Vaginal Cytokine Profiles Associated with High-Risk Human Papillomavirus, Sexually Transmitted Microbe Co-Detection, and Cervical Lesions

Abstract

Background: Persistent hrHPV infection is the necessary cause of cervical cancer, but local immune responses and sexually transmitted infections or genital mycoplasma may influence viral persistence and lesion progression. This study examined vaginal cytokine profiles according to hrHPV and sexually transmitted microbe (STM) detection and assessed their association with cervical lesions. Methods: Self-collected vaginal samples were obtained from 80 women classified into four mutually exclusive groups: hrHPV infection alone (n = 16), STM detection alone (n = 16), hrHPV/STM co-detections (n = 26), and negative controls (n = 22). Among 80 participants, 10 (13%) were women living with HIV. Detection of target organisms was performed using real-time PCR on a CFX96 Real-Time PCR Detection System (Bio-Rad, Hercules, CA, USA). Histological analysis included 33 women: 25 were women with normal histology or cervical intraepithelial neoplasia 1 (CIN1), and 8 women with CIN2+ lesions. Vaginal cytokine concentrations (pg/mL) were analyzed using the Invitrogen ProcartaPlex™ Multiplex Immunoassay (Vienna, Austria). Statistical analyses assessed group differences in cytokine levels. Results: Women with hrHPV/STM showed significantly elevated levels of Eotaxin (p = 0.04), IL-2 (p = 0.045), IL-10 (p = 0.02), and IP-10 (p = 0.04) compared to negative controls. Elevated IL-2 (p = 0.016) was also observed in women with STMs alone; women with hrHPV infection showed lower IL-15 levels (p = 0.02). Higher concentrations of TNF-α (p = 0.04), IL-1β (p = 0.02), and EGF (p = 0.01) were associated with CIN2+ lesions. Conclusions: Women with hrHPV/sexually transmitted microbe co-detection showed higher levels of Eotaxin, IL-2, IL-10, and IP-10, and the association of hrHPV alone with lower IL-15 levels. The findings also show that higher levels of EGF, IL-1β, and TNF-α were associated with CIN2+ lesions.