Meeting the Challenge of Cervical Cancer Screening in Low-Resources Countries

Issue 22, Winter/Spring 2014

Cervical cancer is now a rare disease in the U.S. thanks to Pap smear screening which was introduced in the 1940s. Unfortunately, this is not the case in low-resource countries where cervical cancer remains the leading cause of cancer-related death among women. Failure to implement adequate screening programs in these low-resource countries explains these global disparities. However, new developments in cervical cancer screening approaches offer renewed hope that these disparities may be eased.

HPV tests to replace the Pap smear

Dr. Harald zur Hausen was awarded the Nobel Prize in Medicine in 2008 for his discoveries some 30 years earlier that human papillomavirus (HPV) causes cervical cancer. However, it was only about 10 years ago that tests for HPV became available for use in routine screening. These tests detect about a dozen HPV types – all of which are known to cause cervical cancer, including the two most common types, HPV 16 and HPV 18. Like the Pap smear, the HPV test requires the collection of a swab of cells from the cervix during a gynecologic exam.

A major advantage of the HPV test over the Pap smear is that it is much less prone to miss women who have lesions on their cervix likely to progress to cancer if left untreated. It is always a bit disconcerting to be reminded that the Pap smear misses about half the women who actually have cervical disease in need of treatment. In fact, the poor performance of this test necessitated guidelines in the U.S. that advised screening almost every year for many age groups. Such frequent screening drives up the cost of cervical cancer prevention and places it beyond the reach of low-resource countries.

When the HPV test is used instead, since it is less prone to overlook women with disease, screening can be done less frequently, bringing the price-tag down. With the HPV test, even a “oncein-a-lifetime” round of screening, if targeted to the right age group, has the potential to considerably reduce suffering and death from cervical cancer.

Single-visit approaches

Doctor with patient

Shifting away from a multi-visit to a single- or two-visit strategy is another hallmark of new approaches to cervical cancer screening in low-resource countries. Conventional screening programs in the U.S. use an initial screening test (Pap smear and/or HPV test) to identify which women require further follow-up and testing to reach a definitive diagnosis. Treatment is only given if the diagnostic test confirms disease.

The follow-up diagnostic testing that is recommended requires a colposcopy. This is a procedure undertaken by a specially-trained gynecologist who examines the cervix with high magnification and takes a small piece of tissue (biopsy) from where the cervix appears to be most abnormal. The biopsy is examined by a specially-trained pathologist who determines whether there are tissue changes consistent with the type of lesions that may progress to cervical cancer.

It is quite obvious that thismulti-step process to identify who should be treated adds considerable cost and complexity to cervical cancer screening. In low resource countries, there simply are not enough gynecologists and pathologists to cope with a program designed along these lines even were the training and materials to be provided. In addition, this multi-step process offers plenty of opportunity for women to be lost from the system since it requires a minimum of 3 to 5 well-coordinated visits to accomplish a single-round of screening. Thus, simplification is essential.

Simplification has mostly taken the form of eliminating the diagnostic step and offering treatment purely on the basis of the screening test result. In other words, a woman who tests positive for HPV is offered treatment at that initial point – no further confirmatory tests are done. In many low-resource settings, trained nurse practitioners have taken over the traditional gynecologists’ role and collect the samples for the screening test and undertake the treatment procedure which usually involves cryotherapy or freezing of the top layer of the cervix to eliminate the lesion.

Microscopic view of a cell

Ideally, the result of the screening test should be available before the woman leaves the health facility so that if the screening test is abnormal, treatment could be done on the same day. In practice this has proved difficult to accomplish as usually samples need to be sent to a central laboratory. Thus even this simple “screen-and-treat” approach has mostly required two visits. New developments in point-of care tests that can be done quickly and easily at clinical sites using inexpensive machines will allow this approach to become truly “single-visit.”

A disadvantage of screen-and-treat is that it results in over-treatment since a sizable number of women with abnormal screening tests do not actually require treatment. In the case of HPV testing, the problem of over-treatment has largely been addressed by limiting screening to women over 35 years of age. In this age group, any HPV infection detected is more likely to be a persistent one. Persistent infections more strongly predict progression to cancer over the long-term than the often transient HPV infections observed in younger women.

Vinegar tests controversies

A highly appealing approach to cervical cancer screening in low-resource countries is one using a simple vinegar test. Vinegar is put on the cervix which makes abnormal areas of the cervix turn white. These white spots can then be observed by trained clinicians. Nurses and even lay health workers have been trained to detect these white areas and the cost is minimal. Most importantly, the result is available immediately, it can be communicated in an intuitive way, and treatment can be offered right away. Several programs in low-resource countries have implemented cervical cancer screening using this approach, naming it “see-and-treat”.

The downside of this approach is that the detection capabilities of the vinegar test are poor. At best, it misses about half of the women at risk, but at the same time classifies almost a third of women who are at very low risk of cancer as being abnormal. Its performance is also highly variable and dependent on the training and supervision of the clinicians. However, lack of access to the better option of HPV testing has forced many programs to adopt this approach despite its shortcomings.

Cancer prevention vaccine

The HPV vaccine, which can prevent acquisition of HPV 16 and HPV 18, is being given at pilot sites in a few low resource countries. Since HPV 16 and HPV 18 are estimated to account for 60 to 70% of all cervical cancer, subsequent cervical cancer should be reduced by this amount within the cohort of women now getting access to this vaccine. For the generation too old to benefit from the new HPV vaccine (essentially all those who became sexually-active before the vaccine became available) as well as all those without access to the HPV vaccine, screening will remain the primary modality to prevent cervical cancer for the foreseeable future.

Yin and Yang of screening

No screening approach is perfect. A test may miss some disease but be accurate in those it defines as abnormal. A test may miss almost no disease but classify as abnormal many women who are not at risk. Program planners need to balance the dangers of allowing women to potentially go on to develop cancer (either because they are missed by the imperfect screening tests or cannot be adequately maintained in the program) against the side effects and costs of providing treatment unnecessarily. In addition, low-resource countries have health service challenges and competing health priorities to juggle. The new approaches to cervical cancer screening based on the simplified “screen-and-treat” concept, usually utilizing HPV testing, have the potential to improve health and wellbeing of women globally if the resources can be mobilized to implement screening more widely.

Louise Kuhn, Ph.D.

Louise Kuhn, Ph.D.
Professor of Epidemiology
Mailman School of Public Health, Columbia University
New York, NY