The same team undertook a preliminary clinical study of 10 women, persistently infected with high-risk HPV, that was encouraging enough to lead to a larger clinical trial. Smith is now undertaking a NIH-funded, double-blinded, placebo-controlled study of 50 women with persistent high-risk HPV infection with results expected to be published by 2021. There are limited effective treatment options for clearing HR-HPV infections; majority being local treatment modalities is to alleviate symptoms and remove symptomatic lesions that often reoccur. Fortunately, most HR-HPV infections are cleared within 6–18 months on their own without interventions; only ~10% of women will suffer from persistent HR-HPV infections ( 15, 24). To date, there is no readily available effective systemic interventions to clear HR-HPV infections. Currently prevention of HR-HPV infections with the HPV vaccine nine-valent product before exposure to HPV has demonstrated the best potential for eliminating HR-HPV infections. However, these vaccines have little benefit in those already infected with HR-HPV infections. Results: HR -HPV clearance was observed in vitro and confirmed in the animal studies as a durable response. Four of six (66.7%) patients had confirmed HR-HPV clearance after 3–6 months of AHCC 3g. Similarly, 4 of 9 (44%) patients had confirmed HR-HPV clearance after 7 months of AHCC 1g. Suppression of IFNβ<25 pg/mL was observed in those clearing the HR-HPV infection. Patients of childbearing age must agree to use effective methods of contraception (oral contraceptives, condoms, etc.) while on study.

A huge amount of research has been done on alpha/beta-glucans from medicinal mushrooms over the last decade showing increased performance when specific mushrooms and alpha/beta-glucans are used together.Two pilot studies recently were conducted on women who had documented persistent HPV positive for greater than 2 years, were otherwise healthy, and met the remaining eligibility criteria ( 15). Ten women were enrolled in the first study to evaluate the effectiveness of AHCC supplementation of 3 g by mouth once daily to support the host immune system to eliminate persistent high-risk HPV infections. The regimen was repeated monthly until the patient tests HPV negative or until 6 months of active treatment has elapsed. Patients who test positive after 6 months of treatment were considered a treatment failure. HPV testing and immune marker panel screening were completed once a month to monitor for clearance of high-risk HPV persistent infections. There was an encouraging response in 4 of 8 (50%) patients with confirmed HR-HPV DNA eradication after at least 3 months and up to 6 months of daily 3-g AHCC supplementation ( 15). In the second pilot study with 1-g AHCC supplementation once daily, a similar response was observed in 4 of 9 (44%) patients with confirmed clearance of high-risk HPV persistent infections after 7 months of supplementation ( 15). These results from two pilot studies confirm the previous preclinical findings that AHCC supplementation has the potential to be effective to support the host immune system to clear persistent high-risk HPV infections and supported the rationale to continue forward with a formal phase II evaluation to confirm these preliminary findings ( 16). Materials and Methods Study Design The human immune system begins to weaken at about 25 years of age, which perhaps could be the contributing factor to why persistent HPV infections are most often observed in women over the age of 30 or with other immunosuppressive conditions. Patients must agree to return to clinic for follow-up visits (including repeat HPV testing) and complete medication administration calendar. All patients enrolled were included in safety analysis for adverse events. Overall, no study patients reported greater than grade 1 toxicity on either placebo or the AHCC supplement arm. AHCC was well tolerated compared to placebo. In the absence of an available vaccine against coronavirus, there is broad interest in alternative approaches to immune system maintenance.

A) AHCC 3g supplementation (B) AHCC 1g supplementation. IFN-β is a Type-1 IFN often associated with virulence of chronic viral infections. Chronic viral infections are often associated with high levels of IFN-β that leads to suppression of the production of IFN-γ and NK/T-cell cytotoxic cell immunity. It was observed in both pilot studies AHCC supplementation suppression of host IFN-β levels below level of 25 pg/mL that lead to modulation of the cytotoxic cell immunity to a successful, durable clearance of persistent, high risk HR-HPV infections. JS served as principal investigator of the clinical trial and was responsible for study concept, protocol design, data analysis, clinical interpretation of data, writing, and finalization of the manuscript. AG, LM, and BR served as the primary research team responsible for patient screening, clinic visits, sample collection, and analysis and participated in the writing and review of the manuscript. JF served as a clinical collaborator on this study and participated in protocol design, clinical interpretation of data, and final review of the manuscript. JL served as a clinical collaborator on this study and participated in the clinical interpretation of the data and final review of the manuscript. YB served as a research collaborator participating in the interpretation of the sample of analysis, protocol design, and review of the final manuscript. RO served as a research collaborator participating in the interpretation of the sample of analysis and implications for future monitoring assays. He participated in the review and finalization of the manuscript. TB served as a clinical collaborator on this study and participated in protocol design, clinical interpretation of data, and final review of the manuscript. All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication. FundingAHCC is able to modulate and improve the non-specific immune functions in our body to a range of risk factors,” says Homma. Objective: There is currently no effective medicine or supplement for clearance of high risk- human papillomavirus (HR-HPV) infections. We have taken a systematic approach evaluating the potential use of AHCC supplementation to support clearance of HR-HPV infections. The primary objective of this research was to evaluate AHCC supplementation to modulation of the host immune system to clear HR-HPV infections from bench to bedside.