Prospective evaluation of the efficiency of treatment for cervical intraepithelial neoplasias associated with papillomavirus infection


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Abstract

Objective. To optimize the treatment of young reproductive-aged patients with cervical intraepithelial neoplasias associated with papillomavirus infection (PVI). Subjects and methods. This was a prospective cohort study of 94 sexually active young reproductive-aged (18-35-year-old; mean age, 27.0±3.2 years) women who were infected with high-risk human papillomavirus (HPV) types and had cytologic and/or colposcopic signs of PVI and/or low-grade squamous intraepithelial lesions. Results. Group 1 (n = 34) took isoprinosine 1000 mg (2 tablets) thrice daily for 28 days; Group 2 (n = 38) received the drug for 14 days; Group 3 (n = 22) was not medically treated. Therapeutic effectiveness was evaluated from primary and secondary outcomes. The primary outcomes were HIV elimination or a considerably reduced viral load; normalization of cytologic findings and colposcopic patterns after 6 and 12 months. The secondary outcomes were the presence or absence of a recurrence within 2 years after treatment; the occurrence, course, and outcomes of pregnancy following treatment. Conclusion. Inosine pranobex used for 28 days, unlike that for 14 days and wait-to-see therapy, accelerated HPV elimination, promoted a rapider normalization of cytologic and colposcopic values, and ensured no disease recurrences during a 2-year further follow-up. The 28-day inosine pranobex regimen statistically significantly reduced the risk of ectopic pregnancy and increased the rate of full-term deliveries, which was due to the higher rate of complete recovery from cervical disease as a possible trigger of early miscarriage.

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About the authors

Tatiana E. Belokrinitskaya

Chita State Medical Academy

Email: tanbell24@mail.ru
MD, Professor, Head of the Department of Obstetrics and Gynecology, Faculty of Pediatrics Chita, Russia

Tatiana E. Belokrinitskaya

Chita State Medical Academy

MD, Professor, Head of the Department of Obstetrics and Gynecology, Faculty of Pediatrics Chita, Russia

Antonina A. Zolotareva

Clinical Medical Center

obstetrician-gynecologist Chita, Russia

Olga Yur'evna Kotelnikova

OOO "Zdorovye plus" (Health plus) Medical Center

obstetrician-gynecologist Chita, Russia

Tatyana Veniaminovna Maltseva

Akademiya Zdorv'ya (Health Academy) Medical Center

obstetrician-gynecologist Chita, Russia

Natalia Ivanovna Frolova

Chita State Medical Academy, Ministry of Health of Russia

Email: taasyaа@mail.ru
PhD, Assistant of the Department of Obstetrics and Gynecology, Faculty of Pediatrics Chita, Russia

