{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T18:52:08Z","timestamp":1793040728357,"version":"4.5.0"},"reference-count":122,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T00:00:00Z","timestamp":1659398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"CONACyT PRONAII-7-VIRUS Y CA\u00c1NCER","doi-asserted-by":"publisher","award":["303044"],"award-info":[{"award-number":["303044"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cervical cancer (CC) continues to be a major public health problem in Mexico, ranking second among cancers in women. A persistent infection with human papillomaviruses (HPV) is the main risk factor for CC development. In addition, a significant fraction of other cancers including those of the anus, oropharynx, and penis are also related to HPV infection. In CC, HPV-16 is the most prevalent high-risk HPV type, followed by HPV-18, both being responsible for 70% of cases. HPV intratype variant lineages differ in nucleotide sequences by 1\u201310%, while sublineages differ by 0.5\u20131%. Several studies have postulated that the nucleotide changes that occur between HPV intratype variants are reflected in functional differences and in pathogenicity. Moreover, it has been demonstrated that HPV-16 and -18 intratype variants differentially affect molecular processes in infected cells, changing their biological behavior that finally impacts in the clinical outcome of patients. Mexico has participated in providing knowledge on the geographical distribution of intratype variants of the most prevalent HPVs in premalignant lesions of the cervix and cervical cancer, as well as in other HPV-related tumors. In addition, functional studies have been carried out to assess the cellular effects of intratype variations in HPV proteins. This review addresses the state of the art on the epidemiology of HPV-16 and HPV-18 intratype variants in the Mexican population, as well as their association with persistence, precancer and cervical cancer, and functional aspects related to their biological behavior.<\/jats:p>","DOI":"10.3390\/ijms23158566","type":"journal-article","created":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T21:41:37Z","timestamp":1659476497000},"page":"8566","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Epidemiology and Molecular Biology of HPV Variants in Cervical Cancer: The State of the Art in Mexico"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6809-0212","authenticated-orcid":false,"given":"J. Omar","family":"Mu\u00f1oz-Bello","sequence":"first","affiliation":[{"name":"Unidad de Investigaci\u00f3n Biom\u00e9dica en C\u00e1ncer, Instituto Nacional de Cancerolog\u00eda, Av. San Fernando No. 22, Col. Secci\u00f3n XVI, Tlalpan, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adela","family":"Carrillo-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n Biom\u00e9dica en C\u00e1ncer, Instituto Nacional de Cancerolog\u00eda, Av. San Fernando No. 22, Col. Secci\u00f3n XVI, Tlalpan, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7553-2541","authenticated-orcid":false,"given":"Marcela","family":"Lizano","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n Biom\u00e9dica en C\u00e1ncer, Instituto Nacional de Cancerolog\u00eda, Av. San Fernando No. 22, Col. Secci\u00f3n XVI, Tlalpan, Mexico City 14080, Mexico"},{"name":"Departamento de Medicina Gen\u00f3mica y Toxicolog\u00eda Ambiental, Instituto de Investigaciones Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Circuito Exterior S\/N, Ciudad Universitaria, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e180","DOI":"10.1016\/S2214-109X(19)30488-7","article-title":"Global Burden of Cancer Attributable to Infections in 2018: A Worldwide Incidence Analysis","volume":"8","author":"Georges","year":"2020","journal-title":"Lancet Glob. Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1016\/S1470-2045(10)70230-8","article-title":"Human Papillomavirus Genotype Attribution in Invasive Cervical Cancer: A Retrospective Cross-Sectional Worldwide Study","volume":"11","author":"Quint","year":"2010","journal-title":"Lancet Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1002\/ijc.34128","article-title":"Different Human Papillomavirus Types Share Early Natural History Transitions in Immunocompetent Women","volume":"151","author":"Adebamowo","year":"2022","journal-title":"Int. J. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e609","DOI":"10.1016\/S2214-109X(16)30143-7","article-title":"Global Burden of Cancers Attributable to Infections in 2012: A Synthetic Analysis","volume":"4","author":"Plummer","year":"2016","journal-title":"Lancet Glob. Health"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1002\/ijc.30716","article-title":"Worldwide Burden of Cancer Attributable to HPV by Site, Country and HPV Type","volume":"141","author":"Plummer","year":"2017","journal-title":"Int. J. Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"552028","DOI":"10.3389\/fpubh.2020.552028","article-title":"Epidemiology and Burden of Human Papillomavirus and Related Diseases, Molecular Pathogenesis, and Vaccine Evaluation","volume":"8","author":"Kombe","year":"2021","journal-title":"Front. Public Health"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA A Cancer J. Clin."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.virol.2013.07.015","article-title":"A Systematic Review of the Prevalence of Mucosal and Cutaneous Human Papillomavirus Types","volume":"445","author":"Bzhalava","year":"2013","journal-title":"Virology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.virol.2010.02.002","article-title":"Classification of Papillomaviruses (PVs) Based on 189 PV Types and Proposal of Taxonomic Amendments","volume":"401","author":"Bernard","year":"2010","journal-title":"Virology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"D499","DOI":"10.1093\/nar\/gkw879","article-title":"The Papillomavirus Episteme: A Major Update to the Papillomavirus Sequence Database","volume":"45","author":"Li","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.1002\/ijc.27485","article-title":"Human Papillomavirus Types in 115,789 HPV-Positive Women: A Meta-Analysis from Cervical Infection to Cancer","volume":"131","author":"Guan","year":"2012","journal-title":"Int. J. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"LeConte, B.A., Szaniszlo, P., Fennewald, S.M., Lou, D.I., Qiu, S., Chen, N.W., Lee, J.H., and Resto, V.A. (2018). Differences in the Viral Genome between HPV-Positive Cervical and Oropharyngeal Cancer. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0203403"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1016\/j.ejca.2015.06.001","article-title":"Human Papillomavirus Genotype Attribution for HPVs 6, 11, 16, 18, 31, 33, 45, 52 and 58 in Female Anogenital Lesions","volume":"51","author":"Serrano","year":"2015","journal-title":"Eur. J. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Schrank, T.P., Landess, L., Stepp, W.H., Rehmani, H., Weir, W.H., Lenze, N., Lal, A., Wu, D., Kothari, A., and Hackman, T.G. (2022). Comprehensive Viral Genotyping Reveals Prognostic Viral Phylogenetic Groups in HPV16-Associated Squamous Cell Carcinoma of the Oropharynx. Mol. Cancer Res.","DOI":"10.1158\/1541-7786.22527345"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"10680","DOI":"10.1128\/JVI.01747-15","article-title":"Human Papillomavirus 18 Genetic Variation and Cervical Cancer Risk Worldwide","volume":"89","author":"Chen","year":"2015","journal-title":"J. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.virol.2004.03.033","article-title":"Classification of Papillomaviruses","volume":"324","author":"Fauquet","year":"2004","journal-title":"Virology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.virol.2013.07.018","article-title":"Human Papillomavirus Genome Variants","volume":"445","author":"Burk","year":"2013","journal-title":"Virology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.1099\/vir.0.80945-0","article-title":"Differential Splicing of E6 within Human Papillomavirus Type 18 Variants and Functional Consequences","volume":"86","year":"2005","journal-title":"J. Gen. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"145709","DOI":"10.1016\/j.gene.2021.145709","article-title":"Degradation of P53 by HPV16-E6 Variants Isolated from Cervical Cancer Specimens of Moroccan Women","volume":"791","author":"Hadami","year":"2021","journal-title":"Gene"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1002\/jmv.25618","article-title":"Genetic Variability and Functional Implication of HPV16 from Cervical Intraepithelial Neoplasia in Shanghai Women","volume":"92","author":"Zhao","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.virol.2016.02.015","article-title":"The Asian-American Variant of Human Papillomavirus Type 16 Exhibits Higher Activation of MAPK and PI3K\/AKT Signaling Pathways, Transformation, Migration and Invasion of Primary Human Keratinocytes","volume":"492","author":"Hochmann","year":"2016","journal-title":"Virology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"djw100","DOI":"10.1093\/jnci\/djw100","article-title":"HPV16 Sublineage Associations with Histology-Specific Cancer Risk Using HPV Whole-Genome Sequences in 3200 Women","volume":"108","author":"Mirabello","year":"2016","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1038\/bjc.2012.508","article-title":"HPV16 Genetic Variation and the Development of Cervical Cancer