{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:57:06Z","timestamp":1791845826500,"version":"4.3.4"},"reference-count":43,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,1,2]],"date-time":"2022-01-02T00:00:00Z","timestamp":1641081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003443","name":"The Ministry of Education and Science of the Russian Federation","doi-asserted-by":"publisher","award":["075-15-2020-912"],"award-info":[{"award-number":["075-15-2020-912"]}],"id":[{"id":"10.13039\/501100003443","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>(1) Purpose: Improving the treatment effectiveness of intraepithelial neoplasia of the cervix associated with human papillomavirus infection, based on the application of the method of photodynamic therapy with simultaneous laser excitation of fluorescence to clarify the boundaries of cervical neoplasms. (2) Methods: Examination and treatment of 52 patients aged 22 to 53 years with morphologically and cytologically confirmed mild to severe intraepithelial cervix neoplasia, preinvasive, micro-invasive, and squamous cell cervix carcinoma. All patients were carriers of human papillomavirus infection. The patients underwent photodynamic therapy with simultaneous laser excitation of fluorescence. The combined use of video and spectral fluorescence diagnostics for cervical neoplasms made it possible to control the photodynamic therapy process at all stages of the procedure. Evaluation of the photodynamic therapy of intraepithelial cervical neoplasms was carried out with colposcopic examination, cytological conclusion, and morphological verification of the biopsy material after the photodynamic therapy course. The success of human papillomavirus therapy was assessed based on the results of the polymerase chain reaction. (3) Results. The possibility of simultaneous spectral fluorescence diagnostics and photodynamic therapy using a laser source with a wavelength of 660 nm has been established, making it possible to assess the fluorescence index in real-time and control the photobleaching of photosensitizers in the irradiated area. The treatment of all 52 patients was successful after the first photodynamic therapy procedure. According to the PCR test of the discharge from the cervical canal, the previously identified HPV types were not observed in 48 patients. Previously identified HPV types were absent after repeated PDT in four patients (CIN III (n = 2), CIS (n = 2)). In 80.8% of patients, regression of the lesion was noted. (4) Conclusions. The high efficiency of photodynamic therapy with intravenous photosensitizer administration of chlorin e6 has been demonstrated both in relation to eradication therapy of human papillomavirus and in relation to the treatment of intraepithelial lesions of the cervix.<\/jats:p>","DOI":"10.3390\/cancers14010211","type":"journal-article","created":{"date-parts":[[2022,1,3]],"date-time":"2022-01-03T22:51:50Z","timestamp":1641250310000},"page":"211","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Phototheranostics of Cervical Neoplasms with Chlorin e6 Photosensitizer"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4343-4813","authenticated-orcid":false,"given":"Aida","family":"Gilyadova","sequence":"first","affiliation":[{"name":"University Clinical Hospital No. 1, Levshin Institute of Cluster Oncology, Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation, 119435 Moscow, Russia"},{"name":"National Medical Research Center Treatment and Rehabilitation Center, Ministry of Health of the Russian Federation, 125367 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Ishchenko","sequence":"additional","affiliation":[{"name":"National Medical Research Center Treatment and Rehabilitation Center, Ministry of Health of the Russian Federation, 125367 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artem","family":"Shiryaev","sequence":"additional","affiliation":[{"name":"University Clinical Hospital No. 1, Levshin Institute of Cluster Oncology, Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation, 119435 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polina","family":"Alekseeva","sequence":"additional","affiliation":[{"name":"Prokhorov General Physics Institute of the Russian Academy of Sciences, 119991 Moscow, Russia"},{"name":"Department of Laser Micro-, Nano-, and Biotechnology, Institute of Engineering Physics for Biomedicine, National Research Nuclear University \u201cMEPhI\u201d, 115409 