High-risk HPV raises women’s risk for heart disease

High-risk strains of human papillomavirus (HPV)—ones that have been linked to anogenital and oral cancers—might also increase a woman’s risk for developing cardiovascular disease, research out of Seoul, South Korea, suggests.

Most CVD can be explained by contributors like high blood pressure, diabetes, dyslipidemia and smoking, senior study author Seungho Ryu and colleagues at Kangbuk Samsung Hospital at the Sungkyunkwan University School of Medicine said in Circulation Research. But a fifth of patients who eventually develop the disease can’t trace its roots to any of those conventional factors.

“Recently, a study using NHANES 2003-2006 demonstrated the association between HPV, especially oncogenic strains, and an increased prevalence of the self-reported diagnosis of myocardial infarction and stroke among community-dwelling women living in the United States,” Ryu and co-authors wrote in the journal Feb. 7. “The study by Kuo et al. hypothesized that HPV infections may contribute to CVD, given that viral oncoproteins bind to cellular tumor-suppressor protein p53 and induce the degradation of p53, which can be associated with atherosclerosis.”

That study relied on self-reported data, though, including self-collected vaginal swabs and self-reported CVD outcomes. For a more comprehensive look, Ryu’s team conducted a cohort study of 63,411 Korean women aged 30 and up who didn’t have heart disease at baseline and underwent a high-risk HPV test. Women were followed-up with annually or biennially from 2011 to 2016.

The prevalence of high-risk HPV infection in the study population was 7.6 percent, the authors reported. Subjects experienced 1,122 cases of new-onset CVD over a total 261,599 person-years of follow-up—an incidence rate of 4.3 cases per 1,000 person-years. High-risk HPV infection was linked to 1.25 times the risk of incident CVD, even after adjustment for possible confounders and high-sensitivity C-reactive protein.

Risk was further elevated in women who were obese or had metabolic syndrome. Obese women with high-risk HPV were 1.73-fold more likely to develop incident CVD, and women with metabolic syndrome were 1.99 times more likely.

“Obesity and metabolic syndrome appear to adversely affect immunity and pathogen defense, including the disruption of lymphoid tissue integrity, alterations in leukocyte development, phenotypes and activity, and the coordination of innate and adaptive immune responses,” Ryu et al. wrote. “Obesity is also closely associated with increased oxidative stress, endothelial dysfunction, metabolic abnormalities and increased pro-inflammatory cytokines.

"Thus, altered immune response in obesity or metabolic syndrome, increased persistent HPV infection and increased levels of dysfunctional adipokines and inflammatory markers in relation to persistent HPV infection might synergistically contribute to the development of CVD.”

The authors said in their large cohort of apparently healthy young and middle-aged women, high-risk HPV infection was significantly associated with an increased risk of CVD, and the virus might disproportionately affect an individual’s CVD risk if they’re also obese or struggle with metabolic syndrome.

“Further studies are required to identify the specific high-risk HPV genotypes that may contribute to CVD and implement vaccine strategies as a modifiable risk factor for the reduction of CVD in addition to prevention of anogenital cancers,” they wrote.