D.A. SADYKOVA, T.P. ZEFIROVA, Z.M. MINGULOVA

 ¹Kazan State Medical Academy — Branch Campus of the FSBEI FPE RMACPE MOH Russia, Kazan

 Contact details:

Sadykova D.A. — postgraduate student of the Department of Obstetrics and Gynecology

Address: 36 Butlerov St., 420012 Kazan, Russian Federation, tel.: +7-987-285-02-63, e-mail: SDina98@mail.ru

The objective was to analyze contemporary Russian and foreign literature devoted to the impact of papillomavirus infection on women’s reproductive health. The review presents data related to the prevalence of human papillomavirus (HPV) among women and men, its genetic diversity, and the characteristics of its oncogenic and non-oncogenic pathogenic effects. The connection between HPV infection and various reproductive failures is examined, including reduced male fertility, female infertility, increased failures of assisted reproductive technology (ART) (6 times more often), disruptions in implantation and developmental defects in the fetus, spontaneous abortions (4 times more often), and premature births. Special attention was given to the issues of human papillomavirus infection of the endometrium in patients with chronic endometritis. Data indicating a high frequency of HPV contamination of the uterine mucosa in this category of women and the associated expression of the protein marker p16ink4a in the endometrium are presented. The review portrays pathogenetic mechanisms aimed at suppressing cell division and their role in impairing nidation and placentation. The role of therapy aimed at correcting immune disorders in women with HPV is shown.

Key words: human papillomavirus, reproductive disorders, endometrium, endometritis, protein p16ink4a.

