Cytokine Profiling in Vaginal Specimens from Asymptomatic Women with Human Papillomavirus and/or Sexually Transmitted Infections

Background: The primary cause of cervical cancer is the high-risk human papillomavirus (hrHPV); the infection patterns may vary depending on the state of the vaginal immune system. Sexually transmitted infections (STIs) such as gonorrhea, trichomoniasis, and chlamydia can alter the local immune response, which in turn may affect the persistence and progression rate of hrHPV infections. The objective of this study was to compare cytokine levels from vaginal specimens collected from hrHPV positive, STI positive, and healthy controls, and to explore correlations with clinical parameters. Methods: Vaginal samples were collected from women diagnosed with hrHPV, asymptomatic STIs, and healthy controls. HrHPV and STIs status were confirmed through multiplex real time PCR. Vaginal cytokines and various growth factors were analyzed by Invitrogen ProcartaPlex™ Multiplex Immunoassay. Statistical analyses were performed to compare cytokine levels across different groups and to explore correlations with clinical parameters. Results: Women having STIs and hrHPV coinfection(n=26) had increased median concentration levels of Eotaxin (P=0.04), IL-2 (P=0.01), IL-10 (P=0.02), and IP-10 (P=0.04) compared to the control groups(n=22). Asymptomatic women with STIs (n=16) exhibited a distinct cytokine profile characterized by elevated levels of IL-2 (P=0.02) compared with control groups. Women with hrHPV(n=16) had lower levels of IL-15 (P=0.02) compared to controls. The median concentration levels of TNF-α (P=0.04), IL-1β (P=0.02), and EGF (P=0.01) were significantly greater in ≥CIN2+(n=8) than ≤CIN1(n=25). The area under the curve (AUC) of EGF, IL-1β, and the combination of EGF+IL-1β +TNF-α was good predictor for high-grade cervical lesions. Conclusion: The cytokine profiling revealed significant alterations in the vaginal immune environment in women with asymptomatic STIs and co-infection with hrHPV. The findings suggest that an inflammatory response in hrHPV infection may be modulated by co-existing STIs, potentially influencing disease progression. Elevated levels of EGF, IL-1β, and TNF-α in vaginal swabs suggest an inflammatory and proliferative environment that can contribute to the development and progression of cervical dysplasia.