HPV Infection May Raise Risk for Cardiovascular Disease

Individuals testing positive for human papillomavirus (HPV) had a 40% greater risk for overall cardiovascular disease (CVD) than HPV-negative individuals, based on the data from nearly 250,000 patients. The findings were presented at the American College of Cardiology Annual Scientific Session and Expo.

“Although high-risk HPV is known to play a role in anogenital cancers, emerging research suggests a possible association with cardiovascular disease (CVD) as well,” said co-author Stephen Akinfenwa, MD, in an interview. “Given that CVD remains the leading cause of mortality worldwide, identifying nontraditional risk factors, especially those that may be preventable through vaccination, could significantly impact public health,” said Akinfenwa, who presented the findings at the meeting.

The researchers examined seven studies that included data on the relationship between HPV status and cardiovascular outcomes. Some of the analyses also adjusted for known CVD risk factors including smoking and diabetes. Follow-up times ranged from 3 to 17 years. The study population included 249,366 patients with HPV, with a mean age ranging from 20 to 75 years.

Overall, HPV-positive patients were significantly more likely to have any CVD (odds ratio [OR], 1.40; P < .001) and twice as likely to have coronary artery disease (OR, 2.00; P = .002) as HPV-negative patients. No significant association appeared between HPV infection and hypertension (OR, 0.96; P > .05). An additional pooled analysis adjusting for confounding variables showed a 33% increased risk for development of CVD in HPV-positive patients vs HPV-negative patients.

“While we anticipated some degree of association between high-risk HPV (HR-HPV) and cardiovascular disease, the magnitude of the risk increase was striking,” Akinfenwa told Medscape Medical News. “Our meta-analysis showed that HPV-positive individuals had a 40% greater risk of CVD and a twofold increased risk of coronary artery disease. However, we found no significant association between HPV and hypertension, suggesting that the impact of HPV on cardiovascular health may be more specific to atherosclerosis-related diseases rather than overall blood pressure regulation,” he said. “The potential mechanistic link between chronic viral infections and vascular inflammation deserves further research,” Akinfenwa added.

“Primary care clinicians should recognize HR-HPV as a possible nontraditional risk factor for cardiovascular disease,” Akinfenwa told Medscape Medical News. “Patients with persistent HPV infections may be at an increased risk of developing atherosclerotic disease, making it essential to incorporate comprehensive cardiovascular risk assessments in their care,” he said. Patients also need to know all the benefits of HPV vaccination, not only for cancer prevention but also for the potential reduced risk of cardiovascular complications, Akinfenwa noted. “Routine monitoring for early signs of CVD in HPV-positive patients could allow for earlier interventions to mitigate risk,” he added.

The study findings were limited by several factors including the reliance on observational data, which prevents conclusions of causality, Akinfenwa said. Other limitations include variation in how HR-HPV was diagnosed, which could limit the consistency of the results, he noted.

“Future research should focus on longitudinal studies to better understand the causal mechanisms linking HR-HPV to atherosclerosis; investigating whether HPV vaccination reduces cardiovascular risk would also be an essential next step in shaping preventive strategies,” Akinfenwa emphasized.

Role of Chronic Inflammation

“Conventional risk factors such as smoking, hypertension, dyslipidemia, and diabetes account for the majority of cardiovascular disease, but about 20% of individuals who develop CVD do not have these traditional risk factors, so recognizing additional causes is crucial,” said Ifeoma Onuorah, MD, a cardiologist at Emory University, Atlanta, and a member of the ACC Prevention of CVD Council, in an interview.

Previous research suggests that HPV infection can lead to cardiovascular disease as a result of chronic inflammation, which in turn promotes the development of atherosclerosis, said Onuorah. “HPV may contribute to atherogenesis by infecting the vascular endothelium, inducing persistent systemic inflammation, which then accelerates the process of atherogenesis,” she said. “Prior studies using NHANES [National Health and Nutrition Examination Survey] data also have shown a higher occurrence of CVD in women with HPV infection,” she added. “However, HPV vaccination is available and recommended for all individuals starting at age 11-12 years,” Onuorah said.

“Screening for the well-established conventional risk factors for cardiovascular disease should remain first line,” Onuorah told Medscape Medical News. “Routine screening for HPV infections is also critical, and for individuals with HPV infection, it is essential to be aggressive in managing modifiable risk factors,” she said.

“Most of the current data on HPV and CVD are association related, and a long-term prospective study is needed to establish causality,” Onuorah said. “Randomized controlled trials also are needed to determine whether HPV vaccination leads to a reduction in CVD,” she added.

The study received no outside funding. The researchers disclosed no financial conflicts of interest. Onuorah disclosed receiving an investigational grant from AstraZeneca.