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Human Papillomavirus (HPV) infection represents a global health concern. HPV infects the mucosa, particularly in the uterine cervix, where it may establish a persistent infection, exposing women to a risk of developing cancer. The available treatments include surgery or topic solutions, while a systemic treatment is still unavailable. In recent years, natural molecules such as epigallocatechin gallate (EGCG), folic acid (FA), vitamin B12, and hyaluronic acid (HA) gained importance as innovative therapies for HPV. We enrolled 163 women with a positive HPV DNA test or previous history of HPV infections, and a PAP test indicating LSIL/AGUS/ASCUS cytology. The patients in the treatment group (n = 86) received an oral combination of EGCG 200 mg, FA 400 µg, vitamin B12 1 mg, and HA 50 mg (1 cps/day) for 3 months (T1), while the control group (n = 77) underwent standard clinical surveillance. Both groups repeated a PAP test and an HPV DNA test after 3 (T1) months, and another PAP test after 6 months (T2) as a follow up. The treatment group experienced a significant reduction in HPV positivity at T1 compared to the control group. Moreover, the treatment group exhibited an improvement in cervical lesions either at T1 (p < 0.0001) or T2 (p < 0.00001).