Annals of the Russian academy of medical sciencesAnnals of the Russian academy of medical sciencesВестник Российской академии медицинских наук0869-60472414-3545"Paediatrician" Publishers LLC133210.15690/vramn1332OBSTETRICS AND GYNAECOLOGY: CURRENT ISSUESАКТУАЛЬНЫЕ ВОПРОСЫ АКУШЕРСТВА И ГИНЕКОЛОГИИResearch ArticlePapillomavirus infection and reproductionПапилломавирусная инфекция и репродукцияhttps://orcid.org/0000-0002-6857-91309537-1147KrasnopolskyVladislav I.КраснопольскийВладислав Иванович
Russian Federation

MD, PhD, Professor, Academician of the RAS

д.м.н., профессор, академик РАН

it@moniiag.ruhttps://orcid.org/0000-0001-6155-788X4737-5826ZarochentsevaNina V.ЗароченцеваНина Викторовна
Russian Federation

MD, PhD, Professor

д.м.н., профессор РАН

ninazar11@mail.ruhttps://orcid.org/0000-0002-1275-92201252-3811KrasnopolskayaKsenia V.КраснопольскаяКсения Владиславовна
Russian Federation

MD, PhD, Corresponding Member of the RAS

д.м.н., чл.-корр. РАН

deti222@mail.ruhttps://orcid.org/0000-0002-7844-93641328-2868BashankaevaYulia N.БашанкаеваЮлия Николаевна
Russian Federation

MD

аспирант поликлинического отделения Московского областного НИИ акушерства и гинекологии

julia.bashankaeva@gmail.comhttps://orcid.org/0000-0002-3797-63601635-4913KuzmichevaVarvara S.КузьмичеваВарвара Сергеевна
Russian Federation

MD

аспирант отделения репродуктологии Московского областного НИИ акушерства и гинекологии

barbarakuzmicheva@gmail.comMoscow Regional Research Institute of Obstetrics and Gynecology, Ministry of Health of the Moscow RegionМосковский областной научно-исследовательский институт акушерства и гинекологии Минздрава Московской области310820207531891951004202002062020Copyright ©; 2020, "Paediatrician" Publishers LLCCopyright ©; 2020, Издательство "Педиатръ"2020"Paediatrician" Publishers LLCИздательство "Педиатръ"https://vestnikramn.spr-journal.ru/jour/article/view/1332

The purpose of the review — a synthesis of research data on the role of human papillomavirus infection in the reproductive health of women and men.

Key Points. Human papillomavirus (HPV) is one of the most common sexually transmitted viruses worldwide. According to the World Health Organization, HPV is the main cause of the development of HPV-associated diseases among both women and men. Viruses are subdivided into HPV with low carcinogenic risk, which cause benign warts, and HPV with high carcinogenic risk, which cause cancer. Different types of human papillomaviruses depending on their characteristic tropism, are divided into skin and mucous types. Viral infection in men leads to a decrease in the quality of sperm (for example, asthenozoospermia) due to apoptosis in sperm cells and due to the development of antisperm immunity. A negative viral effect on the fertility of women is manifested in an increase in the frequency of spontaneous miscarriages and a premature rupture of the amniotic membranes during pregnancy. There is evidence that HPV decreases the number of trophoblastic cells and abnormal trophoblastic-endometrial adhesion is also observed. In trophoblastic cells transfected with high-risk HPV, the level of apoptosis increases. HPV vaccination is safe, and the results show not only protection against HPV-associated diseases in women and men, but also a reduction of gestational complications, reduced preterm birth rates and the protection of newborns from infection.

