HPV Infection May Increase the Risk of Heart Disease. Could Vaccination Lower It?

Scientific American

29-04-2025

Human papillomavirus (HPV) causes nearly 38,000 cancers a year, including most cervical and throat cancers. Now recent research suggests HPV infection also increases the risk of heart disease. An analysis of seven studies with a total of nearly 250,000 participants found that those who tested positive for HPV were 33 percent more likely than those who tested negative to develop cardiovascular disease.
Now Stephen Akinfenwa, an internal medicine resident at the University of Connecticut School of Medicine and one of the lead authors of the analysis, says he would like to study whether the HPV vaccine, which can prevent 90 percent of cervical cancers, also reduces the risk of heart disease.
The vaccine, which has been recommended for adolescents since 2006, protects against infection with nine strains of HPV, including high-risk types that are the most likely to cause cervical cancer, as well as strains that cause genital warts. The Centers for Disease Control and Prevention recommends that boys and girls receive a series of two HPV shots at ages 11 or 12 as part of their routine childhood vaccinations—and that people receive three shots if their first dose is instead administered between the ages of 15 and 26. The vaccine is most protective when given before people become sexually active.
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The HPV vaccine has been strikingly effective. Cervical cancer deaths in women under age 25—the first generation eligible to receive the vaccine— fell by 65 percent from 2012 to 2019.
Learning that heart disease may be related to HPV is exciting because HPV infection is preventable, Akinfenwa explains. 'It feels like good news,' he says. 'We're hoping that [the vaccine] will be a powerful tool for prevention.'
Akinfenwa and his colleagues presented a condensed version of their analysis in March at the annual meeting of the American College of Cardiology. It has not yet been published as a peer-reviewed study. The analysis included studies published between 2011 and 2024 that followed women for three to 17 years.
The largest study included in the analysis was published by researchers in South Korea in 2024 and followed apparently healthy women who were tested for 13 strains of high-risk HPV as part of a routine screening for cervical cancer. The women returned for health checks every year or two for an average of 8.6 years. Although heart disease and death were rare among these women, who had an average age of 40, those who tested positive for high-risk HPV were nearly four times as likely as those who tested negative to develop blocked arteries or die from heart disease, the study found.
Women aren't the only ones at risk, Akinfenwa says. In one paper included in the analysis, a 2017 study of people undergoing radiation therapy for head and neck cancer, 75 percent of patients were men. (Head and neck cancers are more than twice as common in men as they are in women, according to the National Cancer Institute.) The 2017 study found that people who tested positive for HPV were more likely to have strokes compared with those who tested negative.
HPV is ubiquitous and the most common sexually transmitted infection in the U.S. Among sexually active people, more than 90 percent of men and more than 80 percent of women are infected with HPV during their lifetime. About half of HPV infections involve high-risk strains that cause the bulk of cancers of the cervix, throat, vagina, vulva, anus and penis.
Vaccine hesitancy and lack of awareness about HPV has kept many parents from vaccinating their children against the infection, research shows. Some parents are reluctant to vaccinate their kids against HPV because they don't think their children will have sex as teenagers. Only 61 percent of adolescents are up to date on all HPV vaccines.
Even without a study that has specifically analyzed the effect of HPV vaccination on heart disease, the link between HPV and heart disease suggests that 'vaccination is a good idea, and our study definitely supports that,' Akinfenwa says.
Given what scientists know about HPV, it's likely that the vaccine could prevent cases of heart disease related to the virus or at least the nine strains of the virus that are included in the shot, says Amesh Adalja, a senior scholar at the Johns Hopkins Center for Health Security, who studies emerging infectious diseases and was not involved in the new analysis.
Other experts aren't so sure about the link between HPV and heart disease. Mark Einstein, chair of obstetrics and gynecology and women's health at Montefiore Einstein, who also was not involved in the analysis, says researchers have a long way to go before they can confidently say that the virus causes heart disease. 'This sort of association has come up a number of times over the years,' Einstein says. 'When you have a common disease—heart disease—and a common infection—HPV—it's easy to use statistical nuance to show a correlation,' he says. But 'association is different than causality.'
