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Part of the book series: Comprehensive Gynecology and Obstetrics ((CGO))

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Abstract

Human papillomavirus (HPV) infection is the leading cause of cervical cancer, resulting in a significant global disease burden. HPV consists of a large family of small DNA viruses; with a limited protein-coding capacity due to its ~8000-bp genome, HPV relies heavily on host cell proteins to support the viral life cycle, both productive and persistent phases of infection. Although the viral oncoproteins E6 and E7 (targeting TP53 and RB1, respectively) play critical roles in cervical carcinogenesis, accumulation of somatic mutations in the host genome is required for cancer progression. With regard to this latter point, APOBEC3 cytosine deaminases, which are upregulated by E6/E7, are a major mutagenic source of the HPV-related cancer genome. Moreover, deep sequencing of HPV genomes has shown high levels of variability in the viral genomic sequences in clinical specimens, and elucidated evolutionary pressures on the HPV genome. Cellular mechanisms hijacked by HPV include the intracellular transport pathways for infectious cell entry, DNA damage responses and homologous recombination repair for viral genome replication, and double-strand DNA break repair for viral integration into the host genome. These novel insights pave the way for the development of promising anti-HPV therapeutics to treat and eliminate HPV-infected lesions.

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References

  1. Durst M, Gissmann L, Ikenberg H, Zur Hausen H. A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions. Proc Natl Acad Sci USA. 1983;80(12):3812–5.

    Google Scholar 

  2. McBride AA. Human papillomaviruses: diversity, infection and host interactions. Nat Rev Microbiol. 2021;20:95.

    Google Scholar 

  3. Munoz N, Bosch FX, de Sanjose S, Herrero R, Castellsague X, Shah KV, Snijders PJ, Meijer CJ, International Agency for Research on Cancer Multicenter Cervical Cancer Study G. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 2003;348(6):518–27.

    Article  PubMed  Google Scholar 

  4. de Sanjose S, Quint WG, Alemany L, Geraets DT, Klaustermeier JE, Lloveras B, Tous S, Felix A, Bravo LE, Shin HR, et al. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol. 2010;11(11):1048–56.

    Article  PubMed  Google Scholar 

  5. Schiffman M, Doorbar J, Wentzensen N, de Sanjose S, Fakhry C, Monk BJ, Stanley MA, Franceschi S. Carcinogenic human papillomavirus infection. Nat Rev Dis Primers. 2016;2:16086.

    Article  PubMed  Google Scholar 

  6. Della Fera AN, Warburton A, Coursey TL, Khurana S, McBride AA. Persistent human papillomavirus infection. Viruses. 2021;13(2):321.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, Bignell GR, Bolli N, Borg A, Borresen-Dale AL, et al. Signatures of mutational processes in human cancer. Nature. 2013;500(7463):415–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Harris RS, Dudley JP. APOBECs and virus restriction. Virology. 2015;479-480:131–45.

    Article  CAS  PubMed  Google Scholar 

  9. Roberts SA, Lawrence MS, Klimczak LJ, Grimm SA, Fargo D, Stojanov P, Kiezun A, Kryukov GV, Carter SL, Saksena G, et al. An APOBEC cytidine deaminase mutagenesis pattern is widespread in human cancers. Nat Genet. 2013;45(9):970–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Burns MB, Temiz NA, Harris RS. Evidence for APOBEC3B mutagenesis in multiple human cancers. Nat Genet. 2013;45(9):977–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Cancer Genome Atlas Research N, Albert Einstein College of M, Analytical Biological S, Barretos Cancer H, Baylor College of M, Beckman Research Institute of City of H, Buck Institute for Research on A, Canada’s Michael Smith Genome Sciences C, Harvard Medical S, Helen FGCC, et al. Integrated genomic and molecular characterization of cervical cancer. Nature. 2017;543(7645):378–84.

    Article  Google Scholar 

  12. Henderson S, Chakravarthy A, Su X, Boshoff C, Fenton TR. APOBEC-mediated cytosine deamination links PIK3CA helical domain mutations to human papillomavirus-driven tumor development. Cell Rep. 2014;7(6):1833–41.

    Article  CAS  PubMed  Google Scholar 

  13. Vieira VC, Leonard B, White EA, Starrett GJ, Temiz NA, Lorenz LD, Lee D, Soares MA, Lambert PF, Howley PM, et al. Human papillomavirus E6 triggers upregulation of the antiviral and cancer genomic DNA deaminase APOBEC3B. MBio. 2014;5(6):e02234.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Mori S, Takeuchi T, Ishii Y, Yugawa T, Kiyono T, Nishina H, Kukimoto I. Human papillomavirus 16 E6 upregulates APOBEC3B via the TEAD transcription factor. J Virol. 2017;91(6):e02413.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Warren CJ, Xu T, Guo K, Griffin LM, Westrich JA, Lee D, Lambert PF, Santiago ML, Pyeon D. APOBEC3A functions as a restriction factor of human papillomavirus. J Virol. 2015;89(1):688–702.