Цель обзора — обобщение научных данных о роли папилломавирусной инфекции в репродуктивном здоровье мужчин и женщин. Основные положения. Вирус папилломы человека (ВПЧ) является одним из наиболее распространенных вирусов, передаваемых половым путем, во всем мире. По данным Всемирной организации здравоохранения (ВОЗ) ВПЧ выступает основной причиной развития ВПЧ-ассоциированных заболеваний как среди женщин, так и среди мужчин. Вирусы подразделяются на ВПЧ низкого канцерогенного риска, которые вызывают доброкачественные бородавки, и ВПЧ высококанцерогенного риска, которые способны вызывать раковые заболевания. Различные типы вирусов папилломы человека проявляют характерный тропизм, подразделяются на кожные и слизистые типы. Вирусная инфекция у мужчин приводит к снижению качества сперматозоидов (главным образом астенозооспермии) в связи с апоптозом в клетках спермы и увеличению частоты появления антиспермальных антител. Отрицательное вирусное влияние на фертильность женщин проявляется в увеличении частоты самопроизвольных выкидышей и преждевременного разрыва околоплодных оболочек во время беременности. Есть данные, указывающие на то, что при ВПЧ уменьшается количество трофобластических клеток и наблюдается аномальная трофобластическо-эндометриальная адгезия. В трофобластических клетках, трансфицированных ВПЧ высококанцерогенного риска, повышается уровень апоптоза. Вакцинация против ВПЧ безопасна, результаты демонстрируют не только защиту от ВПЧ-ассоциированных заболеваний у женщин и мужчин, но и снижение гестационных осложнений, частоты преждевременных родов, а также гарантирует защиту новорожденных от инфицирования.

