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PublishedJournal ArticleThis is the author accepted manuscript. The final version is available from Royal Society of Chemistry via the DOI in this record.© The Royal Society of Chemistry.This study evaluates the capability of Fourier transform infrared spectroscopy (FTIR-S) in the differentiation of molecular changes in vulval intraepithelial neoplasia (VIN) and lichen sclerosus (LS) found in association with vulval squamous cell carcinoma (SCC), compared with VIN and LS found in isolation. 48 sections of vulval epithelium with features of VIN (n = 24) or LS (n = 24) underwent FTIR-S micro-spectroscopic mapping. Spectra from each section were correlated with the pathological diagnoses and the presence of concurrent SCC. Spectral variance was explored using principal component analysis and a multivariate linear discriminant classification model was developed and validated with leave one sample out cross validation. The discriminant model was able to correctly identify FTIR-S spectra taken from samples of VIN and LS found in association with SCC from those found in isolation with a sensitivity of 82% and specificity of 93% for LS and sensitivity of 75% and specificity of 94% for VIN. The discriminant model was adjusted to maximise sensitivity whilst conceding specificity on a per patient basis and could differentiate LS associated with SCC with a sensitivity of 100% and specificity of 84% and VIN associated with SCC sensitivity of 100% and specificity 58%. In distinguishing VIN and LS found in association with SCC from that found in isolation FTIR-S offers a potential technique for the assessment of molecular changes in the vulva that predispose to the development of SCC. Further study is needed to assess the ability of FTIR-S to risk stratify patients with VIN or LS.We acknowledge the British Society for the Study of Vulval Disease and the Gloucestershire Hospitals NHS Foundation Trust Research and Innovation Forum for financial support. We thank Jo Motte and the team at the Gloucestershire Hospitals NHS Foundation Trust histopathology department for the preparation of the tissue sections. The study was supported by the NIHR Exeter Clinical Research Facility. The interpretations of data in the paper are those of the authors and not of NIHR or the Department of Health

analytical methods

Identification of cancer associated molecular changes in histologically benign vulval disease found in association with vulval squamous cell carcinoma using Fourier transform infrared spectroscopy