References

  1. Роговская С.И., Липова Е.В., ред. Шейка матки, влагалище, вульва: физиология, патология, кольпоскопия, эстетическая коррекция. Руководство для практикующих врачей. М.: «Status Praesens»; 2014. 832c. [Rogovskaya S.I., Lipova E.V., ed. The cervix, vagina, vulva: physiology, pathology, colposcopy, aesthetic correction. Guidance for practitioners. Moscow: «Status Praesens»; 2014. 832p. (in Russian)]
  2. Bosch F.X., Broker T.R., Forman D., Moscicki A.B. Comprehensive control of human papillomavirus infections and related diseases. Vaccine. 2013; 31(Suppl. 7): H1-31.
  3. Белокриницкая Т.Е., Пономарева Ю.Н., Бунина Е.Н., Ладыгина Н.М. Генитальные инфекции и локальная продукция цитокинов при диспластических процессах шейки матки. Сибирский медицинский журнал. (Иркутск). 2005; 7: 29-31. [Belokrinitskaya T.E., Ponomareva Yu.N., Bunina E.N., Ladyigina N.M. Genital infection and local production of cytokines in dysplastic cervical processes. Sibirskiy meditsinskiy zhurnal. (Irkutsk). 2005; 7: 29-31. (in Russian)]
  4. Whitworth M.K., Pafilis I., Vince G., Quenby S. Cervical leukocyte sub-populations in idiopathic preterm labour. J. Reprod. Immunol. 2007; 75(1): 48-55.
  5. Stock S.J., Duthie L., Tremaine T., Calder A.A., Kelly R.W., Riley S.C. Elafin (SKALP/Trappin-2/proteinase inhibitor-3) is produced by the cervix in pregnancy and cervicovaginal levels are diminished in bacterial vaginosis. Reprod. Sci. 2009; 16(12): 1125-34.
  6. Сухих Г.Т., Ванько Л.В. Иммунология беременности. М.: Издательство РАМН; 2003. 400c. [Suhih G.T., Vanko L.V. Immunology of pregnancy. Moscow: Publisher of Russian Academy of Medical Sciences; 2003. 400p. (in Russian)]
  7. Chaouat G., Sandra O, Lédée N. Immunology of pregnancy. Bentham, UK; 2014. 902p.
  8. Werner C.L., Lo J.Y., Heffernan T., Griffith W.F., McIntire D.D., Leveno K.J. Loop electrosurgical excision procedure and risk of preterm birth. Obstet. Gynecol. 2010; 115(3): 605-8. doi: 10.1097/A0G.0b013e3181d068a3.
  9. Bruinsma F., Quinn M. The risk of preterm birth following treatment for precancerous changes in the cervix: a systematic review and meta-analysis. BJOG. 2011; 118(9): 1031-41.
  10. Heinonen A., Gissler M., Riska A., Paavonen J., Tapper A.-M., Jakobsson M. Loop electrosurgical excision procedure and the risk for preterm delivery. Obstet. Gynecol. 2013; 121(5): 1063-8. doi: 10.1097/A0G.0b013e31828caa31.
  11. Kalliala I., Anttila A., Dyba T., Hakulinen T., Halttunen M., Nieminen P. Pregnancy incidence and outcome among patients with cervical intraepithelial neoplasia: a retrospective cohort study. BJOG. 2012; 119(2): 227-35. doi: 10.1111/j.1471-0528.2011.03042.x.
  12. Reilly R., Paranjothy S., Beer H., Brooks C.J., Fielder H.M., Lyons R.A. Birth outcomes following treatment for precancerous changes to the cervix: a population-based record linkage study. BJOG. 2012; 119(2): 236-44. doi: 10.1111/j.1471-0528.2011.03052.x.
  13. Белокриницкая Т.Е., Фролова Н.И., Тарбаева Д.А., Глотова Е.Ю., Золотарева А.А., Мальцева Т.В. Конфаундинг-факторы папилломавирусной инфекции и цервикальной дисплазии у молодых женщин. Доктор Ру. 2015; 14(115): 7-11. [Belokrinitskaya T.E., Frolova N.I., Tarbaeva D.A., Glotova E.Yu., Zolotareva A.A., Maltseva T.V. Konfaunding factors of HPV infection and cervical dysplasia in young women. Doktor Ru. 2015; 14(115): 7-11. (in Russian)]
  14. Remschmidt C., Kaufmann A.M., Hagemann I., Vartazarova E., Wichmann O., Delere Y. Risk factors for cervical human papillomavirus infection and high-grade intraepithelial lesion in women aged 20 to 31 years in Germany. Int. J. Gynecol. Cancer. 2013; 23(3): 519-26.
  15. De Vuyst H., Clifford G., Li N., Franceschi S. HPV infection in Europe. Eur. J. Cancer. 2009; 45(15): 2632-3.
  16. Доброхотова Ю.Э., Венедиктова М.Г., Гришин И.И., Саранцев А.Н., Морозова К.В., Луценко Н.Н. Эффективность комплексного подхода к лечению дисплазии эпителия шейки матки умеренной и тяжелой степени на фоне инфицирования вирусом папилломы человека. Фарматека. 2015; 3: 44-7. [Dobrohotova Yu.E., Venediktova M.G., Grishin I.I., Sarantsev A.N., Morozova K.V., Lutsenko N.N. The effectiveness of a comprehensive approach to the treatment of cervical dysplasia epithelium of moderate to severe on the background of the human papilloma virus infection. Farmateka. 2015; 3: 44-7. (in Russian)]
