Effect of EGCG, Folic Acid, Vitamin B12 and Hyaluronic Acid on HPV DNA Integration

NCT07697196 | Not Yet Recruiting DMC

• 1 other identifier: PERVISTOP_2025
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

This interventional, single-center, open-label randomized clinical study evaluates the efficacy of an oral dietary supplement (Pervistop®) in women with persistent Human Papillomavirus (HPV) infection. The supplement is a combination of four natural molecules: Epigallocatechin gallate (EGCG), folic acid (FA), vitamin B12 (B12), and hyaluronic acid (HA).The primary objective is to describe the effect of this association on HPV DNA integration into the host genome by measuring the clearance rate of viral oncoproteins E6 and E7. A total of 42 women aged 25 or older with persistent HPV infection and low-grade cervical lesions will be randomized 1:1 into two groups. The treated group will receive one tablet of Pervistop® daily for six months, while the control group will follow standard clinical practice. The study aims to determine if this nutritional intervention can counteract viral persistence.

Conditions

HPV Infection; HPV Integration; HPV Disease; HPV Genital Infection; HPV Persistence; Low Grade Squamous Intraepithelial Lesions of the Cervix

Outcome Measures

Primary Outcomes (1)

• Rate of clearance of viral oncoproteins E6 and E7

  The percentage of participants showing a negative result for viral E6/E7 mRNA, which are key indicators of HPV DNA integration into the host genome. Analysis will be performed using the Aptima HPV assay, a transcription-mediated amplification (TMA) technique. A negative test result indicates viral clearance or loss of viral integration.

  6 months

Secondary Outcomes (2)

• HPV DNA Clearance Rate

  6 months

• Treatment Adherence score

  6 months

Other Outcomes (1)

• Quantitative Variation of E6/E7 Levels from baseline to T1

  6 months

Study Arms (2)

Treated Group (Pervistop®)

EXPERIMENTAL

Patients in this group will receive the oral supplement Pervistop®. The intervention consists of 1 tablet per day for a total duration of 6 months.

Dietary Supplement: Epigallocatechin gallate (EGCG), Folic Acid (FA), Vitamin B12 (B12), and Hyaluronic Acid (HA)

Non treated group

NO INTERVENTION

Participants in this group will receive no treatment. They will follow standard clinical practice

Interventions

Epigallocatechin gallate (EGCG), Folic Acid (FA), Vitamin B12 (B12), and Hyaluronic Acid (HA) DIETARY_SUPPLEMENT

Participants will self-administer one oral tablet of the dietary supplement Pervistop daily

Treated Group (Pervistop®)

Eligibility Criteria

• Age: 25 Years+
• Gender Eligibility Details: Only biological women will be eligible for the study, regardless gender identity.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 25 years old
• Positive HPV DNA test with genotyping 9-24 months prior to Day 0
• Positive HPV DNA test with genotyping at Day 0
• Presence of an HPV-related cervical lesion within 5-24 months prior to Day 0. This lesion will be defined alternatively as:
• Pap test: LSIL, ASC-US.
• Colposcopic impression suggestive of a low-grade lesion.
• Histologic report of a colposcopic biopsy consistent with a low-grade lesion.
• Previous HPV vaccination (latest dose at least 24 months earlier than Day 0)
• Patients able to accept and sign informed consent for the study
• Patients able to adhere to the proposed study protocol

You may not qualify if:

• High grade cervical lesions (HSIL)
• Ongoing pregnancy, evaluated through a rapid chromatographic immunoassay for qualitative detection of hCG in urine
• Ongoing breastfeeding
• Primary or secondary immunodepression due to pharmacological treatments
• No HPV vaccination
• Daily assumption of other products containing green tea
• Hypersensitivity or allergy to the substances contained in the supplement

Sponsors & Collaborators

• IRCCS San Raffaele: lead

Study Sites (1)

IRCCS San Raffele Hospital

Milan, Italy, 20100, Italy

Location

Related Publications (20)

• Porcaro G, Pavone-Cossut MR, Moretti S, Bilotta G, Aragona C, Unfer V. Oral Treatment with EGCG, Folic Acid, Vitamin B12, and Hyaluronic Acid Improves HPV Clearance and Counteracts Its Persistence: A Clinical Study. Int J Mol Sci. 2025 May 29;26(11):5251. doi: 10.3390/ijms26115251.

