DNA methylation in cervical intraepithelial neoplasia and cervical cancer

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The primary cause of cervical cancer development is an infection resulting from the persistent presence of oncogenic human papillomavirus (HPV). Choosing the optimal strategy for risk stratification among HPV-positive women can help identify subgroups with a higher probability of disease progression. One of the key areas of research into carcinogenesis mechanisms involves studying epigenetic changes, such as DNA methylation.

The review presents the current data on DNA methylation of high-risk HPV and host cell DNA in cervical intraepithelial neoplasia (CIN) and cervical cancer. The paper focuses on the most studied epigenetic markers, including CADM1, MAL, PAX1, FAM19A4, as well as new genes such as ZNF582, SOX1, and EPB41L3. The review shows their role in the progression of precancerous lesions, their sensitivity and specificity in comparison with conventional screening methods. Particular attention is paid to the potential of integrating epigenetic markers into screening programs, including the practices in the Russian Federation.

Conclusion: DNA methylation is considered to be a promising approach to the early detection of severe CIN and breast cancer that requires further validation. The currently available DNA methylation markers, particularly their combined panels, still need to be optimized by increasing the specificity of sorting but without reducing their high sensitivity. This process requires identification of both individual markers and methylation panels.

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作者简介

M. Anisimova

Lomonosov Moscow State University, Medical Scientific and Educational Center

编辑信件的主要联系方式.
Email: manecha35@mail.ru
ORCID iD: 0009-0002-6081-5597

PhD student at the Faculty of Medicine

俄罗斯联邦, Moscow

L. Shcherbakova

Lomonosov Moscow State University, Medical Scientific and Educational Center

Email: liya.fbm@gmail.com
ORCID iD: 0000-0003-2681-4777

Dr. Med. Sci., Professor at the Department of Obstetrics and Gynecology, Faculty of Medicine

俄罗斯联邦, Moscow

O. Panina

Lomonosov Moscow State University, Medical Scientific and Educational Center

Email: olgapanina@yandex.ru
ORCID iD: 0000-0003-1397-6208

Dr. Med. Sci., Professor, Head of the Department of Obstetrics and Gynecology, Faculty of Medicine

