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-gamma, IL-4, IL-10, IL-17, IL-23, TGF-beta I) 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-beta I concentrations in serum were found to be increased from patients with UCC or CIN, while INF-gamma 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.