{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T02:56:55Z","timestamp":1792205815562,"version":"4.4.0"},"reference-count":171,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,21]],"date-time":"2025-09-21T00:00:00Z","timestamp":1758412800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human papillomavirus (HPV) integration is recognized as a hallmark event in cervical carcinogenesis. However, it does not represent a routine phase of the viral life cycle but rather a stochastic occurrence, often constituting a dead-end pathway for the virus. High-risk human papillomavirus (hr-HPV) exhibits a greater propensity for integration. The progression from initial infection to genomic integration constitutes a dynamic multi-step oncogenic process in the development of cervical cancer (CC). This process involves viral entry, immune evasion, persistent infection, and ultimately integration. This article innovatively provides a comprehensive overview of this multi-stage mechanism: HPV, via the L1\/L2 proteins, mediates internalization and establishes infection. Subsequently, under the influence of factors such as the host\u2019s genetic background, vaginal microbiota imbalance, and immune evasion, the host\u2019s DNA damage response (DDR) pathways are activated. Viral DNA integrates into host genome vulnerable sites (e.g., 3q28 and 8q24) through microhomology-mediated end joining (MMEJ) or other alternative pathways. Following integration, the expression of viral oncogenes persists, triggering host genomic rearrangements, aberrant epigenetic modifications, and immune microenvironment remodeling, all of which collectively drive cervical cancer progression. The study further reveals the clinical potential of HPV integration as a highly specific molecular biomarker, offering new perspectives for precision screening and targeted therapy. This dynamic model deepens our understanding of the HPV carcinogenic mechanism and provides a theoretical basis for intervention strategies.<\/jats:p>","DOI":"10.3390\/ijms26189214","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T13:04:44Z","timestamp":1758546284000},"page":"9214","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["From Viral Infection to Genome Reshaping: The Triggering Role of HPV Integration in Cervical Cancer"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4734-858X","authenticated-orcid":false,"given":"Junlan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1933-679X","authenticated-orcid":false,"given":"Shuang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,21]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA. Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e197","DOI":"10.1016\/S2214-109X(22)00501-0","article-title":"Global Estimates of Incidence and Mortality of Cervical Cancer in 2020: A Baseline Analysis of the WHO Global Cervical Cancer Elimination Initiative","volume":"11","author":"Singh","year":"2023","journal-title":"Lancet Glob. Health"},{"key":"ref_3","unstructured":"World Health Organization (2020). Global Strategy to Accelerate the Elimination of Cervical Cancer as a Public Health Problem, World Health Organization."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/S1470-2045(22)00270-4","article-title":"Cancer in Sub-Saharan Africa in 2020: A Review of Current Estimates of the National Burden, Data Gaps, and Future Needs","volume":"23","author":"Bray","year":"2022","journal-title":"Lancet Oncol."},{"key":"ref_5","unstructured":"(2025, September 07). Cervical Cancer. Available online: https:\/\/www.who.int\/health-topics\/cervical-cancer."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"F88","DOI":"10.1016\/j.vaccine.2012.06.095","article-title":"Evidence Regarding Human Papillomavirus Testing in Secondary Prevention of Cervical Cancer","volume":"30","author":"Arbyn","year":"2012","journal-title":"Vaccine"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1093\/jnci\/djr532","article-title":"Pooled Analysis of a Self-Sampling HPV DNA Test as a Cervical Cancer Primary Screening Method","volume":"104","author":"Zhao","year":"2012","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1093\/jnci\/dji187","article-title":"The Elevated 10-Year Risk of Cervical Precancer and Cancer in Women with Human Papillomavirus (HPV) Type 16 or 18 and the Possible Utility of Type-Specific HPV Testing in Clinical Practice","volume":"97","author":"Khan","year":"2005","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.bpobgyn.2017.08.015","article-title":"The Natural History of Human Papillomavirus Infection","volume":"47","author":"Brotons","year":"2018","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1111\/1471-0528.17597","article-title":"Testing for Viral DNA Integration among HPV-Positive Women to Detect Cervical Precancer: An Observational Cohort Study","volume":"131","author":"Hu","year":"2024","journal-title":"BJOG Int. J. Obstet. Gynaecol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e70008","DOI":"10.1002\/jmv.70008","article-title":"LAMP-Based Electrochemical Platform for Monitoring HPV Genome Integration at the mRNA Level Associated with Higher Risk of Cervical Cancer Progression","volume":"96","author":"Izadi","year":"2024","journal-title":"J. Med. Virol."},{"key":"ref_12","first-page":"84","article-title":"Correlation between Integration of High-Risk HPV Genome into Human DNA Detected by Molecular Combing and the Severity of Cervical Lesions: First Results of the EXPL-HPV-002 Study","volume":"84","author":"Bouchilloux","year":"2019","journal-title":"Ceska Gynekol."},{"key":"ref_13","first-page":"134","article-title":"Understanding the HPV Integration and Its Progression to Cervical Cancer","volume":"61","year":"2018","journal-title":"Infect. Genet. Evol. J. Mol. Epidemiol. Evol. Genet. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"McBride, A.A. (2017). Oncogenic Human Papillomaviruses. Philos. Trans. R. Soc. B Biol. Sci., 372.","DOI":"10.1098\/rstb.2016.0273"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/s41579-021-00617-5","article-title":"Human Papillomaviruses: Diversity, Infection and Host Interactions","volume":"20","author":"McBride","year":"2022","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_16","unstructured":"World Health Organization (2021). Special Programme of Research, Development, and Research Training in Human Reproduction (World Health Organization). WHO Guideline for Screening and Treatment of Cervical Pre-Cancer Lesions for Cervical Cancer Prevention, World Health Organization. [2nd ed.]