俄罗斯联邦, Moscow

参考

  1. Ашрафян Л.А., Киселев В.И., Кузнецов И.Н., Серова О.Ф., Узденова З.Х., Герфанова Е.В. Рак шейки матки: проблемы профилактики и скрининга в Российской Федерации. Доктор.Ру. 2019; 11(166): 50-4. [Ashrafyan L.A., Kiselev V.I., Kuznetsov I.N., Serova O.F., Uzdenova Z.Kh., Gerfanova E.V. Сervical cancer: Issues with prevention and screening in the Russian Federation. Doctor.Ru. 2019; 11(166): 50-4 (in Russian)]. https:// dx.doi.org/10.31550/1727-2378-2019-166-11-50-54
  2. Ершов В.А. Концепции генеза ВПЧ-ассоциированной цервикальной неоплазии. Новости клинической цитологии России. 2021; 25(1): 20-9. [Ershov V.A. Concepts of the genesis of HPV-associated cervical cancer. Russian News of Clinical Cytology. 2021; 25(1): 20-9 (in Russian)]. https:// dx.doi.org/10.24412/1562-4943-2021-1-0004
  3. Файзулоев Е.Б., Каира А.Н., Узбеков А.А., Поромов А.А., Волынская Е.А., Свитич О.А., Зверев В.В. Распространенность папилломавирусов человека высокого и низкого онкогенного риска на территории Российской Федерации. Молекулярная генетика, микробиология и вирусология. 2021; 39(4): 39-47. [Faizuloev E.B., Kaira A.N., Uzbekov T.R., Poromov A.A., Volynskaya E.A., Svitich O.A., Zverev V.V. The prevalence of high- and low-risk human papillomaviruses in the Russian Federation. Molecular Genetics, Microbiology and Virology. 2021; 36(4): 39-47 (in Russian)]. https:// dx.doi.org/10.17116/molgen20213904139
  4. Hortlund M., van Mol T., Van de Pol F., Bogers J., Dillner J. Human papillomavirus load and genotype analysis improves the prediction of invasive cervical cancer. Int. J. Cancer. 2021; 149(3): 684-91. https://dx.doi.org/10.1002/ijc.33519
  5. Scott-Wittenborn N., Fakhry C. Epidemiology of HPV related malignancies. Semin. Radiat. Oncol. 2021; 31(4): 286-96. https://dx.doi.org/10.1016/ j.semradonc.2021.04.001
  6. Huber J., Mueller A., Sailer M., Regidor P.A. Human papillomavirus persistence or clearance after infection in reproductive age. What is the status? Review of the literature and new data of a vaginal gel containing silicate dioxide, citric acid, and selenite. Women’s Health. 2021; 17: 61-5. https:// dx.doi.org/10.1177/17455065211020702
  7. Hussain S., Tulsyan S., Dar S.A., Sisodiya S., Abiha U., Kumar R. et al. Role of epigenetics in carcinogenesis: recent advancements in anticancer therapy. Semin. Cancer Biol. 2022; 83: 441-51. https://dx.doi.org/10.1016/ j.semcancer.2021.06.023
  8. Mac M., Cary A.M. Epigenetic regulation of the human papillomavirus life cycle. Pathogens. 2020; 9(6): 483. https://dx.doi.org/10.3390/pathogens9060483
  9. Cuschieri K., Ronco G., Lorincz A., Smith L., Ogilvie G., Mirabello L. et al. Eurogin roadmap 2017: Triage strategies for the management of HPV-positive women in cervical screening programs. International J. Cancer. 2018; 143(4): 735-45. https://dx.doi.org/10.1002/ijc.31261
  10. Bowden S.J., Lathouras K., Kyrgiou M. Can DNA methylation tests improve the accuracy of cervical screening? BJOG. 2021; 128(3): 515. https:// dx.doi.org/10.1111/1471-0528.16448
  11. Clarke M.A., Luhn P., Gage J.C., Bodelon C., Dunn S.T., Walker J. et al. Discovery and validation of candidate host DNA methylation markers for detection of cervical precancer and cancer. International J. Cancer. 2017; 141(4): 701-10. https://dx.doi.org/10.1002/ijc.30781
  12. Минниахметов И.Р., Забелин М.В., Ольков И.Г., Хусаинова Р.И. Пилотный проект по скринингу рака шейки матки с применением ВПЧ-тестирования. Вопросы онкологии. 2020; 66(6): 618-24. [Minniakhmetov I.R., Zabelin M.V., Olkov I.G., Khusainova R.I. Pilot project for screening cervical cancer using HPV testing. Problems of Oncology. 2020; 66(6): 618-24 (in Russian)]. https://dx.doi.org/10.37469/0507-3758-2020-66-6-618-624
  13. Масюкова С.А., Киселев В.И., Потекаев Н.Н., Назарова М.Н., Полозников А.А., Бабкина И.О., Ахтямов С.Н., Тарасенко Э.Н. Изучение статуса метилирования гена WIF1 при ВПЧ-ассоциированных доброкачественных образованиях кожи и слизистых оболочек. Клиническая дерматология и венерология. 2017; 16(4): 38-43. [Masiukova S.A., Kiselev V.I., Potekaev N.N., Nazarova M.N., Poloznikov A.A., Babkina I.O., Ahtyamov S.N., Tarasenko E.N. The study of methylation status of WIF1 gene in patients with HPV-associated benign lesions of the skin and mucous membranes. Journal of Clinical Dermatology and Venereology. 2017; 16(4): 38 43 (in Russian)]. https://dx.doi.org/10.17116/ klinderma201716438-43
