{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T21:02:30Z","timestamp":1786741350522,"version":"build-2736575974"},"reference-count":59,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T00:00:00Z","timestamp":1718755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Human papilloma virus (HPV) infection and the management of its persistence is still a great medical challenge. Recently, scientific evidence has supported the potential therapeutic effects of four combined natural molecules\u2014epigallocatechin gallate (EGCG), folic acid, vitamin B12 and hyaluronic acid (HA)\u2014in counteracting HPV DNA positivity and related cytological lesions. Methods: Each patient of these five clinical cases had persistent HPV positivity in the anogenital site and assumed a dietary supplement based on a combination of 200 mg of EGCG, 50 mg of HA, 1 mg of vitamin B12 and 400 mcg of folic acid (Pervistop\u00ae, Farmares s.r.l., Rome, Italy) at a dosage of 1 or 2 caps\/day for 6 or 3 months, respectively, depending on clinical history. Results: After treatment, all the patients reported a negative HPV DNA test and improved cytological lesions, thus demonstrating the ability of these combined molecules to counteract both anal and cervical HPV infection and related manifestations. Conclusions: Overall, these data corroborate previous evidence about the effectiveness of such natural molecules in the management of HPV infection and its persistence. Naturally, further studies with a larger population and long-term follow-up will contribute to reinforce the positive effects of this dietary supplement in counteracting HPV infection.<\/jats:p>","DOI":"10.3390\/jcm13123597","type":"journal-article","created":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T11:47:17Z","timestamp":1718797637000},"page":"3597","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Counteracting HPV Cervical and Anal Infection through Dietary Supplementation of EGCG, Folic Acid, Vitamin B12 and Hyaluronic Acid: Clinical Case Reports"],"prefix":"10.3390","volume":"13","author":[{"given":"Marco","family":"Calcagno","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Santo Spirito Hospital, 00193 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4984-2255","authenticated-orcid":false,"given":"Bernadette","family":"Incocciati","sequence":"additional","affiliation":[{"name":"Di Fraia Laboratori s.r.l., 00034 Colleferro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludovica","family":"Di Fraia","sequence":"additional","affiliation":[{"name":"Di Fraia Laboratori s.r.l., 00034 Colleferro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1805-3181","authenticated-orcid":false,"given":"Vittorio","family":"Unfer","sequence":"additional","affiliation":[{"name":"A.G.Un.Co. Obstetrics and Gynaecology Center, 00155 Rome, Italy"},{"name":"UniCamillus\u2013Saint Camillus International University of Health Sciences, 00131 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,19]]},"reference":[{"key":"ref_1","first-page":"552028","article-title":"Epidemiology and Burden of Human Papillomavirus and Related Diseases, Molecular Pathogenesis, and Vaccine Evaluation","volume":"8","author":"Li","year":"2020","journal-title":"Front. Public. Health"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Van Doorslaer, K. (2022). Revisiting Papillomavirus Taxonomy: A Proposal for Updating the Current Classification in Line with Evolutionary Evidence. Viruses, 14.","DOI":"10.3390\/v14102308"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"16086","DOI":"10.1038\/nrdp.2016.86","article-title":"Carcinogenic human papillomavirus infection","volume":"2","author":"Schiffman","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_4","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_5","first-page":"686","article-title":"Study on the impact of sexually transmitted infections on Quality of Life, mood and sexual function","volume":"156","author":"Ciccarese","year":"2021","journal-title":"Ital. J. Dermatol. Venerol."},{"key":"ref_6","unstructured":"World Health Organization (2021). WH Guideline for Screening and Treatment of Cervical Pre-Cancer Lesions for Cervical Cancer Prevention. WHO Guidelines Approved by the Guidelines Review Committee, World Health Organization. [2nd ed.]."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1002\/ijgo.14340","article-title":"Risk factors analysis of recurrent disease after treatment with a loop electrosurgical excision procedure for high-grade cervical intraepithelial neoplasia","volume":"160","author":"Ding","year":"2023","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"ref_8","first-page":"473","article-title":"HPV infection and intraepithelial lesions from the anal region: How to diagnose?","volume":"15","author":"Carvalho","year":"2011","journal-title":"Braz. J. