Elizabeth L. Bird-Lieberman, Kevin M. Brindle, Michael Sheaff, Peter Sasieni, Naveena Singh, Anita W. W. Lim, Sarah Lam Shang Leen, André A. Neves, Tony Hollingworth, Pierre Lao-Sirieix, Neves, André [0000-0003-2740-5166], Brindle, Kevin [0000-0003-3883-6287], Apollo - University of Cambridge Repository, Lim, Anita WW [0000-0002-4407-7451], and Sheaff, Michael [0000-0001-9189-0181]
Cervical screening in low-resource settings remains an unmet need. Lectins are naturally occurring sugar-binding glycoproteins whose binding patterns change as cancer develops. Lectins discriminate between dysplasia and normal tissue in several precancerous conditions. We explored whether lectins could be developed for cervical screening via visual inspection. Discovery work comprised lectin histochemistry using a panel of candidate lectins on fixed-human cervix tissue (high-grade cervical intraepithelial neoplasia (CIN3, n = 20) or normal (n = 20)), followed by validation in a separate cohort (30 normal, 25 CIN1, 25 CIN3). Lectin binding was assessed visually according to staining intensity. To validate findings macroscopically, near-infra red fluorescence imaging was conducted on freshly-resected cervix (1 normal, 7 CIN3), incubated with topically applied fluorescently-labelled lectin. Fluorescence signal was compared for biopsies and whole specimens according to regions of interest, identified by the overlay of histopathology grids. Lectin histochemistry identified two lectins&mdash, wheat germ agglutinin (WGA) and Helix pomatia agglutinin (HPA)&mdash, with significantly decreased binding to CIN3 versus normal in both discovery and validation cohorts. Findings at the macroscopic level confirmed weaker WGA binding (lower signal intensity) in CIN3 vs. normal for biopsies (p = 0.0308) and within whole specimens (p = 0.0312). Our findings confirm proof-of-principle and indicate that WGA could potentially be developed further as a probe for high-grade cervical disease.