Detection of cervical intraepithelial neoplasia in vivo using confocal endomicroscopy

Abstract

A high resolution optical imaging device may offer a clinically useful adjunct to colposcopy for the diagnosis and assessment of cervical precancer. This study describes the clinical evaluation of a miniaturised confocal endomicroscope for the quantitative and qualitative assessment of cervical intraepithelial neoplasia (CIN) in vivo. A descriptive study (n = 25) was performed to assess the usability of confocal endomicroscopy to image the cervix. A prospective study (n = 15) then evaluated the diagnostic accuracy of the technique. Patients undergoing colposcopy for treatment of CIN1-CIN3 were examined using confocal endomicroscopy. A 5% solution of acetic acid was used to enhance the colposcopic features of the atypical region. Normal and abnormal regions of the cervix were then imaged following topical application of a fluorescent dye (acriflavine). Confocal images were analysed to develop a scoring system to grade different levels of CIN. Microscopic features were correlated with histology from biopsy. Confocal endomicroscopy enabled microscopic imaging of cellular and subcellular structures in vivo at colposcopy. Imaging at increasing depth showed morphological features including dermal papillae, endocervical glands and the squamo-columnar junction. CIN was characterised by an increase in nuclear density, size and cellular atypia. The sensitivity for detection of CIN was 97%. The specificity for predicting the grade of abnormality was 80% for normal-CIN1 and 93% for CIN2-CIN3. Confocal endomicroscopy is a sensitive imaging tool for detection and assessment of CIN. The technique enables in vivo imaging of cervical histology and the potential for 'see-and-treat' workflows.