Understanding cervical cancer in the context of developing countries

Cancer is one of the leading causes of deaths worldwide. Among the women, gynecological cancers are most common. Cervical cancer is a main gynecological cancer of the women. The global burden of cervical cancer is disproportionately high among the developing countries where 85 per cent of the estimated 493, 000 new cases and 273, 000 deaths occur worldwide. There are several dimensions of the problem. Cervical cancer is a problem where people are poor, where the socio-economic status of the women is low and sometimes specific ethnicity also posses additional risk to the women to develop cervical cancer. Human papillomavirus infection is a main risk factor for the cervical cancer however there are some other factors which increase the risk. Among them some are number of sexual partners, age of first sexual intercourse, infection of sexually transmitted diseases, use of hormonal contraceptives, parity, age, smoking, food and diet. Apart from these factors, some other issues, such as policy on cancer, capacity of health system, socio-economic and cultural factors and awareness among the women are also associated with the cervical cancer related morbidity and mortality across the developing countries. There some interventions which give promising results in terms of reducing cervical cancer related morbidity and mortality. Among them visual inspection of cervix with acetic acid followed by treatment is one such effective method.

Keywords: Cervical cancer, developing countries, VIA

Cancer is one of the leading causes of death in many parts of the world. According to an estimation there were around 10.9 million new cases of cancer around the world in the year 2002. Segregating this number between men and women, we find that more men get cancer (5.8 million) than women (5.1 million). In the same year the total number of deaths caused by cancer was 6.7 million. Out of this number, 3.8 million were men and 2.9 million were women. ^[1]

Among the women the most important types of cancer are gynecological cancers including cancers of the uterine body, cervix, ovary, vagina, vulva, and choriocarcinoma. In the year 2002, the total number of reported gynecological cancers was 9, 42, 000. This constitutes around 18.6% of all incident cases of cancer among the women. In the developing countries gynecological cancers account for 22.1% per cent of all incident cases among the women and in the developed countries they account for only 14.5%. ^[1]

Among the total number of gynecological cancer cases, the number of cervical cancer cases are highest being 4,93,000 as reported in the year 2002. The number of women who died due to cervical cancer was 2,73,000 in that year. Cervical cancer is one of the most common cancers among the women in many developing countries. It is estimated that around 83% per cent of all the new cases of cervical cancer and 85% of all the deaths occur in the developing countries. ^[1] According to an estimation recently published in Vaccine in the year 2006, the author expressed the possibility that cervical cancer may cause an additional 5 million deaths among the women, mostly in the developing countries, in the coming five years. ^[2] The number of new cervical cancers in Eastern Africa in the year 2002 was 33,900 and the deaths were 27,100. The number of new cases of cervical cancer for Ethiopia was 7,619 and the number of deaths reported in the year 2002 was 6,081. ^[3]

Cervical cancer as a public health problem in the developing world

As cervical cancer is one of the most common cancers among the women in most of the developing countries, ^[1] substantial measures need to be taken to address such a situation. There is a significant burden of cervical cancer in the world mostly localized in the developing countries even though most of the women mainly poor and unaware do not have access to the appropriate screening tests and treatment. ^[2] The disease is a problem of developing countries in general and particularly in Sub-Saharan Africa. In this part of the world, mortality caused by cervical cancer is highest in the countries that are least equipped to deal with the problem.

Cervical cancer screening as a solution

The screening for cervical cancer is based on two assumptions. The first is that prevention is better than cure and the second is that early detection may allow early treatment as the primary pathologic process is still reversible. Screening tests are relatively simple procedures that separate healthy persons from those with a high probability of having the disease. ^[4]

By using systematic and nationwide screening programs, many developed countries have reduced the incidence and mortality caused by cervical cancer in the past few decades. Among them some of the Nordic countries such as Iceland, Norway, Sweden and Finland have been very successful in reducing cervical cancer incidence and mortality. The United States of America has also been very successful in reducing the incidence and mortality caused by cervical cancer. The highest reduction in the disease burden was achieved in Iceland. Here the mortality came down by 80% followed by Sweden where mortality came down by 34%. ^[5]

