Possibilities of using photodynamic therapy in the treatment of cervical precancers and cancers

Gilyadova A.V., Ishchenko A.A., Apolikhina I.A., Saidova А.S., Shiryaev A.A., Samoilova S.I., Alekseeva P.M., Efendiev K.T., Reshetov I.V.

1) I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), Moscow, Russia; 2) National Medical Research Center “Treatment and Rehabilitation Center”, Ministry of Health of Russia, Moscow, Russia; 3) Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, Moscow, Russia; 4) A.M. Prokhorov General Physics Institute, Russian Academy of Sciences, Moscow, Russia; 5) National Research Nuclear University “Moscow Engineering Physics Institute (MEPhI)”, Moscow, Russia
Literature data on the main areas of treatment for cervical precancers and cancers are analyzed. Human papillomavirus (HPV) is indicated to be the leading etiological agent in the development of squamous intraepithelial lesions and squamous cervical cell cancer of the cervix. Persistent HPV in the cervical epithelium is largely due to the presence of the virus in the vaginal mucosa. Therefore, it is relevant to develop treatments to achieve viral elimination from the mucous membrane of the genital tract, by taking into account the tropism of HPV to the epithelial cells of this area.
The promising organ-sparing highly selective treatment for cervical intraepithelial neoplasia is photodynamic therapy (PDT) that is based on the systemic or local administration of special substances, such as photosensitizers, that are affected by laser radiation after their injection into the body. The interaction of photosensitizer molecules and light quanta is accompanied by the formation of reactive oxygen species that damage cells and trigger a cascade of processes leading to the death of tumor cells. At the same time, the tumor cells absorb the photosensitizer more actively than healthy ones, which is responsible for the selective antitumor effect of laser radiation.
The requirements for the ideal photosensitizer are considered. These substances during PDT are administered intravenously or topically as a gel or ointment.
Conclusion: The analysis of the literature data has demonstrated the clinical efficiency of PDT in the treatment of patients with cervical intraepithelial neoplasia and HPV carriers without adverse effects on fertility. PDT contributes to the successful treatment of pathological foci on the cervical mucous membrane; the efficiency and safety of the technique are ensured by tissue selectivity of the effect. During the treatment, the surrounding intact tissues are not damaged, there is no gross scarring or stenosis of the cervical canal; thus, PDT makes it possible to preserve the normal anatomical and functional characteristics of the cervix.

Keywords

cervical cancer
precancerous diseases
photodynamic therapy
photosensitizers
eradication
human papillomavirus
squamous intraepithelial lesions of the cervix
preinvasive cancer
colposcopy
conization
ablation

