MSACL 2025 Abstract

Enhancing the Early Detection, Diagnosis and Treatment of Cervical Disease Through Laser Desorption-Rapid Evaporative Ionization Mass Spectrometry (LD-REIMS)

Maria Paraskevaidi (1), Stefania Maneta-Stavrakaki (1), Apostolia Galani (1,2), Yuchen Xiang (1), Daniel Simon (1), Jinshi Zhao (1), Burak Temelkuran (1), Robert Murray (3), Yu Wang (3), Deirdre Lyons (2), Maria Kyrgiou (1,2), Zoltan Takats (1)
(1) Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, W12 0NN, UK, (2) West London Gynaecological Cancer Center, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, W12 0HS, UK, (3) Department of Physics, Faculty of Natural Sciences, Imperial College London, SW7 2AZ, UK

Maria Paraskevaidi, PhD (Presenter) Imperial College London

Presenter Bio: Research Fellow at Imperial College London. My work involves the use of ambient mass spectrometry techniques (REIMS, DESI) to improve the diagnosis and management of gynaecological cancers, such as cervical, endometrial and ovarian.

Relevant Financial Disclosures (within past 24 months, reported on Apr 16, 2026) No relevant financial relationship(s) to disclose.

INTRODUCTION:
Cervical cancer is caused by persistent infection with high-risk subtypes of human papillomavirus (hrHPV), which is sexually transmitted. Considering the widespread prevalence of HPV, cytology is employed as a secondary, reflex test to identify any abnormal cells and identify women who should be further referred to colposcopy. However, cytological assessment exhibits only moderate diagnostic performance, is susceptible to human error, and lacks efficacy in self-collected samples(1). Given the abundant occurrence of non-carcinogenic passenger HPV infections and the variable performance of existing triage tests, there is a pressing need for innovative technologies capable of providing rapid and simultaneous HPV testing, along with automated triaging for women at high risk of high-grade precancer and cancer.

Moreover, women referred to colposcopy often undergo multiple punch biopsies for a definitive diagnosis before local excision of precancer is performed at a subsequent visit. 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).

To address these challenges, novel technologies are essential to enable bedside diagnosis in one-stop clinics, minimising the likelihood of non-compliance, repeat visits, and unnecessary treatment. Preliminary data from ambient ionisation metabolomics-based technologies, such as Laser Desorption Rapid Evaporative Ionisation Mass Spectrometry (LD-REIMS), suggests their capability to detect hrHPV infection or abnormal cytology in cell pellets(3) and identify cervical cancer and precancer in tissue samples.

METHODS:
Liquid-based cytology (LBC) and tissue specimens were gathered from women visiting the colposcopy/gynaecology clinics at Imperial College NHS Healthcare Trust due to suspected cervical disease. Following LD-REIMS analysis, we measured diagnostic accuracy parameters to examine the technology's ability to differentiate between women with or without an hrHPV infection and identify high-grade precancer using cell pellets. Additionally, we evaluated whether LD-REIMS could detect precancerous alterations in tissue samples.

RESULTS:
LD-REIMS in the cell pellets (n=657) achieved 97% sensitivity and 94% specificity (AUC: 98%) after comparing women with and without hrHPV infections using a validated hrHPV assay as the gold standard. The technique also discriminated high-grade precancer and cancer from normal cases with 99% sensitivity and 98% specificity (AUC: 99%). In the HPV+ cohort alone, normal cases were discriminated from women with high-grade precancer and cancer with 99% sensitivity and 98% specificity. In a pilot study using tissue biopsies taken during colposcopy, the technology discriminated between normal, low-grade precancer (CIN1) and high-grade precancerous and cancerous (CIN2+) cases.

CONCLUSION:
In a substantial case-control study with over 600 participants, it was shown that LD-REIMS holds promise as a single, automated test that could significantly improve disease prevention. Implementing this technology in colposcopy clinics has the potential to advance cervical disease diagnostics and refine precision treatment. Current efforts are directed towards incorporating the REIMS technology with a colposcope for real-time, in vivo applications during outpatient colposcopy examinations.


REFERENCES:
1 Cuzick, J. et al. Overview of the European and North American studies on HPV testing in primary cervical cancer screening. Int J Cancer 119, 1095-1101 (2006).
2 Arbyn, M. et al. Incomplete excision of cervical precancer as a predictor of treatment failure: a systematic review and meta-analysis. Lancet Oncol 18, 1665-1679 (2017).
3 Paraskevaidi, M. et al. Laser-assisted rapid evaporative ionisation mass spectrometry (LA-REIMS) as a metabolomics platform in cervical cancer screening. EBioMedicine 60, 103017 (2020).