Abstract
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—wheat germ agglutinin (WGA) and Helix pomatia agglutinin (HPA)—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.
Highlights
Cervical cancer remains the most common female malignancy in many developing countries [1]where high-quality organised screening has not been possible [2]
Lectin staining was significantly less intense in 20 CIN3 slides compared with 20 slides of normal squamous epithelium tissue for three of the eight candidate lectins: Wheat germ agglutinin (WGA)
Lectin histochemistry was performed on 120 formalin fixed paraffin embedded (FFPE) cervical tissue samples
Summary
Cervical cancer remains the most common female malignancy in many developing countries [1]where high-quality organised screening has not been possible [2]. Cervical screening involves detecting and treating high-grade cervical intraepithelial neoplasia (CIN grade 2 or worse, CIN2+) to prevent cancer from developing. Due to financial constraints and limited infrastructure, many low resource countries favour cervical screening via visual inspection (with acetic acid (VIA) and/or Lugol’s iodine (VILI), topically applied to the cervix making high-grade disease visible) [3]. Visual inspection enables women to be seen and treated at the same visit but has much room for improvement due to its low specificity (14–98%) and variable sensitivity (41–98%) to detect CIN2+ [4,5]. Given the heavy and disproportionate burden of disease in developing countries, there is a need to identify a specific, reproducible and affordable imaging method that can be used for cervical screening in low-resource settings. There is a need for visualization methods to identify precursor lesions on the cervix
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