A virus responsible for the majority of cervical cancers might also raise a woman's risk of heart attack and stroke, according to researchers who suggest HPV might underlie some cardiovascular disease in people who do not have such traditional risk factors as obesity, diabetes or smoking.
If additional research supports an association between cancer-linked strains of human papillomavirus (HPV) and clogged arteries, doctors might want to monitor HPV-infected women for heart disease, the researchers suggested. In addition, they proposed that HPV vaccines, now used to protect young women and men against cervical and anal cancers, might offer "additional benefit in cardiovascular health."
Writing in the Nov. 1 issue of the Journal of the American College of Cardiology, Dr. Keniche Fujise, director of cardiology at the University of Texas Medical Branch in Galveston, and Dr. Hsu-Ko Kuo, a UTMB internist, said they were the first to link HPV and cardiovascular disease. They said their work didn't establish that HPV infection caused heart attacks and strokes, but instead provided a path for further investigation. They also said that because their findings were limited to women, that left open the question of whether they could apply to men too.
HPV is among the most common sexually transmitted infections in the United States. HPV strains are present in more than a quarter of the population, according to federal statistics. Most HPV infections are transient and cause no major health problems, while others produce genital warts, which require medical treatment to avoid further spread. Two strains, HPV 16 and HPV 18, are responsible for 70 percent of cervical cancer, while HPV 16 accounts for about 85 percent of anal cancers and many tongue and throat cancers.
The authors set about studying the potential role of HPV in heart disease because of previous evidence that some proteins present in cancer-causing HPV strains disarm an important tumor-suppressing gene called p53, which also plays a role in clogging of the arteries, called atherosclerosis. Furthermore, patients in whom the p53 gene is disabled or inactivated are more prone to reclogging of their arteries after blockages have been surgically scraped away. So Fujise and Kuo reviewed HPV and heart disease data from an ethnically and geographically diverse sample of 2,450 women, ages 20 to 59, who participated in the National Health and Nutrition Examination Survey in 2003-2006, a large federally funded study.
They homed in on the 60 survey respondents told by health professionals that they'd suffered a stroke or heart attack. The doctors reviewed laboratory analyses of HPV from vaginal swabs each of the women provided, for the presence of 13 types of HPV defined as either cancer-causing or cancer-associated. Samples from nearly a quarter of the women tested positive for cancer-associated HPV. Women with those strains tended to be younger and have a greater prevalence of cardiovascular disease than the uninfected women.
In an accompanying editorial, Dr. Joseph B. Muhlestein, a cardiologist at the University of Utah in Salt Lake City, wrote that investigators for years have been pursuing the possibility that cardiovascular disease may be rooted in infection. In 1996, Muhlestein discovered that a large proportion of patients undergoing coronary bypass surgery were infected with Chlamydia pneumoniae. He's been among investigators who have failed to prove that antibiotic treatment of C. pneumoniae prevents strokes and heart attacks. Nevertheless, he expressed the hope that "in the end, the infectious hypothesis of atherosclerosis may still pan out."
Findings Provocative, But Need Validation
The findings are provocative, but need further validation from larger studies of both men and women, said two outside experts who reviewed the study for ABCNews.com. "This is an intriguing analysis," said Dr. Mark Einstein, head of the HPV Vaccine Clinic at Montefiore Medical Center in the Bronx, N.Y. "HPV is related to cancers -- but might be relevant in other diseases as well." He agreed with the study authors that people who test positive for HPV may have other risk factors for cardiovascular disease, like smoking. Einstein called it "too early to say" if HPV vaccination could protect the heart or influence more parents to have their children vaccinated.
Dr. Sharonne N. Hayes, director of the Mayo Clinic Women's Heart Clinic in Rochester, Minn., said the study deserved attention because it raised "important new biologically plausible connections between an infectious agent and coronary heart disease." However, Hayes tempered her enthusiasm by pointing out that the study doesn't rule out HPV infection as some kind of "intermediate marker" for cardiovascular disease when the "true risk" might come from an unidentified or unappreciated factor. Also, she said, there's a precedent for infectious agents that initially appeared related to cardiovascular disease risk not panning out when subjected to further scrutiny.
Dr. Diane Harper, director of the Gynecologic Cancer Prevention Research Group at the University of Missouri-Kansas City, offered unbridled criticism for the study, calling the association between HPV and atherosclerosis "biologically implausible."
"This is a classic study of correlation without causation," she told ABCNews.com. "It is unfortunate that it is being published in this form, as there are many assumptions that are incorrectly understood by these authors that make the likelihood of genital HPV infection a causative factor for CVD unlikely." HPV cannot damage the cells lining blood vessels, said Harper, a professor of obstetrics and gynecology as well as community and family medicine. HPV proteins only damage the p53 gene within cells that HPV directly infects, she said. Finally, she said: "There is no support for the statement that HPV vaccination may reduce CVD later in women's lives."
The study authors provided several caveats. Because women took their own vaginal swabs, HPV might have been under-recognized and the HPV-heart disease link underestimated, they said. Also, because the women in the study group self-reported heart attacks and strokes, the data might not fully reflect their cardiovascular problems.
Two HPV vaccines currently are on the market. Merck's Gardasil was designed to protect against two cancer-causing strains, HPV 16 and HPV 18, and two strains associated with genital warts, HPV 6 and HPV 11. GlaxoSmithKline's Cervarix protects against the two most important cancer strains HPV 16 and HPV 18, but also offers protection against three other cancer-causing strains, HPV 31, HPV 33 and HPV 45. Fujise and Kuo suggested that it might be worth re-evaluating HPV vaccine clinical trial data for the cardiac health of vaccine recipients. They also floated the idea of launching a prospective study to determine whether HPV vaccinations reduce cardiovascular disease.