Early Detection of Cancer in Developing Countries

by R. Sankaranarayanan ¹

Enumeration of women to be screened as part of a cervical cancer prevention program in Guinea.

Cancer is a generic term that refers to an aggregation (mass) of cells in a human organ that originated from the proliferation of a single cell that has escaped from normal growth control mechanisms (see Table 1 for a glossary of commonly used terms necessary to a general understanding of cancer). Cancer cells, also referred to as malignant cells, can develop from any tissue or organ in the human body. They result from changes in the genetic material in the cell of origin that may have occurred spontaneously or were induced by an agent (referred to as a carcinogen) that causes, or at least, predisposes, to cancer. Carcinogens include tobacco (however used), alcohol, certain viruses such as hepatitis B virus (HBV), human papillomaviruses (HPV), bacteria (e.g., helicobacter pylori), radiation, sunlight and certain chemicals. The mass of cancer cells (or malignant tumor) continues to multiply, resulting in enlargement of the original (primary) tumor and the invasion and destruction of adjacent normal tissues. Cancerous cells from the primary site may also spread to distant organs or tissues, where they produce colonies of cancer cells called metastases. For example, a cancer in the breast (primary site) can invade the skin and chest wall muscles (local spread) and/or can spread to the lymph nodes in the arm pit, or to the lungs, bones and brain (metastases).

All cancers, with the exception of skin cancers, invariably lead to death if not detected and treated properly. For nearly all cancers, treatment options and survival are related to the stage of the cancer, stage being a shorthand notation for the anatomic extent of disease. When cancers are diagnosed in early stages, i.e., when the extent is limited, high cure rates can be achieved by relatively simple, inexpensive therapy that is less toxic and ensures a high quality of life after treatment. More aggressive treatment that may entail more extensive surgery and/or radiotherapy and/or more intensive and more toxic systemic therapy (e.g., chemotherapy and hormonal therapy), is required when cancer is detected in moderately advanced stages when prospects of cure are more limited. Treatment of any kind is rarely effective in curing patients with very advanced cancer, particularly when it has spread to distant organs; almost all cancer patients with metastatic disease die within two years from diagnosis (exceptions include testicular cancer, placental tumors, and some leukemias and lymphomas). The early detection of cancer followed by prompt treatment, therefore, represents an important means of improving survival rates as well as decreasing the cost and toxicity of required treatment and lessening the risk of late treatment complications (including second malignancies). Early detection is particularly important in developing countries where, at the present time, up to 80% of cancers are diagnosed in advanced stages and less than 50% of patients survive for more than five years. The most common cancers in developing countries are cancers of the lung, stomach, liver, breast, uterine cervix (neck of the womb), head and neck, oesophagus, large bowel, urinary bladder and lymphoma and leukemia, which together account for four-fifths of all cancers. Of these, early detection and appropriate treatment is currently feasible for the control of cancers of the breast, uterine cervix, head and neck, large bowel and urinary bladder.

Aggressiveness: The speed with which a cancer grows and spreads to adjacent and distant organs. Carcinogen: An agent that causes cancer. Cure: Complete and permanent elimination of the cancer from the body. Diagnosis: The process of identifying and/or confirming disease in persons with symptoms or with a positive screening test. Early cancer: Cancer diagnosed in stage 0 or stage I. Invasion: The capacity of a cancer to infiltrate and destroy surrounding tissue. Metastasis: A colony of cancerous cells in a location distant from the primary site of disease. Cancer cells can metastasize via the lymphatic system or blood stream. The term is not used for leukemias and lymphomas, which are often widespread from the onset of disease. Neoplasm: General term for a tumor or “new growth”; benign tumors are not cancerous, while malignant tumors are. Precancerous lesions: A situation in which cancer cells remain confined to a part of the organ in which they first arose and have not yet developed the capacity to invade adjacent tissues or spread to other parts of the body (stage 0). Primary site: The organ in which the cancer initially developed. Recurrence: The return of cancer after effective treatment – in the case of solid tumors, either in the primary location or as one or more metastases in other organs. Remission: Partial or complete disappearance of a cancer after radiation or systemic treatment. Response: A diminution in the size and extent of tumor following treatment. Response, corresponding to remission, can also be partial or complete. Screening: Checking for early-stage cancer in apparently healthy people who have no symptoms. Stage of cancer: A defined notation representing the size and spread of cancer in the body. Stage 0 is precancerous lesion, stage I corresponds to early cancer, stages II and III, moderately advanced and stage IV, metastatic cancer. Staging of cancer: Investigative procedures directed towards evaluating the stage of cancer. Survival rate: The percentage of cancer patients who survive for a given time period after diagnosis (e.g., the five-year survival rate is the percentage of people who survive five years).