REFERENCES

1. Into the archives: the story of HPV and cervical cancer. Cancer research center, available at: https://news.cancerresearchuk.org/2022/11/21/into-the-archives-the-story-of-hpv-and-cervical-cancer/ (accessed on: 15.11.2024).
2. Bruni L.A.G., Serrano B., Mena M. et al. de Sanjosé S (2021) ICO/IARC Information Centre on HPV and Cancer (HPV Information Centre). Human papillomavirus and related diseases in the world. Summ Rep 22 October 2021.
3. Khairkhah N., Bolhassani A., Najafipour R. Current and future direction in treatment of HPV-related cervical disease. J. Mol. Med. (Berl), 2022, vol. 100 (6), pp. 829–845. DOI: 10.1007/s00109-022-02199-y
4. Moreno‐Sepulveda J., Rajmil O. Seminal human papillomavirus infection and reproduction: a systematic review and meta‐analysis. Andrology, 2020, vol. 9 (2), pp. 478–502. DOI: 10.1111/andr.12948
5. Le Tortorec A., Matusali G., Mahe D. et al. From ancient to emerging infections: the odyssey of viruses in the male genital tract. Physiol. Rev, 2020, vol. 100 (3), pp. 1349–414. DOI: 10.11 52/physrev.00021.2019
6. Isaguliants M., Krasnyak S., Smirnova O. et al. Genetic instability and anti-HPV immune response as drivers of infertility associated with HPV infection. Infect. Agents Cancer, 2021, vol. 16, p. 29. DOI: 10.1186/s13027-021-00368-1
7. Chambuso R., Kaambo E., Denny L. et al. Investigation of cervical tumor biopsies for chromosomal loss of Heterozygosity (LOH) and microsatellite instability (MSI) at the HLA II locus in HIV-1/HPV co-infected women. Front. Oncol, 2019, vol. 9, p. 951. DOI: 10.3389/fonc.2019.00951
8. Organization WH (2021) WHO guideline for screening and treatment of cervical pre-cancer lesions for cervical cancer prevention: web annex A: syntheses of evidence.
9. Kombe A.J., Li B., Zahid A. et al. Epidemiology and burden of human papillomavirus and related diseases, molecular pathogenesis, and vaccine evaluation. Front. Pub. Health, 2021, vol. 8, 552028.
10. Ibragimova M.K., Kokorina E.V., Tsyganov M.M. et al. Endometrial cancer and human papillomavirus (literature review and meta-analysis). Opukholi zhenskoy reproduktivnoy sistemy, 2020, vol. 16, no. 4, pp. 91–99 (in Russ.). DOI: 10.17650/1994-4098-2020-16-4-91-99
11. Moreno E., Ron R., Serrano-Villar S. The microbiota as a modulator of mucosal inflammation and HIV/HPV pathogenesis: From association to causation. Front. Immunol, 2023, vol. 14. 1072655. DOI: 10.3389/fimmu.2023.1072655
12. Vikulov G.Kh., Voznesenskiiy S.L., Frolkin D.I. HPV and herpesvirus infections: epidemiological, pathogenetic and clinical-immunological aspects, principles of diagnosis and therapy. Akusherstvo, ginekologiya i reproduktsiya, 2020, vol. 14, no. 1, pp. 102–111 (in Russ.).
13. Rossiyskoe obshchestvo akusherov-ginekologov. Klinicheskie rekomendatsii po Tservikal’noy intraepitelial’noy neoplazii, erozii i ektropionu sheyki matki [Russian Society of Obstetricians and Gynecologists. Clinical guidelines for cervical intraepithelial neoplasia, erosion and ectropion of the cervix]. Moscow, 2024. 53 p.
14. Slatter T.L. et al. A clinicopathological study of episomal papillomavirus infection of the human placenta and pregnancy complications. Mod. Pathol, 2015, vol. 28 (10), pp. 1369–1382.
15. Lyu Z., Feng X., Li N. et al. Human papillomavirus in semen and the risk for male infertility: a systematic review and meta-analysis. BMC Infect. Dis, 2017, vol. 17 (1), p. 714. DOI: 10.1186/s12879-017-2812-z
16. Dong Ja Kim, Joon Cheol Park. Influence of human papillomavirus infection detected by cervical swap on in-vitro fertilization outcomes. Keimyung Med. J, 2020, vol. 39 (1), pp. 38–42. DOI: 10.46308/kmj.2020.00066
17. Duan L.L., Yin H., Li Q. et al. Correlation between human papillomavirus infection and reproduction. Ginekol. Pol, 2022, vol. 93 (4), pp. 329–333.
18. Ambuhl L.M.M., Leonhard A.K., Widen Zakhary C. et al. Human papillomavirus infects placental trophoblast and Hofbauer cells, but appears not to play a causal role in miscarriage and preterm labor. Acta Obstet. Gynecol. Scand, 2017, vol. 96 (10), pp. 1188–1196. DOI: 10.1111/aogs.13190
19. Zullo F., Fiano V., Gillio-Tos A. et al. Human papillomavirus infection in women undergoing in-vitro fertilization: effects on embryo development kinetics and live birth rate. Reprod. Biol. Endocrinol, 2023, vol. 21, p. 39. DOI: 10.1186/s12958-023-01091-9
20. Condrat C.E., Filip L., Gherghe M. et al. Maternal HPV infection: effects on pregnancy outcome. Viruses, 2021, vol. 13, p. 2455.
21. Sola-Leyva A. et al. Mapping the entire functionally active endometrial microbiota. Hum. Reprod, 2021, vol. 36 (4), pp. 1021–1031.
22. Radzinskiy V.E., Orazov M.R., Toktar L.R. et al. The “scattered puzzle” effect: implantation disorders in chronic endometritis. Ginekologiya, 2020, vol. 22, no. 6, pp. 93–100 (in Russ.).
23. Orazov M.R., Mikhaleva L.M., Semenov P.A. Chronic endometritis: pathogenesis, diagnosis, treatment and its relationship with infertility. Klinicheskaya i eksperimental’naya morfologiya, 2020, no. 9, pp. 16–25 (in Russ.). DOI: 10.31088/CEM2020.9.2.16-25
24. Cho H.-W., Ouh Y.-T., Hong J.H. et al. Comparison of urine, self-collected vaginal swab, and cervical swab samples for detecting human papillomavirus (HPV) with Roche Cobas HPV, Anyplex II HPV, and RealTime HR-S HPV Assay. J. Virol. Methods, 2019, vol. 269, pp. 77–82.
25. Zefirova T.P., Tolibova G. Kh, Sadykova D.A. et al. A new look at the causes of reproductive failures in women with chronic endometritis. Akusherstvo i ginekologiya, 2024, no. 9, pp. 156—162 (in Russ.). DOI: 10.18565/aig.2024.237
26. Hapangama D.K., Kamal A., Saretzki G. Implications of telomeres and telomerase in endometrial pathology. Hum. Reprod. Update, 2017, vol. 23, pp. 166–187. DOI: 10.1093/humupd/dmw044
27. Parvanov D., Ganeva R., Vidolova N. et al. Decreased number of p16-positive senescent cells in human endometrium as a marker of miscarriage. J. Assist. Reprod. Genet, 2021, vol. 38, pp. 2087–2095. DOI: 10.1007/s10815-021-02182-5
28. Brown L. et al. Surgical interventions for precancerous cervical conditions. Gynecol. Oncol, 2019.
29. Gragnaro B. et al. Interferons in the treatment of HPV. J. Clin. Virol, 2016, vol. 45 (2), pp. 120–130.
30. Johnson L., Wang P. Clinical efficacy of interferon alpha in the treatment of HPV infections: A systematic review. Infec. Dis. J, 2018, vol. 47 (7), pp. 567–575.
31. Gonzalez M., Lee R. The role of interferons in treating HPV: Current perspectives and future directions. Immunother. Adv, 2019, vol. 12 (3), pp. 230–243.
32. Anokhova L.I., Belokrinitskaya T.E., Belozertseva E.P. et al. Innovative approach to the treatment of patients with high-risk human papillomavirus using allokin-alpha. MS, 2021, no. 13 (in Russ.), available at: https://cyberleninka.ru/article/n/innovatsionnyy-podhod-k-terapii-patsientok-s-virusom-papillomy-cheloveka-vysokogo-riska-primenyayuschih-allokin-alfa (accessed on: 12.01.2025).
33. Kononova I.N., Dobrokhotova Yu.E., Kareva E.N. et al. Evaluation of the effectiveness of antiviral therapy with Allokin-alpha in the complex treatment of patients with HPV-associated cervical intraepithelial neoplasia of grade II. Akusherstvo i ginekologiya, 2022, no. 11, pp. 155–162 (in Russ.). DOI: 10.18565/aig.2022.11.155-162
34. Smith J. et al. Efficacy of Imiquimod in treating HPV-related genital warts. J. Infec. Dis, 2017.