."},{"key":"ref_17","unstructured":"Albert Einstein College of Medicine, Analytical Biological Services, Barretos Cancer Hospital, Baylor College of Medicine, Beckman Research Institute of City of Hope, Buck Institute for Research on Aging, Canada\u2019s Michael Smith Genome Sciences Centre, Harvard Medical School, Helen F. Graham Cancer Center & Research Institute at Christiana Care Health Services, and HudsonAlpha Institute for Biotechnology (2017). Integrated Genomic and Molecular Characterization of Cervical Cancer. Nature, 543, 378\u2013384."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4647","DOI":"10.1002\/jmv.26928","article-title":"A Meta-Analysis of Human Papillomavirus Prevalence and Types among Iranian Women with Normal Cervical Cytology, Premalignant Lesions, and Cervical Cancer","volume":"93","author":"Salavatiha","year":"2021","journal-title":"J. Med. Virol."},{"key":"ref_19","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_20","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1038\/s41588-020-0673-7","article-title":"Analysis of Ugandan Cervical Carcinomas Identifies Human Papillomavirus Clade-Specific Epigenome and Transcriptome Landscapes","volume":"52","author":"Gagliardi","year":"2020","journal-title":"Nat. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"200247","DOI":"10.1016\/j.tvr.2022.200247","article-title":"Differences in Integration Frequencies and APOBEC3 Profiles of Five High-Risk HPV Types Adheres to Phylogeny","volume":"14","author":"Repesa","year":"2022","journal-title":"Tumour Virus Res."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Mohammed, F.A., Tune, K.K., Jett, M., and Muhie, S. (2023). Cervical Cancer Stages, Human Papillomavirus Integration, and Malignant Genetic Mutations: Integrative Analysis of Datasets from Four Different Cohorts. Cancers, 15.","DOI":"10.3390\/cancers15235595"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Berti, F.C.B., Mathias, C., Garcia, L.E., Gradia, D.F., de Ara\u00fajo-Souza, P.S., Cipolla, G.A., de Oliveira, J.C., and Malheiros, D. (2021). Comprehensive Analysis of ceRNA Networks in HPV16- and HPV18-Mediated Cervical Cancers Reveals XIST as a Pivotal Competing Endogenous RNA. Biochim. Biophys. Acta Mol. Basis Dis., 1867.","DOI":"10.1016\/j.bbadis.2021.166172"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Mir, B.A., Ahmad, A., Farooq, N., Priya, M.V., Siddiqui, A.H., Asif, M., Manzoor, R., Ishqi, H.M., Alomar, S.Y., and Rahaman, P.F. (2023). Increased Expression of HPV-E7 Oncoprotein Correlates with a Reduced Level of pRb Proteins via High Viral Load in Cervical Cancer. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-42022-3"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"270","DOI":"10.18821\/0507-4088-2016-61-6-270-274","article-title":"Integrative and Episomal Forms of Genotype 16 of Human Papillomavirus in Patients with Cervical Intraepithelial Neoplasia and Cervical Cancer","volume":"61","author":"Ibragimova","year":"2016","journal-title":"Vopr. Virusol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"S52","DOI":"10.1016\/j.vaccine.2006.05.031","article-title":"Chapter 6: Epidemiology and Transmission Dynamics of Genital HPV Infection","volume":"24","author":"Burchell","year":"2006","journal-title":"Vaccine"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1093\/jnci\/djt051","article-title":"Genome-Wide Association Study of Susceptibility Loci for Cervical Cancer","volume":"105","author":"Chen","year":"2013","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2458","DOI":"10.1002\/ijc.33171","article-title":"Association of Genomic Variants at the Human Leukocyte Antigen Locus with Cervical Cancer Risk, HPV Status and Gene Expression Levels","volume":"147","author":"Ramachandran","year":"2020","journal-title":"Int. J. Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1093\/hmg\/ddy390","article-title":"Genome-Wide Association Study of Cervical Cancer Suggests a Role for ARRDC3 Gene in Human Papillomavirus Infection","volume":"28","author":"Takeuchi","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/S1470-2045(21)00028-0","article-title":"Genetic Variation in Cervical Preinvasive and Invasive Disease: A Genome-Wide Association Study","volume":"22","author":"Bowden","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1038\/ng.2687","article-title":"A Genome-Wide Association Study Identifies Two New Cervical Cancer Susceptibility Loci at 4q12 and 17q12","volume":"45","author":"Shi","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Joo, J., Omae, Y., Hitomi, Y., Park, B., Shin, H.-J., Yoon, K.-A., Sawai, H., Tsuiji, M., Hayashi, T., and Kong, S.-Y. (2019). The Association of Integration Patterns of Human Papilloma Virus and Single Nucleotide Polymorphisms on Immune- or DNA Repair-Related Genes in Cervical Cancer Patients. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-49523-0"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.tig.2014.10.005","article-title":"Lessons and Implications from Association Studies and Post-GWAS Analyses of Cervical Cancer","volume":"31","author":"Chen","year":"2015","journal-title":"Trends Genet. TIG"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Yu, T., Gao, S., Jin, F., Yan, B., Wang, W., and Wang, Z. (2024). Characteristics of the Vaginal Microbiota and Vaginal Metabolites in Women with Cervical Dysplasia. Front. Cell. Infect. Microbiol., 14, Erratum in Front. Cell. Infect. Microbiol. 2024, 14, 1527287.","DOI":"10.3389\/fcimb.2024.1457216"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Ntuli, L., Mtshali, A., Mzobe, G., Liebenberg, L.J., and Ngcapu, S. (2022). Role of Immunity and Vaginal Microbiome in Clearance and Persistence of Human Papillomavirus Infection. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.927131"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1111\/j.1749-6632.2011.06041.x","article-title":"The Genital Econiche: Focus on Microbiota and Bacterial Vaginosis","volume":"1230","author":"Danielsson","year":"2011","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Yang, Q., Wang, Y., Wei, X., Zhu, J., Wang, X., Xie, X., and Lu, W. (2020). The Alterations of Vaginal Microbiome in HPV16 Infection as Identified by Shotgun Metagenomic Sequencing. Front. Cell. Infect. Microbiol., 10.","DOI":"10.3389\/fcimb.2020.00286"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/mi.2015.86","article-title":"Cervicovaginal Microbiome Dysbiosis Is Associated with Proteome Changes Related to Alterations of the Cervicovaginal Mucosal Barrier","volume":"9","author":"Borgdorff","year":"2016","journal-title":"Mucosal Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1093\/infdis\/jiu004","article-title":"Bacteria in the Vaginal Microbiome Alter the Innate Immune Response and Barrier Properties of the Human Vaginal Epithelia in a Species-Specific Manner","volume":"209","author":"Doerflinger","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/j.immuni.2015.04.019","article-title":"Cervicovaginal Bacteria Are a Major Modulator of Host Inflammatory Responses in the Female Genital Tract","volume":"42","author":"Anahtar","year":"2015","journal-title":"Immunity"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1968257","DOI":"10.1080\/19490976.2021.1968257","article-title":"Microbiota Metabolite Butyrate Constrains Neutrophil Functions and Ameliorates Mucosal Inflammation in Inflammatory Bowel Disease","volume":"13","author":"Li","year":"2021","journal-title":"Gut Microbes"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"106302","DOI":"10.1016\/j.micpath.2023.106302","article-title":"Exploring the Correlation between Progression of Human Papillomavirus Infection towards Carcinogenesis and Nutrition","volume":"183","author":"Letafati","year":"2023","journal-title":"Microb. Pathog."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1159\/000357187","article-title":"Management of Cutaneous Human Papillomavirus Infection in Immunocompromised Patients","volume":"45","author":"Varada","year":"2014","journal-title":"Curr. Probl. Dermatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1097\/00006250-199203000-00001","article-title":"High Frequency of Latent and Clinical Human Papillomavirus Cervical Infections in Immunocompromised Human Immunodeficiency Virus-Infected Women","volume":"79","author":"Johnson","year":"1992","journal-title":"Obs. Gynecol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.canlet.2020.10.004","article-title":"APOBEC: A molecular driver in cervical cancer pathogenesis","volume":"496","author":"Revathidevi","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1084\/jem.20122394","article-title":"The Human Papillomavirus Type 16 E7 Oncoprotein Induces a Transcriptional Repressor Complex on the Toll-like Receptor 9 Promoter","volume":"210","author":"Hasan","year":"2013","journal-title":"J. Exp. Med."},{"key":"ref_47","first-page":"680","article-title":"Human Papillomavirus Infection and Cervical Cancer: Pathogenesis and Epidemiology","volume":"1","author":"Santos","year":"2007","journal-title":"Commun. Curr. Res. Educ. Top. Trends Appl. Microbiol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Liu, Y., and Ai, H. (2024). Comprehensive insights into human papillomavirus and cervical cancer: Pathophysiology, screening, and vaccination strategies. Biochim. Biophys. Acta (BBA)-Rev. Cancer, 1879.","DOI":"10.1016\/j.bbcan.2024.189192"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/s41525-021-00264-y","article-title":"Recurrent Integration of Human Papillomavirus Genomes at Transcriptional Regulatory Hubs","volume":"6","author":"Warburton","year":"2021","journal-title":"npj Genom. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e01084-17","DOI":"10.1128\/JVI.01084-17","article-title":"High-Risk Alphapapillomavirus Oncogenes Impair the Homologous Recombination Pathway","volume":"91","author":"Wallace","year":"2017","journal-title":"J. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Moody, C.A., and Laimins, L.A. (2009). Human Papillomaviruses Activate the ATM DNA Damage Pathway for Viral Genome Amplification upon Differentiation. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000605"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e01012-17","DOI":"10.1128\/JVI.01012-17","article-title":"Impact of Replication Stress in Human Papillomavirus Pathogenesis","volume":"93","author":"Moody","year":"2019","journal-title":"J. Virol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0065-3527(08)00404-1","article-title":"Replication and Partitioning of Papillomavirus Genomes","volume":"72","author":"McBride","year":"2008","journal-title":"Adv. Virus Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"10076","DOI":"10.1038\/s41467-024-54373-0","article-title":"Glycan-Induced Structural Activation Softens the Human Papillomavirus Capsid for Entry through Reduction of Intercapsomere Flexibility","volume":"15","author":"Feng","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/S0955-0674(00)00131-9","article-title":"Deposition of Laminin 5 in Epidermal Wounds Regulates Integrin Signaling and Adhesion","volume":"12","author":"Nguyen","year":"2000","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"8940","DOI":"10.1128\/JVI.00724-06","article-title":"Keratinocyte-Secreted Laminin 5 Can Function as a Transient Receptor for Human Papillomaviruses by Binding Virions and Transferring Them to Adjacent Cells","volume":"80","author":"Culp","year":"2006","journal-title":"J. Virol."},{"key":"ref_57","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_58","doi-asserted-by":"crossref","first-page":"4638","DOI":"10.1128\/JVI.00143-08","article-title":"Mechanisms of Human Papillomavirus Type 16 Neutralization by L2 Cross-Neutralizing and L1 Type-Specific Antibodies","volume":"82","author":"Day","year":"2008","journal-title":"J. Virol."},{"key":"ref_59","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_60","doi-asserted-by":"crossref","first-page":"7765","DOI":"10.1128\/JVI.00370-13","article-title":"Human Papillomavirus Types 16, 18, and 31 Share Similar Endocytic Requirements for Entry","volume":"87","author":"Spoden","year":"2013","journal-title":"J. Virol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"eadc9830","DOI":"10.1126\/sciadv.adc9830","article-title":"HPV Is a Cargo for the COPI Sorting Complex during Virus Entry","volume":"9","author":"Harwood","year":"2023","journal-title":"Sci. Adv."