References

  1. Cohen P.A., Jhingran A., Oaknin A., Denny L. Cervical cancer. Lancet. 2019; 393(10167): 169-82. https://dx.doi.org/10.1016/S0140-6736(18)32470-X.
  2. Siegel R.L., Miller K.D., Jemal A. Cancer statistics, 2020. CA Cancer J. Clin. 2020; 70(1): 7-30. https://dx.doi.org/10.3322/caac.21590.
  3. Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2021; 71(3): 209-49. https://dx.doi.org/10.3322/caac.21660.
  4. Cancer Today. International Agency for Research on Cancer, World Health Organization. Available at: http://gco.iarc.fr/
  5. Боровкова Л.В., Ионова Е.В., Игнатьев А.А. Ранняя диагностика заболеваний шейки матки. Вопросы гинекологии, акушерства и перинатологии. 2019; 18(4): 28-34. [Borovkova L.V., Ionova E.V., Ignatiev A.A. Early diagnosis of diseases of the cervix. Voprosy ginekologii, akusherstva i perinatologii/Issues of gynecology, obstetrics and perinatology. 2019; 18(4): 28-34. (in Russian)]. https://dx.doi.org/10.20953/1726-1678-2019-4-28.
  6. Sayed S.A., Naugler C., Chen G., Dickinson J.A. Cervical screening practices and outcomes for young women in response to changed guidelines in Calgary, Canada, 2007-2016. J. Low. Genit. Tract Dis. 2021; 25(1): 1-8. https://dx.doi.org/10.1097/LGT.0000000000000574.
  7. Graham S.V. The human papillomavirus replication cycle, and its links to cancer progression: a comprehensive review. Clin. Sci. (Lond). 2017; 131: 2201-21. https://dx.doi.org/10.1042/CS20160786.
  8. Balasubramaniam S.D., Balakrishnan V., Oon C.E., Kaur G. Key molecular events in cervical cancer development. Medicina (Kaunas). 2019; 55(7): 384. https://dx.doi.org/10.3390/medicina55070384.
  9. Dudea-Simon M., Dudea S.M., Ciortea R., Ciortea R., Măluțan A., Simon V. et al. Elastography of the uterine cervix in gynecology: normal appearance, cervical intraepithelial neoplasia and cancer. A systematic review. Med. Ultrason. 2021; 23(1): 74-82. https://dx.doi.org/10.11152/mu-2646.
  10. Hoffman S.R., Le T., Lockhart A., Sanusi A., Dal Santo L., Davis M. et al. Patterns of persistent HPV infection after treatment for cervical intraepithelial neoplasia (CIN): A systematic review. Int. J. Cancer. 2017; 141(1): 8-23. https://dx.doi.org/10.1002/ijc.30623.
  11. Mello V., Sundstrom R.K. Cervical intraepithelial neoplasia. StatPearls. Treasure Island (FL): StatPearls Publishing; 22020.
  12. Hillemanns P., Einstein M.H., Iversen O.E. Topical hexaminolevulinate photodynamic therapy for the treatment of persistent human papilloma virus infections and cervical intraepithelial neoplasia. Expert Opin. Investig. Drugs. 2015; 24(2): 273-81. https://dx.doi.org/10.1517/13543784.2015.990150.
  13. Дуванский Р.А., Странадко Е.Ф., Ковалев М.И., Дуванский В.А., Ковалева А.М. Лечение неопухолевых заболеваний и дисплазий шейки матки с применением фотодинамической терапии. Biomedical Photonics. 2018; 7(Приложение): 37. [Duvansky R.A., Stranadko E.F., Kovalev M.I. et al. Treatment of non-tumor diseases and cervical dysplasia using photodynamic therapy. Biomedical Photonics/Biomedical Photonics. 2018; 7: 37 (in Russian)].
  14. Novikova T. Optical techniques for cervical neoplasia detection. Beilstein J. Nanotechnol. 2017; 8: 1844-62. https://dx.doi.org/10.3762/bjnano.8.186.
  15. Kyrgiou M., Mitra A., Arbyn M., Stasinou S.M., Martin-Hirsch P., Bennett P., Paraskevaidis E. Fertility and early pregnancy outcomes after treatment for cervical intraepithelial neoplasia: systematic review and meta-analysis. BMJ. 2014; 349: g6192. https://dx.doi.org/10.1136/bmj.g6192.
  16. Баранов И.И., Зароченцева Н.В., Малиновская В.В., Выжлова Е.Н. Неинвазивные методы лечения пациенток с ВПЧ-инфекцией и цервикальными интраэпителиальными неоплазиями: Систематический обзор и метаанализ. Акушерство и гинекология: новости, мнения, обучение. 2021; 9(1): 31-43. [Baranov I.I., Zarochentseva N.V., Malinovskaya V.V., Vyzhlova E.N. Noninvasive methods of therapy for human papillomavirus infection in patients with cervical intraepithelial neoplasia: a systematic review and meta-analysis. Akusherstvo i ginekologiya: novosti, mneniya, obuchenie/Obstetrics and Gynecology: News, Opinions, Training. 2021; 9(1): 31-43 (in Russian)]. https://dx.doi.org/10.33029/2303-9698-2021-9-1-31-43.