Table 1. Commonly used terms relating to cancer.

Cancer Control

Cancer control, as discussed in previous issues of Network, refers to all actions taken to prevent or reduce the occurrence of cancer, the morbidity or suffering from cancer, and cancer-related deaths. These actions include preventing exposure to carcinogens, often referred to as primary prevention, the early detection of cancer followed by prompt and efficient treatment, and the control of symptoms from cancer, including the pain and suffering caused by very advanced cancer (palliative care). Due to massive investments in cancer control activities in the last few decades, cancer deaths have declined in the more developed countries of Europe, North America and Australia, particularly in the last ten years. On the other hand, there has been an increase in cancer deaths in many developing countries, due to the increasing cancer burden in these countries coupled to a paucity of planned cancer control actions. Recently, the World Health Organization (WHO) strongly recommended that each country develops and implements a comprehensive national cancer control program (NCCP), to reduce the suffering from cancer and improve quality of life, as an important element of its overall public health initiatives.

Early Detection of Cancer

Most cancers could be detected earlier if the index of suspicion of cancer on the part of primary health care workers were higher, particularly when providing care for persons known to be at high risk for cancer (because of exposure to carcinogens or a strong family history). Symptoms and signs that may give an early warning of cancer, however, should also trigger an informed and empowered individual to seek medical care. The early warning signs of cancer are listed in Table 2. Some of these are general changes that do not help pinpoint any particular cancer. Nevertheless, their presence can lead to physical examinations and laboratory tests necessary to exclude or confirm the diagnosis and they should not be ignored. Fortunately, most of these symptoms are usually caused by far less serious conditions. Other symptoms such as a lump in the breast or a red patch in the mouth or bleeding after sexual intercourse are much more specific and help doctors to detect a particular kind of cancer.

A sore or ulcer that does not heal: Ulcers that not do not get better or are increasing in size, becoming more painful, or starting to bleed. Change in bowel or bladder habits: Changes in frequency; changes in the color, consistency (diarrhoea or constipation), size or shape of stools; blood in urine or stools. Unusual bleeding or discharge: Blood in urine or stools; a discharge (particularly if blood stained) from any part of the body, e.g., nipples, penis, vagina; bleeding after sexual intercourse, intermenstrual bleeding. Thickening or lump in breast or elsewhere: Any lump in the breast or scrotum detected by self examination or a lump detected elsewhere in the body. Indigestion or difficulty in swallowing: A feeling of pressure in the throat or chest which make swallowing uncomfortable; feeling full without food or after eating only a small amount of food. Obvious change in a wart or mole: Asymmetry: Does the mole look the same in all parts or are there differences? Are the borders sharp or ragged? What color or colors is the mole? Is the mole bigger than 6 mm and/or increasing in size? Nagging cough or hoarseness: A change in the voice; a cough that does not go away; sputum containing blood. A white or red patch in the mouth: Lasts for more than four weeks; cannot be rubbed off.

Table 2. Warning symptoms and signs of cancer.

The early detection of a small number of cancers (e.g. uterine cervix, breast, large bowel and oral cavity) can be achieved by screening persons with no symptoms. Such programs may be opportunistic i.e., members of the public must seek appropriate tests (which requires, of course, knowledge of their existence) or are offered them only if and when they access the health system for another reason. Alternatively, programs may involve recruitment i.e., the establishment of a program in which there is a systematic and organized effort to invite and test specifically targeted persons (e.g., of appropriate age and sex) in a particular geographical region for the possible presence of the cancer being screened for. Screening programs for cervical, breast and large bowel cancer have been in place in the more developed countries since the 1970s, or in some cases even earlier. Women aged 30-60 years, for example, are screened by Pap test for cervical cancer every 3-5 years, which has resulted in an 80% reduction in deaths from cervical cancer. Screening tests are not usually definitive and a positive test only indicates a high probability of having the disease. A positive result should normally be confirmed or disproved with further diagnostic tests (although when treatment is very simple and non-toxic, as in premalignant cervical cancer, treating all screen-positive patients is a strategy adopted in some programs to avoid the problem of patients failing to report subsequently for treatment).