Worldwide","volume":"108","author":"Cornet","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1158\/1055-9965.EPI-10-1187","article-title":"Risks for Persistence and Progression by Human Papillomavirus Type 16 Variant Lineages among a Population-Based Sample of Danish Women","volume":"20","author":"Gheit","year":"2011","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3159","DOI":"10.1158\/0008-5472.CAN-09-4179","article-title":"A Population-Based Prospective Study of Carcinogenic Human Papillomavirus Variant Lineages, Viral Persistence, and Cervical Neoplasia","volume":"70","author":"Schiffman","year":"2010","journal-title":"Cancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1002\/ijc.22481","article-title":"High Grade Cervical Lesions Are Caused Preferentially by Non-European Variants of HPVs 16 and 18","volume":"120","author":"Sichero","year":"2007","journal-title":"Int. J. Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Freitas, L.B., Chen, Z., Muqui, E.F., Boldrini, N.A.T., Miranda, A.E., Spano, L.C., and Burk, R.D. (2014). Human Papillomavirus 16 Non-European Variants Are Preferentially Associated with High-Grade Cervical Lesions. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0100746"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"001475","DOI":"10.1099\/jmm.0.001475","article-title":"Genetic Variations in the Long Control Region of Human Papillomavirus Type 16 Isolates from India: Implications for Cervical Carcinogenesis","volume":"71","author":"Mane","year":"2022","journal-title":"J. Med. Microbiol."},{"key":"ref_29","first-page":"2839708","article-title":"Determination of Human Papillomavirus Type 18 Lineage of E6: A Population Study from Iran","volume":"2022","author":"Larijani","year":"2022","journal-title":"Biomed. Res. Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2286","DOI":"10.2741\/1971","article-title":"Papillomavirus Genome Structure, Expression, and Post-Transcriptional Regulation","volume":"11","author":"Zheng","year":"2006","journal-title":"Front. Biosci. A J. Virtual Libr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.coviro.2021.07.010","article-title":"The Long and Winding Road: Human Papillomavirus Entry and Subcellular Trafficking","volume":"50","author":"Ozbun","year":"2021","journal-title":"Curr. Opin. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Schelhaas, M., Shah, B., Holzer, M., Blattmann, P., K\u00fchling, L., Day, P.M., Schiller, J.T., and Helenius, A. (2012). Entry of Human Papillomavirus Type 16 by Actin-Dependent, Clathrin- and Lipid Raft-Independent Endocytosis. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002657"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"13125","DOI":"10.1128\/JVI.77.24.13125-13135.2003","article-title":"Different Heparan Sulfate Proteoglycans Serve as Cellular Receptors for Human Papillomaviruses","volume":"77","author":"Handisurya","year":"2003","journal-title":"J. Virol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2508","DOI":"10.1128\/JVI.02319-12","article-title":"Cellular Entry of Human Papillomavirus Type 16 Involves Activation of the Phosphatidylinositol 3-Kinase\/Akt\/MTOR Pathway and Inhibition of Autophagy","volume":"87","author":"Surviladze","year":"2013","journal-title":"J. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1128\/jvi.71.3.2449-2456.1997","article-title":"Identification of the Alpha6 Integrin as a Candidate Receptor for Papillomaviruses","volume":"71","author":"Evander","year":"1997","journal-title":"J. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Spoden, G., Freitag, K., Husmann, M., Boller, K., Sapp, M., Lambert, C., and Florin, L. (2008). Clathrin- and Caveolin-Independent Entry of Human Papillomavirus Type 16\u2014Involvement of Tetraspanin-Enriched Microdomains (TEMs). PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0003313"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/s00430-020-00683-1","article-title":"HPV Caught in the Tetraspanin Web?","volume":"209","author":"Finke","year":"2020","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"7502","DOI":"10.1128\/JVI.00519-13","article-title":"Annexin A2 and S100A10 Regulate Human Papillomavirus Type 16 Entry and Intracellular Trafficking in Human Keratinocytes","volume":"87","author":"Dziduszko","year":"2013","journal-title":"J. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"7038","DOI":"10.1128\/JVI.00234-15","article-title":"Kallikrein-8 Proteolytically Processes Human Papillomaviruses in the Extracellular Space to Facilitate Entry into Host Cells","volume":"89","author":"Cerqueira","year":"2015","journal-title":"J. Virol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1073\/pnas.0508815103","article-title":"Cleavage of the Papillomavirus Minor Capsid Protein, L2, at a Furin Consensus Site Is Necessary for Infection","volume":"103","author":"Richards","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3545","DOI":"10.1083\/jcb.201804171","article-title":"\u03b3-Secretase Promotes Membrane Insertion of the Human Papillomavirus L2 Capsid Protein during Virus Infection","volume":"217","author":"Inoue","year":"2018","journal-title":"J. Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Harwood, M.C., Dupzyk, A.J., Inoue, T., DiMaio, D., and Tsai, B. (2020). P120 Catenin Recruits HPV to \u03b3-Secretase to Promote Virus Infection. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008946"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1111\/j.1600-0854.2011.01320.x","article-title":"Human Papillomavirus L2 Facilitates Viral Escape from Late Endosomes via Sorting Nexin 17","volume":"13","author":"Ozbun","year":"2012","journal-title":"Traffic"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"7452","DOI":"10.1073\/pnas.1302164110","article-title":"Genome-Wide SiRNA Screen Identifies the Retromer as a Cellular Entry Factor for Human Papillomavirus","volume":"110","author":"Lipovsky","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"6289","DOI":"10.1073\/pnas.1600638113","article-title":"Incoming Human Papillomavirus Type 16 Genome Resides in a Vesicular Compartment throughout Mitosis","volume":"113","author":"Luszczek","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Calton, C.M., Bronnimann, M.P., Manson, A.R., Li, S., Chapman, J.A., Suarez-Berumen, M., Williamson, T.R., Molugu, S.K., Bernal, R.A., and Campos, S.K. (2017). Translocation of the Papillomavirus L2\/VDNA Complex across the Limiting Membrane Requires the Onset of Mitosis. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006200"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Aydin, I., Villalonga-Planells, R., Greune, L., Bronnimann, M.P., Calton, C.M., Becker, M., Lai, K.Y., Campos, S.K., Schmidt, M.A., and Schelhaas, M. (2017). A Central Region in the Minor Capsid Protein of Papillomaviruses Facilitates Viral Genome Tethering and Membrane Penetration for Mitotic Nuclear Entry. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006308"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"14252","DOI":"10.1073\/pnas.0404229101","article-title":"Establishment of Papillomavirus Infection Is Enhanced by Promyelocytic Leukemia Protein (PML) Expression","volume":"101","author":"Day","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.virol.2013.06.006","article-title":"The Papillomavirus E2 Proteins","volume":"445","author":"McBride","year":"2013","journal-title":"Virology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.virol.2013.07.020","article-title":"The E1 Proteins","volume":"445","author":"Bergvall","year":"2013","journal-title":"Virology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.virol.2011.03.019","article-title":"Persistence of Viral DNA in the Epithelial Basal Layer Suggests a Model for Papillomavirus Latency Following Immune Regression","volume":"414","author":"Maglennon","year":"2011","journal-title":"Virology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"13620","DOI":"10.1038\/s41598-019-49886-4","article-title":"The Human Papillomavirus (HPV) E1 Protein Regulates the Expression of Cellular Genes Involved in Immune Response","volume":"9","author":"Lizano","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1038\/nrc2886","article-title":"Human Papillomavirus Oncoproteins: Pathways to Transformation","volume":"10","author":"Moody","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4734","DOI":"10.3390\/v7082842","article-title":"Regulation of the Wnt\/\u03b2-Catenin Signaling Pathway by Human Papillomavirus E6 and E7 Oncoproteins","volume":"7","author":"Bello","year":"2015","journal-title":"Viruses"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.arcmed.2014.10.008","article-title":"The Role of Signaling Pathways in Cervical Cancer and Molecular Therapeutic Targets","volume":"45","author":"Lizano","year":"2014","journal-title":"Arch. Med. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e1988","DOI":"10.1002\/rmv.1988","article-title":"Deregulation of the Notch Pathway as a Common Road in Viral Carcinogenesis","volume":"28","author":"Lizano","year":"2018","journal-title":"Rev. Med. Virol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1158\/1541-7786.MCR-20-0491","article-title":"Cellular Functions of HPV16 E5 Oncoprotein during Oncogenic Transformation","volume":"19","year":"2021","journal-title":"Mol. Cancer Res. MCR"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.virol.2013.07.008","article-title":"The E4 Protein; Structure, Function and Patterns of Expression","volume":"445","author":"Doorbar","year":"2013","journal-title":"Virology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2810","DOI":"10.1242\/jcs.061978","article-title":"E1\u2013E4-Mediated Keratin Phosphorylation and Ubiquitylation: A Mechanism for Keratin Depletion in HPV16-Infected Epithelium","volume":"123","author":"McIntosh","year":"2010","journal-title":"J. Cell Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1007\/978-1-4614-0980-9_18","article-title":"The Papillomavirus Virion: A Machine Built to Hide Molecular Achilles\u2019 Heels","volume":"726","author":"Buck","year":"2012","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Hussain, S.S., Lundine, D., Leeman, J.E., and Higginson, D.S. (2021). Genomic Signatures in HPV-Associated Tumors. Viruses, 13.","DOI":"10.3390\/v13101998"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1097\/OLQ.0000000000000193","article-title":"The Estimated Lifetime Probability of Acquiring Human Papillomavirus in the United States","volume":"41","author":"Chesson","year":"2014","journal-title":"Sex. Transm. Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4593","DOI":"10.1172\/JCI57149","article-title":"The Known Unknowns of HPV Natural History","volume":"121","author":"Gravitt","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Shanmugasundaram, S., and You, J. (2017). Targeting Persistent Human Papillomavirus Infection. Viruses, 9.","DOI":"10.3390\/v9080229"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1093\/jnci\/djr283","article-title":"Persistence of Type-Specific Human Papillomavirus Infection and Increased Long-Term Risk of Cervical Cancer","volume":"103","author":"Chen","year":"2011","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"355","DOI":"10.3389\/fonc.2019.00355","article-title":"Mucosal and Cutaneous Human Papillomavirus Infections and Cancer Biology","volume":"9","author":"Gheit","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2201","DOI":"10.1042\/CS20160786","article-title":"The Human Papillomavirus Replication Cycle, and Its Links to Cancer Progression: A Comprehensive Review","volume":"131","author":"Graham","year":"2017","journal-title":"Clin. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.bpobgyn.2011.04.005","article-title":"Histology of Cervical Intraepithelial Neoplasia and the Role of Biomarkers","volume":"25","author":"Martin","year":"2011","journal-title":"Best Pract. Research. Clin. Obstet. Gynaecol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"6413","DOI":"10.1128\/jvi.67.11.6413-6423.1993","article-title":"The Genetic Drift of Human Papillomavirus Type 16 Is a Means of Reconstructing Prehistoric Viral Spread and the Movement of Ancient Human Populations","volume":"67","author":"Ho","year":"1993","journal-title":"J. Virol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2463","DOI":"10.1128\/jvi.71.3.2463-2472.1997","article-title":"Human Papillomavirus Type 16 Sequence Variation in Cervical Cancers: A Worldwide Perspective","volume":"71","author":"Yamada","year":"1997","journal-title":"J. Virol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1128\/jcm.35.1.11-19.1997","article-title":"Human Papillomavirus Type 16 Sequence Variants: Identification by E6 and L1 Lineage-Specific Hybridization","volume":"35","author":"Wheeler","year":"1997","journal-title":"J. Clin. Microbiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"6855","DOI":"10.1128\/JVI.00483-12","article-title":"Human Papillomavirus Type 16 Genetic Variants: Phylogeny and Classification Based on E6 and LCR","volume":"86","author":"Cornet","year":"2012","journal-title":"J. Virol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Mirabello, L., Clarke, M.A., Nelson, C.W., Dean, M., Wentzensen, N., Yeager, M., Cullen, M., Boland, J.F., Alemany, L., and Banks, L. (2018). The Intersection of HPV Epidemiology, Genomics and Mechanistic Studies of HPV-Mediated Carcinogenesis. Viruses, 10.","DOI":"10.3390\/v10020080"},{"key":"ref_74","unstructured":"PaVE (2022, June 29). The Papillomavirus Episteme, Available online: https:\/\/pave.niaid.nih.gov\/."},{"key":"ref_75","first-page":"118","article-title":"A Straightforward HPV16 Lineage Classification Based on Machine Learning","volume":"5","author":"Alemany","year":"2022","journal-title":"Front. Artif. Intell."