HPVfertilityassisted reproductive technologycryopreservationvaccinationВПЧЭКОфертильностьвспомогательные репродуктивные технологиикриоконсервациявакцинацияNoronha AS, Markowitz LE, Dunne EF. Systematic review of human papillomavirus vaccine coadministration. Vaccine. 2014;32(23):2670–2674. doi; 10.1016/j.vaccine.2013.12.037.Bosch FX, Broker TR, Formen D, Moscicki AB, Gillison ML, Doorbar J, et al. Comprehensive control of human papillomavirus infections and related diseases. Vaccine. 2013;31(7): H1–H31. doi: 10.1016/j.vaccine.2013.10.003.Laprise C, Trrottier H, Monnier P, Coutlee F, Mayrand MH. Prevalence of human papillomaviruses in semen: a systematic review and meta-analysis. Hum Reprod. 2014;29(4):640–665. doi: 10.1093/humrep/det453.WHO. Human papillomavirus (HPV) and cervical cancer. 24.01.2019. URL: https://www.who.int/ru/news-room/fact-sheets/detail/human-papillomavirus-(hpv)-and-cervical-cancer.Pereira N, Kucharczyk KM, Estes JL, Gerber RS, Lekovich JP, Elias RT, Spandorfer SD. Human papillomavirus infection, infertility, and assisted reproductive outcomes. Journal of Pathogens. 2015;(4):1–8. doi: 10.1155/2015/578423.Souho T, Benlemlih M, Bennani B. Human papillomavirus infection and fertility alteration: a systematic review. PloS One. 2015;10(5):e0126936. doi: 10.1371/journal.pone.0126936.Jeršovienė V, Gudlevičienė Ž, Rimienė J, Butkauskas D. Human papillomavirus and infertility. Medicina (Kaunas). 2019;55(7):377. doi: 10.3390/medicina55070377. PMID: 31311196; PMCID: PMC6681313.Альтери Р., Калидас М., Ядао Л., Огоро С. Рекомендации Американского онкологического общества по профилактике и раннему выявлению рака шейки матки. 2019. [Alteri R, Kalidas M, Yadao L, Ogoro S. American Cancer Society guidelines for the prevention and early detection of cervical cancer. 2019.] URL: http://www.cancer.org/cancer/cervicalcancer/detailedguide/cervical-cancer-key-statistics .Stanley M. Pathology and epidemiology of HPV infection in females. Gynecologic Oncology. 2010;117(2): S5–S10. doi: 10.1016/j.ygyno.2010.01.024.Foresta C, Noventa M, De Toni L, Gizzo S, Garolla A. HPV–DNA sperm infection and infertility: from a systematic literature review to a possible clinical management proposal. Andrology. 2014;3(2):163–173. doi: 10.1111/andr.284.Foresta C, Garolla A, Zuccarello D, Pizzol D, Moretti A, Barzon L, Palù G. Human papillomavirus found in sperm head of young adult males affects the progressive motility. Fertility and Sterility. 2010;93(3):802–806. doi: 10.1016/j.fertnstert.2008.10.050.Garolla A, Pizzol D, Foresta C. The role of human papillomavirus on sperm function. Current Opinion in Obstetrics and Gynecology. 2011;23(4):232–237. doi: 10.1097/gco.0b013e328348a3a4.Zacharis K, Messini C, Anifandis G, Koukoulis G, Satra M, Daponte A. Human papilloma virus (HPV) and fertilization: a mini review. Medicina. 2018;54(4):50. doi: 10.3390/medicina54040050.Yang Y, Jia C-W, Ma Y-M, Zhou L-Y, Wang S-Y. Correlation between HPV sperm infection and male infertility. Asian Journal of Andrology. 2013;15(4):529–532. doi: 10.1038/aja.2013.36.Foresta C, Pizzol D, Moretti A, Barzon L, Palù G, Garolla A. Clinical and prognostic significance of human papillomavirus DNA in the sperm or exfoliated cells of infertile patients and subjects with risk factors. Fertility and Sterility. 2010;94(5):1723–1727. doi: 10.1016/j.fertnstert.2009.11.012.Schillaci R, Capra G, Bellavia C, Ruvolo G, Scazzone C, Venezia R, Perino A. Detection of oncogenic human papillomavirus genotypes on spermatozoa from male partners of infertile couples. Fertility and Sterility. 2013;100(5):1236–1240. doi: 10.1016/j.fertnstert.2013.06.042.Depuydt CE, Verstraete L, Berth M., et al. Human papillomavirus positivity in women undergoing intrauterine insemination has a negative effect on pregnancy rates. Gynecologic and Obstetric Investigation. 2016;81(1):41–46. doi: 10.1159/000434749.Garolla A, Engl B, Pizzol D, Ghezzi M, Bertoldo A, Bottacin A, et al. Spontaneous fertility and in vitro fertilization outcome: new evidence of human papillomavirus sperm infection. Fertil. Steril. 