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5864-1172","authenticated-orcid":false,"given":"Kanamat","family":"Efendiev","sequence":"additional","affiliation":[{"name":"Prokhorov General Physics Institute of the Russian Academy of Sciences, 119991 Moscow, Russia"},{"name":"Department of Laser Micro-, Nano-, and Biotechnology, Institute of Engineering Physics for Biomedicine, National Research Nuclear University \u201cMEPhI\u201d, 115409 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radmila","family":"Karpova","sequence":"additional","affiliation":[{"name":"University Clinical Hospital No. 1, Levshin Institute of Cluster Oncology, Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation, 119435 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxim","family":"Loshchenov","sequence":"additional","affiliation":[{"name":"Prokhorov General Physics Institute of the Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Loschenov","sequence":"additional","affiliation":[{"name":"Prokhorov General Physics Institute of the Russian Academy of Sciences, 119991 Moscow, Russia"},{"name":"Department of Laser Micro-, Nano-, and Biotechnology, Institute of Engineering Physics for Biomedicine, National Research Nuclear University \u201cMEPhI\u201d, 115409 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0909-6278","authenticated-orcid":false,"given":"Igor","family":"Reshetov","sequence":"additional","affiliation":[{"name":"University Clinical Hospital No. 1, Levshin Institute of Cluster Oncology, Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation, 119435 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0140-6736(18)32470-X","article-title":"Cervical cancer","volume":"393","author":"Cohen","year":"2019","journal-title":"Lancet J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","unstructured":"(2021, October 24). Cancer Today, International Agency for Research on Cancer. Available online: http:\/\/gco.iarc.fr\/."},{"key":"ref_4","unstructured":"(2021, November 12). Cancer Tomorrow, International Agency for Research on Cancer. Available online: https:\/\/gco.iarc.fr\/tomorrow\/en."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"veaa036","DOI":"10.1093\/ve\/veaa036","article-title":"The characterization of two novel neotropical primate papillomaviruses supports the ancient within-species diversity model","volume":"6","author":"Moreira","year":"2020","journal-title":"Virus Evol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e10179","DOI":"10.7717\/peerj.10179","article-title":"Human papillomavirus infection and follow-up on positive results in 7222 female samples obtained from 2016 to 2019 in Hefei, China","volume":"8","author":"Peng","year":"2020","journal-title":"Peer J."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Balasubramaniam, S.D., Balakrishnan, V., Oon, C.E., and Kaur, G. (2019). Key Molecular Events in Cervical Cancer Development. Medicina, 55.","DOI":"10.3390\/medicina55070384"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.ejca.2019.10.009","article-title":"Oral contraceptive and intrauterine device use and the risk of cervical intraepithelial neoplasia grade III or worse: A population-based study","volume":"124","author":"Loopik","year":"2020","journal-title":"Eur. J. Cancer"},{"key":"ref_9","unstructured":"(2021, November 15). National Cancer Institute, Available online: https:\/\/www.cancer.gov\/about-cancer\/causes-prevention\/risk\/infectious-agents\/hpv-and-cancer."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"74","DOI":"10.11152\/mu-2646","article-title":"Elastography of the uterine cervix in gynecology: Normal appearance, cervical intraepithelial neoplasia and cancer. A systematic review","volume":"23","author":"Dudea","year":"2021","journal-title":"Med. Ultrason."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Kato, M., Onoyama, I., Kawakami, M., Yoshida, S., Kawamura, K., Kodama, K., Hori, E., Cui, L., Matsumura, Y., and Yagi, H. (2020). Downregulation of 5-hydroxymethylcytosine is associated with the progression of cervical intraepithelial neoplasia. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0241482"},{"key":"ref_12","unstructured":"Ndifon, C.O., and Al-Eyd, G. (2021). Atypical Squamous Cells of Undetermined Significance, StatPearls Publishing."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1159\/000477556","article-title":"The Bethesda System for Reporting Cervical Cytology: A Historical Perspective","volume":"61","author":"Nayar","year":"2017","journal-title":"Acta Cytol."},{"key":"ref_14","unstructured":"Mello, V., and Sundstrom, R.K. (2020). Cervical Intraepithelial Neoplasia, StatPearls Publishing."