Objective To investigate potential causative associations between immunophenotype traits and cervical cancer by using two-sample Mendelian randomization (MR) analysis.

Methods The genetic instrumental variables (IVs) of 731 immunophenotypes of peripheral blood were obtained from the GWAS Catalog database. The GWAS summary data of cervical cancer were obtained from FinnGen database. The inverse-variance weighted (IVW), weighted mode, weighted median, and MR Egger methods were used for evaluations. The sensitivity analysis and reverse Mendelian randomization analysis were conducted to eliminate bias and reverse causality. The MR Steiger directionality test was further used to ascertain the reverse causal relationship between immune cells and cervical cancer.

Results A total of 71 immune cell subtypes associated with cervical cancer were identified, of which 31 had a strong association. The majority of the B cell panel was protective factors for cervical cancer. B-cell activating factor receptor (BAFF-R) was the most frequently expressed molecule in this analysis. It is expressed on several B cell subtypes. The CD20 on IgD+ CD38+ B cell (OR=1.887, 95%CI: 1.078-3.306, P=0.026) is the risk factor for cervical cancer. In cDC panels, the CD123 expression on plasmacytoid dendritic cell (OR=2.48, 95%CI: 1.229-5.003, P=0.011), CD123 expression on CD62L+ plasmacytoid dendritic cell (OR=2.5, 95%CI: 1.231-5.077, P=0.011), CD80 expression on plasmacytoid dendritic cell (OR=2.62,95%CI:1.244-5.515, P=0.011), and CD80 expression on CD62L+ plasmacytoid dendritic cell (OR=2.641, 95%CI: 1.246-5.596, P=0.011) were positively associated with the incidence of cervical cancer. All gynecological cancers in this study have no statistically significant effect on immune cells, according to reverse MR analysis.

Conclusion This study emphasized the genetically predicted causality between immune cells and cervical cancer. In clinical practice, it is important to pay attention to the screening of peripheral blood immune cells for patients with cervical cancer.