoogle ScholarPubMed
Wang, Q et al. (2004) Functional analysis of the human papillomavirus type 16 E1 = E4 protein provides a mechanism for in vivo and in vitro keratin filament reorganization. Journal of Virology 78, 821–833.CrossRefGoogle ScholarPubMed
Davy, CE et al. (2002) Identification of a G(2) arrest domain in the E1 wedge E4 protein of human papillomavirus type 16. Journal of Virology 76, 9806–9818.CrossRefGoogle Scholar
Nakahara, T et al. (2002) Modulation of the cell division cycle by human papillomavirus type 18 E4. Journal of Virology 76, 10914–10920.CrossRefGoogle ScholarPubMed
Knight, GL, Turnell, AS and Roberts, S (2006) Role for Wee1 in inhibition of G2-to-M transition through the cooperation of distinct human papillomavirus type 1 E4 proteins. Journal of Virology 80, 7416–7426.CrossRefGoogle ScholarPubMed
Davy, CE et al. (2005) Human papillomavirus type 16 E1 E4-induced G2 arrest is associated with cytoplasmic retention of active Cdk1/cyclin B1 complexes. Journal of Virology 79, 3998–4011.CrossRefGoogle ScholarPubMed
Griffin, H et al. (2020) Human papillomavirus type 16 causes a defined subset of conjunctival in situ squamous cell carcinomas. Modern Pathology 33, 74–90.CrossRefGoogle ScholarPubMed
Davy, C et al. (2009) A novel interaction between the human papillomavirus type 16 E2 and E1–E4 proteins leads to stabilization of E2. Virology 394, 266–275.CrossRefGoogle ScholarPubMed
Tsakogiannis, D et al. (2012) Molecular and phylogenetic analysis of the HPV 16 E4 gene in cervical lesions from women in Greece. Archives of Virology 157, 1729–1739.CrossRefGoogle Scholar
Roberts, S et al. (1994) Mutational analysis of human papillomavirus E4 proteins: identification of structural features important in the formation of cytoplasmic E4/cytokeratin networks in epithelial cells. Journal of Virology 68, 6432–6445.CrossRefGoogle ScholarPubMed
McIntosh, PB et al. (2010) E1–E4-mediated keratin phosphorylation and ubiquitylation: a mechanism for keratin depletion in HPV16-infected epithelium. Journal of Cell Science 123, 2810–2822.CrossRefGoogle Scholar
Gutierrez-Xicotencatl, L et al. (2021) Cellular functions of HPV16 E5 oncoprotein during oncogenic transformation. Molecular Cancer Research 19, 167–179.CrossRefGoogle ScholarPubMed
Wetherill, LF et al. (2012) High-risk human papillomavirus E5 oncoprotein displays channel-forming activity sensitive to small-molecule inhibitors. Journal of Virology 86, 5341–5351.CrossRefGoogle ScholarPubMed
Wetherill, LF et al. (2018) Alkyl-imino sugars inhibit the pro-oncogenic ion channel function of human papillomavirus (HPV) E5. Antiviral Research 158, 113–121.CrossRefGoogle ScholarPubMed
Oetke, C et al. (2000) Human papillomavirus type 16 E5 protein localizes to the Golgi apparatus but does not grossly affect cellular glycosylation. Archives of Virology 145, 2183–2191.CrossRefGoogle Scholar
DiMaio, D and Petti, LM (2013) The E5 proteins. Virology 445, 99–114.CrossRefGoogle ScholarPubMed
Ashrafi, GH et al. (2006) E5 protein of human papillomavirus 16 downregulates HLA class I and interacts with the heavy chain via its first hydrophobic domain. International Journal of Cancer 119, 2105–2112.CrossRefGoogle Scholar
Campo, MS et al. (2010) HPV-16 E5 down-regulates expression of surface HLA class I and reduces recognition by CD8T cells. Virology 407, 137–142.CrossRefGoogle Scholar
Kabsch, K and Alonso, A (2002) The human papillomavirus type 16 E5 protein impairs TRAIL- and FasL-mediated apoptosis in HaCaT cells by different mechanisms. Journal of Virology 76, 12162–12172.CrossRefGoogle ScholarPubMed
Pim, D, Collins, M and Banks, L (1992) Human papillomavirus type 16 E5 gene stimulates the transforming activity of the epidermal growth factor receptor. Oncogene 7, 27–32.Google ScholarPubMed
