Abstract
Researchers around the world are working to evolve vaccines, screening tests, and treatments that are already in place in the developed world for cervical cancer into solutions that work in developing nations.
Research on prevention, detection, and treatment fights disease in the developing world
The cause of most cervical cancer is known: infection with one of the high-risk types of the human papillomavirus (HPV). Vaccines prevent infection, screening allows for early detection, and treatments cure early-stage disease. In the United States, where the disease once killed more women than any other cancer, it will claim fewer than 4,000 lives this year.
Yet in the developing world, this preventable and curable disease kills 242,000 women each year, according to the World Health Organization (WHO) GLOBOCAN 2008 project. Death tolls may rise to 430,000 per year by 2030 without additional intervention.
“If you look at the amount of prevention in places that need it most, it's very limited,” says Mark Schiffman, MD, a senior investigator at the National Cancer Institute (NCI), who specializes in cervical cancer. “You may have this sense that if you can just figure out what causes a cancer, then the rest will come automatically. But it turns out there's this whole science of translation that doesn't come automatically.”
Although the biggest challenges may be economic and cultural, researchers are working to transform vaccines, screening tests, and treatments that are already in place in the developed world into solutions for developing nations.
Cutting Costs
Current HPV vaccines, Merck's Gardasil and GlaxoSmithKline's Cervarix, cost hundreds of dollars. In addition, the U.S. Food and Drug Administration–approved regimen requires 3 doses over 6 months for women at a young age.
However, recent research suggests that 2 or even 1 dose may suffice, which could make the vaccine more affordable and easier to get. In an analysis of data from an ongoing NCI-sponsored HPV vaccine trial in Costa Rica, Aimee Kreimer, PhD, an NCI cancer epidemiologist, found that participants who did not receive all 3 doses showed similar levels of protection as those fully vaccinated 4 years after their last shot.
Other investigators are testing 1- and 2-dose regimens in resource-poor areas of Africa. “Studies like this are really important in places where malnourishment or infections may alter immune responses,” says Kreimer.
In parallel, work is under way to develop a plant-based vaccine grown in tobacco that could drop the vaccine cost to just a few dollars and allow some regions to grow the vaccines locally. “In the past year, the plant technology has finally advanced enough that we have a much better chance of succeeding than we did 10 years ago when we started,” says Alfred Bennet Jenson, MD, an immunobiologist at the Brown Cancer Center at the University of Louisville in Kentucky who helped develop the original HPV vaccine.
For women who are already sexually active or who may already have HPV, screening provides a second tier of defense.
A 2009 study in the New England Journal of Medicine revealed that the HPV DNA test outperformed the Pap smear and visual inspection in detecting cervical cancer in rural India (N Engl J Med 2009;360:1385–94). The test reduced the incidence of advanced cancers by 50% through early detection and treatment.
Cervical cancer, the third most common cancer in women, claimed 275,000 lives worldwide in 2008, the overwhelming majority in developing countries.
Cervical cancer, the third most common cancer in women, claimed 275,000 lives worldwide in 2008, the overwhelming majority in developing countries.
But, says Schiffman, “most HPV DNA tests are too expensive, too labor intensive, and too technical to be used in low-resource areas.” Efforts are under way to develop low-cost, easy-to-use versions. For instance, the careHPV test from QIAGEN is on trial in China and Africa. The test requires no electricity, running water, or specialized training, and it returns batched results in a few hours.
An inexpensive, less sensitive but more specific alternative is visual inspection with acetic acid (VIA). With this lowtech test, a nurse paints vinegar on the cervix and inspects it for precancerous lesions. If found, lesions can be frozen off immediately, an effective form of early treatment, says Cynthia Firnhaber, head of the cervical cancer program at Right to Care, an HIV-focused nonprofit in Johannesburg, South Africa. Firnhaber says VIA is “a decent choice” in resource-limited areas.
The Pap smear, considered the gold standard, is also being used to screen large populations in areas with access to laboratories and electricity. For example, in December 2012, Fortis Hospital in Mumbai, India, set a Guinness World Record for screening 751 women for cervical cancer in 8 hours. “The most important lesson learned during the screening event was the lack of awareness,” says Vandana Gawdi, MD, consultant obstetrician and gynecologist at Fortis.
Approximately 75% of newly detected cervical cancer cases in India are too advanced to be cured, Jenson estimates. Many hospitals in developing nations can't support standard chemotherapy and radiation treatments for the disease. Some are not outfitted to treat cancer at all because of more pressing concerns such as malnourishment, sanitation, and HIV.
New treatments are still moving ahead, including one on trial in India with promise to eliminate the need for chemotherapy. Jenson and colleague Partha Basu, MD, head of gynecologic oncology at the Chittaranjan National Cancer Institute in Kolkata, India, are comparing standard treatment to a new therapy that combines radiation with immunotherapy, including interferon α given as a shot and retinoic acid as a pill. — Elizabeth Dougherty
For more news on cancer research, visit Cancer Discovery online at http://CDnews.aacrjournals.org.
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