Abstract: Objective To evaluate the detection of BHLHE22/CDO1 and COL2A1 gene methylation in cervical scrapings for early screening of endometrial cancer. Methods A total of 78 patients who required diagnostic curettage under hysteroscopy to exclude endometrial lesions in Xuzhou Maternal and Child Health Hospital from February 2022 to May 2024 were selected. Cervical scraping cells were collected during gynecological examination. Methylation detection of BHLHE22/CDO1 and COL2A1 genes was performed. Meanwhile, their basic clinical data and endometrial blood flow indices such as flow index (FI), vascularization index (VI), and vascularization-flow index (VFI) under three-dimensional energy Doppler ultrasound were collected. The histopathological results obtained through hysteroscopy surgery were used as the gold standard. The influencing factors of endometrial cancer were analyzed by univariate logistic regression model. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the application of methylation detection of relevant genes alone and in combination of endometrial blood flow indices for early screening of endometrial cancer. Results Patient age, body mass index, VI, FI, VFI, and high-risk methylation of BHLHE22/CDO1 and COL2A1 were significant influencing factors for endometrial cancer (P<0.05). The AUC for endometrial cancer screening through gene methylation detection in cervical scrapings was 0.926 (0.846-1.000), with a sensitivity of 90.48% and a specificity of 94.74%. The combined detection of endometrial blood flow index VFI and gene methylation detection in cervical scrapings increased sensitivity to 100%, but the specificity decreased to 68.42%. Conclusions The accuracy of BHLHE22/CDO1 and COL2A1 gene methylation detection in cervical scrapings for screening endometrial cancer is relatively high. Its combination with endometrial blood flow indices can improve screening sensitivity, but lowers specificity and increases the risk of invasive procedures.