Tsakogiannis, D et al. (2015) Sites of disruption within E1 and E2 genes of HPV16 and association with cervical dysplasia. Journal of Medical Virology 87, 1973–1980.CrossRefGoogle ScholarPubMed
Tsakogiannis, D et al. (2014) Determination of human papillomavirus 16 physical status through E1/E6 and E2/E6 ratio analysis. Journal of Medical Microbiology 63, 1716–1723.CrossRefGoogle ScholarPubMed
Hafner, N et al. (2008) Integration of the HPV16 genome does not invariably result in high levels of viral oncogene transcripts. Oncogene 27, 1610–1617.CrossRefGoogle Scholar
Stunkel, W and Bernard, HU (1999) The chromatin structure of the long control region of human papillomavirus type 16 represses viral oncoprotein expression. Journal of Virology 73, 1918–1930.CrossRefGoogle Scholar
Kammer, C et al. (2000) Sequence analysis of the long control region of human papillomavirus type 16 variants and functional consequences for P97 promoter activity. Journal of General Virology 81, 1975–1981.CrossRefGoogle Scholar
Dong, XP et al. (1994) Prevalence of deletions of YY1-binding sites in episomal HPV 16 DNA from cervical cancers. International Journal of Cancer 58, 803–808.CrossRefGoogle ScholarPubMed
Chin, MT, Broker, TR and Chow, LT (1989) Identification of a novel constitutive enhancer element and an associated binding protein: implications for human papillomavirus type 11 enhancer regulation. Journal of Virology 63, 2967–2976.CrossRefGoogle Scholar
Cid, A et al. (1993) Cell-type-specific activity of the human papillomavirus type 18 upstream regulatory region in transgenic mice and its modulation by tetradecanoyl phorbol acetate and glucocorticoids. Journal of Virology 67, 6742–6752.CrossRefGoogle ScholarPubMed
Cripe, TP et al. (1990) Transcriptional activation of the human papillomavirus-16 P97 promoter by an 88-nucleotide enhancer containing distinct cell-dependent and AP-1-responsive modules. The New Biologist 2, 450–463.Google ScholarPubMed
O'Connor, MJ et al. (1996) YY1 represses human papillomavirus type 16 transcription by quenching AP-1 activity. Journal of Virology 70, 6529–6539.CrossRefGoogle ScholarPubMed
Ribeiro, AL, Caodaglio, AS and Sichero, L (2018) Regulation of HPV transcription. Clinics 73, e486s.CrossRefGoogle ScholarPubMed
Fang, L et al. (2020) Genetic variability, phylogeny and functional implication of the long control region in human papillomavirus type 16, 18 and 58 in Chengdu, China. Virology Journal 17, 106.CrossRefGoogle Scholar
Cornet, I et al. (2012) Human papillomavirus type 16 genetic variants: phylogeny and classification based on E6 and LCR. Journal of Virology 86, 6855–6861.CrossRefGoogle ScholarPubMed
Dai, S et al. (2020) Association of human papillomavirus type 16 long control region variations with cervical cancer in a Han Chinese population. International Journal of Medical Sciences 17, 931–938.CrossRefGoogle Scholar
Vidal, JP et al. (2016) Genetic diversity of HPV16 and HPV18 in Brazilian patients with invasive cervical cancer. Journal of Medical Virology 88, 1279–1287.CrossRefGoogle ScholarPubMed
Martinelli, M et al. (2020) Analysis of human papillomavirus (HPV) 16 variants associated with cervical infection in Italian women. International Journal of Environmental Research and Public Health 17, 306.CrossRefGoogle ScholarPubMed
Ramas, V et al. (2018) Analysis of human papillomavirus 16 E6, E7 genes and long control region in cervical samples from Uruguayan women. Gene 654, 103–109.CrossRefGoogle ScholarPubMed
Moussavou, PB et al. (2016) Molecular analysis of human Papillomavirus detected among women positive for cervical lesions by visual inspection with acetic acid/Lugol's iodine (VIA/VILI) in Libreville, Gabon. Infectious Agents and Cancer 11, 50.CrossRefGoogle Scholar
