Toward ovarian cancer screening with protein biomarkers using dried, self-sampled cervico-vaginal fluid

Julia Hedlund Lindberg; Anna Widgren; Emma Ivansson; Inger Gustavsson; Karin Stålberg; Ulf Gyllensten; Karin Sundfeldt; Jonas Bergquist; Stefan Enroth

doi:10.1016/j.isci.2024.109001

Toward ovarian cancer screening with protein biomarkers using dried, self-sampled cervico-vaginal fluid

iScience. 2024 Jan 24;27(2):109001. doi: 10.1016/j.isci.2024.109001. eCollection 2024 Feb 16.

Authors

Julia Hedlund Lindberg¹, Anna Widgren², Emma Ivansson¹, Inger Gustavsson¹, Karin Stålberg³, Ulf Gyllensten¹, Karin Sundfeldt⁴, Jonas Bergquist², Stefan Enroth^{1

5}

Affiliations

¹ Department of Immunology, Genetics, and Pathology, Biomedical Center, SciLifeLab Uppsala, Uppsala University, SE-75108 Uppsala, Sweden.
² Analytical Chemistry, Department of Chemistry-Biomedical Center, Uppsala University, SE-75237 Uppsala, Sweden.
³ Department of Women's and Children's Health, Uppsala University, SE-75185 Uppsala, Sweden.
⁴ Department of Obstetrics and Gynaecology, Institute of Clinical Sciences, Sahlgrenska Academy at Gothenburg University, SE-41685 Gothenburg, Sweden.
⁵ Swedish Collegium for Advanced Study, Thunbergsvägen 2, SE-752 38 Uppsala, Sweden.

Abstract

Early detection is key for increased survival in ovarian cancer, but no general screening program exists today due to lack of biomarkers and overall cost versus benefit over traditional clinical methods. Here, we used dried cervico-vaginal fluid (CVF) as sampling matrix coupled with mass spectrometry for detection of protein biomarkers. We find that self-collected CVF on paper cards yields robust results and is suitable for high-throughput proteomics. Artificial intelligence-based methods were used to identify an 11-protein panel that separates cases from controls. In validation data, the panel achieved a sensitivity of 0.97 (95% CI 0.91-1.00) at a specificity of 0.67 (0.40-0.87). Analyses of samples collected prior to development of symptoms indicate that the panel is informative also of future risk of disease. Dried CVF is used in cervical cancer screening, and our results opens the possibility for a screening program also for ovarian cancer, based on self-collected CVF samples.

Keywords: Body substance sample; Cancer; Fluid; Proteomics; Women’s health.