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1002\/cncy.22675","article-title":"Incidence of abnormal anal cytology in HIV-infected and HIV-uninfected men who have sex with men","volume":"131","author":"Benevolo","year":"2023","journal-title":"Cancer Cytopathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"50","DOI":"10.4251\/wjgo.v9.i2.50","article-title":"Anal intraepithelial neoplasia: A review of diagnosis and management","volume":"9","author":"Roberts","year":"2017","journal-title":"World J. Gastrointest. Oncol."},{"key":"ref_11","first-page":"343","article-title":"Intraepithelial neoplasia in the anal canal. The appearance and relation to genital neoplasia","volume":"94","author":"Fenger","year":"1986","journal-title":"Acta Pathol. Microbiol. Immunol. Scand. A"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1001\/jama.287.16.2114","article-title":"The 2001 Bethesda System: Terminology for reporting results of cervical cytology","volume":"287","author":"Solomon","year":"2002","journal-title":"JAMA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1750-9378-5-17","article-title":"Detection of multiple human papillomavirus genotypes in anal carcinoma","volume":"5","author":"Ramamoorthy","year":"2010","journal-title":"Infect. Agent. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Dzundova, M.N., Sehnal, B., Zikan, M., Kocian, R., Dubova, O., Hubka, P., Dostalek, L., Kabele, P., Brtnicky, T., and Slama, J. (2023). Risk Factors for the Anal and Oral Human Papillomavirus (HPV) Infections among Women with Severe Cervical Lesions: A Prospective Case-Control Study. Biomedicines, 11.","DOI":"10.3390\/biomedicines11123183"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2550","DOI":"10.1158\/1055-9965.EPI-05-0460","article-title":"Anal human papillomavirus infection in women and its relationship with cervical infection","volume":"14","author":"Hernandez","year":"2005","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Shanmugasundaram, S., and You, J. (2017). Targeting Persistent Human Papillomavirus Infection. Viruses, 9.","DOI":"10.3390\/v9080229"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1086\/341782","article-title":"Incidence, prevalence, and clearance of type-specific human papillomavirus infections: The Young Women\u2019s Health Study","volume":"186","author":"Giuliano","year":"2002","journal-title":"J. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1086\/424466","article-title":"Risk of high-grade squamous intraepithelial lesion in HIV-infected adolescents","volume":"190","author":"Moscicki","year":"2004","journal-title":"J. Infect. Dis."},{"key":"ref_19","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. Obstet. Gynaecol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1080\/15384101.2016.1191257","article-title":"HPV-mediated inactivation of tumor suppressor p53","volume":"15","author":"Zanier","year":"2016","journal-title":"Cell Cycle"},{"key":"ref_21","first-page":"197","article-title":"Interactions of HPV E6 and E7 oncoproteins with tumour suppressor gene products","volume":"12","author":"Scheffner","year":"1992","journal-title":"Cancer Surv."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1007\/s10096-020-04073-6","article-title":"Prevalence of genital HPV infection in STI and healthy populations and risk factors for viral persistence","volume":"40","author":"Ciccarese","year":"2021","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e6862","DOI":"10.1002\/cam4.6862","article-title":"A comprehensive narrative review of challenges and facilitators in the implementation of various HPV vaccination program worldwide","volume":"13","author":"Aggarwal","year":"2024","journal-title":"Cancer Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1111\/ajco.13513","article-title":"A systematic review of the barriers to implementing human papillomavirus vaccination programs in low- and middle-income countries in the Asia-Pacific","volume":"17","author":"Ver","year":"2021","journal-title":"Asia Pac. J. Clin. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Grandi, G., Botticelli, L., Fraia, P.D., Babalini, C., Masini, M., and Unfer, V. (2023). The Association of Four Natural Molecules-EGCG, Folic Acid, Vitamin B12, and HA-To Counteract HPV Cervical Lesions: A Case Report. J. Pers. Med., 13.","DOI":"10.3390\/jpm13030567"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Aragona, C., Bezerra Espinola, M.S., Bilotta, G., Porcaro, G., and Calcagno, M. (2023). Evaluating the Efficacy of Pervistop((R)), a New Combination Based on EGCG, Folic Acid, Vitamin B12 and Hyaluronic Acid on Patients with Human Papilloma Virus (HPV) Persistent Infections and Cervical Lesions: A Pilot Study. J. Clin. Med., 12.","DOI":"10.3390\/jcm12062171"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Lagan\u00e0, A.S., Chiantera, V., Gerli, S., Proietti, S., Lepore, E., Unfer, V., Carugno, J., and Favilli, A. (2023). Preventing Persistence of HPV