Abstract

BackgroundThe introduction of high-risk human papillomavirus (hrHPV) testing as part of primary cervical screening is anticipated to improve sensitivity, but also the number of women who will screen positive. Reflex cytology is the preferred triage test in most settings but has limitations including moderate diagnostic accuracy, lack of automation, inter-observer variability and the need for clinician-collected sample. Novel, objective and cost-effective approaches are needed.MethodsIn this study, we assessed the potential use of an automated metabolomic robotic platform, employing the principle of laser-assisted Rapid Evaporative Ionisation Mass Spectrometry (LA-REIMS) in cervical cancer screening.FindingsIn a population of 130 women, LA-REIMS achieved 94% sensitivity and 83% specificity (AUC: 91.6%) in distinguishing women testing positive (n = 65) or negative (n = 65) for hrHPV. We performed further analysis according to disease severity with LA-REIMS achieving sensitivity and specificity of 91% and 73% respectively (AUC: 86.7%) in discriminating normal from high-grade pre-invasive disease.InterpretationThis automated high-throughput technology holds promise as a low-cost and rapid test for cervical cancer screening and triage. The use of platforms like LA-REIMS has the potential to further improve the accuracy and efficiency of the current national screening programme.FundingWork was funded by the MRC Imperial Confidence in Concept Scheme, Imperial College Healthcare Charity, British Society for Colposcopy and Cervical Pathology, National Research Development and Innovation Office of Hungary, Waters corporation and NIHR BRC.

Highlights

  • Cervical cancer is largely preventable through treatment of screen-detected cervical lesions

  • The results suggest that LA-Rapid Evaporative Ionisation Mass Spectrometry (REIMS) can rapidly discriminate high-risk human papillomavirus (hrHPV) positive from negative samples with good accuracy (94% sensitivity, 83% specificity) when compared to currently validated hrHPV tests

  • The two groups had similar mean age (36.6y for hrHPV positive vs 34.3y for hrHPV negative women) (P value=0.139, t-test), with the majority being Caucasian in both groups (86 vs 78%) (P value=0.077, Fisher’s exact test) and Patient Characteristics hrHPV+ (N = 65) hrHPV- (N = 65) P value

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Summary

Introduction

Cervical cancer is largely preventable through treatment of screen-detected cervical lesions. # Joint senior authors risk oncogenic HPV (hrHPV) infection is replacing cytology in primary screening programmes. This has been found to have superior performance to that of cytology in the detection of high-grade CIN with better sensitivity and negative predictive value and can provide 60À70% greater protection against cervical cancer in women over the age of 30 1-3. The introduction of high-risk human papillomavirus (hrHPV) testing as part of primary cervical screening is anticipated to improve sensitivity, and the number of women who will screen positive. Interpretation: This automated high-throughput technology holds promise as a low-cost and rapid test for cervical cancer screening and triage.

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