Abstract 5272: Development of a novel radiation-induced vaginal tissue injury model

Abstract Introduction: Vaginal stenosis (VS), characterized by thickening and shortening of the vaginal wall tissue, occurs in up to 80% of women receiving pelvic radiotherapy (PRT), the most common treatment for gynecologic cancers. Yet, a critical barrier to developing more effective therapies is a lack of clinically relevant models to dissect underlying mechanisms. Using the Food and Drug Administration gold-standard for vaginal irritation testing, we have developed a rabbit model of radiation-induced vaginal injury. Methods: Female New Zealand white rabbits were either left untreated or radiated at low dose (LD) (6 Gy) or high dose (HD) (20 Gy) by external beam radiation. After the final radiation fraction, vaginoscopies were conducted once per week for six weeks. Changes to vaginal tissue were scored using five clinical morphological parameters for VS: mucosal pallor, telangiectasia, fragility of the vaginal wall, ulceration, and adhesions/occlusion. Gross vaginal tissue was measured to determine changes in length and diameter. Histopathologic changes to vaginal tissue were determined under H&E and Masson’s trichrome. Results: Vaginoscopy of HD rabbits revealed a consistently higher degree of changes to the vaginal tissue. Compared to untreated rabbits, high-dose radiation induced vaginal wall thinning, smooth muscle tissue loss, replacement fibrosis, and increased interstitial fibrosis. HD-treated rabbits also demonstrated higher VS scores. While the inner perimeter of vaginas from high-dose rabbits decreased compared to untreated control rabbits, the difference was not statistically significant. Conclusion: Here, we present a radiation-induced vaginal injury model of VS. Given the current gaps in available animal models for basic and translational research in vaginal health, the proposed model addresses key anatomical and physiological parameters that parallel the human vagina. This innovative model will strengthen the translational-to-clinical pipeline by enhancing the rigor of therapeutic testing after radiotherapy. Citation Format: Julie Hakim, Dan Kennedy, Melissa Grunlan, Manuel Rausch, Ashley Hicks, Elizabeth Cosgriff-Hernandez. Development of a novel radiation-induced vaginal tissue injury model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5272.