The study evaluated the clinical efficacy of the ZNF582 gene methylation test (ZNF582m) for the detection of cervical intraepithelial neoplasia grade 3 or higher (CIN3+) in women with high-risk HPV (HR-HPV) infection. The test was performed on samples from 168 women with different degrees of cervical lesions and normal findings. The results showed that ZNF582 methylation significantly distinguished between CIN2 and CIN3 (p < 0.001). The test had a high specificity of 88.4% (95% CI: 82.1–93.1%) in detecting CIN3+, which was significantly better than classical cytology (specificity 28.6%) and P16/Ki67 double staining (specificity 43.7%). The area under the curve (AUC) for the ZNF582m assay was high, confirming its accuracy. The ZNF582m test enables accurate identification of severe lesions while reducing the number of unnecessary colposcopies, which is especially important in resource-limited settings. ZNF582 methylation thus represents a promising biomarker for sorting HR-HPV positive women with suspected high-grade cervical lesions.