{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:36:38Z","timestamp":1787027798428,"version":"build-2736575974"},"reference-count":60,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T00:00:00Z","timestamp":1738800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: O3-O2 therapy is an alternative medical treatment that introduces a mixture of O3-O2 into the body for therapeutic purposes. The objective of this study is to evaluate its margins of applicability in the eradication of HPV infection from the lower gynecological tract by means of vaginal insufflation. Methods: An in-depth review of the international literature on this topic is carried out; in addition, O3-O2 therapy is compared with other treatments currently available in terms of its advantages, disadvantages, and exploited technologies. Results: The possible benefits and limitations of O3-O2 vaginal insufflation are explained in detail; overall, it appears to be an interesting tool as part of complex management to prevent HPV-related cancers of the lower gynecological tract in infected patients. Conclusions: The rationale and guidelines of this innovative procedure have been successfully illustrated, providing the technical specifications for further developments.<\/jats:p>","DOI":"10.3390\/cancers17030543","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T08:53:41Z","timestamp":1738832021000},"page":"543","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Ozone\u2013Oxygen Therapy to Prevent HPV-Related Cancers of the Lower Gynecological Tract in Infected Patients: The Rationale for Further Developments"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6949-2216","authenticated-orcid":false,"given":"Luca","family":"Roncati","sequence":"first","affiliation":[{"name":"Department of Life Sciences, Health, and Health Care Professions, Link Campus University, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,6]]},"reference":[{"key":"ref_1","unstructured":"(2023, October 18). National Cancer Institute\u2014HPV and Cancer, Available online: https:\/\/www.cancer.gov\/about-cancer\/causes-prevention\/risk\/infectious-agents\/hpv-and-cancer."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5523","DOI":"10.1073\/pnas.88.13.5523","article-title":"The state of the p53 and retinoblastoma genes in human cervical carcinoma cell lines","volume":"88","author":"Scheffner","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1056\/NEJMoa021641","article-title":"Epidemiologic classification of human papillomavirus types associated with cervical cancer","volume":"348","author":"Bosch","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_4","unstructured":"(2024, December 31). Global Cancer Observatory\u2014Cancers Attributable to Infections. Available online: https:\/\/gco.iarc.who.int\/causes\/infections\/home."},{"key":"ref_5","unstructured":"(2024, December 31). Global Cancer Observatory\u2014Cervix Uteri. Available online: https:\/\/gco.iarc.who.int\/media\/globocan\/factsheets\/cancers\/23-cervix-uteri-fact-sheet.pdf."},{"key":"ref_6","unstructured":"(2024, December 31). Global Cancer Observatory\u2014Vagina. Available online: https:\/\/gco.iarc.who.int\/media\/globocan\/factsheets\/cancers\/22-vagina-fact-sheet.pdf."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"66","DOI":"10.4103\/0976-9668.82319","article-title":"Ozone therapy: A clinical review","volume":"2","author":"Elvis","year":"2011","journal-title":"J. Nat. Sci. Biol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Baeza-Noci, J., and Pinto-Bonilla, R. (2021). Systemic review: Ozone\u2014A potential new chemotherapy. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111796"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1126\/science.1077642","article-title":"Evidence for antibody-catalyzed ozone formation in bacterial killing and inflammation","volume":"298","author":"Wentworth","year":"2002","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"El Meligy, O.A., Elemam, N.M., and Talaat, I.M. (2023). Ozone therapy in medicine and dentistry: A review of the literature. Dent. J., 11.","DOI":"10.3390\/dj11080187"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Cenci, A., Macchia, I., La Sorsa, V., Sbarigia, C., Di Donna, V., and Pietraforte, D. (2022). Mechanisms of action of ozone therapy in emerging viral diseases: Immunomodulatory effects and therapeutic advantages with reference to SARS-CoV-2. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.871645"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"125658","DOI":"10.1016\/j.jhazmat.2021.125658","article-title":"Can ozone inactivate SARS-CoV-2? A review of mechanisms and performance on viruses","volume":"415","author":"Bayarri","year":"2021","journal-title":"J. Hazard. Mater."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1016\/S0140-6736(01)92422-5","article-title":"The internal administration of ozone in the treatment of phthisis","volume":"140","author":"Norris","year":"1892","journal-title":"Lancet"},{"key":"ref_14","first-page":"484","article-title":"Clinical study of medical ozone therapy in chronic hepatitis B of 20 patients","volume":"22","author":"Jiao","year":"2008","journal-title":"Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1089\/acm.2010.0016","article-title":"Preliminary results of ozone therapy as a possible treatment for patients with chronic hepatitis C","volume":"17","author":"Zaky","year":"2011","journal-title":"J. Altern. Complement. Med."},{"key":"ref_16","first-page":"168","article-title":"Topical ozone therapy: An innovative solution to patients with herpes zoster","volume":"43","author":"Huang","year":"2018","journal-title":"Zhong Nan Da Xue Xue Bao Yi Xue Ban"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"693","DOI":"10.5114\/ada.2023.130522","article-title":"Clinical efficacy and metabolomic analysis of ozone major autohemotherapy for the treatment of herpes zoster","volume":"40","author":"Yang","year":"2023","journal-title":"Postepy Dermatol. Alergol."},{"key":"ref_18","first-page":"469","article-title":"Computed tomography-guided dorsal root ganglion ozone injection combined with pulsed radiofrequency for acute herpes zoster neuralgia treatment of middle-aged and elderly people: A randomized, double-blinded, controlled trial","volume":"40","author":"Wang","year":"2024","journal-title":"Clin. J. Pain"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"232","DOI":"10.4103\/2045-9912.273962","article-title":"Ozone and oxidation therapies as a solution to the emerging crisis in infectious disease management: A review of current knowledge and experience","volume":"9","author":"Rowen","year":"2019","journal-title":"Med. Gas Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1097\/00002030-199108000-00009","article-title":"The use of ozone-treated blood in the therapy of HIV infection and immune disease: A pilot study of safety and efficacy","volume":"5","author":"Garber","year":"1991","journal-title":"Aids"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1882","DOI":"10.1182\/blood.V78.7.1882.1882","article-title":"Inactivation of human immunodeficiency virus type 1 by ozone in vitro","volume":"78","author":"Wells","year":"1991","journal-title":"Blood"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/0166-3542(91)90007-E","article-title":"Ozone inactivates HIV at noncytotoxic concentrations","volume":"16","author":"Carpendale","year":"1991","journal-title":"Antivir. Res."},{"key":"ref_23","first-page":"1","article-title":"The immune response behavior in HIV-AIDS patients treated with ozone therapy for two years","volume":"2","year":"2019","journal-title":"J. Ozone Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"102907","DOI":"10.1016\/j.ctim.2022.102907","article-title":"Benefits of ozone on mortality in patients with COVID-19: A systematic review and meta-analysis","volume":"72","author":"Shang","year":"2023","journal-title":"Complement. Ther. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3029","DOI":"10.1007\/s10787-023-01288-9","article-title":"Cytokine profile and antioxidants status in the moderate and severe COVID-19 patients: A trial of ozone therapy impact as a medicinal supplement","volume":"31","author":"Ghaleh","year":"2023","journal-title":"Inflammopharmacology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"165","DOI":"10.4103\/2045-9912.369237","article-title":"The role of ozone therapy in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19): A review","volume":"13","author":"Harapan","year":"2023","journal-title":"Med. Gas Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"172","DOI":"10.4103\/2045-9912.372819","article-title":"Clinical effectiveness of medical ozone therapy in COVID-19: The evidence and gaps map","volume":"13","author":"Serra","year":"2023","journal-title":"Med. Gas Res."},{"key":"ref_28","unstructured":"Seifer, M. (2023). Ozone Therapy for the Treatment of Viruses: The Science and the Promise of Healing with Ozone, Inner Traditions\u2014Bear & Company."