  17. Короленкова Л.И., Брюзгин В.В. Тяжелые цервикальные интраэпителиальные неоплазии (CIN Н-Ш/преинвазивный рак) и микрокарцинома шейки матки у беременных. Акушерство и гинекология. 2011; 5: 68-73. [Korolenkova L.I., Bryuzgin V.V. Severe cervical intraepithelial neoplasias (CIN II-III/carcinoma in situ) and microcarcinoma of the cervix uteri in pregnant women. Akusherstvo i ginekologiya/Obstetrics and gynecology. 2011; (5): 68-73. (in Russian)]
  18. Короленкова Л.И. Беременность при преинвазивном и микроинвазивном раке шейки матки - возможности донашивания, особенности диагностики, течения заболевания, исходы и прогноз. Акушерство и гинекология. 2015; 6: 53-8. [Korolenkova L.I. Pregnancy in in-situ and microinvasive carcinoma of the uterine cervix: Chances of carrying pregnancy to full term, specific features of diagnosis and disease course, and outcomes and prognosis. Akusherstvo i ginekologiya/Obstetrics and gynecology. 2015; 6: 53-8. (in Russian)]
  19. Kalliala I., Anttila A., Nieminen P., Halttunen M., Dyba T. Pregnancy incidence and outcome before and after cervical intraepithelial neoplasia: a retrospective cohort study. Cancer Med. 2014; 3(6):1512-65.
  20. Kyrgiou M., Mitra A., Arbyn M., Stasinou S.M., Martin-Hirsch P., Bennett Ph., Paraskevaidis E. Fertility and early pregnancy outcomes after treatment for cervical intraepithelial neoplasia: systematic review and meta-analysis. BMJ. 2014; 349: g6192. doi: 10.1136/bmj.g6192.
  21. Кедрова А.Г., Подистов Ю.И., Кузнецов В.В., Брюзгин В.В., Козаченко В.П., Никогосян С.О. Роль противовирусной терапии в комплексном лечении больных эпителиальными дисплазиями и преинвазивным раком шейки матки. Гинекология. 2005; 7(3): 170-3. [Kedrova A.G., Podistov Yu.I., Kuznetsov V.V., Bryuzgin V.V., Kozachenko V.P., Nikogosyan S.O. The role of antiviral therapy in the complex treatment of patients with epithelial dysplasia and preinvasive cervical cancer. Ginekologiya. 2005; 7(3): 170-3. (in Russian)]
  22. Короленкова Л.И. Роль ВПЧ-тестирования методом гибридного захвата (Hybrid Capture 2) в оценке эффективности органосохраняющего лечения тяжелых интраэпителиальных неоплазий, преинвазивного и микроинвазивного рака шейки матки. Вопросы онкологии. 2011; 57(3): 322-6. [Korolenkova L.I. The role of HPV testing by hybrid capture (Hybrid Capture 2) to assess the effectiveness of organ treat severe intraepithelial neoplasia, preinvasive and microinvasive cervical cancer. Voprosyi onkologii. 2011; 57(3): 322-6. (in Russian)]
  23. Ciapponi A., Bardach A., Glujovsky D., Gibbons L., Picconi M.A. Type-specific HPV prevalence in cervical cancer and high-grade lesions in Latin America and the Caribbean: systematic review and meta-analysis. PLoS One. 2011; 6(10): e25493. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC3186785/
  24. Khan M.J., Castle P.E., Lorincz A.T., Wacholder S., Sherman M., Scott D.R. et al. 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. J. Natl. Cancer Inst. 2005; 97:1072-9.
  25. Castellsague X., Diaz M., de Sanjose S., Munoz N., Herrero R., Franceschi S. et al. Worldwide human papillomavirus etiology of cervical adenocarcinoma and its cofactors: implications for screening and prevention. J. Natl. Cancer Inst. 2006; 98: 303-15.
  26. Moscicki A. CIN management guidelines in adolescents and young women. In: Abstracts the International papillomavirus society symposium. April 13-14 2007. Warsaw; 2007: 17.
  27. Елисеева М.Ю., Манухин И.Б., Мынбаев О.А., Зверева Н.С., Мишутина А.А., Царев В.Н. Противовирусный эффект инозина пранобекса при ВПЧ-ассоциированных заболеваниях. Акушерство и гинекология. 2012; 2: 107-14. [Eliseeva M.Yu., Manukhin I.B., Mynbaev O.A., Zvereva N.S., Mishutina A.A., Tcarev V.N. Antiviral effect of isoprinosine in HPV-associated diseases. Akusherstvo i ginekologiya/Obstetrics and gynecology. 2012; 2: 107-14. (in Russian)]
  28. Jenkins M., Chiriva-Internati M., Mirandola L., Tonroy C., Tedjarati S.S., Davis N. et al. Perspective for prophylaxis and treatment of cervical cancer: an immunological approach. Int. Rev. Immunol. 2012; 31(1): 3-21.
  29. Schiffman M. Integration of human papillomavirus vaccination, cytology, and human papillomavirus testing. Cancer. 2007; 111(3): 145-53.
