Optical Coherence Tomography Compared With Colposcopy for Assessment of Vaginal Epithelial Damage

Abstract

Objective Colposcopy has been used to detect epithelial damage with vaginal microbicides. In animal models, optical coherence tomography (OCT) provided increased sensitivity over colposcopy in detecting epithelial injury. This randomized double-blinded clinical study compared OCT to colposcopy for the evaluation of epithelial injury in women using placebo or nonoxynol-9. Methods Thirty women aged 18–45 were randomized to use hydroxyethyl cellulose placebo or nonoxynol-9 vaginal gel twice daily for 5.5 days. Imaging with colposcopy and OCT was performed prior to product use, after the last dose, and 1 week later. Colposcopy was graded using standard criteria. OCT images were scored for epithelial integrity based on a published scoring system and measured for epithelial thickness. Results Colposcopy findings and OCT scores and epithelial thicknesses were similar between treatment groups at baseline. After treatment, there were significant differences between the nonoxynol-9 (1.37) and control group (1.15) OCT scores (p<0.001, indicating epithelial injury, and there was epithelial thinning in the nonoxynol-9 group (237μm) compared to the control group (292μm) (p=0.008). There were no significant posttreatment colposcopic differences in epithelial disruption between treatment groups, with only increased erythema noted after nonoxynol-9 use (p=0.02). Conclusion OCT detected epithelial disruption and thinning not identified by colposcopy. Vaginal epithelial thickness, a measure previously available only through biopsy, decreased after nonoxynol-9 use, a finding that may contribute to increased susceptibility to HIV after frequent use. OCT shows promise for the noninvasive clinical assessment of vaginal epithelial damage. Clinical Trial Registration UMIN Clinical Trials Registry, www.umin.ac.jp/ctr/index.htm, R000006186.

Colposcopic imaging using visible-light optical coherence tomography

“…2 Thinning or loss of epithelial barrier is a risk factor for acquisition of human immunodeficiency virus (HIV). [3][4][5] In recent years, concern has been raised that a microbicide, nonoxynol-9 (N-9), which was developed for contraception and STI prevention, may disrupt vaginal epithelium upon frequent use and even increase HIV transmission. 6 Therefore, there is compelling demand for technologies to map vaginal epithelial morphology and provide measures of the FRT, which can be used for screening STI susceptible populations and evaluating vaginal products.…”

“…In addition, colposcopy itself only provides surface examination and cannot effectively measure the thinning of epithelial layers. 4,6 Previous investigators relied on colposcopy-directed biopsy to obtain a cross-sectional view of the vaginal wall. 7 Yet, biopsy is time-consuming and only can provide histology on a limited number of tissue sampling sites.…”

Automated segmentation algorithm for detection of changes in vaginal epithelial morphology using optical coherence tomography

“…Our group has recently demonstrated the use of OCT for assessing the effects of BZK and N9 on the integrity of epithelial tissue of cervicovaginal tract of macaques, sheep, and humans. 2,3,5 In all of these studies, we have demonstrated that monitoring and manual quantification of microbicide-induced changes in epithelial integrity could be used as a biomarker for the assessment of microbicide toxicity. In this study, an automatic segmentation algorithm was developed for the identification of the epithelium in OCT B-scans of the cervicovaginal tract.…”

“…2,3,5 OCT imaging of the cervicovaginal epithelium provides depth-resolved information on morphological features and thickness of the epithelial layer. Until now, microbicideinduced changes in the morphology and thickness of vaginal epithelium as detected by OCT imaging have been delineated manually, a time-intensive process that often requires postprocessing of OCT images.…”

“…[1][2][3][4][5] To attempt to fight the HIV epidemic, microbicides, vaginal products for prevention of acquisition of the infection, have been developed. However, some of these products have been toxic to the genital tract, and more specifically, the cervicovaginal tract, and have increased or failed to prevent transmission of HIV.…”