A Source of Chronic Inflammation
Scientists don't know exactly how HPV may increase the risk of heart disease, but it's unlikely that the virus directly infects the heart or blood vessels, says C. Noel Bairey Merz, director of the Barbra Streisand Women's Heart Center at the Cedars-Sinai Smidt Heart Institute in Los Angeles, who was not involved in the new research.
HPV causes cancer in parts of the body that come into direct contact with the virus through sexual activity, says Kevin Ault, a professor of obstetrics and gynecology at the Western Michigan University Homer Stryker M.D. School of Medicine. The virus is not thought to travel to distant organs and cause lung or liver cancer, for example. 'We usually don't think of human papillomavirus as going all around the body,' Ault says. 'It's going to infect mostly skin' or mucous membranes.
Instead, Merz says, HPV probably increases the risk of heart disease by causing inflammation, which occurs as the immune system attempts to control the virus. Chronic inflammation has been shown to irritate blood vessels and can lead to the hardening of fatty plaques in the lining of the arteries, which reduces blood flow to the heart. Inflammation can also cause those plaques to burst and form blood clots, which can lead to a heart attack or stroke.
Although the immune system naturally controls most HPV infections within a year or two, a small number of infections become chronic, a problem that increases the risk of cervical cancer, says Rebecca Perkins, obstetrician and gynecologist at the Woman, Mother and Baby Research Institute at Tufts Medical Center.
Even after HPV is controlled, the virus doesn't disappear from the body. Like the virus that causes chicken pox (varicella-zoster), HPV can lie dormant in the body for decades. And just as the varicella-zoster virus can reactivate decades after a childhood infection and cause shingles, HPV can wake up and cause women to test positive during cervical cancer screenings, Perkins says.
The studies included in the new analysis typically cited the result of a single test for HPV, Akinfenwa says. HPV tests are now included in most routine cervical cancer screenings, either alone or in combination with a Pap smear. So a positive test result cannot distinguish among a recent exposure, a reactivation of the virus and a chronic infection, Akinfenwa says.
How Infections Can Damage the Heart
Many pathogens can cause heart disease, Adalja says. A wide variety of viruses, bacteria, parasites and fungi can trigger myocarditis, an inflammation of the heart muscle, which can make the heart too weak to pump blood efficiently. Those include the viruses that cause influenza and COVID. And untreated strep throat and scarlet fever, caused by Streptococcus bacteria, can lead to rheumatic fever, which can damage heart valves and cause heart failure.
'Many infectious diseases set off inflammatory cascades that can prompt cardiovascular and neurological events like heart attacks, blood clots and strokes,' Adalja says. 'By staving off infection, [vaccinating] against these agents—such as influenza, varicella-zoster virus and, presumably, HPV—these events will be prevented or become less likely.'
Doctors have frequently been surprised by unexpected or off-target benefits from vaccines, Adalja says. A growing number of studies suggest that the shingles vaccine also reduces the risk of dementia —possibly by preventing the inflammation that contributes to the disease, Adalja says. The bacillus Calmette-Guérin (BCG) vaccine against tuberculosis also has been found to reduce risk of other diseases in which the immune system goes awry, including type 1 diabetes, cancer, multiple sclerosis and Alzheimer's disease. And an analysis published in 2024 found that meningitis vaccines reduced the incidence of gonorrhea by 30 to 59 percent. Such cross-protective immunity can occur when two bacteria are from similar families. The bacterium that causes gonorrhea is related to the meningococcus bacterium, which causes most cases of meningitis, an inflammation of the protective membranes around the brain, Adalja says.
To better understand how HPV damages the heart and whether the HPV vaccine might offer protection, Merz says, researchers could compare rates of chronic inflammation in adolescents who were vaccinated with rates in those who weren't vaccinated. 'It's logical to think preventing the HPV infection itself via vaccination will reduce the risk of cardiovascular disease,' Akinfenwa says. 'Having said that, it needs to be tested.'