Phase II Evaluation of AHCC for the Eradication of HPV Infections

This is a phase II randomized, double-blind placebo-controlled, crossover trial. The primary
outcome of this trial is achieving durable eradication HPV infection determined by HPV
negative test results achieved while on active treatment with AHCC and maintained for 6 month
post supplementation and 12 months post completion of AHCC treatment for Group 1. We will
follow all patients for at least 12 months and up to 30 months depending on success of
achieving a negative HPV testing results. After receiving AHCC 3 grams x 6 months if positive
at the end of 12 months of study treatment, they are considered a treatment failure. If
negative after completion of 6 months of AHCC supplementation + 6 months of placebo, they
will continue on study for another six months (2 visits) to confirm they remain HPV negative
and durable response. Group 2 will serve as untreated control for all time points (end of
supplementation, then 6, 9, and 12 months post end of AHCC supplementation.

Inclusion Criteria:

- • Women over 30 years of age who have a HPV positive test and normal/negative
cytology, atypical cells, ASCUS, or CIN1 or CIN2 cervical dysplasia within three
months of study entry.

- Women must have had 2 other HPV positive tests with normal/negative cytology,
atypical cells, ASCUS, or CIN1 or CIN2 cervical dysplasia

- 1 greater than 6 months and no more than 18 months prior to study entry

- 1 greater than 24 months prior to study entry.

- Women of child bearing potential must have a negative urine pregnancy test within
7 days of therapy start.

- Patients must have adequate hematologic, renal, and hepatic function as noted
from labs within the previous 12 months: ANC >/= 1,500 cells/mm3, platelets
100,000 >/= cells/mm3; Creatinine clearance>/= 60 mL/min (estimated by Cockcroft
Gault equation), total bilirubin, SGPT, SGOT, and alkaline phosphatase times normal.

- Patients of child-bearing age must agree to use effective methods of
contraception (oral contraceptives, condoms, etc.) while on study.

Exclusion Criteria:

- • History of myocardial infarction within past 6 months, unstable angina, CHF, or
uncontrolled hypertension (> 140/90).

- Women with a current or prior diagnosis of cancer

- Women with a current diagnosis of CIN3 cervical dysplasia

- Women that are pregnant or breast feeding.

- Women with a history of Hepatitis (autoimmune, A, B, or C) or antigen positive

- Patients with history of significant psychiatric disorders (schizophrenia,
bipolar, psychosis) or uncontrolled seizures.

- Patients with significant medical co-morbidities at the discretion of the primary
Gynecologist. Including immunosuppressive conditions (i.e. HIV+, rheumatoid
arthritis, etc) or taking immune modulation mediations (i.e. immunosuppressants)

- Women that have taken AHCC within the past six months.

- Women currently taking other immune modulating nutritional supplements.

- Patients who have undergone a hysterectomy (supracervical hysterectomy allowed)