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.3762\/bjnano.8.186","article-title":"Optical techniques for cervical neoplasia detection","volume":"8","author":"Novikova","year":"2017","journal-title":"Beilstein J. Nanotechnol."},{"key":"ref_16","first-page":"CD012847","article-title":"Obstetric outcomes after conservative treatment for cervical intraepithelial lesions and early invasive disease","volume":"11","author":"Kyrgiou","year":"2017","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"479","DOI":"10.5468\/ogs.2016.59.6.479","article-title":"Clinical efficacy of photodynamic therapy","volume":"59","author":"Park","year":"2016","journal-title":"Obstet. Gynecol. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e10864","DOI":"10.1097\/MD.0000000000010864","article-title":"Efficacy and safety of photodynamic therapy for cervical intraepithelial neoplasia and human papillomavirus infection: A systematic review and meta-analysis of randomized clinical trials","volume":"97","author":"Zhang","year":"2018","journal-title":"Medicine"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"102","DOI":"10.32607\/actanaturae.11028","article-title":"Near-Infrared Activated Cyanine Dyes As Agents for Photothermal Therapy and Diagnosis of Tumors","volume":"12","author":"Shramova","year":"2020","journal-title":"Acta Nat."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1002\/lsm.22041","article-title":"Photodynamic therapy of cervical intraepithelial neoplasia 1\u20133 and human papilloma virus (HPV) infection with methylaminolevulinate and hexaminolevulinate\u2014A double-blind, dose-finding study","volume":"44","author":"Soergel","year":"2012","journal-title":"Lasers Surg. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"061615","DOI":"10.1117\/1.OE.59.6.061615","article-title":"Investigated spectral-fluorescent properties of endogenous porphyrins of the wild boar hepatobiliary system optimize the diagnostics and treatment of cholangiocarcinoma with FD and PDT","volume":"59","author":"Shiryaev","year":"2020","journal-title":"Opt. Eng."},{"key":"ref_22","unstructured":"(2018). Methodical Recommendations for the Prevention of Cervical Cancer, All-Russian Public Organization \u201cRussian Society of Specialists in the Prevention and Treatment of Tumors of the Reproductive System\u201d."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Istomin, Y.P., Kaplan, M.A., Shliakhtsin, S.V., Lapzevich, T.P., Cerkovsky, D.A., Marchanka, L., Fedulov, A., and Trukhachova, T.V. (2009). Immediate and Long-Term Efficacy and Safety of Photodynamic Therapy with PHOTOLON (Fotolon): A Seven-Year Clinical Experience, International Society for Optics and Photonics. Photodynamic Therapy: Back to the Future.","DOI":"10.1117\/12.823840"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.pdpdt.2010.06.005","article-title":"Photodynamic therapy of cervical intraepithelial neoplasia grades II and III with Photolon\u00ae","volume":"7","author":"Istomin","year":"2010","journal-title":"Photodiagnosis Photodyn. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.canlet.2005.12.041","article-title":"Chlorin e6-polyvinylpyrrolidone as a fluorescent marker for fluorescence diagnosis of human bladder cancer implanted on the chick chorioallantoic membrane model","volume":"245","author":"Chin","year":"2007","journal-title":"Cancer Lett."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Farrakhova, D., Shiryaev, A., Yakovlev, D., Efendiev, K., Maklygina, Y., Borodkin, A., Loschenov, M., Bezdetnaya, L., Ryabova, A., and Amirkhanova, L. (2019). Trials of a fluorescent endoscopic video system for diagnosis and treatment of the head and neck cancer. J. Clin. Med., 8.","DOI":"10.3390\/jcm8122229"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"101005","DOI":"10.1016\/j.tranon.2020.101005","article-title":"Photodynamic therapy exploiting the anti-tumor activity of mannose-conjugated chlorin e6 reduced M2-like tumor-associated macrophages","volume":"14","author":"Soyama","year":"2021","journal-title":"Transl. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6357","DOI":"10.1039\/D1TB00377A","article-title":"Photodynamic therapy using self-assembled nanogels comprising chlorin e6-bearing pullulan","volume":"9","author":"Kawasaki","year":"2021","journal-title":"J. Mater. Chem. B"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Wang, Y.-Y., Ryu, A.-R., Jin, S., Jeon, Y.-M., and Lee, M.-Y. (2017). Chlorin e6-mediated photodynamic therapy suppresses P. acnes-induced inflammatory response via NF\u03baB and MAPKs signaling pathway. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0170599"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1002\/2211-5463.12359","article-title":"Comparison of a new nanoform of the photosensitizer chlorin e6, based on plant phospholipids, with its free form","volume":"8","author":"Kostryukova","year":"2018","journal-title":"FEBS Open Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep41506","article-title":"Photodynamic therapy monitoring with optical coherence angiography","volume":"7","author":"Sirotkina","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_32","first-page":"008","article-title":"Comparative study of tissue distribution of chlorin e6 complexes with amphiphilic polymers in mice with cervical carcinoma","volume":"1","author":"Shirmanova","year":"2014","journal-title":"J. Anal. Bioanal. Tech. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1039\/b817175k","article-title":"In vitro and in vivo evaluation of Radachlorin\u00ae sensitizer for photodynamic therapy","volume":"8","author":"Douillard","year":"2009","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"101974","DOI":"10.1016\/j.pdpdt.2020.101974","article-title":"Treatment of HPV Infection-Associated Low Grade Cervical Intraepithelial Neoplasia with 5-Aminolevulinic Acid-Mediated Photodynamic Therapy","volume":"32","author":"Li","year":"2020","journal-title":"Photodiagnosis Photodyn. Ther."},{"key":"ref_35","first-page":"138","article-title":"Histological Evaluation of Tumor Response to Chemotherapy\/Radiotherapy","volume":"6","author":"Grabovoy","year":"2012","journal-title":"Exp. Res. Oncomorphol. Oncoimmunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.2147\/NDT.S78182","article-title":"Near-infrared photonic energy penetration: Can infrared phototherapy effectively reach the human brain?","volume":"11","author":"Henderson","year":"2015","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1039\/b605772a","article-title":"The potential application of chlorin e6\u2013polyvinylpyrrolidone formulation in photodynamic therapy","volume":"5","author":"Chin","year":"2006","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1002\/lsm.20340","article-title":"Clinical pharmacokinetics of the PDT photosensitizers porfimer sodium (Photofrin), 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (Photochlor) and 5-ALA-induced protoporphyrin IX","volume":"38","author":"Bellnier","year":"2006","journal-title":"Lasers Surg. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1002\/lsm.10111","article-title":"Photodynamic therapy of high-grade cervical intraepithelial neoplasia with 5-aminolevulinic acid","volume":"31","author":"Keefe","year":"2002","journal-title":"Lasers Surg. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1002\/ijc.10888","article-title":"A randomised, double-blind, placebo-controlled trial of photodynamic therapy using 5-aminolaevulinic acid for the treatment of cervical intraepithelial neoplasia","volume":"103","author":"Barnett","year":"2003","journal-title":"Int. J. Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"102004","DOI":"10.1016\/j.pdpdt.2020.102004","article-title":"Efficacy of 5-aminolevulinic acid and LED photodynamic therapy in cervical intraepithelial neoplasia: A clinical trial","volume":"32","author":"Mizuno","year":"2020","journal-title":"Photodiagnosis Photodyn. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"102172","DOI":"10.1016\/j.pdpdt.2020.102172","article-title":"The effect of local photodynamic therapy with 5-aminolevulinic acid for the treatment of cervical low-grade squamous intraepithelial lesions with high-risk HPV infection: A retrospective study","volume":"33","author":"Gu","year":"2021","journal-title":"Photodiagnosis Photodyn. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1002\/(SICI)1096-9101(1999)24:3<178::AID-LSM2>3.0.CO;2-W","article-title":"In vitro and in vivo photosensitizing capabilities of 5-ALA versus Photofrin\u00ae in vascular endothelial cells","volume":"24","author":"Chang","year":"1999","journal-title":"Lasers Surg. Med."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/1\/211\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:26:42Z","timestamp":1760362002000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/1\/211"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,2]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["cancers14010211"],"URL":"https:\/\/doi.org\/10.3390\/cancers14010211","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,2]]}}}