A simple DNA screening test for human papillomavirus (HPV) followed by treatment reduced the risk of developing precancerous lesions of the cervix by 80 percent in HIV-positive women over three years, according to a study published in the October 23 issue of AIDS. This method could dramatically expand early intervention efforts designed to reduce cervical cancer rates in women from resource-poor nations.
Women with HIV are at much higher risk of HPV infection—strains of which cause either genital warts or cervical and anal cancer—and of progression to cervical cancer than HIV-negative women. For this reason, regular screening and treatment for precancerous cervical lesions is a routine part of HIV care for women in the United States.
In fact, while cervical cancer was once a leading cause of death among all women, it is now relatively rare in wealthier countries. In resource-poor countries, however, the lack of resources means that many women are not appropriately screened or treated for precancerous lesions and that cervical cancer remains a significant threat to women’s health.
The gold standard for cervical cancer screening is to have an expert examine the cervix using a magnifying device called a colposcope; if lesions are found, biopsies of the tissue determine the severity. In poorer countries, colposcopy is simply too expensive to screen the many thousands of women who need it. Plus, it requires a level of expertise that most health care providers don’t have.
For this reason, Louise Kuhn, PhD, from Columbia University in New York City, and her colleagues examined two less expensive methods to screen and treat HIV-positive and HIV-negative women in Cape Town. In all, 956 HIV-positive women and 5,596 HIV-negative women participated in the study, which ran from 2000 to 2006.
Only women ages 35 to 65 were asked to participate. Before the study started, all of the women had their cervixes and vaginas swabbed. The swab was then tested for HPV DNA. All of the women also had a visual inspection of their cervix, with acid staining to detect abnormal tissue. No biopsies were performed at study entry.
Women were randomized to one of three arms in the study regardless of their initial HPV DNA or visual inspection results. In the first group, the DNA results were used, and all women with a positive HPV DNA had a second examination and all detectable lesions were ablated (burned off). In the second group, DNA results were ignored. Instead, nurses used the results of the initial visual inspection to determine which women had lesions that required ablation.
In the third group, the researchers delayed treating the women for six months regardless of their HPV DNA or visual inspection results, in order to provide a group to which they could compare the two screen-and-treat approaches.
At study initiation, roughly 45 percent of HIV-positive women and 17 percent of HIV-negative women in all three groups had detectable HPV DNA. Otherwise, the groups were very similar. As the study took place before CD4 testing or antiretroviral (ARV) therapy was rolled out in South Africa, neither factor was included in the analysis.
Six months after the women were randomized to one of the three arms, they had a colposcopy, any lesions were biopsied, and any serious lesions were cut out. All of the women who initially tested HPV DNA positive, or who had lesions detected based on visual exam—plus one third of the remaining women—were followed for an additional 30 months, with further colposcopies and biopsies at months 12, 24 and 36.
Kuhn and her colleagues found that DNA testing was highly effective as a screening method regardless of HIV status. HPV DNA screening and treatment reduced the risk of developing further precancerous lesions by 80 percent in HIV-positive women and 69 percent in HIV-negative women. What’s more, the reduction in lesions held up over three years of follow-up. Visualization as a screening method was far less effective, with only 49 percent of HIV-positive women and 24 percent of HIV-negative women remaining lesion-free.
“Our trial advances the field by providing a randomized evaluation of a new screening approach that has the potential to expand access to cervical cancer prevention in low-resource settings,” the authors concluded. “Therefore, priority should be given to better understanding of the safety and efficacy of screen-and-treat programs in HIV-positive women.”
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