Abstract
CYB5D2 is a novel tumor suppressor gene that exhibits ectopic expression in various tumors. This study explored its significance in cervical cancer screening and prognosis by examining its expression in cervical precancerous lesions and cancer tissues and analyzing follow-up data. CYB5D2 expression was comprehensively assessed in 112 clinical samples, combined with routine cervical cancer screening methods to evaluate its early detection potential. Postoperative survival data from cervical cancer patients were analyzed using Kaplan-Meier curves to examine the association between CYB5D2 protein expression and clinicopathological characteristics, as well as its prognostic implications. Results revealed a progressive downregulation of CYB5D2 expression with advancing cervical lesions. Immunohistochemical detection of CYB5D2 protein outperformed ThinPrep cytology test (TCT), DNA aneuploidy analysis, and HR-HPV E6/E7 mRNA testing (mRNA expression of the E6 and E7 genes in high-risk HPV virus) in diagnosing high-grade squamous intraepithelial lesions (HSIL+) of the cervix. Combined testing of TCT, HR-HPV E6/E7 mRNA, and CYB5D2 achieved 100% sensitivity and negative predictive value for HSIL+. In conclusion, low CYB5D2 expression was identified as an independent risk factor for progression-free survival (PFS) in cervical cancer patients. Incorporating CYB5D2 testing into routine screening protocols for squamous cell lesions, along with TCT and HPV testing, may enhance diagnostic efficiency and provide prognostic value for adverse outcomes.