Infection of human papillomavirus and overexpression of dihydrodiol dehydrogenase in uterine cervical cancer

ObjectiveTo determine the association of human papillomavirus (HPV) infection with the expression of dihydrodiol dehydrogenase (DDH) in uterine cervical cancer (UCC).MethodsIn situ hybridization (ISH) and immunohistochemistry were applied to examine pathological specimens of 145 patients with UCC.ResultsBy ISH, HPV16/18 DNA was detected in 108 (74.5%) UCC cases. DDH expression determined by immunohistochemistry was detected in 81 (75%) lesions among 108 HPV-positive cases. In contrast, of 37 HPV-negative cases, DDH was only detected in 16 (43.2%) of the lesions. A significant correlation was found between DDH expression and the presence of HPV (P < 0.001), FIGO stage (P = 0.004), lymph node involvement (P < 0.001), as well as patients' survival (P = 0.002). In vitro, DDH expression was also found closely associated with HPV infection, and DDH content was proportional to cell sensitivity for cisplatin and doxorubicin.ConclusionsHPV infection provokes local inflammation, which can then induce DDH expression and drug resistance in UCC. The detailed biological relationship among HPV infection, expression of DDH and drug resistance, however, remains to be clarified.