Objective:To investigate the molecular alterations and potential biomarkers associated with the progression of cervical cancer due to persistent human papillomavirus(HPV)infection.Methods:Gene expression and methylation profiles were analyzed from normal HPV positive cervical epithelium,high-grade precancerous lesions(CIN),and squamous cell carcinoma(SCC)were obtained from the GSE138080 and GSE99511 datasets,respectively.Differentially expressed genes and differentially methylated probes were identified between CIN and HPV positive,as well as SCC and CIN samples.Co-expression analysis on differentially expressed genes was performed,modules significantly associated with disease progression were screened,and enrichment analysis was performed.Genes within these modules potentially subject to methylation were further analyzed,and receiver operating characteristic(ROC)curves were generated.From November 2022 to September 2023,30 cervical tissue samples were collected from our hospital,including 10 HPV positive cervical epithelium samples,10 CIN3 samples,and 10 SCC tissue samples.Real time-quantitative PCR(RT-qPCR)was used to detect gene expression.Results:A total of 1 832 genes were differentially expressed between CIN and HPV positive,as well as between SCC and CIN simultaneously.Enrichment analysis indicated that D4S234E,DOCK9,KLK10,and NUCKS1 may be differentially expressed genes subject to methylation modifications between CIN and HPV positive,while TM7SF2 may be a differentially expressed gene subject to methylation modifications between SCC and CIN.The ROC results suggest that D4S234E,DOCK9,KLK10,NUCKS1,and TM7SF2 have good diagnostic value for CIN.D4S234E,DOCK9,KLK10 and TM7SF2 exhibit the lowest expression in SCC and the highest expression in HPV positive(P<0.05),whereas NUCKS1 shows the highest expression in SCC and the lowest expression in HPV positive(P<0.05).Conclusion:D4S234E,DOCK9,KLK10,TM7SF2,NUCKS1 may potentially serve as early diagnostic markers for cervical cancer.