Relationship Between Tobacco Smoking and HPV Tobacco smoking exposes the mucosa with nitric oxide which initiates DNA damage by mutations and DNA double-strand breaks (DSBs). When high-risk HPV infects skin or mucosal cells, tobacco smoking exaggerates the infection by increasing the HPV DNA. It ultimately leads to increase in E6 and E7 protein causing a decrease in p53/pRb. The high-risk HPV progresses and triggers a cascade of events including loss of cell cycle control, survival of mutant cells, early carcinogenesis and immune suppression. Cancer is the last event.