2016;105:65–72 doi: https://doi.org/10.1016/j.fertnstert.2015.09.018.Perez-Andino J, Buck CB, Ribbeck K. Absorption of human papillomavirus 16 to live human sperm. PLoS One. 2009. doi: 10.1371/journal.pone.0005847.Garolla A, Pizzol D, Bertoldo A, De Toni L, Barzon L, Foresta C. Association, prevalence, and clearance of human papilloma virus and anti spermantibodies in infected semen samples from infertile patients. Fertil Steril. 2013;99:125–131. doi: 10.1016/j.fertnstert.2012.09.006. PMID:23043686.Gomez LM, Ma Y, Ho C, McGrath CM, Nelson DB, Parry S. Placental infection with human papillomavirus is associated with spontaneous preterm delivery. Hum. Reprod. 2008. doi: 10.1093/humrep/dem404.Hong LJ, Oshiro BT, Chan PJ. HPV-16 exposed mouse embryos: a potential model for pregnancy wastage. Archives of Gynecology and Obstetrics. 2013;287(6):1093–1097. doi: 10.1007/s00404-013-2711-5.Zuo Z, Goel S, Carter JE. Association of cervical cytology and HPV DNA status during pregnancy with placental abnormalities and preterm birth. Am J Clin Pathol. 2011. doi: 10.1309/ AJCP93JMIUEKRPIW.Noventa MA, Andrisani S, Gizzo GB, Nardelli G, Ambrosini G. Is it time to shift the attention on early stages embryo development to avoid inconclusive evidence on HPV-related infertility: debate and proposal. Reproductive Biology and Endocrinology. 2014;12(48). doi: 10.1186/1477-7827-12-48.Каткова Н.Ю., Кабатин Н.А., Чернов М.В., Качалина О.В. Морфологические изменения плацентарной ткани у женщин с папилломавирусной инфекцией // Актуальные вопросы педиатрии, перинатологии и репродуктологии: межвузовский сборник научных работ. Нижний Новгород, 2013. [Katkova NYu, Kabatin NA, Chernov MV, Kachalina OV. Morfologicheskie izmeneniya placentarnoj tkani u zhenshchin s papillomavirusnoj infekciej. Aktual’nye voprosy pediatrii, perinatologii i reproduktologii: мezhvuzovskij sbornik nauchnyh rabot. Nizhnij Novgorod; 2013. (In Russ.)]Кустова М.А., Барановская Е.И., Теслова О.А. Персистенция вируса папилломы человека в шейке матки и в плаценте // Материалы ежегодной научно-практической конференции. Гомель, 7 октября 2011 г. Гомель, 2011. [Kustova MA, Baranovskaya EI, Teslova OA. Persistenciya virusa papillomy cheloveka v shejke matki i v placente. Materialy ezhegodnoj nauchno-prakticheskoj konferencii. Gomel’, 7 oktyabrya 2011 g. Gomel; 2011. (In Russ.)]Hamont D, Nissen LHC, Siebersetal AG, Abnormal cervical cytology in women eligible for IVF. Human Reproduction. 2006;21(9):2359–2363. doi: 10.1093/humrep/del132.Wang Y, Wang C, Qiao J, Wang L, Liang S. Relationship of cytopathology and cervical infection to outcome of in vitro fertilization and embryo transfer. International Journal of Gynecology and Obstetrics. 2008;101(1):21–26. doi: 10.1016/j.ijgo.2007.09.035.Henneberg AA, Patton WC, Jacobson JD, Chan PJ. Human papilloma virus DNA exposure and embryo survival is stage-specific. J. Assist. Reprod. Genet. 2006;23(6):255– 259. doi: 10.1007/s10815-006-9030-8.Skoczynski M, Gozdzicka-Jozefiak A, Kwasniewska A. Prevalence of human papilloma virus in spontaneously aborted products of conception. Acta Obstetricia et Gynecologica Scandinavica. 2011;90(12):1402–1405. doi: 10.1111/j.1600-0412.2011.01189.x.Conde-Ferraez L, Chan May ADA, Carrillo-Martınez JR, Ayora-Talavera G, Gonzalez-Losa MDR. Human papilloma virus infection and spontaneous abortion: a case-control study performed in Mexico. European Journal of Obstetrics Gynecology and Reproductive Biology. 2013;170(2):468–473. doi: https://doi.org/10.1016/j.ejogrb.2013.07.002.Matovina M, Husnjak K, Milutin N, Ciglar S, Grce M. Possible role of bacterial and viral infections in miscarriages. Fertil. Steril. 2004;81(3):662–669. doi: https://doi.org/10.1016/j.fertnstert.2003.08.020.Bennani B, Bennis S, Nejjari C, Ouafik L, Melhouf MA, Rhazi KEI, et al. Correlates of HPV: across ectional study in women with normal cytology in north-central Morocco. J Infect Dev Ctries. 2011;6:543–550. doi: https://doi.org/10.3855/jidc.1675.Ticconi C, Pietropolli A, Fabbri G, Capogna MV, Perno CF, Piccione E. Recurrent miscarriage and cervical human papillomavirus infection. Am J Reprod Immunol. 