Cervical cell lift: A novel triage method for the spatial mapping and grading of precancerous cervical lesions
EBioMedicine, vol. 82, pp. 104157
Abstract
BACKGROUND: Primary HPV screening, due to its low specificity, requires an additional liquid-based cytology (LBC) triage test. However, even with LBC triage there has been a near doubling in the number of patients referred for colposcopy in recent years, the majority having low-grade disease. METHODS: To counter this, a triage test that generates a spatial map of the cervical surface at a molecular level has been developed which removes the subjectivity associated with LBC by facilitating identification of lesions in their entirety. 50 patients attending colposcopy were recruited to participate in a pilot study to evaluate the test. For each patient, cells were lifted from the cervix onto a membrane (cervical cell lift, CCL) and immunostained with a biomarker of precancerous cells, generating molecular maps of the cervical surface. These maps were analysed to detect high-grade lesions, and the results compared to the final histological diagnosis. FINDINGS: We demonstrated that spatial molecular mapping of the cervix has a sensitivity of 90% (95% CI 69-98) (positive predictive value 81% (95% CI 60-92)) for the detection of high-grade disease, and that AI-based analysis could aid disease detection through automated flagging of biomarker-positive cells. INTERPRETATION: Spatial molecular mapping of the CCL improved the rate of detection of high-grade disease in comparison to LBC, suggesting that this method has the potential to decisively identify patients with clinically relevant disease that requires excisional treatment. FUNDING: CRUK Early Detection Project award, Jordan-Singer BSCCP award, Addenbrooke's Charitable Trust, UK-MRC, Janssen Pharmaceuticals/Advanced Sterilisation Products, and NWO.
Authors 9
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University of Cambridge · Cambridge University Hospitals NHS Foundation Trust
Affiliation as printed
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK; Department of Gynae-Oncology, Cambridge University Hospitals, Cambridge, CB2 0QQ, UK
Department of Gynae-Oncology, Cambridge University Hospitals, Cambridge, CB2 0QQ, UK
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK
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Affiliation as printed
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK
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Affiliation as printed
Leiden Institute of Advanced Computer Science (LIACS), Leiden University, Niels Bohrweg 1, 2333 CA Leiden, the Netherlands
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University of Cambridge · Cambridge University Hospitals NHS Foundation Trust
Affiliation as printed
Department of Gynae-Oncology, Cambridge University Hospitals, Cambridge, CB2 0QQ, UK
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Affiliation as printed
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK
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Affiliation as printed
Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Puddicombe Way, Cambridge, CB2 0AW, UK
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Affiliation as printed
Cancer Prevention Group, School of Cancer & Pharmaceutical Sciences, Faculty of Medicine and Life Sciences, King's College London, London, UK
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Affiliation as printed
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK
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John Doorbar corresponding
Affiliation as printed
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK. Electronic address: jd121@cam.ac.uk
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK
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