The reason for this success is attributed to a cytology-based cervical cancer screening program. These countries run nationwide cervical cancer screening programs and the screening coverage achieved here was more than 80%. However, many developing countries that tried cytology-based cervical cancer screening programs did not get such success in terms of reducing the mortality and incidence of cervical cancer. Mexico is an example of such an unsuccessful program. ^[5]

There are different methods of screening for cervical cancer. Some popular screening methods are Papanicolaou (Pap) smear, visual inspection of cervix with acetic acid (VIA), HPV DNA test and colposcopy. ^[6] Colposcopy is not used as a primary screening test but it is combined with other tests. Each test has its advantages and disadvantages and applicability in a specific situation. ^[6]

Issues in cervical cancer screening in developing countries

Cervical cancer screening requires infrastructure, human resources, quality assurance, monitoring and evaluation of the screening programs and financial means in general. But reduction of the cervical cancer mortality in the developing world is only one of the many priorities competing for scarce resources. ^[7] Well-organized programs to detect and treat precancerous abnormalities and the early stages of cancer prevent up to 80% of cervical cancers deaths in developed countries. However, effective screening programs have been difficult to implement in low-resource settings. This is one reason why cervical cancer mortality rates are much higher in the developing world. ^[8]

Public health screening programs followed by treatment are very effective even in the resource-poor settings. Screening and treating approach or single-visit approach using VIA is a very effective prevention strategy for cervical cancer. ^[9] These programs have positive effects on reducing the morbidity and mortality caused by cervical cancer even in resource-poor settings. However, to be effective, three most important aspects of the program have to be focused upon: high coverage of the screening programs, effective and acceptable tests to the women and appropriate treatment of the women who are found positive in the screening tests and their follow-up. ^[10]

Low coverage of cervical cancer screening is a serious problem and a major barrier in reducing the mortality and morbidity in the developing countries. Specifically in Sub-Saharan Africa very few women are ever screened for cervical cancer. In Ethiopia coverage of screening for cervical cancer is very poor. The national average for the country is 0.6% in the age group of 18 to 69 (rural and urban). The coverage in the rural area is 0.4% for the same age group. ^[11]

The problem of gynecological cancers in women and cervical cancer

In the year 2002, the estimated number of new cancer cases in the world among the women was 5.1 million. The total number of deaths caused by cancer in the same year was 2.9 million. The five years prevalent cases of cancers of the women were 13 million as recorded at the end of year 2002.

Out of the total 5.1 million cases of cancer among the women in the year 2002, the total number of gynecological cancer cases accounted for 9,69,000. This was 19% of the total number of cases. Among the total number of gynecological cancer cases, the number of cervical cancer cases were highest, being 4,93,000. The number of women who died due to cervical cancer was 2,73,000 in that year. Other gynecological cancers were uterine body cancer, ovarian cancer and cancers of the vagina, vulva and choriocarcinoma. Among these cancer cases, uterine body cancer accounted for 1,99,000 cases and 50,000 deaths, ovarian cancer accounted for 2,04,000 cases and 1, 25, 000 deaths and there were 45,900 cases of cancer of the vagina, vulva and choriocarcinoma put together. ^[1] Cervical cancer contributes around 12% of all types of cancers among the women. ^[12]