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"C\u00f3rdoba-Lan\u00fas, E., Garc\u00eda-P\u00e9rez, O., Rodr\u00edguez-Esparrag\u00f3n, F., Bethencourt-Estrella, C.J., Torres-Mata, L.B., Blanco, A., Villar, J., Sanz, O., D\u00edaz, J.J., and Mart\u00edn-Barrasa, J.L. (2022). Ozone treatment effectively eliminates SARS-CoV-2 from infected face masks. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0271826"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Jafari-Oori, M., Vahedian-Azimi, A., Ghorbanzadeh, K., Sepahvand, E., Dehi, M., Ebadi, A., and Izadi, M. (2022). Efficacy of ozone adjuvant therapy in COVID-19 patients: A meta-analysis study. Front. Med., 9.","DOI":"10.3389\/fmed.2022.1037749"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ataei-Pirkooh, A., Alavi, A., Kianirad, M., Bagherzadeh, K., Ghasempour, A., Pourdakan, O., Adl, R., Kiani, S.J., Mirzaei, M., and Mehravi, B. (2021). Destruction mechanisms of ozone over SARS-CoV-2. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-97860-w"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"107301","DOI":"10.1016\/j.intimp.2020.107301","article-title":"Safety and efficacy of ozone therapy in mild to moderate COVID-19 patients: A phase 1\/11 randomized control trial (SEOT study)","volume":"91","author":"Shah","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"198207","DOI":"10.1016\/j.virusres.2020.198207","article-title":"Ozone therapy in COVID-19: A narrative review","volume":"291","author":"Cattel","year":"2021","journal-title":"Virus Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1007\/s42399-020-00374-1","article-title":"Effect of rectal ozone (O3) in severe COVID-19 pneumonia: Preliminary results","volume":"2","year":"2020","journal-title":"SN Compr. Clin. Med."},{"key":"ref_35","first-page":"100060","article-title":"Recovery of four COVID-19 patients via ozonated autohemotherapy","volume":"1","author":"Wu","year":"2020","journal-title":"Innovation"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.biopha.2018.05.018","article-title":"Ozone therapy prevents the onset of dysplasia in HPV16-transgenic mice\u2014A pre-clinical efficacy and safety analysis","volume":"104","author":"Peirone","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"479","DOI":"10.4103\/ijd.ijd_152_22","article-title":"Effectiveness and safety of ozone therapy for dermatological disorders: A literature review of clinical trials","volume":"67","author":"Machado","year":"2022","journal-title":"Indian J. Dermatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2376","DOI":"10.1111\/iwj.14060","article-title":"Ozone therapy for skin diseases: Cellular and molecular mechanisms","volume":"20","author":"Liu","year":"2023","journal-title":"Int. Wound J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.intimp.2018.01.040","article-title":"Mechanisms of action involved in ozone-therapy in skin diseases","volume":"56","author":"Zeng","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/01.ASW.0000789064.09407.30","article-title":"Effectiveness of ozone therapy as an adjunct treatment for lower-limb ulcers: A systematic review","volume":"34","author":"Bomfim","year":"2021","journal-title":"Adv. Skin Wound Care"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1097\/DSS.0000000000002174","article-title":"Successful treatment of multiple common warts with intralesional ozone","volume":"46","author":"Ibrahim","year":"2020","journal-title":"Dermatol. Surg."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.jfma.2013.06.020","article-title":"Ozone therapy in the management and prevention of caries","volume":"114","author":"Almaz","year":"2015","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Al-Omiri, M.K., Alqahtani, N.M., Alahmari, N.M., Hassan, R.A., Al Nazeh, A.A., and Lynch, E. (2021). Treatment of symptomatic, deep, almost cariously exposed lesions using ozone. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-90824-0"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"151","DOI":"10.4103\/0976-9668.92318","article-title":"Ozone therapy in dentistry: A strategic review","volume":"2","author":"Saini","year":"2011","journal-title":"J. Nat. Sci. Biol. Med."},{"key":"ref_45","first-page":"636","article-title":"Thermo-mineral therapy of genital phlogosis; vaginal insufflation of thermal sulfur","volume":"36","author":"Chizzolini","year":"1954","journal-title":"Riv. Ostet. Ginecol. Prat."