    Article  PubMed  Google Scholar 

  16. Burns MB, Lackey L, Carpenter MA, Rathore A, Land AM, Leonard B, Refsland EW, Kotandeniya D, Tretyakova N, Nikas JB, et al. APOBEC3B is an enzymatic source of mutation in breast cancer. Nature. 2013;494(7437):366–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Chan K, Roberts SA, Klimczak LJ, Sterling JF, Saini N, Malc EP, Kim J, Kwiatkowski DJ, Fargo DC, Mieczkowski PA, et al. An APOBEC3A hypermutation signature is distinguishable from the signature of background mutagenesis by APOBEC3B in human cancers. Nat Genet. 2015;47(9):1067–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Law EK, Levin-Klein R, Jarvis MC, Kim H, Argyris PP, Carpenter MA, Starrett GJ, Temiz NA, Larson LK, Durfee C, et al. APOBEC3A catalyzes mutation and drives carcinogenesis in vivo. J Exp Med. 2020;217(12):e20200261.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Petljak M, Dananberg A, Chu K, Bergstrom EN, Striepen J, von Morgen P, Chen Y, Shah H, Sale JE, Alexandrov LB, et al. Mechanisms of APOBEC3 mutagenesis in human cancer cells. Nature. 2022;607(7920):799–807.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Burk RD, Harari A, Chen Z. Human papillomavirus genome variants. Virology. 2013;445(1–2):232–43.

    Article  CAS  PubMed  Google Scholar 

  21. Mirabello L, Yeager M, Yu K, Clifford GM, Xiao Y, Zhu B, Cullen M, Boland JF, Wentzensen N, Nelson CW, et al. HPV16 E7 genetic conservation is critical to carcinogenesis. Cell. 2017;170(6):1164–1174.e1166.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Pinheiro M, Harari A, Schiffman M, Clifford GM, Chen Z, Yeager M, Cullen M, Boland JF, Raine-Bennett T, Steinberg M, et al. Phylogenomic analysis of human papillomavirus type 31 and cervical carcinogenesis: a study of 2093 viral genomes. Viruses. 2021;13(10):1948.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Hirose Y, Onuki M, Tenjimbayashi Y, Mori S, Ishii Y, Takeuchi T, Tasaka N, Satoh T, Morisada T, Iwata T, et al. Within-host variations of human papillomavirus reveal APOBEC signature mutagenesis in the viral genome. J Virol. 2018;92(12):e00017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Dube Mandishora RS, Gjotterud KS, Lagstrom S, Stray-Pedersen B, Duri K, Chin’ombe N, Nygard M, Christiansen IK, Ambur OH, Chirenje MZ, et al. Intra-host sequence variability in human papillomavirus. Papillomavirus Res. 2018;5:180–91.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Lagstrom S, van der Weele P, Rounge TB, Christiansen IK, King AJ, Ambur OH. HPV16 whole genome minority variants in persistent infections from young Dutch women. J Clin Virol. 2019;119:24–30.

    Article  CAS  PubMed  Google Scholar 

  26. Zhu B, Xiao Y, Yeager M, Clifford G, Wentzensen N, Cullen M, Boland JF, Bass S, Steinberg MK, Raine-Bennett T, et al. Mutations in the HPV16 genome induced by APOBEC3 are associated with viral clearance. Nat Commun. 2020;11(1):886.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kuchino Y, Mori F, Kasai H, Inoue H, Iwai S, Miura K, Ohtsuka E, Nishimura S. Misreading of DNA templates containing 8-hydroxydeoxyguanosine at the modified base and at adjacent residues. Nature. 1987;327(6117):77–9.

    Article  CAS  PubMed  Google Scholar 

  28. Matsuda T, Bebenek K, Masutani C, Hanaoka F, Kunkel TA. Low fidelity DNA synthesis by human DNA polymerase-eta. Nature. 2000;404(6781):1011–3.

