Cervical Microbiota Influences Cytokine Diversity in Cervical Intraepithelial Neoplasia among Rural Women in the Akyemansa District of Ghana

Abstract

Background. In recent times, cervical dysbiosis which mostly causes and aggravates infections is highlighted for its role in immune modulation in cervical dysplasia, which promotes the shifting of Th1 phenotype immunity to Th2 phenotype immunity. This study therefore estimated and compared the levels of circulatory IL-4, IL-6, IL-10, TNF-α, and IFN-γ cytokines among adult women identified to have different grades of cervical intraepithelial neoplasia (CIN) and with cervicovaginal infection. Methods. A total of 157 participants were recruited from the Akyemansa District of Ghana, and cervical swabs and blood samples were taken. The Pap smear test, microbiological culture, and ELISA were employed for cytology analysis, bacteria isolation, and identification and estimation of IL-4, IL-6, IL-10, TNF-α, and IFN-γ cytokines, respectively. Results. Overall, 14/157 (8.9%) had CIN with 7.6% having CIN 1 and 1.3% having CIN 2. The main predictor for CIN was age above 46 years (OR 11.16, 95% CI: 2.4-51.8). Bacterial vaginosis ( $p=0.003$ ) and Candida infection ( $p=0.012$ ) were significantly higher in CIN. Again, Staphylococcus aureus (60% vs. 17.6%, $p=0.005$ ), Citrobacter sp. (40.0% vs. 13.2%, $p=0.017$ ), and Morganella morganii (40.0% vs. 4.4%, $p=0.002$ ) isolates were significantly higher in CIN-positive participants. IL-10 and TNF-α concentrations were elevated in participants with CIN 1+ (TNF-α NIL vs. CIN 1+ only, $p<0.05$ ) while IL-6 was decreased among participants with CIN 1+. In the presence of vaginal infection, TNF-α decreased among CIN 1+ participants while IL-10 remained elevated. Conclusion. The findings of this study suggest that cervical dysbiosis causes immune suppression, which creates a suitable microenvironment for the development of CIN.