Impact of fractional CO2 laser therapy on vaginal wall histology in breast cancer survivors

To investigate histological changes in the vaginal wall of breast cancer survivors (BCSs) with genitourinary syndrome of menopause (GSM) treated with five sessions of fractional CO₂ vaginal laser therapy, focusing on epithelial morphology and stromal extracellular matrix composition. In this prospective single-center study, 26 BCSs underwent five sessions of fractional CO₂ vaginal laser therapy. Vaginal punch biopsies were collected at baseline and four to six weeks after completing the final session. Mucosal morphology was classified (Type 1, 2, or 3) independently by two pathologists, blinded to baseline and follow-up status. Stromal elastin, total collagen, and collagen types I and III were quantified by digital image analysis of Verhoeff-Van Gieson, Masson's trichrome, and immunohistochemistry. Paired tests and the Stuart-Maxwell test evaluated changes over time. At baseline, 42.3% of participants were classified as Type 1, 19.2% as Type 2, and 38.5% as Type 3 mucosal morphology. Elastin index increased from 33.1% to 56.8% (p < 0.01), and collagen type III index from 44.5% to 58.4% (p = 0.03), while total collagen and collagen type I showed no significant change. No significant differences in epithelial microscopic features were observed (Stuart-Maxwell p = 0.16). Fractional vaginal CO₂ laser therapy was associated with selective stromal remodelling in BCSs - higher elastin and collagen type III indices, but without detectable improvement in epithelial morphology. Given the absence of a control group, the short follow-up, and limited epithelial morphometry due to section orientation, these findings should be interpreted as preliminary histological evidence of a stromal response rather than a confirmation of functional or regenerative benefit. Registry: ClinicalTrials.gov, TRN: (NCT06007027). Registration date: 1 August 2023.