Infection with Natural Molecules. Pathogens, 12.","DOI":"10.3390\/pathogens12030416"},{"key":"ref_28","first-page":"5240","article-title":"Epigallocatechin gallate, folic acid, vitamin B12, and hyaluronic acid significantly increase apoptosis and p53 expression in HeLa cells","volume":"27","author":"Frega","year":"2023","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Yap, J.K.W., Kehoe, S.T., Woodman, C.B.J., and Dawson, C.W. (2021). The Major Constituent of Green Tea, Epigallocatechin-3-Gallate (EGCG), Inhibits the Growth of HPV18-Infected Keratinocytes by Stimulating Proteasomal Turnover of the E6 and E7 Oncoproteins. Pathogens, 10.","DOI":"10.3390\/pathogens10040459"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"245","DOI":"10.3727\/096504011X13021877989711","article-title":"Tea polyphenols induce apoptosis through mitochondrial pathway and by inhibiting nuclear factor-kappaB and Akt activation in human cervical cancer cells","volume":"19","author":"Singh","year":"2011","journal-title":"Oncol. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3281","DOI":"10.1016\/j.fct.2011.09.023","article-title":"Catechin hydrate inhibits proliferation and mediates apoptosis of SiHa human cervical cancer cells","volume":"49","author":"Alshatwi","year":"2011","journal-title":"Food Chem. Toxicol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Song, J.Y., Han, J.H., Song, Y., Lee, J.H., Choi, S.Y., and Park, Y.M. (2021). Epigallocatechin-3-gallate Can Prevent Type 2 Human Papillomavirus E7 from Suppressing Interferon-Stimulated Genes. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052418"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1111\/j.1365-2133.2009.09375.x","article-title":"Polyphenon E: A new treatment for external anogenital warts","volume":"162","author":"Tatti","year":"2010","journal-title":"Br. J. Dermatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1097\/00008469-200310000-00007","article-title":"Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions","volume":"12","author":"Ahn","year":"2003","journal-title":"Eur. J. Cancer Prev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1023\/A:1011290103779","article-title":"Elevated serum homocysteine levels and increased risk of invasive cervical cancer in US women","volume":"12","author":"Weinstein","year":"2001","journal-title":"Cancer Causes Control"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1158\/1940-6207.CAPR-14-0143","article-title":"Folate and vitamin B12 may play a critical role in lowering the HPV 16 methylation-associated risk of developing higher grades of CIN","volume":"7","author":"Piyathilake","year":"2014","journal-title":"Cancer Prev. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s00404-010-1650-7","article-title":"Human papilloma virus persistence and neopterin, folate and homocysteine levels in cervical dysplasias","volume":"284","author":"Abike","year":"2011","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1093\/jn\/129.4.779","article-title":"Folate metabolism and requirements","volume":"129","author":"Bailey","year":"1999","journal-title":"J. Nutr."},{"key":"ref_39","first-page":"293","article-title":"The role of vitamin B12 and folate in carcinogenesis","volume":"206","author":"Herbert","year":"1986","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"8788","DOI":"10.1158\/0008-5472.CAN-04-2402","article-title":"Folate is associated with the natural history of high-risk human papillomaviruses","volume":"64","author":"Piyathilake","year":"2004","journal-title":"Cancer Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"7","DOI":"10.2147\/IJWH.S6522","article-title":"Indian women with higher serum concentrations of folate and vitamin B12 are significantly less likely to be infected with carcinogenic or high-risk (HR) types of human papillomaviruses (HPVs)","volume":"2","author":"Piyathilake","year":"2010","journal-title":"Int. J. Womens Health"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrc2050","article-title":"The natural history of cervical HPV infection: Unresolved issues","volume":"7","author":"Woodman","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1021\/acsabm.0c01364","article-title":"Role of Hyaluronic Acids and Potential as Regenerative Biomaterials in Wound Healing","volume":"4","author":"Yang","year":"2021","journal-title":"ACS Appl. Bio Mater."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"E106","DOI":"10.25011\/cim.v31i3.3467","article-title":"Hyaluronan oligosaccharides are potential stimulators to angiogenesis via RHAMM mediated signal pathway in wound healing","volume":"31","author":"Gao","year":"2008","journal-title":"Clin. Investig. