Mediating Effect of White Blood Cells and Tobacco Exposure on Cervical Neoplasm Risk Among Taiwanese Women

Background: Both the high-risk human papillomavirus (HR-HPV) infection and tobacco exposure are significantly associated with cervical neoplasm risk. Immune cells play important roles in carcinogenesis. However, it is still unclear whether immune cells have a mediating effect on the HR-HPV infection and tobacco exposure with cervical neoplasm development. Aim: The aim of this study was to determine how the increased white blood cell (WBC) count affects the relationship between HR-HPV DNA load and tobacco exposure in the development of cervical neoplasia. Methods: A hospital-based case–control study design was conducted with a total of 108 cases of Taiwanese women with ≥ cervical intraepithelial neoplasia (CIN) I confirmed by biopsy, and 222 healthy Taiwanese female subjects with negative findings on a Pap smear were assigned to the control group. The study evaluated HR-HPV status and immune cell counts (WBCs, natural killer (NK) cells) and tobacco exposure by a self-construct questionnaire. Results: Both HR-HPV DNA load and tobacco exposure significantly independently increased cervical neoplasm risk (AORs: 1.28 and 1.42, respectively). Similar significant results were found for WBCs and NK cells, with respective AORs of 1.20 and 1.00. Moreover, increased WBCs (β = 0.04, 95% CI corrected: 0.01–0.07) and tobacco exposure (β = 0.02, 95% CI corrected: 0.01–0.04) mediated the relationship between the high-risk HPV DNA load and cervical neoplasm risk. Conclusions: Elevated WBC count acts as both predictor and mediator in cervical neoplasm development linked to HR-HPV DNA load. Monitoring and maintaining WBC levels within the normal range could be a preventive strategy for cervical neoplasm development.