In the developed countries 83,400 cases of cervical cancer and 39,500 deaths caused by cervical cancer were estimated in the year 2002. In the same year, in the less developed world these figures were 4,09,400 and 2, 33, 700 respectively. This reflects a clear divide between the developed and non-developed world. ^[1] In most of the developed countries, the incidence of cervical cancer is reducing at a slow rate. There has been some notable reduction in the incidence of cervical cancer in Denmark, Finland, Sweden, Japan and New Zealand. ^[12] The countries in Sub-Saharan Africa, South and Central Asia and South America have higher rates of cervical cancer incidence and deaths. ^[13] In the developing countries more than 80% cases of cervical cancer occurred in the year 2002. ^[13] There is an eight times difference between the developed world and the developing world in terms of cervical cancer incidence and mortality. Cervical cancer constitutes the most common type of cancer of women in the developing countries where 85% of deaths caused by cervical cancer occur. The highest rate of cervical cancer incidence is reported from Sub-Saharan Africa. Among the Sub-Saharan African countries, East African countries bear the highest burden of the disease and the mortality caused by it. ^[13]

The mortality caused by cervical cancer in Africa is very high. In the year 2002, the reported mortality in Eastern Africa was 35 deaths per 100,000 women. However, the mortality rates in the developed world where screening programs run successfully, remained below 5 per 100,000 women during the same year. In the year 1999, survival rate for five years in African countries such as Uganda was only 18% whereas during the same year it was 72% in the United States of America. On an average in Sub-Saharan Africa the survival rate in the year 2002 was 21% compared to 70% in the United States and 66% in Europe. ^[14]

The crude incidence rate of cervical cancer in Ethiopia is 23 per 100,000 women. The average for Eastern Africa is 25.7 per 100,000 women. It is far more than the world average of 16 cases per 100,000 women. But if we take the age-standardized incidence rate of cervical cancer in Ethiopia which is 35.9, we find that it is more than twofold the world average which is 16.2. The cumulative risk for Ethiopian women (2.8%) to suffer from cervical cancer is more than double than that of world average (1.3%). The annual number of new cervical cases in Ethiopia is 7619 which is around 1.5% of the global cases annually. The incidence of cervical cancer in Ethiopia for women of all ages is more than that of breast cancer which is 15.5 per 100,000 women. In the year 2002 the estimated number of annual deaths caused by cervical cancer in Ethiopia was 6081 against 2,73,505 deaths in the world which is around 2.2% of the global deaths. Cervical cancer causes highest mortality compared to other types of cancers among the women in Ethiopia. The mortality reported in the year 2002 was 18.3 per 100,000 women for all ages. The reported crude mortality rate in the world was 8.3 in the year 2002. ^[11]

Human Papillomavirus

Human Papillomavirus (HPV) is the cause of almost all types of cervical cancer. It is now an established fact. Human Papillomavirus is the etiological agent which has a causal relationship with cervical cancer. ^[15] The prevalence level of HPV types in various parts of the world varies and thus the risk of cervical cancer caused by the infection also varies. ^[15] A study conducted by Clifford and coworkers reveals that the infection of HPV in the women of Sub-Saharan Africa is five times more than in the women of Europe. The infection was lowest in Spain and highest in Nigeria. The most common HPV type was found to be HPV 16. HPV 18 was found to be less common than HPV 16. In the same study other HPV types found were HPV 42, HPV 56, HPV 58, HPV 81, etc. They also reported that around 70% of the women who were sexually active were infected with HPV but all of them did not develop cervical cancer. ^[15]

There are around 100 different types of HPV but all are not reported to be causal agents of cervical cancer and only 40 of them infect the human genital tract. In a meta-analysis it was found that around two-thirds of all the cervical cancer is caused by HPV 16 and HPV 18. HPV 16 was responsible for 51% of the cervical cancer and HPV 18 was responsible for 16%. ^[16]

There are epidemiological evidences that in over 90% of the cervical cancer cases, HPV viral DNA was found in the cellular genome of the cervical carcinoma. Millikan and coworkers found that a greater number of cases with cervical intraepithelial neoplasia (CIN) can be a result of the infection caused by HPV. They concluded that the natural history of HPV has an etiological association with cervical cancer. ^[17]

Anorlu and coworkers reported that women in Sub-Saharan Africa have the highest prevalence of all HPV types. The women in this region are also susceptible to multiple infections with high-risk types. They also reported that this situation may be because of reasons such as HIV infection, low cellular immunity, parasitic infection, micronutrient deficiency and chronic cervical inflammation. ^[14]

