Human papillomavirus infection is associated with a 40% increased risk of cardiovascular disease and doubles the risk of coronary artery disease, according to a comprehensive meta-analysis to be presented at the American College of Cardiology's Annual Scientific Session (ACC.25).

This first-of-its-kind pooled analysis encompassing nearly 250,000 patients from seven international studies provides substantial evidence that strengthens the emerging connection between human papillomavirus (HPV) infection and cardiovascular pathology, even after adjusting for traditional cardiovascular risk factors.

The meta-analysis demonstrated that HPV-positive status maintained a 33% elevated cardiovascular disease risk compared with HPV-negative participants after controlling for confounding variables, including sociodemographic factors, medical history, lifestyle behaviors, family history, and antihypertensive medication use.

"Our study shows that clearly there is an association of some kind between HPV and cardiovascular disease," said Stephen Akinfenwa, MD—an internal medicine resident at UConn School of Medicine and the study's lead researcher—in a press release from the American College of Cardiology ahead of the session presentation. "The biological mechanism has not been determined but is hypothesized to be related to chronic inflammation."

The analysis incorporated seven studies that were conducted between 2011 and 2024 with follow-up periods ranging from 3 to 17 years. The studies originated from diverse geographic locations: three from the U.S., two from South Korea, one from Brazil, and one from Australia. Researchers employed multiple statistical methodologies to extract relationship data between HPV status and cardiovascular outcomes.

While the analysis revealed significant associations with cardiovascular disease and coronary artery disease specifically, investigators found no statistically significant relationship between HPV infection and hypertension.

These findings may have implications for clinical monitoring practices. "We always talk about cardiovascular risk factors like smoking, high blood pressure and so on, but we know that about 20% of cardiovascular disease cannot be explained by these conventional risk factors," Akinfenwa noted. "This makes it important to identify nonconventional risk factors like HPV that could potentially be targeted."

The research team suggests that clinicians might consider implementing enhanced cardiovascular monitoring protocols for patients who are HPV-positive, similar to surveillance strategies employed for patients with established cardiovascular risk factors.

The implications potentially extend to preventive medicine. Akinfenwa said, "We would ultimately like to see if reducing HPV via vaccination could reduce cardiovascular risk." However, many U.S. adults remain unvaccinated against HPV because they were beyond the recommended vaccination age when the vaccine was introduced in 2006.

The study, titled "Human Papillomavirus Infection and Cardiovascular Diseases: A Meta-Analysis of Effect Sizes from 249,366 Patients," warrants further investigation into both the mechanistic underpinnings of this association and the potential cardiovascular benefits of HPV vaccination.

Akinfenwa will present the complete findings on Monday, March 31, 2025, at 12:00 p.m. CT in the South Hall at ACC.25.