Imbalance of Th1/Th2 and Th17/Treg during the development of uterine cervical cancer.

Uterine cervical cancer (UCC) causes more than one quarter of a million deaths per year in many developing countries. Nearly all cases of cervical cancer result from infection with the human papillomavirus. After high-risk HPV infection, most HPV infections are cleared naturally as a result of humoral and cell-mediated immune responses. Only a limited number of patients’ cervical lesions progress through CIN to cervical cancer, from persistent oncogenic human papillomavirus (HPV) infection. This indicated that immunoregulation may play a central role in the HPV-induced carcinogenesis. However, the natural history of clearance of a cervical HPV infection or its progression to a UCC needs clarification. We examined the related immune cells (Th1, Th2, Th17 and Treg cells) and related immune factors (INF-γ, IL-4, IL-10, IL-17, IL-23, TGF-βI) of UCC patients, CIN patients, HPV infected patients, and healthy controls. Compared with healthy controls, patients with UCC or CIN had a lower proportion of Th1 cells, and a higher proportion of Th2, Th17, and Treg cells. IL-4, IL-10, IL-17, IL-23 and TGF-βI concentrations in serum were found to be increased from patients with UCC or CIN, while INF-γ concentration in serum with UCC or CIN decreased. Our findings suggested that there were attractive imbalances of Th1/Th2 and Th17/Treg cells in UCC and CIN patients. HPV persistent infection induced an immunologic dissonance, and the degree of imbalance is aggravated with the progression of the disease.