The prevalence of HPV 16 and/or HPV 18 among the women with normal cytology is not available for Ethiopia but prevalence of HPV 16 and/or HPV 18 among the women with cervical cancer was reported to be 90.2% (as reported in January 2010). ^[11] HPV burden in healthy Ethiopian men has been reported to be around 73%. HPV can easily be transmitted from men to women and from women to men. ^[18]

Number of sexual partners

The number of sexual partners has a direct bearing on the risk of cervical cancer. The risk increases with the increase in the number of sexual partners. The women with one sex partner are at low risk of cervical cancer compared to women who have five or more sex partners. Green and coworkers reported that the trend in the risk with the number of sex partners is highly significant. The evidences show that squamous cell carcinoma and adenocarcinoma of the cervix both are associated with the number of sex partners. Evidences from the case control studies show that women with cervical cancer reported more number of sex partners. ^[19]

The risk associated with squamous cell carcinoma in relation to the number of sex partners over the lifetime is more than the risk for adenocarcinoma of the cervix. ^[19]

A study on the number of sexual partners in Eastern and Southern Africa published in the year 2009 reveals that 90% of males and females between the ages of 25 and 45 years were sexually active and most of them were having at least one sex partner. Males reported having more number of sex partners than females. Most of the men reported that in their lifetime they have more than one sex partner. The reported male to female sex partnership ratio ranged from 1.41 to 1.86 in the last one year. ^[18]

Age of first sexual intercourse

The age of first sexual intercourse is directly related to the risk of cervical cancer. The women who started their sexual life early are more at risk than women who started their sexual life late. Several studies reveal that those women who started their sexual life before the age of 16 years were at double the risk than those women who started their sexual life after 20 years. This is because the period of exposure to HPV is increased for these women. The risk associated with early age of first sexual contact is similar for squamous cell carcinoma and adenocarcinoma of the cervix. ^[19]

The reported median age of first sexual intercourse in Ethiopia is 16.1 years for young women (15 to 24 years) and 21.2 years for men. It is also reported that 16% of the young women (15-24 years) have their first intercourse before the age of 15 years. ^[18]

Sexually transmitted diseases and risk of cervical cancer

The history of the presence of sexually transmitted diseases (STDs) is a risk factor for cervical cancer. Multiple STDs are cofactors for cervical cancer. Schmauz and coworkers reported that a number of such infections are associated with the increased risk of cervical cancer. ^[20] Human immunodeficiency virus (HIV) which is responsible for immune suppression significantly increases the risk of cervical cancer in comparison to the women who are not infected with HIV. ^[21] Smith and coworkers reported that Chlamydia trachomatis increased the risk of squamous cervical cancer among HPV-positive women. They also concluded that Chlamydia trachomatis was found to be a possible cofactor for HPV in the etiology of squamous cervical cancer. ^[22]

Duncan and coworkers, in a study of Chlamydial infection in 1846 women attending obstetric, gynecological and mother and child health clinics in Addis Ababa reported that 50% per cent of the women had clinical evidence of past or present infection of Chlamydia. They also concluded that low income, bar-girl occupation, five or more sex partners and Amhara ethnicity were risk factors. ^[23]

Hormonal contraceptive use and cervical cancer

There is strong evidence that current and recent use of the combined oral contraceptive pills is associated with increased risk of cervical cancer among women. The relative risk of cervical cancer increases with the duration of the use of combined oral contraceptives and the relative risk comes down once the use of these contraceptives is stopped. The risk goes down with time and after ten years of not using these contraceptives the risk comes down similar to the women who never used these contraceptives. It is also reported that the use of progestagen only injectable contraceptives also makes a small increase in the risk of invasive cervical cancer. A comparison of women between developed and less developed countries who used combined oral contraception for ten years from the age of 20 years shows that the cumulative incidence per 1000 women at the age of 50 years was more in less developed countries than in developed countries. The incidence in less developed countries was almost twofold more than that of developed countries. ^[24] In Ethiopia the use of oral contraception is 3.1%. ^[11]