  17. Xu J., Zhao J., Dong Y., Zhao X., Chen R., Shi Y. et al. Photodetection and safety of 5-aminolevulinic acid-induced porphyrin in patients with cervical intraepithelial neoplasia. Lasers Surg. Med. 2021; 53(5): 654-63. https://dx.doi.org/1010.1002/lsm.23338.
  18. Li D., Zhang F., Shi L., Lin L., Cai Q., Xu Y. Treatment of HPV infection-associated low grade cervical intraepithelial neoplasia with 5-aminolevulinic acid-mediated photodynamic therapy. Photodiagnosis Photodyn. Ther. 2020; 21: 101974. https://dx.doi.org/1010.1016/j.pdpdt.2020.
  19. Лукьянец Е.А. Поиск новых фотосенсибилизаторов для фотодинамической терапии. Фотодинамическая терапия и фотодиагностика. 2013; 3: 3-16. [Lukyanets EA. Search for new photosensitizers for photodynamic therapy. Fotodinamicheskaya terapiya i fotodiagnostika/Photodynamic therapy and photodiagnostics. 2013; 3: 3-16 (in Russian)]
  20. Денисова Е.Д., Аполихина И.А., Булгакова Н.Н. Флуоресцентная диагностика и фотодинамическая терапия: возможности применения при заболеваниях нижних отделов половых путей. Акушерство и гинекология. 2010; 3: 17-20. [Denisova E.D., Apolikhina I.A., Bulgakova N.N. Fluorescent diagnostics and photodynamic therapy: possibilities of application in diseases of the lower genital tract. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2010; 3: 17-20 (in Russian)].
  21. Juarranz A., Jaén P., Sanz-Rodríguez F., Cuevas J., González S. Photodynamic therapy of cancer. Basic principles and applications. Clin. Transl. Oncol. 2008; 10(3): 148-54. https://dx.doi.org/10.1007/s12094-008-0172-2.
  22. Торчинов А.М., Умаханова М.М., Дуванский Р.А., Аубекирова М.А., Дуванский В.А. Фотодинамическая терапия фоновых заболеваний шейки матки. Лазерная медицина. 2013; 4: 8-11. [Torchinov A.M., Umakhanova M.M., Duvansky R.A., Aubekirova M.A., Duvansky V.A. Photodynamic therapy in background diseases of the uterine cervix. Lazernaya medicina/Laser medicine. 2013; 4: 8-11 (in Russian)].
  23. Iqbal Z., Hanack M., Ziegler T. Spectral, photophysical and photochemical properties of tetra- and octaglycosylated zinc phthalocyanines. Photochem. Photobiol. Sci. 2012; 11(4): 679-86. https://dx.doi.org/10.1039/c2pp05348a.
  24. Choi M.C., Jung S.G., Park H., Lee S.Y., Lee C., Hwang Y.Y., Kim S.J. Photodynamic therapy for management of cervical intraepithelial neoplasia II and III in young patients and obstetric outcomes. Lasers Surg. Med. 2013; 45(9): 564-72. https://dx.doi.org/10.1002/lsm.22187.
  25. Давыдов А.И., Шахламова М.Н., Лебедев В.А. Риски рецидивов папилломавирусной инфекции и методы их профилактики. Вопросы гинекологии, акушерства и перинатологии. 2020; 19(3): 101-6. [Davydov A.I., Shakhlamova M.N., Lebedev V.A. Risks for recurrences of papillomavirus infection and methods of their prevention. Voprosy ginekologii, akusherstva i perinatologii/Issues of gynecology, obstetrics and perinatology. 2020; 19(3): 101-6. (in Russian)]. https://dx.doi.org/10.20953/1726-16782020-3-101-106.
  26. Бегларян Г.А., Арутюнян А.Г. Современное представление о роли папилломавирусной инфекции при развитии цервикальной интра­эпителиальной неоплазии. Акушерство и гинекология. 2021; 12: 17-22. [Beglaryan G.A., Arutyunyan A.G. The current concept of the role of papillomavirus infection in the development of cervical intraepitelial neoplasia. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2021; 12: 17-22 (in Russian)]. https://dx.doi.org/10.18565/aig.2021.12.17-22.
  27. Park Y.K., Park C.H. Clinical efficacy of photodynamic therapy. Obstet. Gynecol. Sci. 2016; 59(6): 479-88. https://dx.doi.org/10.5468/ogs.2016.59.6.479.