  PMID: 40508059 BACKGROUND

• Serrano L, Lopez AC, Gonzalez SP, Palacios S, Dexeus D, Centeno-Mediavilla C, Coronado P, de la Fuente J, Lopez JA, Vanrell C, Cortes J. Efficacy of a Coriolus versicolor-Based Vaginal Gel in Women With Human Papillomavirus-Dependent Cervical Lesions: The PALOMA Study. J Low Genit Tract Dis. 2021 Apr 1;25(2):130-136. doi: 10.1097/LGT.0000000000000596.

  PMID: 33746195 BACKGROUND

• Abate A, Munshea A, Nibret E, Alemayehu DH, Alemu A, Abdissa A, Mihret A, Abebe M, Mulu A. Persistence and clearance rates of human papillomaviruses in a cohort of women treated or not treated for cervical dysplasia in northwest Ethiopia. Sci Rep. 2025 Mar 10;15(1):8218. doi: 10.1038/s41598-025-87568-6.

  PMID: 40064999 BACKGROUND

• Zhou SG, Wu DF, Yao H, Zhang WY, Tian FJ, Chen G, Zhang CF. REBACIN(R) inhibits E6/E7 oncogenes in clearance of human papillomavirus infection. Front Oncol. 2022 Dec 6;12:1047222. doi: 10.3389/fonc.2022.1047222. eCollection 2022.

  PMID: 36561517 BACKGROUND

• Tinelli A, Gustapane S, Licchelli M, Coluccia AC, Panese G, Proietti S, Gambioli R. Treatment with Epigallocatechin Gallate, Folic Acid, Vitamin B12, and Hyaluronic Acid Decreases HPV Positivity in Women Attending Regional Screening in Puglia. Microorganisms. 2024 Sep 14;12(9):1897. doi: 10.3390/microorganisms12091897.

  PMID: 39338571 BACKGROUND

• Calcagno M, Incocciati B, Di Fraia L, Unfer V. Counteracting HPV Cervical and Anal Infection through Dietary Supplementation of EGCG, Folic Acid, Vitamin B12 and Hyaluronic Acid: Clinical Case Reports. J Clin Med. 2024 Jun 19;13(12):3597. doi: 10.3390/jcm13123597.

  PMID: 38930126 BACKGROUND

• Grandi G, Botticelli L, Fraia PD, Babalini C, Masini M, Unfer V. The Association of Four Natural Molecules-EGCG, Folic Acid, Vitamin B12, and HA-To Counteract HPV Cervical Lesions: A Case Report. J Pers Med. 2023 Mar 22;13(3):567. doi: 10.3390/jpm13030567.

  PMID: 36983748 BACKGROUND

• Aragona C, Bezerra Espinola MS, Bilotta G, Porcaro G, Calcagno M. 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. 2023 Mar 10;12(6):2171. doi: 10.3390/jcm12062171.

  PMID: 36983172 BACKGROUND

• Cullen AP, Reid R, Campion M, Lorincz AT. Analysis of the physical state of different human papillomavirus DNAs in intraepithelial and invasive cervical neoplasm. J Virol. 1991 Feb;65(2):606-12. doi: 10.1128/JVI.65.2.606-612.1991.

  PMID: 1846186 BACKGROUND

• Pirami L, Giache V, Becciolini A. Analysis of HPV16, 18, 31, and 35 DNA in pre-invasive and invasive lesions of the uterine cervix. J Clin Pathol. 1997 Jul;50(7):600-4. doi: 10.1136/jcp.50.7.600.

  PMID: 9306943 BACKGROUND

• Pal A, Kundu R. Human Papillomavirus E6 and E7: The Cervical Cancer Hallmarks and Targets for Therapy. Front Microbiol. 2020 Jan 21;10:3116. doi: 10.3389/fmicb.2019.03116. eCollection 2019.