  30. Назарова H.M., Бестаева H.B., Прилепская B.H., Трофимов Д.Ю., Костава М.Н. Новые направления и дискуссионные вопросы диагностики и лечения заболеваний, ассоциированных с папилломавирусной инфекцией. Акушерство и гинекология. 2012; 5: 10-6. [Nazarova N.M., Bestayeva N.V., Prilepskaya V.N., Trofimov D.Yu., Kostava M.N. The diagnosis and treatment of papillomavirus infection-associated diseases: New directions and controversial issues. Akusherstvo i ginekologiya/Obstetrics and gynecology. 2012; 5: 10-6. (in Russian)]
  31. Woodman C.B., Collins S., Winter H., Bailey A., Ellis J., Prior P. et al. Natural history of cervical human papillomavirus infection in young women: a longitudinal cohort study. Lancet. 2001; 357(9271): 1831-6.
  32. Григорьева И.Н., Кедрова А.Г., Кузнецов В.В., Подистов Ю.И., Глазкова О.А., Афанасьева Е.А. Применение противовирусных и иммуномодулирующих лекарств у больных с преинвазивным раком шейки матки. В кн.: Материалы XI Российского онкологического конгресса. М.; 2007: 214-5. [Grigoreva I.N., Kedrova A.G., Kuznetsov V.V., Podistov Yu.I., Glazkova O.A., Afanaseva E.A. Antiviral and immunomodulating drugs in patients with cervical preinvasive cancer. In: Proceedings of the XI Congress of the Russian Cancer. Moscow; 2007: 214-5. (in Russian)]
  33. Свердлова Е.С. Заболевания шейки матки: алгоритмы диагностики и технологии лечения. Монография. Кулинич С.И., ред. Иркутск: «Иркутская областная типография №1»; 2010. 124с. [Sverdlova E.S Cervical disease diagnostic algorithms and treatment technologies. Monograph. Kulinich S.I., ed. Irkutsk: «Irkutskaya oblastnaya tipografiya #1»; 2010. 124p. (in Russian)]
  34. Роговская С.И., Теребнева Л.И. Клинические аспекты плоскоклеточных интраэпителиальных поражений низкой степени. Акушерство и гинекология. 2013; 2: 136-43. [Rogovskaya S.I., Terebneva L.I. Clinical aspects of low-grade squamous intraepithelial lesions. Akusherstvo i ginekologiya/Obstetrics and gynecology. 2013; (2): 136-43. (in Russian)]
  35. Кедрова А.Г., Леваков С.А., Челнокова H.H. Оптимизация медикаментозной терапии начальных повреждений эпителия шейки матки, ассоциированных с вирусом папилломы человека. Акушерство и гинекология. 2014; 8: 88-93. [Kedrova A.G., Levakov S.A., Chelnokova N.N. Optimization of drug therapy for early human papillomavirus-associated cervical epithelial damages. Akusherstvo i ginekologiya/Obstetrics and gynecology. 2014; (8): 88-93. (in Russian)]
  36. Мотовилова Т.М. Патология шейки матки на фоне папилломавирусной инфекции: реально ли справиться с рецидивами? Клинический опыт использования технологии аблации и инозина пранобекса в комплексном лечении пациенток репродуктивного возраста. Русский медицинский журнал. 2015; 1: 20-4. [Motovilova T.M. Pathology in the background of human papillomavirus infection: Is it possible to cope with relapses? Clinical experience with the use of technology and inosine pranobex ablation in treatment of patients of reproductive age. Russkiy meditsinskiy zhurnal. 2015; 1: 20-4. (in Russian)]
  37. Пешрикова Т.Ю., Пушкарь В.А. Оценка эффективности комплексной терапии патологии шейки матки, ассоциированной с папилломавирусной инфекцией. Гинекология. 2015; 17(4): 50-3. [Pectrikova T.Yu., Pushkar V.A. Evaluating the effectiveness of complex treatment of cervical pathology associated with HPV infection. Ginekologiya. 2015; 17(4): 50-3. (in Russian)]
  38. Petrova M., Jelev D., Ivanova A., Krastev Z. Isoprinosine affects serum cytokine levels in healthy adults. J. Interferon Cytokine Res. 2010; 30(4): 223-8.
  39. Унанян А.Л., Сидорова И.С., Коссович Ю.М. Вопросы патогенеза и терапии заболеваний шейки матки, ассоциированных с папилломавирусной инфекцией. Акушерство, гинекология и репродукция. 2012; 6(1): 27-30. [Unanyan A.L., Sidorova I.S., Kossovich Yu.M. Pathogenesis and treatment of cervical diseases associated with HPV infection. Akusherstvo, ginekologiya i reproduktsiya. 2012; 6(1): 27-30. (in Russian)]
  40. Кисин В.И., ред. Инфекции, передаваемые половым путем. Протоколы ведения больных. М.: НЬЮДИАМЕД; 2014. 264с. [Kisin V.I., ed. Infections transmitted through sexual contact. patient management protocols. Moscow: NYUDIAMED; 2014. 264p. (in Russian)]

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