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e2221","DOI":"10.1097\/GOX.0000000000002221","article-title":"Hyaluronic Acid Accelerates Re-epithelialization and Alters Protein Expression in a Human Wound Model","volume":"7","author":"Nyman","year":"2019","journal-title":"Plast. Reconstr. Surg. Glob. Open"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Riemma, G., Schettino, M.T., Munno, G.M., Fasulo, D.D., Sandullo, L., Amabile, E., La Verde, M., and Torella, M. (2022). Echinacea angustifolia and Echinacea purpurea Supplementation Combined with Vaginal Hyaluronic Acid to Boost the Remission of Cervical Low-Grade Squamous Intraepithelial Lesions (L-SILs): A Randomized Controlled Trial. Medicina, 58.","DOI":"10.3390\/medicina58050646"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1097\/PGP.0b013e31826916c7","article-title":"The Lower Anogenital Squamous Terminology Standardization project for HPV-associated lesions: Background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology","volume":"32","author":"Darragh","year":"2013","journal-title":"Int. J. Gynecol. Pathol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Martinelli, M., Giubbi, C., Sechi, I., Bottari, F., Iacobone, A.D., Musumeci, R., Perdoni, F., Muresu, N., Piana, A., and Fruscio, R. (2022). Evaluation of BD Onclarity\u2122 HPV Assay on Self-Collected Vaginal and First-Void Urine Samples as Compared to Clinician-Collected Cervical Samples: A Pilot Study. Diagnostics, 12.","DOI":"10.3390\/diagnostics12123075"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.pvr.2016.01.003","article-title":"Clinical and analytical performance of the BD Onclarity\u2122 HPV assay for detection of CIN2+ lesions on SurePath samples","volume":"2","author":"Ejegod","year":"2016","journal-title":"Papillomavirus Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e23155","DOI":"10.1097\/MD.0000000000023155","article-title":"Clearance of human papillomavirus infection in patients with cervical intraepithelial neoplasia: A systemic review and meta-analysis","volume":"99","author":"Xiong","year":"2020","journal-title":"Medicine"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.ogc.2008.09.001","article-title":"Management of atypical squamous cells, low-grade squamous intraepithelial lesions, and cervical intraepithelial neoplasia 1","volume":"35","author":"Boardman","year":"2008","journal-title":"Obstet. Gynecol. Clin. N. Am."},{"key":"ref_52","first-page":"239","article-title":"Efficiency of three surgical procedures in eliminating high-risk human papillomavirus infection in women with precancerous cervical lesions","volume":"27","author":"Jancar","year":"2006","journal-title":"Eur. J. Gynaecol. Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1016\/j.ygyno.2020.08.025","article-title":"Recurrence rate after loop electrosurgical excision procedure (LEEP) and laser Conization: A 5-year follow-up study","volume":"159","author":"Bogani","year":"2020","journal-title":"Gynecol. Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"631","DOI":"10.5468\/ogs.20049","article-title":"Risk factors for type-specific persistence of high-risk human papillomavirus and residual\/recurrent cervical intraepithelial neoplasia after surgical treatment","volume":"63","author":"Ouh","year":"2020","journal-title":"Obstet. Gynecol. Sci."},{"key":"ref_55","first-page":"e33917","article-title":"Prevalence, Pattern, and Reasons for Self-Medication: A Community-Based Cross-Sectional Study From Central India","volume":"15","author":"Rathod","year":"2023","journal-title":"Cureus"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e069206","DOI":"10.1136\/bmjopen-2022-069206","article-title":"Self-medication among adults with chronic health conditions: A population-based cross-sectional survey in Saudi Arabia","volume":"13","author":"Alwhaibi","year":"2023","journal-title":"BMJ Open"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"19","DOI":"10.4103\/0976-0105.128253","article-title":"Self-medication: A current challenge","volume":"5","author":"Bennadi","year":"2013","journal-title":"J. Basic. Clin. Pharm."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1111\/IGC.0b013e3181c7ca5c","article-title":"Green tea compound in chemoprevention of cervical cancer","volume":"20","author":"Zou","year":"2010","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1093\/jn\/nxx060","article-title":"Folate Deficiency Facilitates Genomic Integration of Human Papillomavirus Type 16 DNA In Vivo in a Novel Mouse Model for Rapid Oncogenic Transformation of Human Keratinocytes","volume":"148","author":"Xiao","year":"2018","journal-title":"J. Nutr."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/12\/3597\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:01:18Z","timestamp":1760108478000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/12\/3597"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,19]]},"references-count":59,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["jcm13123597"],"URL":"https:\/\/doi.org\/10.3390\/jcm13123597","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,19]]}}}