Xi, J et al. (2017) Genetic variability and functional implication of the long control region in HPV-16 variants in Southwest China. PLoS ONE 12, e0182388.CrossRefGoogle Scholar
Escobar-Escamilla, N et al. (2019) Mutational landscape and intra-host diversity of human papillomavirus type 16 long control region and E6 variants in cervical samples. Archives of Virology 164, 2953–2961.CrossRefGoogle ScholarPubMed
Galati, L et al. (2019) Identification of human papillomavirus type 16 variants circulating in the Calabria region by sequencing and phylogenetic analysis of HPV16 from cervical smears. Infection Genetics and Evolution 68, 185–193.CrossRefGoogle ScholarPubMed
Mosmann, JP et al. (2015) Mutation detection of E6 and LCR genes from HPV 16 associated with carcinogenesis. Asian Pacific Journal of Cancer Prevention: APJCP 16, 1151–1157.CrossRefGoogle ScholarPubMed
Marongiu, L et al. (2014) Human papillomavirus type 16 long control region and E6 variants stratified by cervical disease stage. Infection Genetics and Evolution 26, 8–13.CrossRefGoogle ScholarPubMed
Wang, HY, Lian, P and Zheng, PS (2015) SOX9, a potential tumor suppressor in cervical cancer, transactivates p21WAF1/CIP1 and suppresses cervical tumor growth. Oncotarget 6, 20711–20722.CrossRefGoogle ScholarPubMed
Cowper-Sal lari, R et al. (2012) Breast cancer risk-associated SNPs modulate the affinity of chromatin for FOXA1 and alter gene expression. Nature Genetics 44, 1191–1198.CrossRefGoogle ScholarPubMed
Lin, L et al. (2002) The hepatocyte nuclear factor 3 alpha gene, HNF3alpha (FOXA1), on chromosome band 14q13 is amplified and overexpressed in esophageal and lung adenocarcinomas. Cancer Research 62, 5273–5279.Google Scholar
Li, Z et al. (2012) Foxa1 and Foxa2 are essential for sexual dimorphism in liver cancer. Cell 148, 72–83.CrossRefGoogle ScholarPubMed
Jin, HJ et al. (2013) Androgen receptor-independent function of FoxA1 in prostate cancer metastasis. Cancer Research 73, 3725–3736.CrossRefGoogle ScholarPubMed
Zhao, J et al. (2020) Genetic variability and functional implication of HPV16 from cervical intraepithelial neoplasia in Shanghai women. Journal of Medical Virology 92, 372–381.CrossRefGoogle ScholarPubMed
Pientong, C et al. (2013) Association of human papillomavirus type 16 long control region mutation and cervical cancer. Virology Journal 10, 30.CrossRefGoogle ScholarPubMed
Kjaer, SK et al. (2010) Long-term absolute risk of cervical intraepithelial neoplasia grade 3 or worse following human papillomavirus infection: role of persistence. Journal of the National Cancer Institute 102, 1478–1488.CrossRefGoogle ScholarPubMed
Nikolaidis, M et al. (2021) HPV16-Genotyper: a computational tool for risk-assessment, lineage genotyping and recombination detection in HPV16 sequences, based on a large-scale evolutionary analysis. Diversity 13, 497.CrossRefGoogle Scholar
Kukimoto, I et al. (2013) Genetic variation of human papillomavirus type 16 in individual clinical specimens revealed by deep sequencing. PLoS ONE 8, e80583.CrossRefGoogle ScholarPubMed
Domingo, E, Sheldon, J and Perales, C (2012) Viral quasispecies evolution. Microbiology and Molecular Biology Reviews 76, 159–216.CrossRefGoogle ScholarPubMed
Kottaridi, C et al. (2019) Searching HPV genome for methylation sites involved in molecular progression to cervical precancer. Journal of Cancer 10, 4588–4595.CrossRefGoogle ScholarPubMed
Tsakogiannis, D et al. (2018) Association of p16 (CDKN2A) polymorphisms with the development of HPV16-related precancerous lesions and cervical cancer in the Greek population. Journal of Medical Virology 90, 965–971.CrossRefGoogle ScholarPubMed
Tsakogiannis, D et al. (2016) Identification of rearranged sequences of HPV16 DNA in precancerous and cervical cancer cases. Molecular and Cellular Probes 30, 6–12.CrossRefGoogle ScholarPubMed