In the largest study of its kind, a national team led by a UC San Francisco scientist has found strong new evidence that HIV-positive women run a high risk of infection with human papillomavirus (HPV), a major cause of cervical cancer. Women who already harbor the HIV virus are, on average, twice as likely to be infected with HPV than are high-risk HIV-negative women, the researchers found. The odds jump to a ten-fold greater risk of HPV infection among the most immune-suppressed women.
Although HIV status was by far the single-greatest risk factor for infection with HPV, the large size of the study group enabled the researchers to determine many other risk factors that had eluded previous, much smaller studies. Younger women, African American women and those who currently smoke each face more than a 50 percent increased likelihood of HPV infection than women over 40, Caucasians and non-smokers respectively, the researchers found.
The findings appear in the February 3 issue of the Journal of the National Cancer Institute.
The study provides new support for the view that the increased HPV disease among HIV-positive women results from reactivation or persistence of previously acquired HPV rather than recent acquisition of the virus.
The study was conducted before protease inhibitors were in widespread clinical use. However, it is possible that HIV-positive women who gain a new lease on life through protease inhibitors and other potent new treatments may face increased risk that an HPV condition will lead to cervical cancer as they live longer.
"Cervical cancer may take many years to develop," explains Joel Palefsky, MD, associate professor of laboratory medicine at UCSF and leader of the study. "With powerful new treatments that allow them to live a longer life with HIV, women who also have HPV infections unfortunately may face a greater likelihood than before of developing this cancer if they do not regularly undergo the currently recommended screening procedures such as Pap smears."
The study, involving 1,178 HIV-positive women and 500 high-risk HIV-negative women, is part of the six-city, Women's Interagency HIV Study (WIHS) funded by the National Institutes of Health. The WIHS was established to examine HIV infection and its complications in a large, geographically and ethnically diverse population of women, compared with high-risk HIV-negative women. Cities in the study are Bronx/Manhattan, Brooklyn, Chicago, Los Angeles, San Francisco, and Washington D.C.
The most immune-suppressed HIV-positive women -- those with a CD4+ T cell count below 200/ml - were 10.13 times more likely to have HPV infection than were HIV-negative women, the study found. The risk dropped to about 5.8 for those with a count of 20,000/ml.
"The study shows that both higher HIV viral load and lower CD4 count were predictive of HPV infection," Palefsky said. "However, among the women with the lowest CD4 counts, i.e., those with CD4 less than 200/ml, the risk was high regardless of the HIV viral load."
Women under 30 were about 1.75 times more likely to be infected with HPV than women 40 or older; African American women were 1.64 times more likely than were Caucasian women, and current smokers were 1.55 times more likely than non-smokers to have HPV infection.
Other members of the research team are Robert Burk, MD, Albert Einstein College of Medicine; Howard Minkoff, MD, State University of New York; Leslie Kalish, MD, New England Research Institutes; Alexandra Levine, MD, University of Southern California; Henry Sacks, MD, Mount Sinai Medical Center, New York; Patricia Garcia, MD, Northwestern University; Mary Young, MD, Georgetown University; Sandra Melnick, PhD, National Cancer Institute; and Paolo Miotti, MD, National Institute of Allergy and Infectious Diseases.
Journal
JNCI Journal of the National Cancer Institute