A lab test for the human papilloma virus (HPV) combined with a visual inspection of the cervix could identify pre-cancerous lesions and vastly reduce the number of false positives among women at high risk for cervical cancer in developing countries, according to researchers at Johns Hopkins and the University of Zimbabwe.
In a study published in the January issue of the International Journal of Gynecology & Obstetrics, the visual inspection/HPV test combination accurately detected 132 (63 percent) of the 208 cases of precancerous disease in a sample population of African women. By contrast, combining a Pap smear plus an HPV test detected 84 cases (40 percent), and combining a visual inspection plus a Pap smear detected only 75 cases (36 percent).
Performing the first two tests together also reduced by up to 62 percent the number of false positives – women who test positive for cervical cancer and who later are deemed not to have it. False positives are somewhat common when using only visual inspection, but researchers say reducing them might result in a screening program that could better separate those who should be offered treatment from those who don't need it. Currently, the lack of money and laboratories in poor nations presents a significant barrier to increasing cervical cancer screening and lowering the death rate from the disease.
"Although our results demonstrate a definite potential for combining HPV testing with visual inspection, the test would have to became almost as easy and inexpensive as a take-home pregnancy test for it to become a really useful part of a combination," says Paul D. Blumenthal, M.D., M.P.H., lead author of the study and an associate professor of gynecology and obstetrics at Johns Hopkins.
"Because underdeveloped nations lack the resources needed to implement the kind of laboratory-based screening that has become customary in the United States, alternatives have been sought. Washing the cervix with a vinegar solution (which turns precancerous tissue white) and then inspecting it visually has been shown to be effective and attractive. However, visual inspection alone yields a high number of false positives."
During the study, nurse-midwives at 15 primary care clinics in Zimbabwe screened 2,199 African women for cervical cancer, performing the vinegar/visual inspection method, Pap smears and HPV tests on each. The women ranged in age from 25 to 55 and were not pregnant. Although all were sexually active, fewer than 15 percent had ever been screened for cervical cancer. Colposcopy (high-powered magnification) and when necessary, biopsy, were used to confirm abnormal results.
Researchers took test results from 2,073 women (all that were available) and developed a computer model to simulate cervical cancer detection rates of each of the following combination of tests: visual inspection plus HPV test; HPV test plus Pap smear; and visual inspection plus Pap smear.
"Our results suggest that combining the visual inspection and an HPV test would be a more effective screening approach than a Pap smear followed by an HPV test, or vice versa," Blumenthal says. "Easy screening measures are urgently needed for this population because many women live far from medical facilities and it's very difficult to track them once they leave.
"The down side to the combined test is that there are a few patients who actually have disease that will go unnoticed if both the visual inspection and HPV test must each be positive to consider the combination test positive. But more importantly, if the visual inspection is negative, or if it's positive but the HPV test is negative, so the combination is negative, then it's right 95 percent of the time and there is no disease that needs treatment."
Only 5 percent of women in developing countries are routinely screened for cervical cancer, compared to up to 70 percent in industrialized nations. Cervical cancer – a sexually transmitted disease caused by HPV – is the leading cause of female cancer deaths in parts of Africa, Asia and Latin America, killing 200,000 women each year.
HPV tests currently are performed by swabbing the cervix and sending the specimen to a lab to detect presence of the virus. It doesn't matter whether a patient does the swabbing herself or a clinician does it, Blumenthal says. Therefore, it may be possible to make a streamlined, home kit in the next few years, he says.
Continuing work needs to be done, Blumenthal says, as visual inspection is the only test right now that can give immediate results.
The study was supported by the JHPIEGO Corp. (an affiliate of The Johns Hopkins University committed to international reproductive health interventions in areas with limited resources) with funding from the United States Agency for International Development, the Bill and Melinda Gates Foundation and by public health services grants.
The study's other authors were L. Gaffikin, Dr. P.H.; J. McGrath; S. Womack; and K. Shah, M.D., Dr.P.H., of Hopkins and JHPIEGO; and Z.M. Chirenje, M.D., of the University of Zimbabwe.
Related Web sites:
JHPIEGO: http://www.jhpiego.jhu.edu/
University of Zimbabwe: http://www.uz.ac.zw/
National Cervical Cancer Coalition: http://www.nccc-online.org/
Cancer Bacup: http://www.cancerbacup.org.uk/info/cervix.htm
Alliance for Cervical Cancer Prevention: http://www.alliance-cxca.org
Journal
International Journal of Gynecology & Obstetrics