  28. Дуванский Р.А., Торчинов А.М., Умаханова М.М. Фотодинамическая терапия неопухолевых заболеваний шейки матки с препаратом радагель. Biomedical Photonics. 2015; 4: 58-9. [Duvansky R.A., Torchinov A.M., Umakhanova M.M. PDT of non-tumor diseases of the cervix with Radagel. Biomedical Photonics/Biomedical Photonics. 2015; 4: 58-9 (in Russian)].
  29. Новикова Е.Г., Трушина О.И. Фотодинамическая терапия в профилактике ВПЧ-ассоциированных рецидивов начального рака шейки матки. Акушерство и гинекология: новости, мнения, обучение. 2018; 1: 34-43. [Novikova E.G., Trushina O.I. Photodynamic therapy in prevention of early cervical cancer HPV-related relapses. Akusherstvo i ginekologiya: novosti, mneniya, obuchenie/Obstetrics and Gynecology: News, Opinions, Training. 2018; 1: 34-43. (in Russian)].
  30. Гребенкина E.В., Гамаюнов С.В., Кузнецов С.С., Оноприенко О.В., Илларионова Н.А., Шахова Н.М. Фотодинамическая терапия заболеваний шейки матки. Фотодинамическая терапия и фотодиагностика. 2014; 3(2): 12-4. [Grebenkina E.V., Gamajunov S.V., Kuznetsov S.S., Onoprienko O.V., Illarionova N.A., Shakhova N.M. Photodynamic therapy for cervical lesions. Fotodinamicheskaya terapiya i fotodiagnostika/Photodynamic therapy and photodiagnostics. 2014; 2: 12-4. (in Russian)].
  31. Аминодова И.П., Аминодов С.А. Оптимизация параметров лечения при фотодинамической терапии предрака и рака шейки матки. Фотодинамическая терапия и фотодиагностика. 2015; 4(2): 17-21. [Aminodova I.P., Aminodov S.A. Adjustment of treatment parameters for photodynamic therapy of cervical pre-cancer and cancer. Fotodinamicheskaya terapiya i fotodiagnostika/ Photodynamic therapy and photodyagnosis. 2015; 4(2): 17-21. (in Russian)]. https://dx.doi.org/10.24931/2413-9432-2015-4-2-17-21.
  32. Филоненко Е.В., Серова Л.Г., Иванова-Радкевич В.И. Результаты III фазы клинических исследований препарата радахлорин для фотодинамической терапии предрака и начального рака райки матки. Biomedical Photonics. 2015; 4(3): 36-42. [Filonenko E.V., Serova L.G., Ivanova-Radkevich V.I. Results from phase III clinical trials with radachlorine for photodynamic therapy of pre-cancer and early cancer of cervix. Biomedical Photonics. 2015; 4(3): 36-42 (in Russian)]. https://dx.doi.org/10.24931/2413-9432-2015-4-3-36-42.
  33. Zhang W., Zhang A., Sun W., Yue Y., Li H. Efficacy and safety of photodynamic therapy for cervical intraepithelial neoplasia and human papilloma virus infection: A systematic review and meta-analysis of randomized clinical trials. Medicine (Baltimore). 2018; 97(21): e10864. https://dx.doi.org/10.1097/MD.0000000000010864.
  34. Liu Z., Zheng H., Chen X., Qi N. Comparison of the efficacy of ALA and high-frequency electric ion operating on cervical intraepithelial neoplasia grade I. Int. J. Clin. Exp. Med. 2016; 9: 16782-6.
  35. Inada N.M., Buzzá H.H., Leite M.F., Kurachi C,. Trujillo J.R., de Castro C.A. et al. Long term effectiveness of photodynamic therapy for CIN treatment. Pharmaceuticals (Basel). 2019; 12(3): 107. https://dx.doi.org/10.3390/ph12030107.
  36. Zhu M., He Y., Baak J.P., Zhou X., Qu Y., Sui L. et al. Factors that influence persistence or recurrence of high-grade squamous intraepithelial lesion with positive margins after the loop electrosurgical excision procedure: A retrospective study. BMC Cancer. 2015; 15: 744. https://dx.doi.org/10.1186/s12885-015-1748-1.
  37. Istomin Y.P., Lapzevich T.P., Chalau V.N., Shliakhtsin S.V., Trukhachova T.V. Photodynamic therapy of cervical intraepithelial neoplasia grades II and III with Photolon. Photodiagnosis Photodyn. Ther. 2010; 7(3): 144-51. https://dx.doi.org/10.1016/j.pdpdt.2010.06.005.
  38. Soergel P., Makowski L., Makowski E, Schippert C., Hertel H., Hillemanns P. Treatment of high grade cervical intraepithelial neoplasia by photodynamic therapy using hexylaminolevulinate may be cost-effective compared to conization procedures due to decreased pregnancy-related morbidity. Lasers Surg. Med. 2011; 43(7): 713-20. https://dx.doi.org/10.1002/lsm.21072.