    Article  CAS  PubMed  Google Scholar 

  29. Cruz-Gregorio A, Manzo-Merino J, Gonzalez-Garcia MC, Pedraza-Chaverri J, Medina-Campos ON, Valverde M, Rojas E, Rodriguez-Sastre MA, Garcia-Cuellar CM, Lizano M. Human papillomavirus types 16 and 18 early-expressed proteins differentially modulate the cellular redox state and DNA damage. Int J Biol Sci. 2018;14(1):21–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Wendel SO, Stoltz A, Xu X, Snow JA, Wallace N. HPV 16 E7 alters translesion synthesis signaling. Virol J. 2022;19(1):165.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. van der Weele P, King AJ, Meijer C, Steenbergen RDM. HPV16 variant analysis in primary and recurrent CIN2/3 lesions demonstrates presence of the same consensus variant. Papillomavirus Res. 2019;7:168–72.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Hirose Y, Yamaguchi-Naka M, Onuki M, Tenjimbayashi Y, Tasaka N, Satoh T, Tanaka K, Iwata T, Sekizawa A, Matsumoto K, et al. High levels of within-host variations of human papillomavirus 16 E1/E2 genes in invasive cervical cancer. Front Microbiol. 2020;11:596334.

    Article  PubMed  PubMed Central  Google Scholar 

  33. McBride AA, Warburton A. The role of integration in oncogenic progression of HPV-associated cancers. PLoS Pathog. 2017;13(4):e1006211.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Warren CJ, Van Doorslaer K, Pandey A, Espinosa JM, Pyeon D. Role of the host restriction factor APOBEC3 on papillomavirus evolution. Virus Evol. 2015;1(1):vev015.

    Article  PubMed  PubMed Central  Google Scholar 

  35. King KM, Rajadhyaksha EV, Tobey IG, Van Doorslaer K. Synonymous nucleotide changes drive papillomavirus evolution. Tumour Virus Res. 2022;14:200248.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Simon V, Bloch N, Landau NR. Intrinsic host restrictions to HIV-1 and mechanisms of viral escape. Nat Immunol. 2015;16(6):546–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Cheng AZ, Moraes SN, Shaban NM, Fanunza E, Bierle CJ, Southern PJ, Bresnahan WA, Rice SA, Harris RS. APOBECs and herpesviruses. Viruses. 2021;13(3):390.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Wallace NA, Munger K. The curious case of APOBEC3 activation by cancer-associated human papillomaviruses. PLoS Pathog. 2018;14(1):e1006717.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Ozbun MA, Campos SK. The long and winding road: human papillomavirus entry and subcellular trafficking. Curr Opin Virol. 2021;50:76–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Richards RM, Lowy DR, Schiller JT, Day PM. Cleavage of the papillomavirus minor capsid protein, L2, at a furin consensus site is necessary for infection. Proc Natl Acad Sci U S A. 2006;103(5):1522–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Zhang P, Monteiro da Silva G, Deatherage C, Burd C, DiMaio D. Cell-penetrating peptide mediates intracellular membrane passage of human papillomavirus L2 protein to trigger retrograde trafficking. Cell. 2018;174(6):1465–1476.e1413.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Inoue T, Zhang P, Zhang W, Goodner-Bingham K, Dupzyk A, DiMaio D, Tsai B. Gamma-secretase promotes membrane insertion of the human papillomavirus L2 capsid protein during virus infection. J Cell Biol. 2018;217(10):3545–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Harwood MC, Dupzyk AJ, Inoue T, DiMaio D, Tsai B. p120 catenin recruits HPV to gamma-secretase to promote virus infection. PLoS Pathog. 2020;16(10):e1008946.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Xie J, Zhang P, Crite M, DiMaio D. Papillomaviruses Go Retro. Pathogens. 2020;9(4):267.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Xie J, Zhang P, Crite M, Lindsay CV, DiMaio D. Retromer stabilizes transient membrane insertion of L2 capsid protein during retrograde entry of human papillomavirus. Sci Adv. 2021;7(27):eabh4276.

    Article  CAS  PubMed  Google Scholar 

  46. Xie J, Heim EN, Crite M, DiMaio D. TBC1D5-catalyzed cycling of Rab7 is required for Retromer-mediated human papillomavirus trafficking during virus entry. Cell Rep. 2020;31(10):107750.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Zhang P, Moreno R, Lambert PF, DiMaio D. Cell-penetrating peptide inhibits retromer-mediated human papillomavirus trafficking during virus entry. Proc Natl Acad Sci U S A. 2020;117(11):6121–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Anacker DC, Moody CA. Modulation of the DNA damage response during the life cycle of human papillomaviruses. Virus Res. 2017;231:41–9.