Parity

There is a direct correlation between parity and the risk of the squamous cell carcinoma. More number of fulltime pregnancies is associated with an increased risk of squamous cell carcinoma among the HPV-positive women. There is no significant association reported between parity and adenocarcinoma of the cervix. ^[25] In Ethiopia the total fertility rate is 5.7. ^[11] Castellsagué and coworkers reported that due to hormonal changes during pregnancy, the immune response is modulated to HPV. They also reported that a high number of fulltime pregnancies result in maintaining the transformation zone for a long period of time and thus exposure to HPV and other cofactors increases resulting in a higher risk of cervical cancer. ^[26]

Age and risk of cervical cancer

Older women are at a higher risk of cervical cancer. Women aged 60 years and above form a significantly higher number of cervical cancer patients. ^[27]

Smoking and risk of cervical cancer

Haverkos and coworkers reported that smoking is one of the risk factors of cancer of the cervix . ^[28] Giuliano and coworkers reported in a prospective study that among the smokers the duration of the oncogenic HPV infection increases and this results in early carcinogenic events. They also reported that among the smokers, the probability of self-clearing of oncogenic infections reduces . ^[29] A study conducted among smoking women who have minor-grade lesions reveals that smoking cessation has beneficial effects on early cervical abnormalities. The study suggested that there was a significant correlation between the extent to which smoking was reduced and the size of the lesion. This suggests the possible role of smoking and HPV carcinogenesis. ^[30] In Ethiopia the prevalence of smoking of any tobacco by men is 5.8% and by females is 0.6%. ^[11]

Food habits and Diet

So far research has not proved that food and dietary intake has any kind of causal relationship with cervical cancer among women. However, epidemiological investigations suggest that there is some kind of protection among the women who consume more fruits and vegetables. Case control and prospective studies reveal that those women whose diet was rich in vitamin C, E and carotenoids had less chances of getting precancer legions. ^[31]

Awareness and knowledge about cervical cancer in Africa

Among the African women awareness of cervical cancer is poor in general. Among the regions of different literacy levels the awareness levels are different. In Sub-Saharan Africa, cervical cancer is not recognized as a major public health problem. ^[32] Gichangi and coworkers in a study conducted in Kenya reveal poor knowledge about the disease among the cases. Around 98% of the women had a belief that their disease is curable. Only 12% of the women with cervical cancer thought that it is a serious disease. Only 9% of the women with cervical cancer understood that it is serious because it is cancer. The knowledge about cervical cancer is also not good among the healthcare workers. ^[33]

A study conducted in a maternal and child health clinic in Lagos with 500 women reveals that only 4.3% of the women attending this clinic were aware of cervical cancer. ^[34]

In the same study conducted in Lagos, the researchers also tried to learn the reasons why cases reach late at the tertiary level health facilities. It was found that delay in the primary level health facility occurred with respect to referring the cases and that was the main reason why women were reaching the tertiary level health facility in an advanced stage of the disease. It took a mean of 9.35 ± 12.9 months for primary healthcare providers to diagnose and refer women with cervical cancer to the tertiary level health facility. ^[34]

Hormonal therapy and family history as risk factors for cervical cancer

There are benefits for women who take hormonal therapy after menopause. Hormonal therapy with estrogen and progestin is associated with some cytological abnormalities. However, the research suggests that this combined hormonal therapy has no impact on the cancer of the cervix. ^[35]

Another risk factor is genetic susceptibility. Studies suggest that there is a genetic susceptibility to HPV. It is found that a few individuals are able to clear the early infection but a few individuals are not able to do so. The relative risk of cervical cancer is more in the women where there is a family history of cancer of the cervix. The genetic factors play an important role in developing the response of the body to the infection of HPV. It can be concluded that genetic factors play a significantly important role in determining the risk of developing cervical cancer. ^[36]

