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

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.

Sex

Female

Minimum age

25 Years

Inclusion Criteria:

1. Age ≥ 25 years old
2. Positive HPV DNA test with genotyping 9-24 months prior to Day 0
3. Positive HPV DNA test with genotyping at Day 0
4. Presence of an HPV-related cervical lesion within 5-24 months prior to Day 0. This lesion will be defined alternatively as:

   1. Pap test: LSIL, ASC-US.
   2. Colposcopic impression suggestive of a low-grade lesion.
   3. Histologic report of a colposcopic biopsy consistent with a low-grade lesion.
5. Previous HPV vaccination (latest dose at least 24 months earlier than Day 0)
6. Patients able to accept and sign informed consent for the study
7. Patients able to adhere to the proposed study protocol

Exclusion Criteria:

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

• BACKGROUNDPorcaro 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
• BACKGROUNDSerrano 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
• BACKGROUNDAbate 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
• BACKGROUNDZhou 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
• BACKGROUNDTinelli 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
• BACKGROUNDCalcagno 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