Although screening tests can help to save lives, they can be costly and sometimes have unnecessary psychological or physical repercussions. One reason for this is that screening tests, particularly if not carried out properly, can give false-positive or false-negative results. False-positive results suggest a cancer is present when it is not, leading to other tests that may be expensive, time-consuming and sometimes risky. False-negative results show no hint of a cancer that is present, leading to a false sense of security. For these reasons, there are only a small number of screening tests that are considered reliable enough for routine use. Even then, a significant proportion of premalignant lesions detected may not progress to cancer in the patient’s lifetime, but the risk is such that all such lesions must be treated so that some patients receive unnecessary therapy. Such therapy can vary from a minor, essentially risk-free procedure (e.g., in cervical cancer), to significant surgery and/or radiation (e.g., in breast cancer). All of these issues, in addition to the risk of developing the cancer in question, must be weighed in the balance in the context of available and required additional resources in assessing the potential health benefits and cost of screening appropriate target populations.

The awareness of the general public about common cancers, their causative factors, the value of early detection, the possibility of screening and the location of health service facilities where screening or early diagnosis is available is critical to the success of early detection programs; unfortunately, a fraction of screen-positive patients, particularly in the poorer countries, refuse therapy because of issues of cost, stigma or fear. It is also essential that health care providers are appropriately educated about early detection, and that a sufficient number of adequately trained and skilled health professionals, along with the necessary equipment, supplies and facilities for early detection, diagnosis, treatment and follow-up, are available. It cannot be emphasized enough that early detection is of no value unless followed by effective treatment. Confirmation that cancer is present requires diagnostic tests such as visualization by endoscopy, or imaging by various techniques such as special X-rays (e.g., mammography), ultrasonography, computerized tomographic (CT) scans or magnetic resonance imaging (MRI). Sometimes biochemical tests (e.g., on blood) are valuable diagnostic aids which may also be used for assessing the effect of treatment. Unfortunately, many of these procedures are not always available in developing countries, or are out of the range of the patient’s ability to pay. Ultimately, the examination under the microscope by a trained pathologist of cells or tissue from the suspected lesion (obtained by needle or surgical operation) is required to confirm the diagnosis. Staging studies, using tests similar to those required for diagnosis, will then be required to predict prognosis and determine appropriate therapy.

Stage of Disease and Importance to Therapy

In addition to imaging studies, biopsies are often needed for staging and can sometimes be done at the time of the initial surgical treatment of a cancer. For example, during the removal of a cancer (such as breast cancer or colon cancer), nearby lymph nodes (in the armpit in the case of breast cancer) are removed so that they can be examined by a pathologist to see whether they contain cancer – indicating spread from the primary site. The information from the staging procedures permits the assignment of a disease stage, and this, along with the pathological features of the primary tumor, is used to decide on the most appropriate treatment for the patient. Disease stage influences whether a particular treatment modality is indicated, as well as the extent of a surgical operation, the anatomical regions to be radiated and the details of systemic therapy. When staging is based only on initial biopsy results, physical examination and imaging, the stage is referred to as clinical. When the results of a surgical procedure and additional biopsies (e.g., of regional lymph nodes) are used to determine stage, the stage is referred to as pathologic.

Stage 0 cancer is the designation used for precancerous lesions (e.g. carcinoma in-situ of the breast, cervical intraepithelial neoplasia grade III or adenocarcinoma in-situ of the cervix), whereas a stage I cancer denotes a small localized tumor, generally measuring less than 2 centimeters in its maximum dimension with no spread elsewhere. Stage 0 and I cancers are considered to be early-stage cancers. Limited local spread to surrounding tissues, generally measuring 2 to 4 centimeters in maximum dimension and/or limited spread to regional lymph nodes indicate stage II cancer. Stage III cancers are those with more extensive local spread measuring over 4 centimeters or more extensive regional lymph node spread. Stages II and III are considered moderately advanced cancers. Stage IV cancers are those which have already spread to distant organs by metastasis at the time of diagnosis and are considered very advanced cancers. The cure rates for stage 0 cancers are generally 100% and often exceed 90% for stage I disease. Cure rates for patients with stage II cancer range from 40% to 60% and for stage III cancers, between 10% to 30% with optimal therapy (which, unfortunately, is not always available in developing countries). Patients with stage IV cancers are seldom curable.