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"6424","DOI":"10.1128\/jvi.67.11.6424-6431.1993","article-title":"Evolution of Human Papillomavirus Type 18: An Ancient Phylogenetic Root in Africa and Intratype Diversity Reflect Coevolution with Human Ethnic Groups","volume":"67","author":"Ong","year":"1993","journal-title":"J. Virol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.virol.2012.06.011","article-title":"Oncogenic Potential Diverge among Human Papillomavirus Type 16 Natural Variants","volume":"432","author":"Sichero","year":"2012","journal-title":"Virology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.virol.2021.03.007","article-title":"Genetic Variants of HPV-16 and Their Geographical and Anatomical Distribution in Men: A Systematic Review with Meta-Analysis","volume":"558","author":"Ferreira","year":"2021","journal-title":"Virology"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1186\/s12985-021-01688-9","article-title":"Exploring the Roles of HPV16 Variants in Head and Neck Squamous Cell Carcinoma: Current Challenges and Opportunities","volume":"18","author":"Cochicho","year":"2021","journal-title":"Virol. J."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"169","DOI":"10.7883\/yoken.JJID.2014.584","article-title":"Genetic Variations of Human Papillomavirus Type 16: Implications for Cervical Carcinogenesis","volume":"68","author":"Kukimoto","year":"2015","journal-title":"Jpn. J. Infect. Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1743-422X-10-30","article-title":"Association of Human Papillomavirus Type 16 Long Control Region Mutation and Cervical Cancer","volume":"10","author":"Pientong","year":"2013","journal-title":"Virol. J."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2959","DOI":"10.1099\/0022-1317-81-12-2959","article-title":"Molecular Variants of Human Papillomavirus Types 16 and 18 Preferentially Associated with Cervical Neoplasia","volume":"81","author":"Villa","year":"2000","journal-title":"J. Gen. Virol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1002\/jmv.27359","article-title":"Genetic Variation in the E6 and E7 Genes of Human Papillomavirus Type 16 in Northeastern Argentina","volume":"94","author":"Totaro","year":"2022","journal-title":"J. Med. Virol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1002\/jmv.21002","article-title":"Molecular Variants of Human Papillomavirus Type 16 and 18 and Risk for Cervical Neoplasia in Portugal","volume":"79","author":"Pista","year":"2007","journal-title":"J. Med. Virol."},{"key":"ref_85","first-page":"4","article-title":"Risk for High-Grade Cervical Intraepithelial Neoplasia Associated with Variants of Human Papillomavirus Types 16 and 18","volume":"16","author":"Xi","year":"2007","journal-title":"Cancer Epidemiol. Biomark. Prev. A Publ. Am. Assoc. Cancer Res. Cosponsored Am. Soc. Prev. Oncol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.pvr.2019.02.001","article-title":"Human Papillomavirus 16 Sub-Lineage Dispersal and Cervical Cancer Risk Worldwide: Whole Viral Genome Sequences from 7116 HPV16-Positive Women","volume":"7","author":"Clifford","year":"2019","journal-title":"Papillomavirus Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1093\/jnci\/89.16.1227","article-title":"Association between Human Papillomavirus Type 18 Variants and Histopathology of Cervical Cancer","volume":"89","author":"Lizano","year":"1997","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_88","first-page":"7215","article-title":"Distribution of Human Papillomavirus Types 16 and 18 Variants in Squamous Cell Carcinomas and Adenocarcinomas of the Cervix","volume":"63","author":"Burk","year":"2003","journal-title":"Cancer Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1002\/ijc.20727","article-title":"Human Papillomavirus Type 18 Variants: Histopathology and E6\/E7 Polymorphisms in Three Countries","volume":"114","author":"Peters","year":"2005","journal-title":"Int. J. Cancer"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1093\/jnci\/93.17.1325","article-title":"Asian-American Variants of Human Papillomavirus 16 and Risk for Cervical Cancer: A Case-Control Study","volume":"93","author":"Berumen","year":"2001","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Alfaro, A., Ju\u00e1rez-Torres, E., Medina-Mart\u00ednez, I., Mateos-Guerrero, N., Bautista-Huerta, M., Rom\u00e1n-Bassaure, E., Villegas-Sep\u00falveda, N., and Berumen, J. (2016). Different Association of Human Papillomavirus 16 Variants with Early and Late Presentation of Cervical Cancer. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0169315"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S1386-6532(03)00094-5","article-title":"Molecular Variants of HPV Type 16 E6 among Mexican Women with LSIL and Invasive Cancer","volume":"29","author":"Mier","year":"2004","journal-title":"J. Clin. Virol. Off. Publ. Pan. Am. Soc. Clin. Virol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.ygyno.2005.12.002","article-title":"Distribution of HPV16 and 18 Intratypic Variants in Normal Cytology, Intraepithelial Lesions, and Cervical Cancer in a Mexican Population","volume":"102","author":"Lizano","year":"2006","journal-title":"Gynecol. Oncol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2953","DOI":"10.1007\/s00705-019-04407-6","article-title":"Mutational Landscape and Intra-Host Diversity of Human Papillomavirus Type 16 Long Control Region and E6 Variants in Cervical Samples","volume":"164","year":"2019","journal-title":"Arch. Virol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"323","DOI":"10.4103\/ijmr.IJMR_61_17","article-title":"High Frequency of HPV16 European Variant E350G among Mexican Women from Sinaloa","volume":"148","year":"2018","journal-title":"Indian J. Med. Res."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"P\u00e9rez-Quintanilla, M., M\u00e9ndez-Mart\u00ednez, R., V\u00e1zquez-Vega, S., Espinosa-Romero, R., Sotelo-Regil, R., P\u00e9rez-Montiel, M.D., Ramos-Alamillo, U., De Jes\u00fas Cabrera-L\u00f3pez, T., Barquet-Mu\u00f1oz, S.A., and P\u00e9rez-Plascencia, C. (2020). High Prevalence of Human Papillomavirus and European Variants of HPV 16 Infecting Concomitantly to Cervix and Oral Cavity in HIV Positive Women. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0227900"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.virol.2003.11.009","article-title":"Genomic Diversity of Human Papillomavirus-16, 18, 31, and 35 Isolates in a Mexican Population and Relationship to European, African, and Native American Variants","volume":"319","author":"Kalantari","year":"2004","journal-title":"Virology"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s12985-015-0242-3","article-title":"Association of Human Papillomavirus 16 E6 Variants with Cervical Carcinoma and Precursor Lesions in Women from Southern Mexico","volume":"12","year":"2015","journal-title":"Virol. J."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Anta\u00f1o-Arias, R., Del Moral-Hern\u00e1ndez, O., Ortiz-Ortiz, J., Alarc\u00f3n-Romero, L.D.C., Navor-Hern\u00e1ndez, J.A., Leyva-V\u00e1zquez, M.A., Jim\u00e9nez-L\u00f3pez, M.A., Organista-Nava, J., and Illades-Aguiar, B. (2021). E6\/E7 Variants of Human Papillomavirus 16 Associated with Cervical Carcinoma in Women in Southern Mexico. Pathogens, 10.","DOI":"10.3390\/pathogens10060773"},{"key":"ref_100","first-page":"110","article-title":"Genetic Variability in E6, E7 and L1 Genes of Human Papillomavirus 62 and Its Prevalence in Mexico","volume":"12","author":"Olszewski","year":"2017","journal-title":"Infect. Agents Cancer"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1159\/000489306","article-title":"Genetic Variability in E6 and E7 Oncogenes from Human Papillomavirus Type 58 in Mexican Women","volume":"60","author":"Canul","year":"2017","journal-title":"Intervirology"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"501","DOI":"10.33073\/pjm-2021-047","article-title":"Identification of Genetic Variants of Human Papillomavirus in a Group of Mexican HIV\/AIDS Patients and Their Possible Association with Cervical Cancer","volume":"70","year":"2021","journal-title":"Pol. J. Microbiol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1002\/(SICI)1097-0215(19991112)83:4<449::AID-IJC3>3.0.CO;2-0","article-title":"Asian-American variants of Human Papillomavirus type 16 have extensive mutations in the E2 gene and are highly amplified in cervical carcinomas","volume":"83","author":"Casas","year":"1999","journal-title":"Int. J. Cancer"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1099\/vir.0.19317-0","article-title":"Enhanced Oncogenicity of Asian-American Human Papillomavirus 16 Is Associated with Impaired E2 Repression of E6\/E7 Oncogene Transcription","volume":"85","author":"Espinosa","year":"2004","journal-title":"J. Gen. Virol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1099\/vir.0.045807-0","article-title":"Intratypic Changes of the E1 Gene and the Long Control Region Affect Ori Function of Human Papillomavirus Type 18 Variants","volume":"94","author":"Mohar","year":"2013","journal-title":"J. Gen. Virol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1007\/s00705-009-0362-4","article-title":"Functional Implication of Sequence Variation in the Long Control Region and E2 Gene among Human Papillomavirus Type 18 Variants","volume":"154","author":"Mohar","year":"2009","journal-title":"Arch. Virol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.virol.2015.11.017","article-title":"Changes in Global Gene Expression Profiles Induced by HPV 16 E6 Oncoprotein Variants in Cervical Carcinoma C33-A Cells","volume":"488","year":"2016","journal-title":"Virology"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.virol.2012.05.029","article-title":"Gene Expression Profiles Induced by E6 from Non-European HPV18 Variants