Study of 2LPAPI® on the Clearance of Genital HR-HPV Infections.

Overview

Human papillomavirus (HPV) is a prevalent pathogen, the epidemiology of which has mostly been studied in the uterine cervix and the vagina. In Belgium, since 2025, HPV testing has become the primary screening method for cervical cancer. For women between 30 and 64 years, a clinical guideline (March 2025) from Sciensano stated the following " The triage of HPV-positive women is based on HPV type and reflex cytology outcome as a threshold for colposcopy. In 30- to 64-year-olds, triage of HR-HPV non-16/18 positives consists of an initial reflex cytology, followed by another HPV test 12 months later if the first step demonstrated Negative for Intraepithelial Lesion or Malignancy (NILM). Women who test positive on the initial HR-HPV test for the most high-risk HPV types 16 or 18 are immediately referred for colposcopy. Besides colposcopy, a reflex cytology will be performed. ". Women from 25 to 29 years are recommended to undergo a cytology testing on cervical smear as primary screening method following Sciensano clinical guideline (March 2025) recommendations. If abnormalities are detected, a HPV testing is performed. For the two age groups, if low grade abnormalities are detected with a diagnosis of HR-HPV, a second triage is recommended at 12 months. There is no treatment that is recommended during this lap time. The 2LPAPI® has been available for more than 20 years, and has received a marketing authorization in Belgium by the FAMHP. It is used as an immune regulator in the treatment of HR-HPV infections. Since 2LPAPI® has been made available, clinical observational data collected on treated patients have shown the beneficial effect on the clearance of HPV. The purpose of this placebo-controlled trial is to evaluate the efficacy of 2LPAPI® on the clearance of genital HR-HPV infections.

The study duration will be 72 months with 60 months of inclusion (that may be extended if the expected number of patients is not reached after 60 months) and 12 months of follow-up. Patients aged between 25 and 45 years presenting a diagnosis of HR-HPV infection during the routine screening visit for cervical cancer prevention. The total number of patients to include will be 284 with 142 patients per group. Primary objective: Comparison of the efficacy of 2LPAPI® versus placebo on the clearance of genital HR-HPV infections after 12 months of follow-up. Secondary objectives: Comparison of 2LPAPI® versus placebo on: * HR-HPV infection clearance rate at 6-month visits, * HR-HPV infection clearance rate by HPV type at 6-month and 12-month visits, * Evolution of cytology, * Normalization of cytology for the subpopulation of patients with a baseline non normal cytology, * Safety: adverse events (AEs) and serious adverse events (SAEs), considered as related or not to the study drug. Treatment phase: Group n°1 = 2LPAPI® (6 months of treatment) Group n°2 = Placebo (6 months of treatment) Post-treatment follow-up phase: 6 months. Treatment will be considered successful if the clearance of HR-HPV is done and the cytology is normal.