Methyl aminolevulinate-PpIX mediated fluorescence-guided mapping of high-grade vulvar intraepithelial neoplasia: a pilot prospective clinical trial (PhotoDiVin)

BACKGROUND: The worldwide prevalence of vulvar intraepithelial neoplasia is increasing and is characterized by the high risk of recurrence and evolution towards vulvar cancer. Positive margins following surgical excision are the most important criteria of recurrence risk. We conducted a pilot clinical study to assess the fluorescence-based cartography of VIN lesions using methyl aminolevulinate (m-ALA), which is a prodrug of the fluorophore protoporphyrin IX (PpIX). A prospective, single-center, single-arm clinical trial included 17 women with histologically confirmed high-grade vulvar intraepithelial neoplasia (dVIN or vHSIL). Following topical methyl aminolevulinate application, fluorescence-guided examination under 405-nm light was performed. Targeted biopsies from fluorescent and non-fluorescent areas were compared with histopathology to assess concordance and the ability of fluorescence to accurately identify high-grade lesions. Among 34 biopsies, histopathological findings were concordant with fluorescence in 91% of cases. The procedure correctly identified intraepithelial neoplasia areas in 14 patients, yielding a success rate of 82% (95%CI 56-96%). Sensitivity and specificity were 93% (95%CI 68-100%) and 89% (95%CI 67-99%), respectively. The tolerance of the procedure was excellent with no pain and no side effects neither after cream application nor after illumination. This pilot study suggests that fluorescence imaging is a workable technique to mark VIN lesions with m-ALA cream. Further studies are needed to improve the reproducibility and ease of use of this method.