Screening for Early Cancer in Developing Countries

Screening for specific cancers in appropriate populations (based on age, sex and, in some cases, exposure to known carcinogens) is much more difficult in developing countries because of the limitations of resources and the lack of knowledge among the general public. National cancer control committees should decide which, if any, cancers to screen for, which techniques will be used, and whether screening will be opportunistic or via recruitment. The latter is more likely to be successful in poorer, less educated populations, and may include the use of mobile clinics, particularly useful in rural, “hard-to-reach” areas, coupled to notification of the community of the visit date(s). The highest priority cancers for screening in developing countries – because of the availability of feasible methodologies coupled to the relative numerical importance of the cancer or the presence of a readily identifiable high-risk population - are cervical, breast, oral and bowel cancers.

Figure 1. Charts showing the uterine cervix as seen on visual inspection after application of A: acetic acid and B: Lugol’s iodine (available from http://screening.iarc.fr/viavili.php).

Cancer of the Uterine Cervix

More than 80% of the cervical cancers in developing countries are diagnosed in stages II or higher, with overall cure rates less than 40%. Cervical precancerous lesions (stage 0 disease) can be easily diagnosed by screening tests several years before they manifest as invasive cervical cancers with symptoms. The Pap test, which relies on examining a smear of cervical cells under the microscope for the presence of cancer cells, the detection of the cancer-causing human papillomavirus (HPV) and visual inspection after the application of 3-5% dilute acetic acid (vinegar), a technique known as VIA (Figure 1A) or 3-5% iodine solution (Lugol’s iodine), referred to as VILI (Figure 1B), are effective screening tests that can detect readily curable stage 0 and stage I cervical cancers. HPV testing is expensive at the moment, though cheaper and rapid HPV tests will be available in the near future. Visual screening can be provided by doctors, nurses and health workers throughout the developing world as results are immediate and a laboratory infrastructure (and in the case of Pap smears, trained cytopathologists) is not required for confirmation, although women who test positive with these or any other screening test can be investigated by magnified inspection of the cervix using a colposcope and pathological examination of a cervical biopsy specimen to confirm disease. In good hands, visual inspection is as sensitive as Pap screening (although less expensive) in populations in developing countries, although the rate of false-positive tests tends to be somewhat higher. Women with stage 0 cervical cancer can be treated with simple, safe and effective day care treatments, such as freezing the cervix for a few minutes (cryotherapy) or by loop electrosurgical excision of the disease-containing cervical tissue (Figure 2). A recent large study in India showed that one round of screening with VIA among 49,000 women reduced cervical cancer deaths by 35% as compared to a group of women who did not have screening. Another study in South Africa showed that treating HPV or VIA screen-positive women with cryotherapy reduced the frequency of future stage 0 cervical cancer by 75% and 35%, respectively – i.e., effectively preventing cervical cancer – a benefit that would equally apply to women with false positives if treated without confirmation of the diagnosis. It is strongly advised that women in the 30-50 years age-group are tested at least once with any of the above tests or preferably once every five or ten years to reduce their risk of death from cervical cancer. Unfortunately, there is limited availability of screening programs in developing countries, particularly for poor women who tend to be at the highest risk for the development of cervical cancer.

Figure 2. Theory/practical lesson on loop electrosurgical excision procedure (LEEP), a treatment procedure for the removal of diseased cervical tissue, in Thailand.

Breast Cancer

More than 70% of breast cancers in developing countries are diagnosed in stages III or IV. Consequently, cure rates are less than 50% in most developing countries. The tests that are useful in the early clinical diagnosis of breast cancer include mammography, clinical breast examination (CBE) and breast self examination (BSE). CBE refers to the physical examination provided by a health care provider to check for lumps and other abnormalities in the breast (Figure 3).

Figure 3. Charts showing findings on CBE examinations (available from http://screening.iarc.fr/doc/breastchart.pdf).

