A non-invasive metabolomic biomarker for detecting cervical intraepithelial neoplasia and cervical cancer.

Abstract

5532 Background: Cervical intraepithelial neoplasia (CIN) is a precancerous lesion that can progress to cervical cancer, a leading malignancy affecting women worldwide. Although current screening strategies and diligent follow-up are essential for identifying high-grade CIN, there remains a critical need for minimally invasive tests to aid in both early detection and disease monitoring. This study evaluated the utility of a blood-based metabolomic liquid biopsy for differentiating CIN from cervical cancer and investigated the role of 2,3,6-Trichlorobenzaldehyde as a novel biomarker. Methods: From September 2023 to December 2024, 177 participants (cervical cancer, n=18; CIN, n=49; healthy controls, n=110) were enrolled at Soonchunhyang University Hospital in Cheonan, South Korea. All participants were adults (≥18 years) with no cancer history in the previous five years and were not receiving anticancer therapy at the time of serum collection. Serum samples underwent untargeted metabolomic profiling via headspace gas chromatography–mass spectrometry (GC–MS). Relative metabolite abundances were compared among the groups, and pairwise t-tests ( p < 0.05) assessed statistical significance. Results: Six metabolites demonstrated strong detection and classification performance, with 2,3,6-Trichlorobenzaldehyde emerging as the most prominent biomarker. This metabolite effectively differentiated among cervical cancer, CIN, and healthy controls (ANOVA, p < 0.0001). Specifically, 2,3,6-Trichlorobenzaldehyde yielded a sensitivity of 94.5% and a specificity of 95% for detecting cervical cancer, and a sensitivity of 95.9% and a specificity of 95% for identifying CIN. It also significantly distinguished Stage I cervical cancer from CIN grades 1, 2, and 3, as well as from adenocarcinoma in situ (AIS) (t-test, p < 0.0001). Five additional metabolites—p-Xylene, 3,6,9,12-Tetraoxahexadecan-1-ol, Ethylbenzene, Indole, and Cyclohexanone—were significantly elevated in both the cervical cancer and CIN groups compared to healthy controls (t-test, p < 0.0001), although they did not differ substantially between the cancer and CIN groups (t-test, p > 0.05). Conclusions: These findings highlight 2,3,6-Trichlorobenzaldehyde as a promising candidate for a blood-based metabolomic panel aimed at distinguishing cervical cancer from CIN and healthy controls. A minimally invasive assay incorporating this biomarker may improve cervical disease screening, refine risk stratification, and support continuous disease surveillance. Further prospective validation in larger cohorts is warranted to establish its clinical applicability.