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Augello, S., Cameli, V., Montanari, A., Tacconi, S., Uccelletti, D., Dini, L., and Schifano, E. (2024). The antifungal potential of ozonated extra-virgin olive oil against Candida albicans: Mechanisms and efficacy. Biomolecules, 14.","DOI":"10.3390\/biom14111472"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Monzillo, V., Lallitto, F., Russo, A., Poggio, C., Scribante, A., Arciola, C.R., Bertuccio, F.R., and Colombo, M. (2020). Ozonized gel against four Candida species: A pilot study and clinical perspectives. Materials, 13.","DOI":"10.3390\/ma13071731"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"45","DOI":"10.17116\/kurort2015545-49","article-title":"Ozonotherapy as an efficient component of the combined treatment of the patients presenting with bacterial vaginosis","volume":"92","author":"Yarustovskaya","year":"2015","journal-title":"Vopr. Kurortol. Fizioter. Lech. Fiz. Kult."},{"key":"ref_49","first-page":"28","article-title":"Treatment of vaginal trichomoniasis by ozone","volume":"26","author":"Cardia","year":"1956","journal-title":"C. R. Soc. Fr. Gyncol."},{"key":"ref_50","first-page":"31","article-title":"Combined treatment of complicated chlamydial infection in males with ozone therapy","volume":"3","year":"2008","journal-title":"Urologiia"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1111\/j.1472-765X.2004.01506.x","article-title":"Inactivation of Chlamydia trachomatis and Chlamydia (Chlamydophila) pneumoniae by ozone","volume":"38","author":"Yamazaki","year":"2004","journal-title":"Lett. Appl. Microbiol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Roncati, L. (2022). Advances in diagnosis and treatment of gynecological malignancies: A special issue in line with 2030 Agenda. J. Clin. Med., 11.","DOI":"10.3390\/jcm11133797"},{"key":"ref_53","first-page":"070135","article-title":"Role of human papillomavirus (HPV) vaccination on HPV infection and recurrence of HPV related disease after local surgical treatment: Systematic review and meta-analysis","volume":"378","author":"Kechagias","year":"2022","journal-title":"BMJ"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.1111\/jog.15726","article-title":"The significance of nonsurgical therapies for cervical infection of high-risk human papilloma virus: A systematic review and meta-analysis","volume":"49","author":"Zhuang","year":"2023","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"101","DOI":"10.4103\/2045-9912.260652","article-title":"Ozone therapy: A potential therapeutic adjunct for improving female reproductive health","volume":"9","author":"Merhi","year":"2019","journal-title":"Med. Gas. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1007\/s00192-022-05383-3","article-title":"Effectiveness of intravesical ozone in interstitial cystitis by the O\u2019Leary-Sant symptom index","volume":"34","author":"Pires","year":"2023","journal-title":"Int. Urogynecol. J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e20240402","DOI":"10.1590\/0001-3765202420240402","article-title":"Clinical evaluation of combined autologous platelet-rich plasma and volume-controlled ozone therapy in facial rejuvenation: A randomized controlled pilot study","volume":"96","author":"Camargo","year":"2024","journal-title":"An. Acad. Bras. Cienc."},{"key":"ref_58","unstructured":"(2016, June 13). International Scientific Committee of Ozone Therapy (ISCO3)\u2014Vaginal Insufflation of an Ozone-Oxygen Mixture (VIO3O2M) ISCO3 MET\/00\/13. Available online: https:\/\/isco3.org\/wp-content\/uploads\/2016\/07\/ISCO3-MET-00-13-Vaginal-insufflation-V1.pdf."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.bcmd.2008.12.005","article-title":"The global prevalence of glucose-6-phosphate dehydrogenase deficiency: A systematic review and meta-analysis","volume":"42","author":"Nkhoma","year":"2009","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/0002-9343(85)90445-0","article-title":"Venous air embolism. Life-threatening complication of orogenital sex during pregnancy","volume":"78","author":"Fyke","year":"1985","journal-title":"Am. J. Med."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/3\/543\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:27:41Z","timestamp":1760027261000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/3\/543"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,6]]},"references-count":60,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["cancers17030543"],"URL":"https:\/\/doi.org\/10.3390\/cancers17030543","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,6]]}}}