Picture of cervical cancer

Imagine this. You are a doctor in Tanzania. Annual health expenditure is $4 (2.50 [pounds sterling]) per head; malaria, tuberculosis, and maternal death are pressing problems; 150 000 people died from AIDS last year; and 9% of adults are infected with HIV.[1] Life expectancy is 53 years. As an oncologist in the country's only cancer centre, you saw 1650 new cases last year. This probably represents about 10% of the total--your centre is inaccessible to the rest of the population. Around 90% of patients present with late stage, incurable disease. How do you begin to tackle cancer in such a context? This was the stark challenge posed by Twalib Ngoma of the Tanzania Cancer Center to a conference on "Cancer Strategies for the New Millennium."[2] This report synthesises selected themes from the discussion on how best to combat cancer in the developing world.

The global picture

By 2020, new cancer cases will double to 20 million a year. Already, over half of new cancers arise in people in the developing world; by 2020 the proportion will reach 70%. Cancer deaths are also set to increase, from 6 million to 12 million annually.[3]

The causes of cancer vary world wide. In developed countries, tobacco is a major culprit, causing 1 in 3 cancer deaths. In the developing world, infection plays the largest part; it is responsible for almost 1 in 4 cancer deaths. One reason for these differences is the deadly impact of decades of widespread tobacco use in richer countries--an epidemic now being propagated globally. Another is the high prevalence of chronic infection in the developing world--in particular, with human papillomavirus, which causes cervical cancer; Helicobacter priori, implicated in stomach cancer; and hepatitis B and C viruses, major causes of liver cancer. Together, these agents account for over 90% of cancers related to infection.[4] Variations in cause are reflected in differences in the cancers that predominate in different parts of the world (fig 1).[5] While the top five cancers in developed countries are (in descending order) lung, colorectum, breast, stomach, and prostate cancer, in developing countries the most common cancers are those of the stomach, lung, liver, breast, and cervix.

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Focusing efforts

What should be the relation between prevention, detection, and management? Comparison of cancer survival between rich and poor countries can inform priorities (see fig 2).[6] For some cancers the difference between rich and poor countries is relatively small, reflecting the modest effects of even optimal existing treatments. These cancers include lung, stomach, and liver cancers, projected to be among the 15 leading causes of death world wide in 2020.[7] For others, such as leukaemia and lymphoma, survival is much better in developed countries. For cancers falling between the extremes--including cancer of the cervix and breast --early detection greatly improves the potential for effective treatment (fig 2).

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Rational assessments of the potential public health impact of prevention, early detection, and treatment identify prevention as the top priority. For detection and treatment, priorities are influenced by the interplay between basic research and technological development, and between the available technology and its implementation. Many screening and treatment protocols used in richer countries do not transfer readily to countries where resources--human, technical, and financial--are in short supply. Implementation of affordable protocols, coupled with research and development of new technologies more suited to environments with fewer resources, might prove more fruitful.

Low technology approaches

Take, for example, cervical cancer, which has a known cause, an accurate detection test, and can be treated effectively. Although cervical cancer has declined in many industrialised countries, it remains the most deadly cancer among women in the developing world, where the increased risk of infection with papillomavirus is compounded by the limited capacity for screening and treatment. Each year over half a million new cases occur--almost 80% in developing countries--and some 250 000 women die from the disease (fig 3). Over 99% of cervical cancers are associated with human papillomavirus.[8] Barrier contraceptives could protect against infection, but even when these are available, women cannot always insist on their use. Research on contraceptives containing microbicide may ultimately yield benefits. However, infection and transmission of papillomavirus might be most effectively controlled if a vaccine were available.

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Two prophylactic papillomavirus vaccines are being tested in clinical trials, as is a therapeutic vaccine that stimulates cell immunity against the oncogenic viral proteins E6 and E7. These vaccines could hold special promise for women in the developing world.

How can the promise become a reality? The meeting was told that in addition to being safe and effective, vaccines must be cheap and readily administered through existing health programmes. Much can be learnt from the experience with hepatitis B vaccination, which highlights the gap between technological advances and their application. Though an effective hepatitis B vaccine has been available since 1982, and WHO has promoted global vaccination since 1991, coverage remains poor. Two thirds of infants at risk in developing countries are unvaccinated (fig 4). Less than $2 (1.25 [pounds sterling]) will protect a child against hepatitis B,[9] yet this is double the price of all six vaccines in WHO's expanded programme of immunisation, and cost remains the major constraint. Finally, even if papillomavirus vaccines were to become available, many people are already infected. Early detection coupled with effective treatment must therefore play a crucial role for years to come.

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In industrialised countries, detection of cervical cancer relies on smear testing. Although cytological testing is feasible in some developing countries, systematic coverage and follow up are beyond the reach of many more. Research is under way into alternative detection methods that can be integrated into ongoing health programmes in resource-poor countries. One approach, known as VIA, involves visual inspection of the cervix after the application of acetic acid and can be performed by trained health workers. A study in India has shown that the specificity and the sensitivity of VIA in detecting early disease related changes are similar to those of cytology. Further research will assess whether VIA reduces mortality from cervical cancer and will evaluate its potential in case finding and screening.

Early detection is useful only where effective treatment is feasible. Traditionally, high grade precursor lesions of cervical cancer are treated with surgical conisation, which requires admission to hospital. One alternative is a "see and treat" approach. Suspect lesions identified by VIA are confirmed by colposcopy, and treated immediately using loop electrosurgical excision procedure or cryotherapy. This approach means that women diagnosed with a lesion are not lost to follow up. Loop excision has particular advantages in resource-poor environments--the equipment is relatively cheap and easy to operate, specialist surgical skills are not required, and complications are rare. Low technology strategies could also prove valuable in early detection of breast cancer. Breast examination by health workers can detect a substantial proportion of early breast cancers. Overall, the evidence suggests that it should be carried out routinely whenever women interact with health services.

Relieving suffering

Curative treatment is crucial. However, in the developing world, around 80% of cancer patients have late stage incurable disease when they are diagnosed. Clearly, health professionals have an ethical duty to prevent avoidable suffering. Effective pain relief should be an integral part of management but unfortunately, access to palliative care is limited. Community based interventions can improve access, deliver effective pain relief and enhance social integration and quality of life, but they also raise equity issues. In many societies, the burden falls mainly on women, who may also be less likely to receive care should they themselves fall ill.

Local action, global action

Controlling cancer in different environments requires tailored strategies. What, then, can an international perspective add? One answer lies in recognising the potential for synergies with other health programmes and the need for concerted action at different levels--local, national, regional, and global.