Reveals a Differential Activation on Cellular Processes Driving to Carcinogenesis","volume":"432","author":"Herrera","year":"2012","journal-title":"Virology"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Perez-Bacho, E.G., Beltr\u00e1n-Anaya, F.O., Arechaga-Ocampo, E., Hern\u00e1ndez-Sotelo, D., Garibay-Cerdenares, O.L., Illades-Aguiar, B., Alarc\u00f3n-Romero, L.D.C., and Del Moral-Hern\u00e1ndez, O. (2022). The E6 Oncoprotein of HPV16 AA-c Variant Regulates Cell Migration through the MINCR\/MiR-28-5p\/RAP1B Axis. Viruses, 14.","DOI":"10.3390\/v14050963"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"273","DOI":"10.21873\/cgp.20258","article-title":"Effect of HPV 16 E6 Oncoprotein Variants on the Alterations of the Proteome of C33A Cells","volume":"18","year":"2021","journal-title":"Cancer Genom. Proteom."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1038\/s41598-022-05995-1","article-title":"Molecular Insights into the Interaction of HPV-16 E6 Variants against MAGI-1 PDZ1 Domain","volume":"12","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1002\/jmv.23568","article-title":"Regulation of P14ARF Expression by HPV-18 E6 Variants","volume":"85","year":"2013","journal-title":"J. Med. Virol."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Mu\u00f1oz-Bello, J.O., Olmedo-Nieva, L., Castro-Mu\u00f1oz, L.J., Manzo-Merino, J., Contreras-Paredes, A., Gonz\u00e1lez-Espinosa, C., L\u00f3pez-Saavedra, A., and Lizano, M. (2018). HPV-18 E6 Oncoprotein and Its Spliced Isoform E6*I Regulate the Wnt\/\u03b2-Catenin Cell Signaling Pathway through the TCF-4 Transcriptional Factor. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19103153"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.virol.2008.09.040","article-title":"E6 Variants of Human Papillomavirus 18 Differentially Modulate the Protein Kinase B\/Phosphatidylinositol 3-Kinase (Akt\/PI3K) Signaling Pathway","volume":"383","author":"Lizano","year":"2009","journal-title":"Virology"},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Olmedo-Nieva, L., Mu\u00f1oz-Bello, J.O., Contreras-Paredes, A., and Lizano, M. (2018). The Role of E6 Spliced Isoforms (E6*) in Human Papillomavirus-Induced Carcinogenesis. Viruses, 10.","DOI":"10.3390\/v10010045"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Bello-Rios, C., Monta\u00f1o, S., Garibay-Cerdenares, O.L., Araujo-Arcos, L.E., Leyva-V\u00e1zquez, M.A., and Illades-Aguiar, B. (2021). Modeling and Molecular Dynamics of the 3D Structure of the HPV16 E7 Protein and Its Variants. Int. J. Mol. Sci., 22.","DOI":"10.20944\/preprints202012.0671.v1"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1007\/s00705-018-04124-6","article-title":"Intratype Variants of the E2 Protein from Human Papillomavirus Type 18 Induce Different Gene Expression Profiles Associated with Apoptosis and Cell Proliferation","volume":"164","author":"Lizano","year":"2019","journal-title":"Arch. Virol."},{"key":"ref_118","unstructured":"IARC (2022, June 29). Cancer Today. Available online: https:\/\/gco.iarc.fr\/today\/home."},{"key":"ref_119","unstructured":"World Health Organization (2022, June 29). Human Papillomavirus (HPV) Vaccination Coverage. Available online: https:\/\/immunizationdata.who.int\/pages\/coverage\/hpv.html."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.pvr.2016.05.001","article-title":"Monitoring the Impact of HPV Vaccine in Males-Considerations and Challenges","volume":"2","author":"Brotherton","year":"2016","journal-title":"Papillomavirus Res."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Maldonado, I., Plata, M., Gonzalez, M., Correa, A., Nossa, C., Giuliano, A.R., Joura, E.A., Ferenczy, A., Ronnett, B.M., and Stoler, M.H. (2022). Effectiveness, Immunogenicity, and Safety of the Quadrivalent HPV Vaccine in Women and Men Aged 27\u201345 Years. Hum. Vaccin. Immunother., 2078626.","DOI":"10.1080\/21645515.2022.2078626"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/S1473-3099(21)00327-3","article-title":"Efficacy, Immunogenicity, and Safety of a Quadrivalent HPV Vaccine in Men: Results of an Open-Label, Long-Term Extension of a Randomised, Placebo-Controlled, Phase 3 Trial","volume":"22","author":"Goldstone","year":"2022","journal-title":"Lancet Infect. Dis."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/15\/8566\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:01:07Z","timestamp":1760140867000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/15\/8566"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,2]]},"references-count":122,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["ijms23158566"],"URL":"https:\/\/doi.org\/10.3390\/ijms23158566","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,2]]}}}