{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:38:38Z","timestamp":1760150318738,"version":"build-2065373602"},"reference-count":35,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T00:00:00Z","timestamp":1699315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Uozu city as the support of university sponsored course"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Objective: This study aimed to validate the use of liquid phenol-based chemical peeling therapy for cervical and vaginal intraepithelial neoplasia (CIN and VaIN, respectively), with the goal of circumventing obstetric complications associated with surgical treatment and to determine the factors associated with treatment resistance. Methods: A total of 483 eligible women diagnosed with CIN, VaIN, or both, participated in this study. Participants underwent phenol-based chemical peeling therapy every 4 weeks until disease clearance. Disease clearance was determined by negative Pap tests for four consecutive weeks or by colposcopy. HPV genotyping was conducted at the onset of the study and after disease clearance in select cases. Our preliminary analysis compared the recurrence and persistence rates between 294 individuals who received phenol-based chemical peeling therapy and 189 untreated patients. Results: At 2 years following diagnosis, persistent disease was observed in 18%, 60%, and 88% of untreated patients with CIN1\u20133, respectively, and &lt;2% of patients with CIN who received phenol-based chemical peeling therapy. Among 483 participants, 10 immune-suppressed patients required multiple treatments to achieve disease clearance, and 7 were diagnosed with cervical cancer. Of the 466 participants, except those with cancer or immune suppression, the number of treatment sessions until CIN\/VaIN clearance ranged from 2 to 42 (average: 9.2 sessions). In total, 43 participants (9.2%) underwent surgical treatment. Six patients (1.3%) experienced recurrence of CIN2 or worse, suggesting that treatment failed in 46 patients (9.9%). No obstetrical complications were noted among the 98 pregnancies following this therapy. Factors associated with resistance to this therapy include immune suppression, ages 35\u201339 years, higher-grade lesions, and multiple HPV-type infections. Conclusions: Phenol-based therapy is safe and effective for CINs and VaINs. Women aged &lt; 35 years and with persistent CIN1 or CIN2 with a single HPV-type infection are suitable candidates for phenol-based chemical peeling therapy. However, this therapy requires multiple lengthy sessions.<\/jats:p>","DOI":"10.3390\/v15112219","type":"journal-article","created":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T11:23:39Z","timestamp":1699356219000},"page":"2219","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Chemical Peeling Therapy Using Phenol for the Cervico-Vaginal Intraepithelial Neoplasia"],"prefix":"10.3390","volume":"15","author":[{"given":"Toshiyuki","family":"Maehama","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Yuai-Medical Center, Tomishiro 901-0224, Okinawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sumire","family":"Shimada","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Kanazawa Medical University, 1-1 Daigaku, Kahoku-gun 920-0293, Ishikawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinichi","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Kanazawa Medical University, 1-1 Daigaku, Kahoku-gun 920-0293, Ishikawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeo","family":"Shibata","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Kanazawa Medical University, 1-1 Daigaku, Kahoku-gun 920-0293, Ishikawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoko","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Kanazawa Medical University, 1-1 Daigaku, Kahoku-gun 920-0293, Ishikawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3707-8691","authenticated-orcid":false,"given":"Masahiro","family":"Takakura","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Kanazawa Medical University, 1-1 Daigaku, Kahoku-gun 920-0293, Ishikawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroaki","family":"Takagi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Kanazawa Medical University, 1-1 Daigaku, Kahoku-gun 920-0293, Ishikawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8480-844X","authenticated-orcid":false,"given":"Toshiyuki","family":"Sasagawa","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Kanazawa Medical University, 1-1 Daigaku, Kahoku-gun 920-0293, Ishikawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","unstructured":"Ferlay, J., Ervik, M., Lam, F., Colombet, M., Mery, L., and Pi\u00f1eros, M. (2020). Global Cancer Observatory: Cancer Today, International Agency for Research on Cancer. Available online: https:\/\/gco.iarc.fr\/today."