Received 24.03.2022

Accepted 28.04.2022

About the Authors

Aida V. Gilyadova, Assistant of the Department of Oncology, Radiotherapy and Plastic Surgery, I.M. Sechenov First MSMU, Ministry of Health of Russia (Sechenov University); doctor of the Gynecology Department, Medical and Rehabilitation Center of the Ministry of Health of Russia, aida-benyagueva@mail.ru,
https://orcid.org/0000-0003-4343-4813, 119991, Russia, Moscow, Trubetskaya str., 8-2.
Anton A. Ishchenko, PhD, Head of the Clinic of Gynecology, Reproductive and Aesthetic Medicine, Medical and Rehabilitation Center of the Ministry of Health of Russia, ra2001_2001@mail.ru, https://orcid.org/0000-0001-6673-3934, 125367, Russia, Moscow, Ivankovskoe highway, 3.
Inna A. Apolikhina, Dr. Med. Sci., Professor, Head of the Department of Aesthetic Gynecology and Development, V.I. Kulakov NMRC for AG&P, Ministry of Health of Russia; Professor of the Department of Obstetrics, Gynecology, Perinatology and Reproductology, Institute of Vocational Education, First MSMU, Ministry of Health of Russia (Sechenov University), i_apolikhina@oparina4.ru, https://orcid.org/0000-0002-4581-6295, 117997, Russia, Moscow, Academician Oparin str., 4.
Aina S. Saidova, PhD, obstetrician-gynecologist of the Department of Aesthetic Gynecology and Fetus, V.I. Kulakov NMRC for AG&P, Ministry of Health of Russia,
a_saidova@oparina4.ru; https://orcid.org/0000-0003-3473-3109, 117997, Russia, Moscow, Academician Oparin str., 4.
Artem A. Shiryaev, PhD, oncologist at the Institute of Oncological Cluster named after Prof. L.L. Levshin, I.M. Sechenov First MSMU, Ministry of Health of Russia
(Sechenov University), artemdoc@mail.ru, https://orcid.org/0000-0001-9421-420X, 119991, Russia, Moscow, Trubetskaya str., 8-2.
Svetlana I. Samoilova, Associate Professor of the Department of Oncology, Radiotherapy and Plastic Surgery, N.V. Sklifosovsky Institute of Clinical Medicine,
I.M. Sechenov First MSMU, Ministry of Health of Russia (Sechenov University), sv_samoilova75@mail.ru, 119991, Russia, Moscow, Trubetskaya str., 8-2.
Polina M. Alekseeva, Junior Researcher at the Laboratory of Laser Biospectroscopy, Prokhorov General Physics Institute RAS, alekseeva.polina2012@mail.ru;
https://orcid.org/0000-0003-2716-4606, 119991, Russia, Moscow, Vavilov str., 38.
Kanamat T. Efendiev, Junior Researcher at the Laboratory of Laser Biospectroscopy, Prokhorov General Physics Institute RAS, kanamatius@mail.ru,
https://orcid.org/0000-0002-5864-1172, 119991, Russia, Moscow, Vavilov str., 38.
Igor V. Reshetov, Academician of the RAS, Dr. Med. Sci., Professor, Head of the Department of Oncology, Radiotherapy and Plastic Surgery, N.V. Sklifosovsky Institute
of Clinical Medicine, I.M. Sechenov First MSMU, Ministry of Health of Russia (Sechenov University); Director of the Institute of Cluster Oncology
named after Prof. L.L. Levshin, I.M. Sechenov First MSMU, Ministry of Health of Russia (Sechenov University), reshetoviv@mail.ru, https://orcid.org/0000-0002-0909-6278, 119991, Russia, Moscow, Trubetskaya str., 8-2.
Corresponding author: Aida V. Gilyadova, aida-benyagueva@mail.ru

Authors' contributions: Gilyadova A.V., Saidova A.S., Shiryaev A.A., Samoilova S.I., Alekseeva P.M., Efendiev K.T. – material collection and processing, writing the text; Ishchenko A.A., Reshetov I.V., Apolikhina I.A. – editing.
Conflicts of interest: The authors declare that there are no conflicts of interest.
Funding: The article has been prepared without sponsorship.
For citation: Gilyadova A.V., Ishchenko A.A., Apolikhina I.A., Saidova А.S., Shiryaev A.A., Samoilova S.I., Alekseeva P.M., Efendiev K.T., Reshetov I.V. Possibilities of using photodynamic therapy in the treatment of cervical precancers and cancers
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2022; 5: 35-42 (in Russian)
https://dx.doi.org/10.18565/aig.2022.5.35-42

Similar Articles

By continuing to use our site, you consent to the processing of cookies that ensure the proper functioning of the site.