Objective: To explore the relationship between the presence of HPV-16 DNA and the expression Treg surface marker Foxp3(+), peripheral blood levels of Th17/Treg cell-associated cytokines and explore their roles and significance in cervical cancer progression.
Methods: Between January 2012 and October 2012 at Shengjing Hospital of China Medical University, a total of 142 HPV16 positive patients were divided into cervical cancer (CC, n = 60), cervical intraepithelial neoplasia (CIN, n = 65) and control group (n = 17). Cervical liquid-based cytological (LBC) samples were collected to detect E2 and E6 genes of HPV type 16 using multiple real-time polymerase chain reaction (PCR). E2/E6 ratio was used to evaluate the physical status of HPV-16 DNA in host cell genome. The SP immunohistochemical method was used to detect the expressions of FOXP3 in cervical lesions. The concentrations of Th17/Treg cell-associated cytokines were detected by enzyme-linked immunosorbent assay (ELISA).
Results: Under the same status of HPV16 DNA in vivo, the levels of Foxp3(+), transforming growth factor-β (TGF-β) and interleukin-10 (IL-10) were significantly higher than those of the control group (P < 0.01) while the levels of interleukin-17 (IL-17) and interleukin-21 (IL-21)were significantly lower than those of the control group (P < 0.05) . In the same disease, HPV16 DNA integration rate grew with the increases of Foxp3(+), TGF-β and IL-10 while IL-17 and IL-21 were opposite. In the different status of HPV16 type DNA, the expression of Foxp3(+) was closely correlated with Federation International of Gynecology and Obstetrics (FIGO) stage, histological grade and lymphnode metastasis (P < 0.05) except for age (P > 0.05).
Conclusion: Treg cytokines, HPV16 integration rate and severity of cervical lesions are positively correlated while Th17 cytokines show opposite effects. Th17/Treg cell-associated cytokines may play an important role in the occurrence and development of cervical cancer.