2013;70(5):343–346. doi: https://doi.org/10.1111/aji.12156.Cho G, Min K-J, Hong H-R, Kim S, Hong J-H, Lee J-K, et al. High-risk human papillomavirus infection is associated with premature rupture of membranes. BMC Pregnancy and Childbirth. 2013;13:173. doi: 10.1186/1471-2393-13-173.Park H, Lee SW, Lee IH, et al. Rate of vertical transmission of human papillomavirus from mothers to infants: relationship between infection rate and mode of delivery. Virology Journal. 2012;9(80). doi: 10.1186/1743-422X-9-80.Trottier H, Mayrand M-H, Coutlée F, Monnier P, Laporte L, Niyibizi J, Audibert F. Human papillomavirus (HPV) perinatal transmission and risk of HPV persistence among children: design, methods and preliminary results of the heritage study. Papillomavirus Research. 2016;2:145–152. doi: 10.1016/j.pvr.2016.07.001.Spandorfer SD, Bongiovanni AM, Fasioulotis S, Rosenwaks Z, Ledger WJ, Witkin SS. Prevalence of cervical humanpapillomavirus in women undergoing in vitro fertilization and association with outcome. Fertility and Sterility. 2006;86(3):765–767. doi: 10.1016/j.fertnstert.2006.01.051.Perino A, Giovannelli L, Schillaci R, et al. Human papillomavirus infection in couples undergoing in vitro fertilization procedures: impact on reproductive outcomes. Fertility and Sterility. 2011;95(5):1845–1848. doi: 10.1016/j.fertnstert.2010.11.047.Comar M, Monasta L, Zanotta N, Vecchi Brumatti L, Ricci G, Zauli G. Human papillomavirus infection is associated with decreased levels of GM–CSF in cervico-vaginal fluid of infected women. Journal of Clinical Virology. 2013;58(2):479–481. doi: 10.1016/j.jcv.2013.07.001.Schillaci R, Capra G, Bellaviaetal C. Detection of oncogenic human papillomavirus genotypes on spermatozoa from male partners of infertile couples. Fertility and Sterility. 2013;100(5):1236–1240. doi: 10.1016/j.fertnstert.2013.06.042.Yang R, Wang Y, Qiao J, Liu P, Geng L, Guo Y-L. Does human papillomavirus infection do harm to in-vitro fertilization outcomes and subsequent pregnancy outcomes? Chinese Medical Journal. 2013;126(4):683–687. doi: 10.3760/cma.j.issn.0366-6999.20121625.Tanaka H, Karube A, Kodama H, Fukuda J, Tanaka T. Mass screening for human papillomavirus type 16 infection in infertile couples. The Journal of Reproductive Medicine. 2000;45(11):907–911. PMID: 11127102.Foresta C, Ferlin A, Bertoldo A, Patassini C, Zuccarello D, Garolla A. Human papilloma virus in the sperm cryobank: an emerging problem? Int. J. Androl. 2011;34:242–246. doi: 10.1111/j.1365-2605.2010.01075.xВОЗ. Weekly epidemiological record, № 19, 12 May, 2017/ URL: https://www.who.int/immunization/policy/position_papers/PP_hpv_2017_RU.pdf?ua=1.WHO. Preparing for the introduction of human papillomavirus vaccines: a policy and program guide for countries. URL: https://apps.who.int/iris/bitstream/handle/10665/69384/WHO_RHR_06.11_rus.pdf;jsessionid=23238B4DAE246800C0A1645A614EDD62?sequence=4.ВОЗ. Weekly epidemiological record, No. 28, 14 July, 2017. URL: https://apps.who.int/iris/bitstream/handle/10665/255870/WER9228.pdf;jsessionid=E9A209121898EE490C61652EA45A40B0?sequence=1.Foresta C, Pizzol D, Bertoldo A, Menegazzo M, Barzon L, Garolla A. Semen washing procedures do not eliminate human papilloma virus sperm infection in infertile patients. Fertility and Sterility. 2011;96(5):1077–1082. doi: https://doi.org/10.1016/j.fertnstert.2011.04.009.Краснопольский В.И., Петрухин В.А., Зароченцева Н.В., Белая Ю.М., и др. Особенности течения беременности и ее исходов у женщин, вакцинированных против папилломавирусной инфекции // Акушерство и гинекология. — 2020. — № 1. — С. 146–154. doi: https://dx.doi.org/10.18565/aig.2020.1.146154. [Krasnopolsky VI, Petrukhin VA, Zarochentseva NV, Belaya YuM, et al. The features of the course of pregnancy and its outcomes in women vaccinated against papillomavirus infection. Obstetrics and Gynecology. 2020;(1):146–154. (In Russ.)]Lawton B, Howe AS, Turner N, Filoche S, Slatter T, Devenish C, Hung NA. Association of prior HPV vaccination with reduced preterm birth: a population based study. Vaccine. 2018;36(1):134–140. doi: 10.1016/j.vaccine.2017.11.020.