},{"key":"ref_3","unstructured":"Cancer Statistics (2023, September 26). Cancer Information Service, National Cancer Center, Japan (Vital Statistics of Japan, Ministry of Health, Labour and Welfare) for Incidence and Mortality. Available online: https:\/\/ganjoho.jp\/public\/qa_links\/report\/statistics\/pdf\/cancer_statistics_2019.pdf."},{"key":"ref_4","unstructured":"World Health Organization (WHO) (2000). Global Strategy to Accelerate the Elimination of Cervical Cancer as a Public Health Problem, World Health Organization (WHO)."},{"key":"ref_5","first-page":"CD012847","article-title":"Cochrane Gynaecological, Neuro-oncology and Orphan Cancer Group. Obstetric outcomes after conservative treatment for cervical intraepithelial lesions and early invasive disease","volume":"2017","author":"Kyrgiou","year":"2017","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.ijgo.2015.07.026","article-title":"Systematic reviews and meta-analyses of benefits and harms of cryotherapy, LEEP, and cold knife conization to treat cervical intraepithelial neoplasia","volume":"132","author":"Santesso","year":"2016","journal-title":"Int. J. Gynecol. Obs."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1136\/jcp.55.4.244","article-title":"The causal relation between human papillomavirus and cervical cancer","volume":"55","author":"Bosch","year":"2002","journal-title":"J. Clin. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1056\/NEJM199802123380703","article-title":"Natural history of cervicovaginal papillomavirus infection in young women","volume":"338","author":"Ho","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"F55","DOI":"10.1016\/j.vaccine.2012.06.083","article-title":"The biology and life-cycle of human papillomaviruses","volume":"30","author":"Doorbar","year":"2012","journal-title":"Vaccine"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1007\/s10156-012-0485-5","article-title":"Immune responses against human papillomavirus (HPV) infection and evasion of host defense in cervical cancer","volume":"18","author":"Sasagawa","year":"2012","journal-title":"J. Infect. Chemother."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Tang, J., Li, M., Zhao, C., Shen, D., Liu, L., Zhang, X., and Wei, L. (2022). Therapeutic DNA Vaccines against HPV-Related Malignancies: Promising Leads from Clinical Trials. Viruses, 14.","DOI":"10.3390\/v14020239"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/nrc700","article-title":"Immune evasion in human papillomavirus-associated cervical cancer","volume":"2","author":"Tindle","year":"2002","journal-title":"Nat. Rev. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.ad.2016.09.014","article-title":"Chemical Peeling: A Useful Tool in the Office","volume":"108","author":"Truchuelo","year":"2017","journal-title":"Actas Dermosifiliogr."},{"key":"ref_14","first-page":"1035","article-title":"Efficacy of 80% phenol solution incomparison with cryotherapy in thetreatment of common warts of hands","volume":"49","author":"Banihashemi","year":"2008","journal-title":"Singapore Med. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1097\/AOG.0000000000001244","article-title":"Short-Term Efficacy of Trichloroacetic Acid in the Treatment of Cervical Intraepithelial Neoplasia","volume":"127","author":"Geisler","year":"2016","journal-title":"Obs. Gynecol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1002\/jmv.24323","article-title":"Population-based study for human papillomavirus (HPV) infection in young women in Japan: A multicenter study by the Japanese human papillomavirus disease education research survey group (J-HERS)","volume":"88","author":"Sasagawa","year":"2016","journal-title":"J. Med. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1002\/jmv.25017","article-title":"Uniplex E6\/E7 PCR method detecting E6 or E7 genes in 39 human papillomavirus types","volume":"90","author":"Okodo","year":"2018","journal-title":"J. Med. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1016\/S1470-2045(17)30700-3","article-title":"Incomplete excision of cervical precancer as a predictor of treatment failure: A systematic review and meta-analysis","volume":"18","author":"Arbyn","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e05193","DOI":"10.1016\/j.heliyon.2020.e05193","article-title":"Analysis of pathological and clinical characteristics of cervical conization according to age group in Japan","volume":"6","author":"Murakami","year":"2020","journal-title":"Heliyon"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/S1470-2045(11)70078-X","article-title":"Risk of recurrent high-grade cervical intraepithelial neoplasia after successful treatment: A long-term multi-cohort study","volume":"12","author":"Kocken","year":"2011","journal-title":"Lancet Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1097\/LGT.0000000000000732","article-title":"The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) Consensus Statement on the Management of Vaginal Intraepithelial Neoplasia","volume":"27","author":"Kesic","year":"2023","journal-title":"J. Low. Genit. Tract. Dis."