Women with a documented HPV infection had a 7 percent higher risk of developing new cardiovascular disease than uninfected women, according to a Swedish national registry study of about 3 million women. The researchers who produced that number went out of their way to tell women not to be alarmed by it.
The study, led by a Karolinska Institutet team and published in PLOS Medicine, is the largest examination yet of a question that has circulated in cardiology for more than a decade, as summarized by the Center for Infectious Disease Research and Policy. It also produces smaller effect estimates than earlier work, which is the more useful finding for anyone trying to decide what this means for them.
The authors concluded that clinicians should be aware of a slightly elevated cardiovascular risk in women with HPV, particularly in the first year after infection, but that given the small absolute difference, women "should not be unduly concerned."
The Absolute Numbers Behind the Percentages
Relative risk figures mislead when the underlying event rate is low, and that is the case here. Researchers compared 497,445 HPV-infected women in Swedish national registries against roughly 2.5 million uninfected controls.
New cardiovascular disease occurred at a rate of 8.27 per 1,000 person-years among infected women and 7.93 among uninfected women. The absolute difference is 0.53 cases per 1,000 person-years. Cardiovascular deaths ran at 33.7 per 100,000 person-years among infected women versus 29.4 among uninfected women, an absolute difference of 6.71 per 100,000.
The 7 percent relative increase in new cardiovascular disease translates into a population-attributable fraction of 1.16 percent. For death, the 25 percent relative increase corresponds to a population-attributable fraction of 4.12 percent. In plain terms, HPV accounts for a very small share of cardiovascular events in this population.
The timing pattern is the most notable result. In the first year after an HPV diagnosis, risks of new cardiovascular disease and related death were 43 percent and 86 percent higher. After that first year, the excess fell to 2 percent for new cardiovascular disease and 21 percent for death.
An Association, Not a Demonstrated Cause
This is an observational study, and it cannot establish that HPV causes heart disease. Women who are tested for HPV, who receive a positive result, and who are recorded in a registry differ from women who are not, in ways that include sexual history, smoking, socioeconomic position, and how often they see a doctor.
The research team addressed one major category of confounding directly. They compared 143,787 infected women with 174,637 of their own unexposed full siblings, a design that holds shared genetics and childhood environment roughly constant. The sibling comparison produced a 5 percent greater risk of new cardiovascular disease and a 25 percent higher risk of death, close to the main analysis. Consistency across designs strengthens the association without proving causation.
The front-loaded risk in the first year invites two readings that the data cannot separate. Inflammation from an acute infection could plausibly raise short-term cardiovascular risk, which is a mechanism seen with other infections. Alternatively, a woman newly diagnosed with HPV enters the medical system, gets examined more, and has existing heart disease detected that was already present. That is detection bias, and it produces the same statistical signal.
The study population was Swedish women. It included no men, and its applicability to other populations and health systems is unestablished.
An Earlier Study Reported a Far Larger Effect
Context matters for readers who have seen alarming headlines on this topic before. A study of Korean women in the European Heart Journal reported that women with high-risk HPV were roughly four times more likely to die of cardiovascular disease, with the risk of death from stroke almost six times higher.
The new work is larger, uses national registry data rather than a screening cohort, and adds a sibling comparison. Its much smaller effect estimates are what typically happens when a finding from a narrower study is tested against a bigger and better-controlled data set.
That does not make the earlier study wrong. The two examined different populations and different exposures, since the Korean cohort screened specifically for high-risk HPV strains. It does mean the size of any real effect is probably closer to the low end than the dramatic multiples reported previously.
Actions That Remain Sensible Regardless
No medical guidance changes because of this study. Cervical cancer screening recommendations are unchanged, HPV vaccination recommendations are unchanged, and no organization has proposed cardiac screening on the basis of an HPV result.
The steps that lower cardiovascular risk in women are the same ones that are already applied. Blood pressure, cholesterol and blood sugar control, not smoking, physical activity and treating diabetes account for the overwhelming majority of modifiable risk. A woman with a positive HPV result who has never had her blood pressure or cholesterol checked has a far more actionable problem than the one this study describes.
HPV vaccination is recommended for adolescents beginning at ages 11 to 12 and through age 26 for those not previously vaccinated, with shared clinical decision-making for some adults through age 45. It is covered without cost sharing by most insurance plans under preventive care rules, and the federal Vaccines for Children program covers eligible children at no cost. Cervical cancer screening is available at reduced cost through many community health centers and the CDC's National Breast and Cervical Cancer Early Detection Program.
Women should not seek cardiac testing based on an HPV result alone, and should not change any medication without speaking to a clinician. Anyone with chest pain, unusual shortness of breath, or sudden weakness or numbness needs urgent evaluation rather than a research discussion.
Further studies in other populations, including men, would be needed before this association could be considered established. MedicalDaily will report significant new findings.
Key Questions Answered
What did the study find? Women with HPV had a 7 percent higher risk of new cardiovascular disease and a 25 percent higher risk of cardiovascular death than uninfected women, with risk concentrated in the first year.
How big is that in real terms? The absolute difference was 0.53 additional cases per 1,000 person-years. HPV accounted for about 1.16 percent of new cardiovascular disease in this population.
Does HPV cause heart disease? No. This is an observational study showing an association. It cannot establish that HPV causes cardiovascular disease.
Who was studied? Nearly 500,000 HPV-infected women in Swedish national registries, compared with about 2.5 million uninfected women, plus a sibling comparison of 143,787 infected women.
Why did an earlier study report a much bigger risk? The Korean study was smaller, screened for high-risk HPV strains and followed a different population. Larger, better-controlled analyses commonly produce smaller effect estimates.
Should I get a heart scan if I test positive for HPV? No organization recommends that. Discuss your overall cardiovascular risk factors with a clinician instead.
Does this change vaccination or screening advice? No. HPV vaccination and cervical cancer screening recommendations are unchanged.