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Aydin, I., Weber, S., Snijder, B., Samperio Ventayol, P., K\u00fchbacher, A., Becker, M., Day, P.M., Schiller, J.T., Kann, M., and Pelkmans, L. (2014). Large Scale RNAi Reveals the Requirement of Nuclear Envelope Breakdown for Nuclear Import of Human Papillomaviruses. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004162"},{"key":"ref_63","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_64","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.virusres.2016.11.014","article-title":"Host Cell Restriction Factors That Limit Transcription and Replication of Human Papillomavirus","volume":"231","author":"Porter","year":"2017","journal-title":"Virus Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e00845-813","DOI":"10.1128\/mBio.00845-13","article-title":"Sp100 Provides Intrinsic Immunity against Human Papillomavirus Infection","volume":"4","author":"Stepp","year":"2013","journal-title":"Mbio"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"11291","DOI":"10.1128\/JVI.76.22.11291-11300.2002","article-title":"Human Papillomavirus Type 31b Infection of Human Keratinocytes and the Onset of Early Transcription","volume":"76","author":"Ozbun","year":"2002","journal-title":"J. Virol."},{"key":"ref_67","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_68","doi-asserted-by":"crossref","unstructured":"Rana, A., Yilmaz, G., Biswas-Fiss, E.E., and Biswas, S. (2025). Mechanisms of Viral DNA Replication of Human Papillomavirus: E2 Protein-Dependent Recruitment of E1 DNA Helicase to the Origin of DNA Replication. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26094333"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Rana, A., Evande, R., Biswas-Fiss, E., and Biswas, S. (2024). Abstract 1637 Molecular Mechanism of HPV DNA Replication Initiation, Mediated by E1 and E2 Proteins. J. Biol. Chem., 300.","DOI":"10.1016\/j.jbc.2024.106943"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Baedyananda, F., Chaiwongkot, A., Varadarajan, S., and Bhattarakosol, P. (2021). HPV16 E1 Dysregulated Cellular Genes Involved in Cell Proliferation and Host DNA Damage: A Possible Role in Cervical Carcinogenesis. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0260841"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"8981","DOI":"10.1128\/JVI.00541-11","article-title":"The Papillomavirus E1 Helicase Activates a Cellular DNA Damage Response in Viral Replication Foci","volume":"85","author":"Sakakibara","year":"2011","journal-title":"J. Virol."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Jang, M.K., Shen, K., and McBride, A.A. (2014). Papillomavirus Genomes Associate with BRD4 to Replicate at Fragile Sites in the Host Genome. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004117"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e0083022","DOI":"10.1128\/jvi.00830-22","article-title":"Interaction with TopBP1 Is Required for Human Papillomavirus 16 E2 Plasmid Segregation\/Retention Function during Mitosis","volume":"96","author":"Prabhakar","year":"2022","journal-title":"J. Virol."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Dreer, M., Fertey, J., van de Poel, S., Straub, E., Madlung, J., Macek, B., Iftner, T., and Stubenrauch, F. (2016). Interaction of NCOR\/SMRT Repressor Complexes with Papillomavirus E8^E2C Proteins Inhibits Viral Replication. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005556"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.virusres.2016.11.005","article-title":"Control of Viral Replication and Transcription by the Papillomavirus E8^E2 Protein","volume":"231","author":"Dreer","year":"2017","journal-title":"Virus Res."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Uhlorn, B.L., Jackson, R., Li, S., Bratton, S.M., Van Doorslaer, K., and Campos, S.K. (2020). Vesicular Trafficking Permits Evasion of cGAS\/STING Surveillance during Initial Human Papillomavirus Infection. PLoS Pathog., 16.","DOI":"10.1101\/2020.03.29.014118"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Guion, L., Bienkowska-Haba, M., DiGiuseppe, S., Florin, L., and Sapp, M. (2019). PML Nuclear Body-Residing Proteins Sequentially Associate with HPV Genome after Infectious Nuclear Delivery. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007590"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Guion, L.G., and Sapp, M. (2020). The Role of Promyelocytic Leukemia Nuclear Bodies during HPV Infection. Front. Cell. Infect. Microbiol., 10.","DOI":"10.3389\/fcimb.2020.00035"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.virusres.2016.11.004","article-title":"Manipulation of the Innate Immune Response by Human Papillomaviruses","volume":"231","author":"Hong","year":"2017","journal-title":"Virus Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s13046-017-0541-1","article-title":"hrHPV E5 Oncoprotein: Immune Evasion and Related Immunotherapies","volume":"36","author":"Barros","year":"2017","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1093\/carcin\/bgp066","article-title":"Involvement of NF-\u03baB and AP-1 in COX-2 Upregulation by Human Papillomavirus 16 E5 Oncoprotein","volume":"30","author":"Kim","year":"2009","journal-title":"Carcinogenesis"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1016\/j.molmed.2024.05.009","article-title":"HPV Integration and Cervical Cancer: A Failed Evolutionary Viral Trait","volume":"30","author":"Molina","year":"2024","journal-title":"Trends Mol. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1002\/jmv.24256","article-title":"Sites of Disruption within E1 and E2 Genes of HPV16 and Association with Cervical Dysplasia","volume":"87","author":"Tsakogiannis","year":"2015","journal-title":"J. Med. Virol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.pvr.2018.04.002","article-title":"HPV DNA Methylation at the Early Promoter and E1\/E2 Integrity: A Comparison between HPV16, HPV18 and HPV45 in Cervical Cancer","volume":"5","author":"Felix","year":"2018","journal-title":"Papillomavirus Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"4665","DOI":"10.62347\/KKLE8602","article-title":"Identification of Novel Genomic Hotspots and Tumor-Relevant Genes via Comprehensive Analysis of HPV Integration in Chinese Patients of Cervical Cancer","volume":"14","author":"Xu","year":"2024","journal-title":"Am. J. Cancer Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"5282","DOI":"10.1128\/JVI.73.7.5282-5293.1999","article-title":"Role of the ATP-Binding Domain of the Human Papillomavirus Type 11 E1 Helicase in E2-Dependent Binding to the Origin","volume":"73","author":"Titolo","year":"1999","journal-title":"J. Virol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e01582-19","DOI":"10.1128\/JVI.01582-19","article-title":"Human Papillomavirus 16 E5 Inhibits Interferon Signaling and Supports Episomal Viral Maintenance","volume":"94","author":"Scott","year":"2020","journal-title":"J. Virol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1016\/0092-8674(90)90409-8","article-title":"The E6 Oncoprotein Encoded by Human Papillomavirus Types 16 and 18 Promotes the Degradation of P53","volume":"63","author":"Scheffner","year":"1990","journal-title":"Cell"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/380079a0","article-title":"Telomerase Activation by the E6 Gene Product of Human Papillomavirus Type 16","volume":"380","author":"Klingelhutz","year":"1996","journal-title":"Nature"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.mrrev.2016.08.001","article-title":"Molecular Mechanisms Underlying Human Papillomavirus E6 and E7 Oncoprotein-Induced Cell Transformation","volume":"772","author":"Mittal","year":"2017","journal-title":"Mutat. Res.\/Rev. Mutat. Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.tim.2017.07.007","article-title":"The HPV E6\/E7 Oncogenes: Key Factors for Viral Carcinogenesis and Therapeutic Targets","volume":"26","author":"Bossler","year":"2018","journal-title":"Trends Microbiol."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"McBride, A.A., and Warburton, A. (2017). The Role of Integration in Oncogenic Progression of HPV-Associated Cancers. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006211"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Yeo-Teh, N.S.L., Ito, Y., and Jha, S. (2018). High-Risk Human Papillomaviral Oncogenes E6 and E7 Target Key Cellular Pathways to Achieve Oncogenesis. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19061706"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"3976","DOI":"10.1158\/0008-5472.CAN-06-4273","article-title":"Cyclooxygenase-2 Transcription Is Regulated by Human Papillomavirus 16 E6 and E7 Oncoproteins: Evidence of a Corepressor\/Coactivator Exchange","volume":"67","author":"Subbaramaiah","year":"2007","journal-title":"Cancer Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"21","DOI":"10.7150\/ijbs.21547","article-title":"Human Papillomavirus Types 16 and 18 Early-Expressed Proteins Differentially Modulate the Cellular Redox State and DNA Damage","volume":"14","author":"Valverde","year":"2018","journal-title":"Int. J. Biol. Sci."},{"key":"ref_96","first-page":"427","article-title":"Expression of HPV16 E6 or E7 Increases Integration of Foreign DNA","volume":"13","author":"Kessis","year":"1996","journal-title":"Oncogene"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"45","DOI":"10.2217\/fvl.10.73","article-title":"HPV-DNA Integration and Carcinogenesis: Putative Roles for Inflammation and Oxidative Stress","volume":"6","author":"Williams","year":"2011","journal-title":"Future Virol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3977","DOI":"10.1038\/sj.onc.1206629","article-title":"A Comprehensive Analysis of HPV Integration Loci in Anogenital Lesions Combining Transcript and Genome-Based Amplification Techniques","volume":"22","author":"Ziegert","year":"2003","journal-title":"Oncogene"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1146\/annurev.biochem.052308.093131","article-title":"The Mechanism of Double-Strand DNA Break Repair by the Nonhomologous DNA End-Joining Pathway","volume":"79","author":"Lieber","year":"2010","journal-title":"Annu. Rev. Biochem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1038\/ng.3178","article-title":"Genome-Wide Profiling of HPV Integration in Cervical Cancer Identifies Clustered Genomic Hot Spots and a Potential Microhomology-Mediated Integration Mechanism","volume":"47","author":"Hu","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Jiang, Y. (2022). Contribution of Microhomology to Genome Instability: Connection between DNA Repair and Replication Stress. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232112937"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Groves, I.J., Drane, E.L.A., Michalski, M., Monahan, J.M., Scarpini, C.G., Smith, S.P., Bussotti, G., V\u00e1rnai, C., Schoenfelder, S., and Fraser, P. (2021). Short- and Long-Range Cis Interactions between Integrated HPV Genomes and Cellular Chromatin Dysregulate Host Gene Expression in Early Cervical Carcinogenesis. PLoS Pathog., 17.","DOI":"10.1101\/2021.02.03.429496"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/nature06337","article-title":"Human CtIP Promotes DNA End Resection","volume":"450","author":"Sartori","year":"2007","journal-title":"Nature"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1016\/j.dnarep.2010.10.001","article-title":"Mre11-Rad50-Nbs1 Conformations and the Control of Sensing, Signaling, and Effector Responses at DNA Double-Strand Breaks","volume":"9","author":"Williams","year":"2010","journal-title":"DNA Repair"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"5082","DOI":"10.1128\/MCB.00293-08","article-title":"ERCC1-XPF Endonuclease Facilitates DNA Double-Strand Break Repair","volume":"28","author":"Ahmad","year":"2008","journal-title":"Mol. Cell. Biol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"5577","DOI":"10.1093\/nar\/gks186","article-title":"Microhomology-Mediated DNA Strand Annealing and Elongation by Human DNA Polymerases \u03bb and \u03b2 on Normal and Repetitive DNA Sequences","volume":"40","author":"Crespan","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"3297","DOI":"10.1093\/nar\/gkn184","article-title":"Human DNA Ligases I and III, but Not Ligase IV, Are Required for Microhomology-Mediated End Joining of DNA Double-Strand Breaks","volume":"36","author":"Liang","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1038\/ng.399","article-title":"The DNA Replication FoSTeS\/MMBIR Mechanism Can Generate Genomic, Genic and Exonic Complex Rearrangements in Humans","volume":"41","author":"Zhang","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/nrg2593","article-title":"Mechanisms of Change in Gene Copy Number","volume":"10","author":"Hastings","year":"2009","journal-title":"Nat. Rev. Genet."