Written by Written by Tabish Mehraj, PhD, Science Writer. 3g of AHCC once daily for a 6-month duration resulted in an overall response rate of 58.8% for HPV infection clearance in women with high-risk HPV, showcasing AHCC’s ability to support the host immune system. 

Human papillomavirus (HPV) is a non-enveloped, double-stranded DNA virus that infects the mucosal and cutaneous layers of the epithelial surfaces. While most HPV infections resolve spontaneously, recurrent infections with high-risk HPV (HR-HPV) viruses are the key factors in the progression of urogenital, cervical, and oropharyngeal cancers. In the United States, approximately 85,890 cancer cases are connected to recurrent HR-HPV every year. Although the vaccines are effective and safe, there is a significant gap in treatment for patients suffering from persistent, recurring infections. Currently, the treatment strategy primarily focuses on ablative procedures, such as LEEP and surgery, that remove lesions but do not significantly reduce the main underlying viral reservoir.

To look into alternative treatments, and for the response of this unmet need, Smith JA and team conducted a Phase II randomized, double-blind, placebo-controlled study in 50 women over 30 years of age with confirmed persistent high-risk HPV infections for greater than 2 years. This study investigates AHCC®, a standardized extract of cultured Lentinula edodes mycelia, a prospective candidate for nutritional supplementation to support the host immune system in removing these chronic infections. The participants were randomized into two groups, The control group (n=25) receiving placebo for 12 months and the intervention group (n=25) received 3g of AHCC orally once in a fasting state for 6 months.

The results of the study are as follows :

• Study Completion : 41 participants completed the study out of 50 enrolled.
• Efficacy Results: For AHCC Arm 14 of 22 patients (63.6%) achieved HPV RNA/DNA negativity after 6 months. 2 of 19 patients (10.5%) achieved clearance. The difference was statistically significant(p<0.05)
• Stability of the response: 9 patients (64.3%) maintained HPV negativity 12 months after stopping supplementation which were classified as Complete Response.
• Clearance: Out of all patients who received 3g daily (n=34), the total clearance rate was 58.8%.
• Safety and Tolerability: AHCC was well tolerated with no adverse events reported.

AHCC may help the body clear persistent HPV infections by supporting the immunological system. In this study, the participants started with higher-than-normal levels of a protein called as IFN-β. The study showed that the AHCC supplement acts by downregulating increased IFN-β signaling appeared to reset the host immunity. The enlargement of Lymphocytes also marked a release of interferon-gamma (IFN-γ) which play a significant role in fighting these viruses. Overall, the findings suggest that AHCC mainly works by strengthening the T-cell immune response.

By altering the host’s adaptive and innate immune systems, particularly by resetting the IFN-β/IFN-γ axis, AHCC provides a non-invasive strategy to reduce the risk of HPV-associated malignancies. The report highlights the potential of using IFN-β levels as an important clinical tool to tailor and personalize the duration of supplement use. These findings mark an important and meaningful advancement for managing persistent HPV, providing a validated nutritional intervention where conventional pharmacological options remain limited.

Here are the key strengths of the study:

• Safety profile
  The supplementation looked promising in terms of its tolerability and mild side effects and no treatment discontinuation after milder side-effects.
• Randomized double-blind, placebo-controlled design
  The reliability of the results increased because there was a strong clinical trial design that reduced bias. Neither of the adults enrolled or the researchers knew who got AHCC or placebo during the study.
• Crossover opportunity
  The placebo group was later given AHCC, which allowed more evaluation of the effectiveness thus increasing the total number of adults exposed to the supplement. Generally, the design of the study, immune analysis and safety results strengthen the results, even though broader population trials are still needed.

Key limitations of the study are as follows:

• Smaller sample size: Only 50 women, out of which only 41 completed the study limits how surely the results could be applied to a larger population.
• Shorter Follow up period: Long term follow up is essential to determine whether the effect is maintained over several years.
• Limited Population and Gender: The study reported only women over 30 with chronic HPV, the results may or may not apply to male or younger women.
• Phase 2 Trial: The study is an early stage clinical trial, much more studies or larger phase trials are required to confirm the stability, effectiveness and reproducibility.
• Immune Markers variability among different individuals must be taken into consideration.

Source:  Smith, Judith A., Anjali A. Gaikwad, Lata Mathew, Barbara Rech, Jonathan P. Faro, Joseph A. Lucci III, Yu Bai, Randall J. Olsen, and Teresa T. Byrd. “AHCC® supplementation to support immune function to clear persistent human papillomavirus infections.” Frontiers in oncology 12 (2022): 881902.

Click here to read the full text study.

Posted February 27, 2026.

References:

1. Smith JA, Gaikwad AA, Mathew L, Rech B, Faro JP, Lucci JA 3rd, Bai Y, Olsen RJ, Byrd TT. AHCC® Supplementation to Support Immune Function to Clear Persistent Human Papillomavirus Infections.FrontOncol.2022Jun22;12:881902. doi: 10.3389/fonc.2022.881902. PMID: 35814366; PMCID: PMC9256908.