Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States and worldwide, with more than 42 million Americans infected with types of HPV that are known to cause disease. Although the link between HPV and the development of a variety of cancers has been strongly established, recent literature has demonstrated a potential association between HPV and increased risk of cardiovascular disease. Nevertheless, despite plausible mechanisms for the development of cardiovascular disease with HPV infection, a causative relationship has yet to be firmly established, in part due to potential confounding risk factors between the two. In this 2-part series, we discuss the emerging relationship between HPV and cardiovascular disease. In part 1, we focus on the pathophysiology of HPV infection and potential mechanisms for the development of cardiovascular disease.