HPV18 oncogenes increase viability and nuclear architecture stability in HaCaT cells exposed to UVB radiation.

Ultraviolet radiation (UVR) is an environmental risk factor and a cofactor in carcinogenesis. UVB radiation (UVBR), mainly from sunlight, is a known risk factor for lip cancer and can also contribute to oral cavity cancer. HPV infection can further increase UVR risk of carcinogenesis, for instance by HPV oncogenes roles in enhancing cell survival. In this study, we evaluated the responses to UVBR in human keratinocytes infected with viral oncogenes of HPV-18. While UVBR induced similar levels of DNA damage in the HaCaT human keratinocyte parental cell line compared to HaCaT cells containing HPV-18 oncogenes E5, E6 and E7, the latter showed increased viability and reduced levels of apoptotic and necrotic markers in response to UVBR. We also observed the formation of deep nuclear invaginations in response to UVBR, which were markedly more frequent in irradiated HaCaT parental cells, which also retained more stress fibers than irradiated HaCaT E5/E6/E7-18 cells. Mechanical modelling suggests that reduced nuclear invaginations in HaCaT E5/E6/E7-18 cells are related to decreased cell spreading forces, in agreement with our previous mechanical studies. Our results show that HPV oncogenes confer increased viability and nuclear architecture stability to keratinocytes exposed to UVBR, which could contribute to their role in cooperating with UVBR induced carcinogenesis in the oral cavity.