Identification of Human Papilloma Viruses in Atheromatous Coronary Artery Disease

Abstract

ObjectiveTo identify human papilloma viruses (HPV) in atheromatous coronary arteries.BackgroundAtheromatous arterial disease is primarily an initial inflammatory response to unknown stimuli. The crucial question is “what causes the initial inflammation in atheromatous disease?” HPV infections may be relevant as US women with vaginal, high risk for cancer, HPV infections, are at up to threefold increased risk of cardiovascular disease as compared with vaginal HPV-negative women. These studies did not include analyses of HPV in atheromatous coronary arteries.MethodsAtheromatous coronary arteries were identified and collected from 20 deceased donors. Polymerase Chain Reaction techniques were used to identify HPV gene sequences. Immunohistochemistry methods were used to identify HPV E7 proteins.ResultsHPV types 16 and 18 were identified in 11 (55%) of 20 specimens. HPV E7 protein was identified in 10 (50%) of 20 specimens. Positive and negative HPV identification and HPV E7 expression in coronary smooth muscle cells were significantly correlated (cc = 0.503, p = 0.024). The HPV E7 proteins were expressed in smooth muscle cells and plasma cells, foam cells, and macrophages located in the atheromatous plaque. HPV E7 proteins were not expressed in infiltrating lymph cells.ConclusionHPV gene sequences were identified in 55% of atheromatous coronary arteries and may have a role in coronary artery disease.

Human Papillomavirus Status and the Risk of Cerebrovascular Events Following Radiation Therapy for Head and Neck Cancer

“…13 Furthermore, recent pathologic data from Lawson et al demonstrated a >50% prevalence of oncogenic HPV infection in the atheromatous coronary plaques of donors deceased from acute myocardial infarction. 25 Taken together, these studies provide support for the underlying association of HPV with the accelerated development of atherosclerosis leading stroke and TIA following RT, as noted in this study.…”

“…In addition, analysis from the US National Health and Nutrition Examination Survey data set revealed a >2‐fold increased risk of cardiovascular disease, including stroke, among young women with vaginal HPV infection without known cancer 13. Furthermore, recent pathologic data from Lawson et al demonstrated a >50% prevalence of oncogenic HPV infection in the atheromatous coronary plaques of donors deceased from acute myocardial infarction 25. Taken together, these studies provide support for the underlying association of HPV with the accelerated development of atherosclerosis leading stroke and TIA following RT, as noted in this study.…”

“…The inhibition of Rb has also been linked to increases in atherosclerotic lesion size as well as smooth muscle cell proliferation 27. Furthermore, inflammation has been postulated as a common pathway of viral‐mediated injury and atherosclerosis 25, 28. Caspases, which are protein enzymes that are vital to the process of vascular inflammation and cellular apoptosis, have been linked with the development of atherosclerosis, and recent reports have suggested that HPV E6 oncoproteins may promote nuclear localization of active caspase 8, leading to increased inflammation and probable atherosclerosis 29, 30.…”

“…23 Although there are no available prior studies investigating the relationship between HPV status and CVEs in RT-treated HNCA patients, multiple investigators have reported parallel findings in other populations that are supportive of the current results. 12,24,25 Data from the National Health Insurance Research Database of Taiwan showed a >50% increase in the risk of ischemic stroke for women treated with RT involving the neck for cervical cancer. 24 In that study, the investigators postulated that the elevated stroke risk was primarily related to systemic injury caused by RT.…”

“…27 Furthermore, inflammation has been postulated as a common pathway of viral-mediated injury and atherosclerosis. 25,28 Caspases, which are protein enzymes that are vital to the process of vascular inflammation and cellular apoptosis, have been linked with the development of atherosclerosis, and recent reports have suggested that HPV E6 oncoproteins may promote nuclear localization of active caspase 8, leading to increased inflammation and probable atherosclerosis. 29,30 Furthermore, it may be reasonable to postulate that the downstream vascular effects of RT-induced endothelial damage and medial fibrosis may be enhanced by oncogenic HPVinduced cellular proliferation, allowing for stimulation of the proliferation of damaged vascular cells and leading to accelerated atherosclerosis 4,31 ; however, further studies are needed.…”