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

An Interventional Study Evaluating the Effect of Epigallocatechin Gallate (EGCG), Folic Acid (FA), Vitamin B12 (B12) and Hyaluronic Acid (HA) in Affecting the DNA Integration of Human Papilloma Virus (HPV) in Women With Persistent Infection

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.

Human Papillomavirus (HPV) is a common sexually transmitted infection that, while often regressing spontaneously, can persist. Persistent high-risk HPV infection is a major risk factor for cervical cancer because it allows viral DNA to integrate into the host genome. This integration triggers the constitutive expression of viral oncoproteins E6 and E7, which block the host's tumor suppressor genes (p53 and prb), leading to uncontrolled cell proliferation.Currently, clinical practice for low-grade lesions typically involves a surveillance approach. This study explores the use of a synergic combination of EGCG (anti-proliferative/pro-apoptotic), Vitamin B12 and Folic Acid (methylation agents), and Hyaluronic Acid (epithelial integrity) to promote viral clearance and inhibit E6/E7 expression.

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