Efficacy of Lentinula Edodes-Derived Supplement (AHCC®) in Promoting Negativity of Persistent HPV Infection

Evaluation of the Efficacy and Safety of an AHCC®-Based Supplement (Lentinula Edodes) in Promoting Negativity of Persistent HPV Infection: A Retrospective Multicenter Clinical Study

This is a retrospective, multicenter, observational study evaluating real-world HPV-DNA clearance in women with documented persistent high-risk HPV infection lasting at least six months. Clinical data were retrospectively collected from medical records of women managed in routine practice with one of three strategies: AHCC® supplementation alone, nonavalent HPV vaccination alone, or the combination of AHCC® supplementation and nonavalent HPV vaccination. The primary objective is to assess HPV-DNA clearance at 4 and 6 months following treatment initiation.

Study Overview

• Status: Completed
• Conditions: HPV Infection
• Intervention / Treatment: Dietary supplement: AHCC® (Active Hexose Correlated Compound); Biological: Gardasil 9®

Detailed Description

This retrospective, multicenter, observational study evaluates HPV-DNA clearance in women with documented persistent high-risk HPV infection managed in routine clinical practice. Eligible participants had confirmed HPV-DNA positivity persisting for at least six months and no high-grade cervical lesions.

Clinical data were retrospectively collected from medical records from January 2023 to December 2024. Participants were categorized into three exposure groups based on treatments already received as part of standard care: AHCC® supplementation alone, nonavalent HPV vaccination alone, or combined AHCC® supplementation and nonavalent HPV vaccination. No randomization or prospective treatment assignment was performed.

The primary outcome is HPV-DNA clearance, defined as conversion from HPV-DNA positive to negative status, assessed at 4 and 6 months after treatment initiation. Secondary outcomes include safety, tolerability, and treatment compliance based on routinely collected clinical data. This study reflects real-world clinical practice and was not designed as a randomized interventional trial.

• Study Type: Observational
• Enrollment (Actual): 289

Contacts and Locations

Study Locations

• Italy
  • Varese, Italy
    • University of Insubria

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Women with documented persistent high-risk HPV infection for at least six months whose clinical data were retrospectively identified from medical records at multiple participating gynecology centers.

Description

Inclusion Criteria:

• Female participants aged 18 years or older.
• Documented persistent high-risk HPV infection for at least 6 continuous months, confirmed by consecutive HPV-DNA tests.
• Absence of high-grade cervical lesions (≤ CIN1).
• Availability of complete clinical records with evaluable HPV-DNA testing at baseline and follow-up.
• Documented management with AHCC® supplementation alone, nonavalent HPV vaccination alone, or combined AHCC® supplementation and nonavalent HPV vaccination in routine clinical practice.
• No prior excisional or ablative treatment of the cervix (including conization or LEEP).

Exclusion Criteria:

• History of cervical excisional or ablative treatment (including conization or LEEP).
• Presence of high-grade cervical lesions (CIN2 or worse) or invasive cervical cancer.
• Incomplete clinical documentation or missing HPV follow-up data.
• Conditions known to significantly alter immune function, including ongoing immunosuppressive therapy, active autoimmune disease requiring systemic treatment, or documented immunodeficiency, when such information was available in medical records.
• Prior systemic antiviral or immunomodulatory therapy specifically aimed at HPV clearance during the observation period.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Unvaccinated with AHCC® Supplement; Women previously managed in routine clinical practice with AHCC® supplementation alone for persistent HPV infection. Participants had not received HPV vaccination prior to treatment. Clinical data were retrospectively collected from medical records to evaluate HPV-DNA clearance following this real-world management strategy.	Dietary supplement: AHCC® (Active Hexose Correlated Compound); AHCC® supplementation previously prescribed as part of routine clinical care. Information on dosage and duration was retrospectively collected from medical records.; Other Names: Lentinula edodes supplement, Papion®
Vaccinated with AHCC® Supplement; Women previously managed in routine clinical practice with combined AHCC® supplementation and nonavalent HPV vaccination for persistent HPV infection. Treatments were prescribed as part of standard care. Clinical data were retrospectively collected to assess HPV-DNA clearance following combined real-world exposure.	Dietary supplement: AHCC® (Active Hexose Correlated Compound); AHCC® supplementation previously prescribed as part of routine clinical care. Information on dosage and duration was retrospectively collected from medical records.; Other Names: Lentinula edodes supplement, Papion®; Biological: Gardasil 9®; Nonavalent HPV vaccination previously administered as part of routine clinical care. Vaccination status was retrospectively obtained from medical records.
Vaccinated Only; Women previously managed in routine clinical practice with nonavalent HPV vaccination alone for persistent HPV infection. No AHCC® supplementation was used. Clinical data were retrospectively collected to assess HPV-DNA clearance following vaccination as standard care.	Biological: Gardasil 9®; Nonavalent HPV vaccination previously administered as part of routine clinical care. Vaccination status was retrospectively obtained from medical records.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HPV-DNA Clearance Rate	Proportion of participants achieving HPV-DNA negativity, defined as conversion from HPV-DNA positive to negative status based on clinically validated HPV-DNA testing.	4 months and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability	Description of adverse events, tolerability, and treatment compliance based on retrospective review of routinely collected clinical records. Adverse events were classified according to CTCAE version 5.0 and analyzed descriptively.	4 months and 6 months

Collaborators and Investigators

• Sponsor: Liaquat University of Medical & Health Sciences
• Collaborators: Università degli Studi dell'Insubria

Publications and helpful links

General Publications

• Gau VL, Benninger MS. Potential Role for Active Hexose Correlated Compound (AHCC) in Treatment of Recurrent Respiratory Papillomatosis. J Voice. 2022 Jul;36(4):441-442. doi: 10.1016/j.jvoice.2022.05.004. Epub 2022 Jun 27. No abstract available.
• Smith JA, Mathew L, Gaikwad A, Rech B, Burney MN, Faro JP, Lucci JA 3rd, Bai Y, Olsen RJ, Byrd TT. From Bench to Bedside: Evaluation of AHCC Supplementation to Modulate the Host Immunity to Clear High-Risk Human Papillomavirus Infections. Front Oncol. 2019 Mar 20;9:173. doi: 10.3389/fonc.2019.00173. eCollection 2019.
• Smith JA, Gaikwad AA, Mathew L, Rech B, Faro JP, Lucci JA 3rd, Bai Y, Olsen RJ, Byrd TT. AHCC(R) Supplementation to Support Immune Function to Clear Persistent Human Papillomavirus Infections. Front Oncol. 2022 Jun 22;12:881902. doi: 10.3389/fonc.2022.881902. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2023
• Primary Completion (Actual): June 30, 2024
• Study Completion (Actual): December 15, 2024

Study Registration Dates

• First Submitted: December 20, 2024
• First Submitted That Met QC Criteria: December 27, 2024
• First Posted (Actual): December 30, 2024

Study Record Updates

• Last Update Posted (Actual): January 28, 2026
• Last Update Submitted That Met QC Criteria: January 26, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pathologic Processes; Disease Attributes; Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; DNA Virus Infections; Tumor Virus Infections; Pathological Conditions, Signs and Symptoms; Papillomavirus Infections; Human Papillomavirus Recombinant Vaccine nonavalent; Active Hexose Correlated Compound
• Other Study ID Numbers: 117_22.112024_Papion®

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No