Clinical and Virologic Outcomes of Topical Imiquimod in Vaginal Intraepithelial Neoplasia: A Retrospective Cohort Study

Purpose: To describe clinical and virologic outcomes after topical 5% imiquimod for VaIN (vaginal intraepithelial neoplasia) within routine clinical practice, including the assessment of available post-treatment high-risk HPV status, and to evaluate its relationship with treatment outcomes. Methods: In this retrospective-cohort study, twenty patients with histologically confirmed VaIN (low-grade VaIN = 10, high-grade VaIN = 10) were evaluated between October 2020 and October 2022. The treatment varied based on the initial VaIN grade. The primary endpoint was complete response, defined as negative cytology and/or benign follow-up biopsy. Secondary endpoints included partial response (downgrading from high-grade to low-grade), persistence/progression, adverse events, and available post-treatment high-risk HPV status. Results: Among seventeen evaluable patients, a complete response was observed in 69.2% (9/13) imiquimod-treated patients. In high-grade VaIN imiquimod-treated patients, complete response was observed in 66.7% (6/9), while 33.3% (3/9) downgraded to low-grade VaIN on biopsy as a secondary outcome, with no persistence over a median follow-up of 24 months. Low-grade VaIN showed 75% clearance with either imiquimod or observation at a median follow-up of 24 months. In one low-grade imiquimod-treated, persistent HPV16 was observed, and the lesion progressed to high-grade VaIN; however, no invasive cancers were observed during follow-up. Adverse events related to imiquimod were mild; there were no discontinuations. Among baseline high-risk HPV positive imiquimod-treated patients, post-treatment follow-up HPV testing was available in a limited subset group, and clearance was confirmed in 44% (4/9) among those with follow-up testing and presented descriptively as exploratory. Conclusions: In this single-center retrospective cohort, outcomes after topical 5% imiquimod are reported as observed findings. Complete and partial responses were observed in high-grade VaIN with acceptable tolerability and no invasive events at available intermediate follow-up (median 24 months). Post-treatment HPV testing provided complementary virologic information alongside clinical outcomes, consistent with recommendations incorporating HPV testing into VaIN follow-up, and longer surveillance is required to assess long-term oncologic outcomes.