  14. Байрамова Г.Р., Файзуллин Л.З., Королькова А.И., Полозников А.А., Киселев В.И. Скрининг рака шейки матки: что нового в мировой практике? Акушерство и гинекология. 2016; 7: 17-21. [Bairamova G.R., Faizullin L.Z., Korolkova A.I., Poloznikov A.A., Kiselev V.I. Cervical cancer screening: What is new in global practice? Obstetrics and Gynecology. 2016; (7): 17-21 (in Russian)]. https://dx.doi.org/10.18565/aig.2016.7.17-21
  15. Li H., Gao J., Zhang S. Functional and clinical characteristics of cell adhesion molecule CADM1 in cancer. Front. Cell Dev. Biol. 2021; 9: 714298. https://dx.doi.org/10.3389/fcell.2021.714298
  16. Mersakova S., Holubekova V., Grendár M., Višňovský J., Ňachajová M., Kalman M. at al. Methylation of CADM1 and MAL together with HPV status in cytological cervical specimens serves an important role in the progression of cervical intraepithelial neoplasia. Oncology Letters. 2018; 16(6): 7166-74. https://dx.doi.org/10.3892/ol.2018.9505
  17. van Baars R., van der Marel J., Snijders P.J., Rodriquez-Manfredi A., ter Harmsel B., van den Munckhof H.A. et al. CADM1 and MAL methylation status in cervical scrapes is representative of the most severe underlying lesion in women with multiple cervical biopsies. Int. J. Cancer. 2016; 138(2): 463-71. https://dx.doi.org/10.1002/ijc.29706
  18. Kremer W.W., Steenbergen R., Heideman D., Kenter G.G., Meijer C. The use of host cell DNA methylation analysis in the detection and management of women with advanced cervical intraepithelial neoplasia: a review. BJOG. 2021; 128(3): 504-14. https://dx.doi.org/10.1111/1471-0528.16395
  19. De Strooper L.M.A., Berkhof J., Steenbergen R.D.M., Lissenberg-Witte B.I., Snijders P.J.F., Meijer C.J.L.M. et al. Cervical cancer risk in HPV-positive women after a negative FAM19A4/mir124-2 methylation test: a post hoc analysis in the POBASCAM trial with 14 year follow-up. Int. J. Cancer. 2018; 143(6): 1541-8. https://dx.doi.org/10.1002/ijc.31539
  20. Leeman A., Del Pino M., Marimon L., Torne A., Ordi J., Harmsel B.T. et al. Reliable identification of women with CIN3+ using hrHPV genotyping and methylation markers in a cytology-screened referral population. Int. J. Cancer. 2019; 144(1): 160-8. https://dx.doi.org/10.1002/ijc.31787
  21. Vink F.J., Meijer C., Clifford G.M., Poljak M., Ostrbenk A., Petry K.U. et al. FAM19A4/miR124-2 methylation in invasive cervical cancer: a retrospective cross-sectional worldwide study. Int. J. Cancer. 2020; 147(4): 1215-21. https://dx.doi.org/10.1002/ijc.32614
  22. Floore A., Hesselink A., Ostrbenk A., Alcaniz E., Rothe B., Pedersen H. et al. Intra- and inter-laboratory agreement of the FAM19A4/mir124-2 methylation test: results from an international study. J. Clini. Lab. Anal. 2019; 33(4): e22854. https://dx.doi.org/10.1002/jcla.22854
  23. Bonde J., Floore A., Ejegod D., Vink F.J., Hesselink A., van de Ven P.M. et al. Methylation markers FAM19A4 and mir124-2 as triage strategy for primary human papillomavirus screen positive women: a large european multicenter study. Int. J. Cancer. 2021; 148(2): 396-405. https://dx.doi.org/10.1002/ijc.33320
  24. Su P.H., Lai H.C., Huang R.L., Chen L.Y., Wang Y.C., Wuet T.I. et al. Paired box-1 (PAX1) activates multiple phosphatases and inhibits kinase cascades in cervical cancer. Sci. Rep. 2019; 9(1): 9195. https://dx.doi.org/10.1038/ s41598-019-45477-5
  25. Boers A., Wang R., van Leeuwen R.W., Klip H.G., de Bock G.H., Hollema H. et al. Discovery of new methylation markers to improve screening for cervical intraepithelial neoplasia grade 2/3. Clin. Epigenetics. 2016; 8: 29. https://dx.doi.org/10.1186/s13148-016-0196-3
  26. van Leeuwen R.W., Oštrbenk A., Poljak M., van der Zee A.G.J., Schuuring E., Wisman G.B.A. DNA methylation markers as a triage test for identification of cervical lesions in a high risk human papillomavirus positive screening cohort. Int. J. Cancer. 2018; 144(4): 746-54. https://dx.doi.org/10.1002/ijc.31897
  27. Kocsis A., Takacs T., Jeney C., Schaff Z., Koiss R., Jaray B. et al. Performance of a new HPV and biomarker assay in the management of hrHPV positive women: subanalysis of the ongoing multicenter TRACE clinical trial (n>6000) to evaluate POU4F3 methylation as a potential biomarker of cervical precancer and cancer. Int. J. Cancer. 2017; 140(5): 1119-33. https://dx.doi.org/10.1002/ijc.30534

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