},{"key":"ref_22","unstructured":"Ministry of Health, Labour and Welfare, Japan (2020, September 26). Changes in Marriage Age in Japan. Available online: https:\/\/www.mhlw.go.jp\/stf\/wp\/hakusyo\/kousei\/19\/backdata\/01-01-01-09.html."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Kim, M., Park, N.J.-Y., Jeong, J.Y., and Park, J.Y. (2021). Multiple Human Papilloma Virus (HPV) Infections Are Associated with HSIL and Persistent HPV Infection Status in Korean Patients. Viruses, 13.","DOI":"10.3390\/v13071342"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.ygyno.2014.03.552","article-title":"Cervical cytology and multiple type HPV infection: A study of 8182 women ages 31\u201365","volume":"133","author":"Dickson","year":"2014","journal-title":"Gynecol. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Bruno, M.T., Scalia, G., Cassaro, N., and Boemi, S. (2020). Multiple HPV 16 infection with two strains: A possible marker of neoplastic progression. BMC Cancer, 20.","DOI":"10.1186\/s12885-020-06946-7"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"505","DOI":"10.3322\/caac.21696","article-title":"Cervical cancer prevention and control in women living with human immunodeficiency virus","volume":"71","author":"Castle","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1093\/cid\/cix135","article-title":"Carcinogenicity of Human Papillomavirus (HPV) Types in HIV-Positive Women: A Meta-Analysis from HPV Infection to Cervical Cancer","volume":"64","author":"Clifford","year":"2017","journal-title":"Clin. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1097\/CCO.0b013e32832f3e1b","article-title":"Oropharyngeal cancer: A potential consequence of concomitant HPV and HIV infection","volume":"21","author":"Gillison","year":"2009","journal-title":"Curr. Opin. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.bpobgyn.2017.08.015","article-title":"The natural history of human papillomavirus infection","volume":"47","author":"Brotons","year":"2018","journal-title":"Best Pract. Res. Clin. Obs. Gynaecol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e13061","DOI":"10.1097\/MD.0000000000013061","article-title":"The relation of passive smoking with cervical cancer: A systematic review and meta-analysis","volume":"97","author":"Su","year":"2018","journal-title":"Medicine"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"113371","DOI":"10.1016\/j.envres.2022.113371","article-title":"Association between involuntary smoking and risk of cervical cancer in Chinese female never smokers: A prospective cohort study","volume":"212","author":"Wen","year":"2022","journal-title":"Environ. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"9956","DOI":"10.3390\/curroncol29120782","article-title":"Smoking Cessation after Cancer Diagnosis and Enhanced Therapy Response: Mechanisms and Significance","volume":"29","author":"Chellappan","year":"2022","journal-title":"Curr. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"268","DOI":"10.18632\/oncotarget.13613","article-title":"Impacts of cigarette smoking on immune responsiveness: Up and down or upside down?","volume":"8","author":"Qiu","year":"2017","journal-title":"Oncotarget"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1038\/s41467-020-15856-y","article-title":"The vaginal microbiota associates with the regression of untreated cervical intraepithelial neoplasia 2 lesions","volume":"11","author":"Mitra","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.1007\/s00432-022-03993-4","article-title":"Blimp-1 is a prognostic indicator for progression of cervical intraepithelial neoplasia grade 2","volume":"148","author":"Saito","year":"2022","journal-title":"J. Cancer Res. Clin. Oncol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/11\/2219\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:18:38Z","timestamp":1760131118000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/11\/2219"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,7]]},"references-count":35,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["v15112219"],"URL":"https:\/\/doi.org\/10.3390\/v15112219","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2023,11,7]]}}}