A Prospective, Non-interventional Observational Study to Assess the Efficacy, Safety, and Tolerability of the Casein Hydrolysate-Based Food Supplement in High-Risk Human Papillomavirus-Positive Women.

Abstract

Objective The study aimed to assess the efficacy, safety, and tolerability of casein hydrolysate-based food supplement, HuPaVir^®, in high-risk human papillomavirus (HR-HPV)-positive women. Methods A prospective, multicenter, and non-interventional observational study was carried out in Spain. At the end of the study, 118 HR-HPV-positive women (20 to 65 years old) were enrolled and completed the follow-up as required by the protocol. All participants performed HPV-DNA testing, liquid-based cytology, and DNA extraction by multiplex PCR at zero and six months. Upon baseline evaluation, participants were provided with a casein hydrolyzed formula or managed with a wait-and-see approach. Supplementation treatment consisted of daily consumption of one dose of the casein hydrolysate formula for six months. The study population was then divided into four groups based on the baseline cytology result and the supplementation treatment performed during the follow-up period. Treated participants underwent blood tests to determine different immune parameters. Treated participants were also provided with case report forms to register any adverse effect during the study and were asked to complete a voluntary survey to assess product tolerance and acceptability by rating their level of agreement. Results At six months, consumption of the casein hydrolysate formula resulted in total or partial clearance of the HR-HPV type and normalization of cervical cytology in a statistically significant percentage of cases compared to the untreated group (74.6% vs. 35.6%; p<0.01 and 67.4% vs. 41.9%; p<0.05, respectively). Notably, a positive trend in increasing serum levels of innate immunity markers, such as natural killer (NK) cells, and adaptive immunity markers, such as CD8 and CD4 T lymphocytes, was observed in the treated participants. Conclusion The results suggest that daily supplementation with the casein hydrolysate formula is effective in causing significant virus clearance and lesion remission compared to the conventional approach in clinical practice for HR-HPV-positive women. However, a large, multicenter, standardized, and randomized study with longer-term follow-up, 12 months after supplementation treatment, is needed to confirm and strengthen these findings. The formula was found to be safe and well-tolerated.