Diagnostic Performance of Serum VEGF and M-CSF in Cervical Cancer and, Their Association with Stage

BACKGROUND: Cervical cancer continues to be one of the most prevalent malignancies affecting women globally. Circulating biomarkers may provide added value by complementing HPV-based screening and enhancing risk stratification. The aim of this study was to investigate vascular endothelial growth factor (VEGF) and macrophage colony-stimulating factor (M-CSF) as candidate serum biomarkers for the diagnosis and disease monitoring of cervical cancer. METHODS: In a single-center case-control study, 45 women with cervical cancer and 45 healthy controls were enrolled. Clinical variables included FIGO 2018 stage, symptoms, smoking status, and HPV vaccination status. Serum VEGF and M-CSF levels were measured using ELISA. Group and stage differences were assessed, and diagnostic performance was evaluated using ROC analysis, Youden's index, and logistic regression. RESULTS: Both biomarkers were significantly elevated in cancer patients compared with controls (M-CSF: 1457 ± 582 vs. 504 ± 250 pg/mL; VEGF: 399.7 ± 136 vs. 106.7 ± 53.2 pg/mL; both p < 0.001). Concentrations increased with advancing stage (M-CSF: p = 0.0006; VEGF: p = 0.0073). Vaccinated patients exhibited lower VEGF levels (p = 0.047). Diagnostic performance was excellent (AUC: M-CSF, 0.95; VEGF, 0.97). At optimal cut-offs, VEGF achieved 95% sensitivity (95% CI: 83.1%-99.4%) and 93% specificity (95% CI: 81.3%-98.5%). The combined model (AUC: 0.974) outperformed M-CSF alone (p = 0.038). Multivariate analysis confirmed that both VEGF and M-CSF remained significant independent predictors after adjusting for age, smoking status, and HPV vaccination status. CONCLUSIONS: Serum VEGF and M-CSF demonstrate diagnostic utility and stage association in cervical cancer. Their combined use enhances discriminatory power. These findings support their potential as adjunct biomarkers; however, external validation and longitudinal studies are needed.