The Impact of HPV/HBV Coinfection on Cervical Cancer Risk: Potential Mediating Role of Ki67

Persistent high-risk human papillomavirus (HPV) infection is the primary cause of cervical cancer, with co-factors such as hepatitis B virus (HBV) playing a role in oncogenic progression. This study investigates the interaction of HPV and HBV coinfection with cervical cancer risk. A total of 4488 women undergoing cervical cancer screening and HPV and HBV testing were included in this study, employing multinomial regression to analyze associations between viral infections and cervical intraepithelial neoplasia and cancer, while interaction analysis assessed synergistic effects on cervical carcinogenesis and examined the mediating role of ki67 in co-infections. Co-infection significantly increases the risk of all levels of cervical lesions compared to the reference group, with odds ratios for LSIL, HSIL, and cervical cancer demonstrating substantial elevation (OR = 3.13, 95% CI: 2.25-4.35; OR = 3.5, 95% CI: 2.55-4.81; and OR = 11.49, 95% CI: 5.85-22.57; respectively). On the additive scale, significant positive interactions were observed between HPV and HBV. Specifically, for cervical cancer, there was an attributable proportion (AP) due to interaction of 0.43 (p = 0.01), and a synergy index (SI) of 1.88 (p < 0.001). Similarly, for HSIL, significant positive interactions were noted with AP = 0.28 (p = 0.01) and SI = 1.65 (p < 0.001). Mediation analysis revealed that Ki67+ accounted for 49.39%, 70.44%, and 78.81% of the total effect of HPV and HBV co-infection on cervical cancer, HSIL, and LSIL, respectively (all p < 0.05). HPV and HBV coinfection significantly impacts cervical lesions, enhancing cervical oncogenesis synergistically. Ki67 may be involved in mediating the process of cancer progression caused by viral co-infection, stressing comprehensive screening and molecular interaction research.