NEWS

Developing Countries Put Cervical Cancer Tests to the Test

Linda Wang

Since the Pap test debuted in the 1960s, countries in the developed world have seen their cervical cancer mortality rates decline. In the United States, cervical cancer rates have dropped about 80% in the last 40 years. But because poorer nations cannot afford nationwide screening programs, their rates of cervical cancer have continued to rise.

"Cervical cancer is one of those health issues between the developed and developing world where there are clear inequities in care," said Thomas C. Wright, M.D., professor of pathology at Columbia University in New York.



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Dr. Thomas C. Wright

 
Simpler and less costly screening tests exist, and researchers are trying to predict how well these tests might perform in different resource settings. But the right test is only one component of an effective screening program.

More important, how do you ensure that all women who test positive for abnormalities will return for treatment? And if cervical cancer is found, is there an ethical obligation to treat the women even when resources are limited?

Alternative Tests

While Pap screening programs have reduced the rates of cervical cancer in many high-income countries, similar programs in poorer countries have had little or no effect, researchers concluded in the October 2001 Bulletin of the World Health Organization.

Most developing countries do not have the capacity to screen women more than once or twice in a lifetime, explained Sue Goldie, M.D., assistant professor of health decision science at Harvard University in Cambridge, Mass.



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Dr. Sue Goldie

 
Pap screening programs in developing countries have focused on women in their 20s—too young to show any specter of cervical cancer. Caused by HPV viruses, cervical cancer grows slowly, and women infected in their 20s may not develop precancerous lesions until their 30s or 40s. Unfortunately, women in developing countries who visit clinics where cervical screening may be available are typically in their 20s. Goldie said that if cervical cancer screening can only be performed once or twice, it will be most effective between the ages of 25 and 45 years.

Some countries with existing screening programs are reorganizing them by expanding their coverage of women, targeting a more appropriate age group, and improving their treatment services. Chile reorganized its cervical screening program in the early 1990s, and since then, deaths from cervical cancer have begun to decline. Costa Rica reorganized their screening program as well, and their incidence of cervical cancer has also started to decline. This April, Singapore’s Health Promotion Board will launch a new cervical screening program to target women in an older age group than previously screened. Brazil is undertaking a similar effort.

But "for many developing countries [without existing programs], I think to organize a cervical cancer screening program may not be feasible because of resource crunches," said Rengaswamy Sankaranarayanan, M.D., of the International Agency for Research on Cancer, Lyon, France, and lead author of the WHO paper. He and his colleagues recommended that these countries consider screening more women, but less frequently. Modeling studies by Goldie and her colleagues have suggested that a once-in-a-lifetime screen with a reasonably sensitive test could reduce the incidence of cervical cancer by 25% to 30%.

Visual inspection with acetic acid (VIA) is one such screening test. Using this approach, nurses or midwives swab a woman’s cervix with vinegar, and any precancers will turn white. A study of women in South Africa has suggested that VIA is similar in sensitivity to the Pap test but lower in specificity.

HPV Testing

HPV testing is another promising approach. Because 90%, if not 100%, of cervical cancers are caused by HPV viruses, screening for the virus can help predict future cancers. HPV tests are simpler to perform than the Pap test, and the same study in South Africa that used an early version of a commercially available HPV test found that the sensitivity of HPV testing was similar in sensitivity to the Pap test but lower in specificity.

Paul Blumenthal, M.D., an obstetrician/gynecologist with JPIEGO Corp., Baltimore, Md., a nonprofit organization affiliated with Johns Hopkins University, said that HPV testing is extremely promising but cautions that "in many countries, it’s still too expensive." For those countries, he said, VIA may be a less costly alternative.

In the WHO report, Sankara-narayanan cautioned that VIA is still an experimental option and that "it remains to be demonstrated whether VIA-based screening programs are associated with a reduction in cervical cancer incidence and mortality. In developing countries, existing ineffective cytology-based programs should be urgently reorganized and monitored."

Nonetheless, several countries have launched small-scale demonstration programs based on VIA. Peru has started a demonstration program in its San Martin region, which they plan to cover in 2 to 3 years. Kenya has also started a VIA-based demonstration program in one of its districts.

Which approach will ultimately work depends on the resources of each country. "The answer is going to be different for different countries," said Goldie. "I think that each test has limitations and certain strengths, and the challenge is to figure out what will work where."

Blumenthal added that countries should not be limited to one test. "Maybe in urban areas you have an effective Pap screening program. But maybe in rural areas you don’t, and so you might have a country that has two approaches," he said. "I think the mantra is not necessarily to implement the single best practice, but to implement those practices which make the best sense in a given environment."

Researchers are turning to computer models to predict which test might work best for a particular setting. "What we hope to do is do a series of cost effectiveness models for a variety of different scenarios," said Columbia’s Wright. "We’re going to look at Peru. We’re going to look at Kenya. We’ve already looked at South Africa. We’re going to model for a group of developing [countries] what they would expect to get using each of these different approaches."

Computer Models

A computer model-based study of a South African women who had no prior cervical screening compared the cost-effectiveness of the Pap test, VIA, and HPV testing. The results, published in the June 27, 2001, Journal of the American Medical Association suggested that, in settings with extremely limited resources, a one-time visit with VIA and HPV would be most cost-effective. Single-visit VIA reduced the incidence of cancer by 26%, and single visit HPV testing reduced cancer by 30%.

Wright said the goal of these models is to be able suggest to the health ministers of each country which test, or tests, might be the best option for their country. "You want to be able to walk in with some well-thought-out programs, and I think in the next couple years we’re going to be at the point where we have those," he said.

New Challenges

One limitation with the Pap test is that it can take weeks for the results to come in. If a woman lives 8 hours from a clinic or if she doesn’t have a telephone, it’s hard to get her to come back for treatment, said Goldie. As a result, "people have lost 50% or 75% of their screened patients," she said.

Eric Suba, M.D., of Kaiser Permanente Medical Center in Redwood City, Calif., noted that some countries have overcome the problem by hiring a person exclusively to contact women with abnormal Pap tests. Studies have suggested that this extra effort raises the return rate to 90%, he said.



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Dr. Eric Suba

 
Goldie agreed that approach may work in some countries but argued that it may not work everywhere. "There’s all kinds of reasons within the culture that it’s not ideal for women to come back in 2 weeks or 3 weeks," she said. A woman in rural South Africa who is caring for 8 kids may not want to leave her home for another day, she said. For them, VIA followed by immediate treatment with outpatient cryotherapy may be a more practical option. Wright and his colleagues are testing the safety of this approach with a randomized clinical trial in South Africa.

Suba cautioned that this approach carries the risk of overtreatment and argued that the long-term safety of large-scale overtreatment has not been established. Blumenthal noted that public health officials in many developing countries are more interested in sensitivity than specificity: "Our colleagues in developing countries are very concerned with trying to eliminate cervical cancer as a public health problem, and in order to do that, you need to cast a net through which very few fish can escape."

Undertreatment may be as much of a concern as overtreatment. A new screening program will inevitably turn up cases of cancer that "carry with them an ethical requirement for treatment," said Suba. "If you start screening in a community and you turn up cases of invasive cancer and you cannot offer treatment services to those women, that program will very soon lose the support of the community."

Goldie agreed and said that the minimal standard radiation therapy must be available to who women who are diagnosed with cancer. "If we’re going to screen women and tell them something’s wrong, there needs to be ability to do something about it," she said. "But over time, you hope that will go away because you’re preventing [the cancer]."


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