Abstract: Abstract： Objective To explore the clinical diagnostic value of quantitative detection of the slit homologue 2 (SLIT2） methylation for cervical high grade precancerous lesions. Methods According to histopathologic diagnostic results, 178 patients infected with high-risk HPV were divided into normal cervix group (n=45), low-grade lesion group (n=50) and high- grade lesion group (n=83). The cervical exfoliated cells were collected in three groups. The methylation levels of SLIT2 were measured by pyrosequencing in three groups. The diagnostic threshold of SLIT2 in high grade precancerous lesions was estimated by receiver operating characteristic (ROC) curve. Results The percentages of SLIT2 methylation were (4.53± 1.37)%, (5.81±2.26)% and (11.80±8.47)% in normal cervix group, low-grade lesion group and high-grade lesion group, respectively. And the differences between three groups were statistically significant (F=27.61, P<0.001). The percentage of SLIT2 methylation was significantly higher in high-grade lesion group than that of normal cervix group and low-grade lesion group (P<0.001). There was no significant difference in the percentage of SLIT2 methylation between normal cervix group and low-grade lesion group (P=0.297). The area under the ROC curve was 0.895 and optimal cut-off value was 6.41%. The sensitivity and specificity were 80.7% and 83.2%, respectively for the detection by SLIT2 methylation. Conclusion The quantitative detection of SLIT2 gene methylation level in cervical exfoliated cells by pyrosequencing can effectively diagnose cervical high grade precancerous lesions.

Key words: uterine cervical neoplasms, precancerous conditions, DNA methylation, alphapapillomavirus, cevical precancerous lesions, slit homologue 2