    Article  CAS  PubMed  Google Scholar 

  49. Spriggs CC, Laimins LA. Human papillomavirus and the DNA damage response: exploiting host repair pathways for viral replication. Viruses. 2017;9(8):232.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Moody CA, Laimins LA. Human papillomaviruses activate the ATM DNA damage pathway for viral genome amplification upon differentiation. PLoS Pathog. 2009;5(10):e1000605.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Gillespie KA, Mehta KP, Laimins LA, Moody CA. Human papillomaviruses recruit cellular DNA repair and homologous recombination factors to viral replication centers. J Virol. 2012;86(17):9520–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Anacker DC, Gautam D, Gillespie KA, Chappell WH, Moody CA. Productive replication of human papillomavirus 31 requires DNA repair factor Nbs1. J Virol. 2014;88(15):8528–44.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Chappell WH, Gautam D, Ok ST, Johnson BA, Anacker DC, Moody CA. Homologous recombination repair factors Rad51 and BRCA1 are necessary for productive replication of human papillomavirus 31. J Virol. 2015;90(5):2639–52.

    Article  PubMed  Google Scholar 

  54. Wallace NA, Khanal S, Robinson KL, Wendel SO, Messer JJ, Galloway DA. High-risk Alphapapillomavirus oncogenes impair the homologous recombination pathway. J Virol. 2017;91(20):e01084.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Edwards TG, Helmus MJ, Koeller K, Bashkin JK, Fisher C. Human papillomavirus episome stability is reduced by aphidicolin and controlled by DNA damage response pathways. J Virol. 2013;87(7):3979–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Sitz J, Blanchet SA, Gameiro SF, Biquand E, Morgan TM, Galloy M, Dessapt J, Lavoie EG, Blondeau A, Smith BC, et al. Human papillomavirus E7 oncoprotein targets RNF168 to hijack the host DNA damage response. Proc Natl Acad Sci U S A. 2019;116(39):19552–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Hustedt N, Durocher D. The control of DNA repair by the cell cycle. Nat Cell Biol. 2016;19(1):1–9.

    Article  PubMed  Google Scholar 

  58. Schmid JA, Berti M, Walser F, Raso MC, Schmid F, Krietsch J, Stoy H, Zwicky K, Ursich S, Freire R, et al. Histone ubiquitination by the DNA damage response is required for efficient DNA replication in unperturbed S phase. Mol Cell. 2018;71(6):897–910.e898.

    Article  CAS  PubMed  Google Scholar 

  59. Kaminski P, Hong S, Kono T, Hoover P, Laimins L. Topoisomerase 2beta induces DNA breaks to regulate human papillomavirus replication. MBio. 2021;12(1):e00005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Mehta K, Laimins L. Human papillomaviruses preferentially recruit DNA repair factors to viral genomes for rapid repair and amplification. MBio. 2018;9(1):e00064.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Kuehner F, Stubenrauch F. Functions of papillomavirus E8;E2 proteins in tissue culture and in vivo. Viruses. 2022;14(5):953.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Dreer M, Fertey J, van de Poel S, Straub E, Madlung J, Macek B, Iftner T, Stubenrauch F. Interaction of NCOR/SMRT repressor complexes with papillomavirus E8;E2C proteins inhibits viral replication. PLoS Pathog. 2016;12(4):e1005556.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Straub E, Dreer M, Fertey J, Iftner T, Stubenrauch F. The viral E8;E2C repressor limits productive replication of human papillomavirus 16. J Virol. 2014;88(2):937–47.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Vande Pol SB, Klingelhutz AJ. Papillomavirus E6 oncoproteins. Virology. 2013;445(1–2):115–37.

    Article  CAS  PubMed  Google Scholar 

  65. Roman A, Munger K. The papillomavirus E7 proteins. Virology. 2013;445(1–2):138–68.

    Article  CAS  PubMed  Google Scholar 

  66. White EA, Howley PM. Proteomic approaches to the study of papillomavirus-host interactions. Virology. 2013;435(1):57–69.