  PMID: 32038557 BACKGROUND

• Giuliano AR, Nyitray AG, Kreimer AR, Pierce Campbell CM, Goodman MT, Sudenga SL, Monsonego J, Franceschi S. EUROGIN 2014 roadmap: differences in human papillomavirus infection natural history, transmission and human papillomavirus-related cancer incidence by gender and anatomic site of infection. Int J Cancer. 2015 Jun 15;136(12):2752-60. doi: 10.1002/ijc.29082. Epub 2014 Jul 26.

  PMID: 25043222 BACKGROUND

• de Sanjose S, Serrano B, Castellsague X, Brotons M, Munoz J, Bruni L, Bosch FX. Human papillomavirus (HPV) and related cancers in the Global Alliance for Vaccines and Immunization (GAVI) countries. A WHO/ICO HPV Information Centre Report. Vaccine. 2012 Nov 20;30 Suppl 4:D1-83, vi. doi: 10.1016/S0264-410X(12)01435-1. No abstract available.

  PMID: 23510764 BACKGROUND

• McLaughlin-Drubin ME, Munger K. Oncogenic activities of human papillomaviruses. Virus Res. 2009 Aug;143(2):195-208. doi: 10.1016/j.virusres.2009.06.008. Epub 2009 Jun 18.

  PMID: 19540281 BACKGROUND

• Sung H, Ferlay J, Siegel RL, 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 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.

  PMID: 33538338 BACKGROUND

• Qiao Y, Cao J, Xie L, Shi X. Cell growth inhibition and gene expression regulation by (-)-epigallocatechin-3-gallate in human cervical cancer cells. Arch Pharm Res. 2009 Sep;32(9):1309-15. doi: 10.1007/s12272-009-1917-3. Epub 2009 Sep 26.

  PMID: 19784588 BACKGROUND

• Xiao S, Jia H, Guo Y, Ding X, Zheng A. Chemoprophylactic Effects of Epigallocatechin Gallate in Female Reproductive Cancers - A Review. J Diet Suppl. 2025;22(4):487-510. doi: 10.1080/19390211.2025.2518409. Epub 2025 Jun 15.

  PMID: 40518686 BACKGROUND

• Yap JKW, Kehoe ST, Woodman CBJ, Dawson CW. 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. 2021 Apr 11;10(4):459. doi: 10.3390/pathogens10040459.

  PMID: 33920477 BACKGROUND

• Frega A, Gentili C, Proietti S, Lepore E, Unfer V, Fuso A. Epigallocatechin gallate, folic acid, vitamin B12, and hyaluronic acid significantly increase apoptosis and p53 expression in HeLa cells. Eur Rev Med Pharmacol Sci. 2023 Jun;27(11):5240-5245. doi: 10.26355/eurrev_202306_32642.

  PMID: 37318498 BACKGROUND

• Aarthy M, Panwar U, Singh SK. Structural dynamic studies on identification of EGCG analogues for the inhibition of Human Papillomavirus E7. Sci Rep. 2020 May 26;10(1):8661. doi: 10.1038/s41598-020-65446-7.

  PMID: 32457393 BACKGROUND

MeSH Terms

Conditions

Papillomavirus Infections

Interventions

epigallocatechin gallate; Folic Acid; Vitamin B 12; Hyaluronic Acid

Condition Hierarchy (Ancestors)

Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; Infections; DNA Virus Infections; Virus Diseases; Tumor Virus Infections; Genital Diseases; Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Corrinoids; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds, 4 or More Rings; Macrocyclic Compounds; Polycyclic Compounds; Glycosaminoglycans; Polysaccharides; Carbohydrates

Central Study Contacts

Massimo Origoni, MD

CONTACT

+39 0226432759; massimo.origoni@hsr.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Università Vita-Salute San Raffaele, Milan, Italy - Head of the Gynecological Oncological Diagnostic Center at IRCCS San Raffaele Hospital

Study Record Dates

• First Submitted: June 23, 2026
• First Posted: July 13, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: July 13, 2026

Record last verified: 2026-06

Locations

IT (1)