Background/Objectives: Non-ablative local therapies are increasingly used in the conservative management of human papillomavirus (HPV) infection. Coriolus versi-color, an immunomodulatory medicinal mushroom, is one such approach. This study aimed to investigate the effect of a Coriolus versicolor–based vaginal gel on HPV clearance and cervical cytological outcomes. Methods: This retrospective cohort study included 600 women with cervical HPV infection (300 treated with a Coriolus versi-color–based vaginal gel and 300 receiving standard follow-up). Baseline and six-month follow-up assessments included HPV DNA testing and cervical cytology. Results: Baseline demographic characteristics, HPV genotype distribution, and cytological findings were comparable between the groups. Overall HPV clearance was signifi-cantly higher in the treatment group than in the control group (89.3% vs. 44.7%, p < 0.001). Complete clearance of high-risk HPV genotypes, including HPV 16 (77.0% vs. 25.4%, p < 0.001) and HPV 18 (73.9% vs. 18.5%, p = 0.017), was also significantly more frequent among treated women. Cytological normalization occurred more often in the treatment group (88.4% vs. 60.4%, p < 0.001). Multivariable analysis identified use of the vaginal gel as the strongest independent factor associated with HPV clearance (adjusted odds ratio [aOR] = 8.45; 95% confidence interval [CI]: 3.05–23.43; p < 0.001). Conclusions: Treatment with a Coriolus versicolor–based vaginal gel was associated with significantly higher rates of high-risk HPV clearance and cervical cytological normalization. These findings suggest that this therapy may represent an effective ad-junct in the conservative management of HPV infection; however, randomized con-trolled trials are warranted to confirm these results.

Background/Objectives: Non-ablative local therapies are increasingly used in the conservative management of human papillomavirus (HPV) infection. Coriolus versicolor, an immunomodulatory medicinal mushroom, is one such approach. This study aimed to investigate the effect of a Coriolus versicolor–based vaginal gel on HPV clearance and cervical cytological outcomes. Methods: This retrospective cohort study included 600 women with cervical HPV infection (300 treated with a Coriolus versicolor–based vaginal gel and 300 receiving standard follow-up). Baseline and six-month follow-up assessments included HPV DNA testing and cervical cytology. Results: Baseline demographic characteristics, HPV genotype distribution, infection type, and cytological findings were comparable between the groups. Overall HPV clearance was significantly higher in the treatment group than in the controls (89.3% vs. 44.7%, p < 0.001). Complete clearance of high-risk HPV genotypes, including HPV 16 (77.0% vs. 25.4%, p < 0.001) and HPV 18 (73.9% vs. 18.5%, p = 0.017), was also significantly more frequent among treated women. Cytological normalization occurred more often in the treatment group (88.4% vs. 60.4%, p < 0.001). Multivariable analysis identified use of the vaginal gel as the strongest independent factor associated with HPV clearance (adjusted odds ratio [aOR] = 10.19; 95% confidence interval [CI]: 3.52–29.47; p < 0.001). Conclusions: Treatment with a Coriolus versicolor–based vaginal gel was associated with significantly higher rates of high-risk HPV clearance and cervical cytological normalization. These findings suggest that this therapy may represent an effective adjunct in the conservative management of HPV infection; however, randomized controlled trials are warranted to confirm these results.