HPV DNA negativity following AHCC or nonavalent vaccination or their combination in women with persistent HPV infection without HSIL

Persistent infection with high-risk human papillomavirus (HR-HPV) is a common clinical condition for which no validated systemic antiviral therapy is currently available, and in the absence of high-grade cervical lesions management is generally limited to surveillance. Active Hexose Correlated Compound (AHCC) is a standardized immunomodulatory extract that has shown potential to promote HPV clearance in controlled clinical studies. This multicenter retrospective cohort study evaluated outcomes observed in routine clinical practice among women with documented persistent HR-HPV infection lasting at least six months who had received AHCC supplementation alone, nonavalent HPV vaccination alone, or both. A total of 289 women were included: 114 had documented AHCC supplementation alone, 60 had documented nonavalent HPV vaccination alone, and 115 had documented concomitant AHCC supplementation and vaccination. In the AHCC-only group, HPV-DNA negativity increased from 51.8% (59/114) at the approximately 4-month assessment to 69.3% (79/114) at 6 months (exact McNemar test, p = 1.9 × 10^-6). At 6 months, HPV-DNA negativity was documented in 60.0% (36/60) of women in the vaccine-only group and in 94.8% (109/115) of women in the AHCC plus vaccine group. The overall comparison across the three exposure groups at 6 months was statistically significant (likelihood-ratio χ² test, p < 0.0001). Pairwise comparisons showed higher observed HPV-DNA negativity rates in the combination group than in either single-intervention group. Exploratory stratified analyses indicated that this overall pattern was maintained across cumulative age strata and in both smokers and non-smokers and was not readily explained, within the limits of the available retrospective covariates, by reproductive history, number of lifetime sexual partners, history of vaginosis/vaginitis, contraceptive use, or prior sexually transmitted diseases in the subgroups for which these data were available. Compliance was generally high, tolerability was acceptable, and adverse events were infrequent, mild, and self-limiting. Within the limitations inherent to a retrospective, non-randomized, center-dependent dataset, these findings identify a clinically relevant pattern of observed HPV-DNA negativity associated with AHCC use, particularly when combined with nonavalent HPV vaccination, and support prospective confirmation in adequately designed three-arm studies.