Differential modulation of human beta-defensin-3 expression in human oral epithelial cells by HPV oncoproteins E6 and E7: potential implication in oral cancer

Abstract

Background Human papillomaviruses (HPVs) are small, non-enveloped DNA viruses that infect stratified squamous mucosal and cutaneous epithelia, causing diseases ranging from benign warts to invasive tumors. Failure of the immune system to detect and clear persistent HPV infections frequently leads to the development of oral warts and cancer. HPV infection has been etiologically linked with oral warts and a subset of oral squamous cell carcinoma, particularly in HIV infected patients. The incidence of HPV-related oral lesions is increased in HIV+ subjects on highly active antiretroviral therapy (HAART). We previously showed that tumor cells in oral carcinoma in situ (CIS) lesions overexpress human beta-defensin-3 (hBD-3), an antimicrobial peptide with immunomodulatory capabilities. Expression of hBD-3 in CIS contributes to the local pro-tumor immune response by selectively chemoattracting tumorassociated macrophages and by enhancing tumor development and progression.