    Article  CAS  PubMed  Google Scholar 

  67. Brimer N, Lyons C, Wallberg AE, Vande Pol SB. Cutaneous papillomavirus E6 oncoproteins associate with MAML1 to repress transactivation and NOTCH signaling. Oncogene. 2012;31(43):4639–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Tan MJ, White EA, Sowa ME, Harper JW, Aster JC, Howley PM. Cutaneous beta-human papillomavirus E6 proteins bind mastermind-like coactivators and repress notch signaling. Proc Natl Acad Sci U S A. 2012;109(23):E1473–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. White EA, Munger K, Howley PM. High-risk human papillomavirus E7 proteins target PTPN14 for degradation. MBio. 2016;7(5):e01530.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Szalmas A, Tomaic V, Basukala O, Massimi P, Mittal S, Konya J, Banks L. The PTPN14 tumor suppressor is a degradation target of human papillomavirus E7. J Virol. 2017;91(7):e00057.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Hatterschide J, Bohidar AE, Grace M, Nulton TJ, Kim HW, Windle B, Morgan IM, Munger K, White EA. PTPN14 degradation by high-risk human papillomavirus E7 limits keratinocyte differentiation and contributes to HPV-mediated oncogenesis. Proc Natl Acad Sci U S A. 2019;116(14):7033–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Hatterschide J, Castagnino P, Kim HW, Sperry SM, Montone KT, Basu D, White EA. YAP1 activation by human papillomavirus E7 promotes basal cell identity in squamous epithelia. elife. 2022;11:11.

    Article  Google Scholar 

  73. Romanczuk H, Howley PM. Disruption of either the E1 or the E2 regulatory gene of human papillomavirus type 16 increases viral immortalization capacity. Proc Natl Acad Sci U S A. 1992;89(7):3159–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Jeon S, Lambert PF. Integration of human papillomavirus type 16 DNA into the human genome leads to increased stability of E6 and E7 mRNAs: implications for cervical carcinogenesis. Proc Natl Acad Sci U S A. 1995;92(5):1654–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Bodelon C, Untereiner ME, Machiela MJ, Vinokurova S, Wentzensen N. Genomic characterization of viral integration sites in HPV-related cancers. Int J Cancer. 2016;139(9):2001–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Parfenov M, Pedamallu CS, Gehlenborg N, Freeman SS, Danilova L, Bristow CA, Lee S, Hadjipanayis AG, Ivanova EV, Wilkerson MD, et al. Characterization of HPV and host genome interactions in primary head and neck cancers. Proc Natl Acad Sci U S A. 2014;111(43):15544–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Warburton A, Markowitz TE, Katz JP, Pipas JM, McBride AA. Recurrent integration of human papillomavirus genomes at transcriptional regulatory hubs. NPJ Genom Med. 2021;6(1):101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Porter VL, Marra MA. The drivers, mechanisms, and consequences of genome instability in HPV-driven cancers. Cancers (Basel). 2022;14(19):4623.

    Article  CAS  PubMed  Google Scholar 

  79. Hu Z, Zhu D, Wang W, Li W, Jia W, Zeng X, Ding W, Yu L, Wang X, Wang L, et al. Genome-wide profiling of HPV integration in cervical cancer identifies clustered genomic hot spots and a potential microhomology-mediated integration mechanism. Nat Genet. 2015;47(2):158–63.

    Article  CAS  PubMed  Google Scholar 

  80. Leeman JE, Li Y, Bell A, Hussain SS, Majumdar R, Rong-Mullins X, Blecua P, Damerla R, Narang H, Ravindran PT, et al. Human papillomavirus 16 promotes microhomology-mediated end-joining. Proc Natl Acad Sci U S A. 2019;116(43):21573–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Akagi K, Li J, Broutian TR, Padilla-Nash H, Xiao W, Jiang B, Rocco JW, Teknos TN, Kumar B, Wangsa D, et al. Genome-wide analysis of HPV integration in human cancers reveals recurrent, focal genomic instability. Genome Res. 2014;24(2):185–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Zhou L, Qiu Q, Zhou Q, Li J, Yu M, Li K, Xu L, Ke X, Xu H, Lu B, et al. Long-read sequencing unveils high-resolution HPV integration and its oncogenic progression in cervical cancer. Nat Commun. 2022;13(1):2563.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Lohmussaar K, Oka R, Espejo Valle-Inclan J, Smits MHH, Wardak H, Korving J, Begthel H, Proost N, van de Ven M, Kranenburg OW, et al. Patient-derived organoids model cervical tissue dynamics and viral oncogenesis in cervical cancer. Cell Stem Cell. 2021;28(8):1380–1396.e1386.

    Article  CAS  PubMed  Google Scholar 

  84. Swanton C, McGranahan N, Starrett GJ, Harris RS. APOBEC enzymes: mutagenic fuel for cancer evolution and heterogeneity. Cancer Discov. 2015;5(7):704–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Kukimoto, I. (2024). Recent Topics of Human Papillomavirus and Cervical Cancer. In: Aoki, D. (eds) Recent Topics on Prevention, Diagnosis, and Clinical Management of Cervical Cancer. Comprehensive Gynecology and Obstetrics. Springer, Singapore. https://doi.org/10.1007/978-981-99-9396-3_1

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