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Hastings, P.J., Ira, G., and Lupski, J.R. (2009). A Microhomology-Mediated Break-Induced Replication Model for the Origin of Human Copy Number Variation. PLoS Genet., 5.","DOI":"10.1371\/journal.pgen.1000327"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1038\/sj.onc.1210001","article-title":"Repression of RAD51 Gene Expression by E2F4\/P130 Complexes in Hypoxia","volume":"26","author":"Bindra","year":"2007","journal-title":"Oncogene"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1101\/gr.164806.113","article-title":"Genome-Wide Analysis of HPV Integration in Human Cancers Reveals Recurrent, Focal Genomic Instability","volume":"24","author":"Akagi","year":"2014","journal-title":"Genome Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"3878","DOI":"10.1158\/0008-5472.CAN-04-0009","article-title":"Systematic Review of Genomic Integration Sites of Human Papillomavirus Genomes in Epithelial Dysplasia and Invasive Cancer of the Female Lower Genital Tract","volume":"64","author":"Wentzensen","year":"2004","journal-title":"Cancer Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1158\/0008-5472.CAN-07-2754","article-title":"Type-Dependent Integration Frequency of Human Papillomavirus Genomes in Cervical Lesions","volume":"68","author":"Vinokurova","year":"2008","journal-title":"Cancer Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"100211","DOI":"10.1016\/j.xgen.2022.100211","article-title":"Multi-Omics Characterization of Silent and Productive HPV Integration in Cervical Cancer","volume":"3","author":"Fan","year":"2023","journal-title":"Cell Genom."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.lfs.2015.01.039","article-title":"Integrated HPV Genomes Tend to Integrate in Gene Desert Areas in the CaSki, HeLa, and SiHa Cervical Cancer Cell Lines","volume":"127","author":"Diao","year":"2015","journal-title":"Life Sci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"7233","DOI":"10.1038\/sj.onc.1207006","article-title":"Preferential Integration of Human Papillomavirus Type 18 near the C-Myc Locus in Cervical Carcinoma","volume":"22","author":"Ferber","year":"2003","journal-title":"Oncogene"},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Li, W., Qi, Y., Cui, X., Huo, Q., Zhu, L., Zhang, A., Tan, M., Hong, Q., Yang, Y., and Zhang, H. (2018). Characteristic of HPV Integration in the Genome and Transcriptome of Cervical Cancer Tissues. BioMed Res. Int., 2018.","DOI":"10.1155\/2018\/6242173"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1038\/s41416-020-01153-4","article-title":"Human Papilloma Virus (HPV) Integration Signature in Cervical Cancer: Identification of MACROD2 Gene as HPV Hot Spot Integration Site","volume":"124","author":"Kamal","year":"2021","journal-title":"Br. J. Cancer"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"17973","DOI":"10.1007\/s00432-023-05494-4","article-title":"Characteristics of HPV Integration in Cervical Adenocarcinoma and Squamous Carcinoma","volume":"149","author":"Bi","year":"2023","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1002\/ijc.30243","article-title":"Genomic Characterization of Viral Integration Sites in HPV-Related Cancers","volume":"139","author":"Bodelon","year":"2016","journal-title":"Int. J. Cancer"},{"key":"ref_122","first-page":"5916","article-title":"Human Papillomavirus Type 16 Integrations in Cervical Tumors Frequently Occur in Common Fragile Sites","volume":"60","author":"Thorland","year":"2000","journal-title":"Cancer Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1038\/s41422-020-0357-y","article-title":"Genome-Wide High-Resolution Mapping of Mitotic DNA Synthesis Sites and Common Fragile Sites by Direct Sequencing","volume":"30","author":"Ji","year":"2020","journal-title":"Cell Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.1038\/s41467-022-30190-1","article-title":"Long-Read Sequencing Unveils High-Resolution HPV Integration and Its Oncogenic Progression in Cervical Cancer","volume":"13","author":"Zhou","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"4081","DOI":"10.1158\/0008-5472.CAN-09-3335","article-title":"In Vitro Progression of HPV16 Episome-Associated Cervical Neoplasia Displays Fundamental Similarities to Integrant-Associated Carcinogenesis","volume":"70","author":"Gray","year":"2010","journal-title":"Cancer Res."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1158\/0008-5472.CAN-22-3030","article-title":"Extrachromosomal Amplification of Human Papillomavirus Episomes Is a Mechanism of Cervical Carcinogenesis","volume":"83","author":"Rossi","year":"2023","journal-title":"Cancer Res."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Chen, A.M. (2025). Epidemiological Trends in the Characterization of of Human Papillomavirus Virus-Related Oropharyngeal Cancer: A Global Perspective. Curr. Oncol. Rep.","DOI":"10.1007\/s11912-025-01656-4"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1007\/s11912-025-01666-2","article-title":"HPV-Mediated Radiosensitivity in Oropharyngeal Squamous Cell Carcinoma: Molecular Mechanisms and Cellular Pathways","volume":"27","author":"Chen","year":"2025","journal-title":"Curr. Oncol. Rep."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Kadaja, M., Isok-Paas, H., Laos, T., Ustav, E., and Ustav, M. (2009). Mechanism of Genomic Instability in Cells Infected with the High-Risk Human Papillomaviruses. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000397"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.jgg.2020.05.006","article-title":"HPV-CCDC106 Integration Alters Local Chromosome Architecture and Hijacks an Enhancer by Three-Dimensional Genome Structure Remodeling in Cervical Cancer","volume":"47","author":"Cao","year":"2020","journal-title":"J. Genet. Genom."