MSACL 2023 Abstract

Introduction
Given the high prevalence of human papillomavirus (HPV), reflex cytology is used in high-risk HPV (hrHPV) positive women to select those that need to be referred to colposcopy. However, reflex cytology only performs moderately, is prone to human error and unlikely to be of value in self-collected samples(1). Given the high prevalence of passenger HPV infections with no carcinogenic potential and the mediocre performance of existing triage tests, novel technologies that offer rapid and simultaneous HPV testing, as well as automated triaging of women at high risk of high-grade precancer, are highly sought after.

Screen-positive women referred to colposcopy often require multiple punch biopsies for diagnosis prior to local excision of precancer at a separate visit, as the diagnostic accuracy is poor. Excision of precancer with clear margins is important as the risk of high-grade recurrence drops to 3.7% as opposed to 17.1% in the case of positive margins(2).

Innovative technologies are needed to offer bedside diagnosis at one-stop clinics minimising the risk of non-compliance, repeat visits and over-treatment. Preliminary data generated by using metabolomics-based technologies, such as the Rapid Evaporative Ionisation Mass Spectrometry (REIMS), suggests that the technology can detect the presence of hrHPV infection or abnormal cytology in cell pellets(3) and detect cervical cancer and precancer in tissue samples(4).

Methods
Liquid-based cytology and tissue samples were collected from women attending the colposcopy/gynaecology clinics at Imperial College NHS Healthcare Trust. After REIMS analysis, the diagnostic accuracy parameters were measured to investigate whether the technology could discriminate between women with or without a hrHPV infection and detect the presence of high-grade precancer using cell pellets. We further assessed whether REIMS could detect precancerous changes in tissue.

Results
REIMS in the cell pellets achieved 94% sensitivity and 83% specificity (AUC: 91.6%) after comparing women with and without hrHPV infections (n=130) using a validated hrHPV assay as the gold standard(3). The technique also discriminated high-grade precancer and cancer from normal with 91% sensitivity and 73% specificity (AUC: 86.7%). We have also tested the technology’s feasibility in tissue biopsies taken during colposcopy, showing good discrimination between normal and cervical precancer.

Conclusion
REIMS has the potential to offer a single, automated highly-accurate screening and triage test that will enhance disease prevention at a reduced cost for the health services. The expansion of laser-REIMS in colposcopy could further enhance diagnostics and ‘precision’ treatment. Ongoing work using the same laser-REIMS technology aims to validate our preliminary results in a larger cohort (n=700 women) and integrate REIMS with a colposcope for bedside in vivo applications during the colposcopy clinics.


References
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