BSE refers to a woman checking her own breasts at intervals in order to become aware of what is normal, such that a newly appearing lump or anything else that seems unusual will be rapidly apparent. Although most abnormalities will not be malignant, BSE can lead to the early diagnosis of breast cancer as long as changes in the breast are reported to a health care provider immediately. BSE is an option that women can begin in their 20s. Women in their 30s should, ideally, have a CBE as part of routine health examination by a health professional every three years, and after age 40, every year, although this is rarely feasible in developing countries. Mammography produces an X-ray image of the breast (Figure 4) that is used to detect and evaluate breast abnormalities, both in women who have no breast complaints or symptoms and in women who have breast symptoms (such as a lump, pain or nipple discharge). Mammography produces a black and white image of the breast on a film (or as a digital image) which may help to detect early cancers that are too small to feel, as well as stage 0 breast cancers (known as ductal carcinoma in-situ). The ability of a mammogram to detect early breast cancer depends on the size of the tumor, the bulkiness and density of the breast and the expertise of the radiologist who reads the mammographic image. Mammography (Figure 4) is an expensive investigation and routine screening of all asymptomatic women using mammography is not an economically and logistically feasible option in many developing countries. On the other hand, a diagnostic mammography is valuable in further evaluating women in whom small lumps have been detected on CBE or BSE. As yet, however, no scientific studies have been performed that have provided evidence that CBE or BSE result in a reduced mortality from breast cancer in developing countries. Moreover, the availability, prompt implementation and quality of care are critical to reducing mortality rates in early stage breast cancer. Nonetheless, if a lump or other abnormality is found by either mammography or breast examination, ultrasound examination may be used to guide needle aspiration of cells for further diagnosis. The term "triple diagnosis" is used when mammography, ultrasonography and fine needle aspiration cytology (FNAC) are used in combination in the diagnostic evaluation of women identified with lumps on CBE or BSE.

Figure 4. Mammography (x-ray images of right and left breasts).

Mouth Cancer

Oral cancer occurs in a location that is easily accessible to visual inspection by a health care provider, such that screening for visible oral precancerous lesions, such as white patches (leukoplakia) (Figure 5A), oral submucous fibrosis (Figure 5B), red lesions (erythroplakia) (Figure 5C) and early oral cancer (Figure 5D) is inexpensive, accurate (with well-trained health providers) and eminently feasible even in the poorest countries. This test can be readily integrated into routine health care, since inspection of the oral cavity is often part of a routine physical examination. However, it is necessary to consciously look for the early signs of oral cancer when routinely performing a mouth examination if suspicious lesions are not to be missed. Screening examination can be made more efficient by inspecting persons at high-risk (users of tobacco or alcohol or both, aged 30 years and above), in whom more than 90% of all oral cancers occur. Careful visual inspection of the lips, cheek mucosa, the floor of the mouth, the tongue and the palate under bright light, and palpation of the neck will result in the detection of a large proportion of early oral cancers. A large study in India revealed that visual screening of tobacco and/or alcohol users resulted in a 35% decline of deaths from oral cancer as compared to a group of unscreened people. Tobacco and alcohol consumers should be urged to give up these habits, particularly tobacco use, and submit to an oral visual screening every three years, since the risk of developing cancer remains high for some years after giving up.

Large Bowel Cancer (Colorectal Cancer)

Large bowel cancer is emerging as an important problem in South East Asian countries and regions such as South Korea, Singapore, Thailand, Hong Kong and Taiwan, as well as in many Latin American countries, because of changing dietary habits. Most large bowel cancers begin as a polyp, which is a small, harmless growth in the large bowel wall, but which can evolve into a cancer. Tests used to screen for colorectal cancer include the following:

• Fecal occult blood test, in which the stool is checked for traces of blood;


• Double contrast barium enema, in which abnormal “filling defects” are detected by X-ray;


• Flexible sigmoidoscopy, which involves close visual inspection of the lower parts of the bowel by inserting a slender, flexible, hollow tube containing a light source and tiny video camera into the bowel and examining the images on a TV screen;


• Colonoscopy, which is similar to a flexible sigmoidoscopy, except that the entire large bowel is examined for signs of cancer or polyps.

Figure 5. A: Oral precancerous lesions such as white patches (leukoplakia). B: Oral submucous fibrosis (OSF). C: Erythroplakia (red lesions). D: Early oral cancer.