},{"key":"ref_131","first-page":"7075","article-title":"The Human Papillomavirus Type 16 E6 and E7 Oncoproteins Independently Induce Numerical and Structural Chromosome Instability","volume":"62","author":"Duensing","year":"2002","journal-title":"Cancer Res."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1186\/s13046-016-0454-4","article-title":"HPV16 Integration Probably Contributes to Cervical Oncogenesis through Interrupting Tumor Suppressor Genes and Inducing Chromosome Instability","volume":"35","author":"Zhao","year":"2016","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1038\/s41588-019-0558-9","article-title":"The Landscape of Viral Associations in Human Cancers","volume":"52","author":"Zapatka","year":"2020","journal-title":"Nat. Genet."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"10002","DOI":"10.1073\/pnas.170093297","article-title":"The Human Papillomavirus Type 16 E6 and E7 Oncoproteins Cooperate to Induce Mitotic Defects and Genomic Instability by Uncoupling Centrosome Duplication from the Cell Division Cycle","volume":"97","author":"Duensing","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"6241","DOI":"10.1038\/sj.onc.1205709","article-title":"Human Papillomaviruses and Centrosome Duplication Errors: Modeling the Origins of Genomic Instability","volume":"21","author":"Duensing","year":"2002","journal-title":"Oncogene"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.ajhg.2024.01.002","article-title":"Insights into the Mechanisms and Structure of Breakage-Fusion-Bridge Cycles in Cervical Cancer Using Long-Read Sequencing","volume":"111","author":"Rodriguez","year":"2024","journal-title":"Am. J. Hum. Genet."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1158\/2159-8290.CD-22-0900","article-title":"Intratumoral Heterogeneity and Clonal Evolution Induced by HPV Integration","volume":"13","author":"Akagi","year":"2023","journal-title":"Cancer Discov."},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Yu, L., Lobanov, A., Majerciak, V., Mirza, S., Band, V., Liu, H., Cam, M., and Zheng, Z.-M. (2020). Expression of HPV Oncogenes from a Single Integration Site in Cervical Cancer Cell Lines. bioRxiv.","DOI":"10.1101\/2020.06.25.171959"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"e00729-24","DOI":"10.1128\/mbio.00729-24","article-title":"HPV Oncogenes Expressed from Only One of Multiple Integrated HPV DNA Copies Drive Clonal Cell Expansion in Cervical Cancer","volume":"15","author":"Yu","year":"2024","journal-title":"mBio"},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Ehrig, F., H\u00e4fner, N., Driesch, C., Kraus Christiansen, I., Beer, K., Schmitz, M., Runnebaum, I.B., and D\u00fcrst, M. (2019). Differences in Stability of Viral and Viral-Cellular Fusion Transcripts in HPV-Induced Cervical Cancers. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010112"},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Warburton, A., Redmond, C.J., Dooley, K.E., Fu, H., Gillison, M.L., Akagi, K., Symer, D.E., Aladjem, M.I., and McBride, A.A. (2018). HPV Integration Hijacks and Multimerizes a Cellular Enhancer to Generate a Viral-Cellular Super-Enhancer That Drives High Viral Oncogene Expression. PLoS Genet., 14.","DOI":"10.1371\/journal.pgen.1007179"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"4237","DOI":"10.1093\/nar\/gkad105","article-title":"HPV Integration Generates a Cellular Super-Enhancer Which Functions as ecDNA to Regulate Genome-Wide Transcription","volume":"51","author":"Tian","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1097\/IGC.0b013e3182158683","article-title":"Human Papillomavirus\u2019s Physical State and Cyclin A1 Promoter Methylation in Cervical Cancer","volume":"21","author":"Yanatatsaneejit","year":"2011","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1101\/gr.279041.124","article-title":"Rearrangements of Viral and Human Genomes at Human Papillomavirus Integration Events and Their Allele-Specific Impacts on Cancer Genome Regulation","volume":"35","author":"Porter","year":"2025","journal-title":"Genome Res."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Sen, S., Mandal, P., Bhattacharya, A., Kundu, S., Roy Chowdhury, R., Mondal, N.R., Chatterjee, T., Chakravarty, B., Roy, S., and Sengupta, S. (2017). Impact of Viral and Host DNA Methylations on HPV16-Related Cervical Cancer Pathogenesis. Tumor Biol., 39.","DOI":"10.1177\/1010428317699799"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1002\/ijc.27906","article-title":"Differential Methylation of E2 Binding Sites in Episomal and Integrated HPV 16 Genomes in Preinvasive and Invasive Cervical Lesions","volume":"132","author":"Chaiwongkot","year":"2013","journal-title":"Int. J. Cancer"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1002\/jmv.24129","article-title":"HPV 16 E2 Binding Sites 1 and 2 Become More Methylated than E2 Binding Site 4 during Cervical Carcinogenesis","volume":"87","author":"Leung","year":"2015","journal-title":"J. Med. Virol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"3207","DOI":"10.1128\/JCM.01106-13","article-title":"Methylation of Human Papillomavirus Type 16 CpG Sites at E2-Binding Site 1 (E2BS1), E2BS2, and the Sp1-Binding Site in Cervical Cancer Samples as Determined by High-Resolution Melting Analysis-PCR","volume":"51","author":"Jacquin","year":"2013","journal-title":"J. Clin. Microbiol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.cca.2019.02.027","article-title":"Study on the Relationship between Methylation Status of HPV 16 E2 Binding Sites and Cervical Lesions","volume":"493","author":"Zhang","year":"2019","journal-title":"Clin. Chim. Acta"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"e28789","DOI":"10.1002\/jmv.28789","article-title":"Multi-Omics Data Reveals Novel Impacts of Human Papillomavirus Integration on the Epigenomic and Transcriptomic Signatures of Cervical Tumorigenesis","volume":"95","author":"Zeng","year":"2023","journal-title":"J. Med. Virol."