We identified hypermethylated PCDHGB7 as a novel cancer marker and applied it to early cervical cancer (CC) screening. It outperforms the widely implemented highrisk human papillomavirus (hrHPV) test and ThinPrep cytologic test (TCT) and even can be used in the selfsampled vaginal secretions, proving itself as a much more convenient yet highly effective screening method. DNA methylation aberration occurs during cancer progression. DNA methylation has emerged as a promising diagnostic, prognostic, and predictive biomarker of various types of cancer. 1 However, the common biomarker of cancers has been rarely explored. Previously, we provided the concept of Universal Cancer Only Marker (UCOM) and identified hypermethylated HIST1H4F as the first UCOM marker. 2 In our genome-wide methylation analysis, we found PCDH family genes were cancer cell-differentially methylated genes (CC-DMG). 2 In the current study, we focused on PCDHGB7, a member of the protocadherin gamma gene cluster, which plays critical roles in the establishment and function of specific neuronal connections, 3 and investigated whether it could be a novel UCOM marker. As CC is one of the most common female malignancies 4 and the widely implemented hrHPV and TCT yield a high false-positive rate, 5, 6 we aimed to applied PCDHGB7 in the early CC screening. We compared the methylation status of PCDHGB7 in 17 cancer types with their corresponding normal tissues in TCGA and GEO database (n= 7114). It turned out PCDHGB7 was hypermethylated in all cancer types (Figure 1A). When analyzing FIGO staging, we found that PCDHGB7 was already hypermethylated in stage I of all cancer types analyzed (Figure S1), suggesting hypermethylated PCDHGB7 could be an early-stage cancer indicator. Additionally, in different histological types, keratinizing squamous cell carcinoma, lymphovascular invasion, or histologic grades, there was no methylation difference of PCDHGB7 (Figure S2). To verify these analytical results, we collected 13 types of clinical cancer samples (n= 727),