},{"key":"ref_151","first-page":"11","article-title":"Modulation of DNA Methylation by Human Papillomavirus E6 and E7 Oncoproteins in Cervical Cancer","volume":"15","author":"Sen","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"e02687-18","DOI":"10.1128\/mBio.02687-18","article-title":"Genome-Wide Profiling of Cervical RNA-Binding Proteins Identifies Human Papillomavirus Regulation of RNASEH2A Expression by Viral E7 and E2F1","volume":"10","author":"Xu","year":"2019","journal-title":"Mbio"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1158\/1078-0432.CCR-14-1101","article-title":"Genomic Landscape of Human Papillomavirus-Associated Cancers","volume":"21","author":"Rusan","year":"2015","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.7150\/ijbs.56970","article-title":"LRP1B Mutation Is Associated with Tumor HPV Status and Promotes Poor Disease Outcomes with a Higher Mutation Count in HPV-Related Cervical Carcinoma and Head & Neck Squamous Cell Carcinoma","volume":"17","author":"Cao","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1093\/carcin\/bgv171","article-title":"Chromosomal Copy Number Alterations and HPV Integration in Cervical Precancer and Invasive Cancer","volume":"37","author":"Bodelon","year":"2016","journal-title":"Carcinogenesis"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s12943-015-0361-x","article-title":"The Role of the PI3K\/Akt\/mTOR Signalling Pathway in Human Cancers Induced by Infection with Human Papillomaviruses","volume":"14","author":"Zhang","year":"2015","journal-title":"Mol. Cancer"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1002\/path.1966","article-title":"Increased Gene Copy Numbers at Chromosome 20q Are Frequent in Both Squamous Cell Carcinomas and Adenocarcinomas of the Cervix","volume":"209","author":"Wilting","year":"2006","journal-title":"J. Pathol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.ejca.2013.08.022","article-title":"Chromosomal Gains and Losses in Human Papillomavirus-Associated Neoplasia of the Lower Genital Tract \u2014A Systematic Review and Meta-Analysis","volume":"50","author":"Thomas","year":"2014","journal-title":"Eur. J. Cancer"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"e1219","DOI":"10.1002\/ctm2.1219","article-title":"Spatiotemporally Deciphering the Mysterious Mechanism of Persistent HPV-Induced Malignant Transition and Immune Remodelling from HPV-Infected Normal Cervix, Precancer to Cervical Cancer: Integrating Single-Cell RNA-Sequencing and Spatial Transcriptome","volume":"13","author":"Guo","year":"2023","journal-title":"Clin. Transl. Med."},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Chen, Z., and Zhao, B. (2025). The Role of Tumor-Associated Macrophages in HPV Induced Cervical Cancer. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1586806"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s12935-025-03725-x","article-title":"Single-Cell Transcriptomic Analyses Reveal Heterogeneity and Key Subsets Associated with Survival and Response to PD-1 Blockade in Cervical Squamous Cell Carcinoma","volume":"25","author":"Li","year":"2025","journal-title":"Cancer Cell Int."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1089\/jir.2009.0075","article-title":"Human Papillomaviruses and the Interferon Response","volume":"29","author":"Beglin","year":"2009","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.it.2010.07.004","article-title":"Impaired Toll-like Receptor 7 and 9 Signaling: From Chronic Viral Infections to Cancer","volume":"31","author":"Hirsch","year":"2010","journal-title":"Trends Immunol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1177\/2051013617717914","article-title":"Human Papillomavirus-Driven Immune Deviation: Challenge and Novel Opportunity for Immunotherapy","volume":"5","author":"Smola","year":"2017","journal-title":"Ther. Adv. Vaccines"},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Konstantopoulos, G., Leventakou, D., Saltiel, D.-R., Zervoudi, E., Logotheti, E., Pettas, S., Karagianni, K., Daiou, A., Hatzistergos, K.E., and Dafou, D. (2024). HPV16 E6 Oncogene Contributes to Cancer Immune Evasion by Regulating PD-L1 Expression through a miR-143\/HIF-1a Pathway. Viruses, 16.","DOI":"10.3390\/v16010113"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1038\/s41419-024-06522-y","article-title":"Single-Cell RNA Sequencing of Cervical Exfoliated Cells Reveals Potential Biomarkers and Cellular Pathogenesis in Cervical Carcinogenesis","volume":"15","author":"Sheng","year":"2024","journal-title":"Cell Death Dis."},{"key":"ref_167","first-page":"311","article-title":"Risk Assessment and Triage Strategy of Cervical Cancer Primary Screening on HPV Integration Status: 5-Year Follow-up of a Prospective Cohort Study","volume":"4","author":"Tian","year":"2024","journal-title":"J. Natl. Cancer Cent."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s12032-022-01840-7","article-title":"Recent Advances in Cancer Therapy Using PARP Inhibitors","volume":"39","author":"Kaur","year":"2022","journal-title":"Med. Oncol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/j.neo.2017.07.005","article-title":"Effect of HPV E6\/E7 siRNA with Chemotherapeutic Agents on the Regulation of TP53\/E2F Dynamic Behavior for Cell Fate Decisions","volume":"19","author":"Rajasekaran","year":"2017","journal-title":"Neoplasia"},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"Wei, Y., Zhao, Z., and Ma, X. (2022). Description of CRISPR-Cas9 Development and Its Prospects in Human Papillomavirus-Driven Cancer Treatment. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1037124"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"5968","DOI":"10.1038\/s41467-022-33359-w","article-title":"Human Papillomavirus Integration Perspective in Small Cell Cervical Carcinoma","volume":"13","author":"Wang","year":"2022","journal-title":"Nat. Commun."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/18\/9214\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:46:35Z","timestamp":1760035595000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/18\/9214"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,21]]},"references-count":171,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["ijms26189214"],"URL":"https:\/\/doi.org\/10.3390\/ijms26189214","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,21]]}}}