Socio-cultural factors

There are some important socio-cultural factors which are widespread in Africa and are also related to HPV transmission and thus risk of cervical cancer. Some of them are high parity, early age of marriage and thus early first sexual contact and polygamy. Polygamy is associated with increased risk of cervical cancer. This risk is twofold with many wives than one wife. Similarly, high parity is common among various cultures in Africa and increases the risk of cervical cancer for women. In some cultures the girls are married too early to old men and are exposed to HPV infection. This also increases the reproductive period and number of pregnancies and thus increases the risk of cervical cancer. ^[37]

Socioeconomic factors

Cervical cancer is a main problem of the developing countries and the burden of the disease is borne by the poor women in these countries. Inadequate resources in the developing world result in the inequitable burden of cervical cancer in the developing countries. ^[13] Cervical cancer is synonymous to poverty and disease of poor women and poverty is endemic and a big problem in Africa. Poverty alone is a very important barrier for education, prevention, treatment and care. ^[13] In a study in Mali it was found that within a population widely infected with HPV, poor social conditions, sanitation and high parity were the main factors for cervical cancer. ^[37] A study conducted in Botswana revealed that the knowledge of screening tests and cervical cancer was inadequate among the women of low-income groups. ^[38]

Policy issues in cervical cancer in developing countries

The developed countries have shown a remarkable progress in the reduction of the incidence of invasive cervical cancer. This success is attributed to cytology-based screening programs in these countries. There are a few prerequisites for the cytology-based cervical cancer screening programs to be successful and effective. These are mainly-well-established laboratories, and qualified and trained cytotechnoligsts. Cytology-based screening programs also require up to three visits, evaluation of the abnormal results and treatment of the women with the abnormalities. But when it comes to applying the same strategy such as Pap-smear screening test in resource-poor settings, issues like implementing and sustaining it, seem to be difficult. Under resource-poor settings direct visual inspection of cervix with acetic acid followed by treatment shows promising results in terms of clinical benefits and cost-effectiveness. So the method of screening is an important policy issue that has to be considered according to the given setting. Goldie and coworkers developed a comprehensive model to analyze the policy for cost-effectiveness and clinical benefits of various screening methods, and found that visual inspection of cervix is the most cost-effective method. They also found it comparable to child immunization programs and HIV/AIDS prevention programs in terms of cost of per year of life saved. ^[39]

Another policy issue is the interval between two screening tests. The current procedures involve screening once every one to five years. More number of screening tests would require more resource allocation and cost to the system. The human resources and financial resources are limited in most of the developing countries. Sustaining the programs would be difficult in such settings if frequent tests are performed. ^[40]

It is important that the age group for starting the screening is clearly defined. A screening program that does not define the age group would not be very successful in terms of cost-effectiveness. An invasive cervical cancer before the age group of 30 years is normally a rare event. So screening tests for the age group of 20 to 25 years would require additional resources without proven benefits. Targeting the age group of 30 to 49 years would be very effective and useful for resource-limited settings. ^[13]

When national priority setting is done for disease control, cost-effectiveness, Disability Adjusted Life Years (DALYs) are taken into account. But, national politics also affects the priority setting. Some governments have some specific agenda. This factor is not accounted in the tools used traditionally for priority settings. A case study of Ghana explains how national politics affected the cervical cancer prioritization process and brought attention to the issues of cervical and breast cancer in this country. ^[41]

Another important policy decision with respect to the cervical cancer screening program is treatment of the precancer abnormalities. In resource-poor settings treatment on outpatient basis would be more appropriate. The treatment should be safe, simple, acceptable and effective. Cryotherapy and Loop Eltrosurgical Excision Procedure (LEEP) are good options. Normally, cryotherapy can be performed by physicians and non-physicians, however, for LEEP, physicians are usually required. Policy decisions are required to be made with respect to the method to be used, treatment to be offered, how often screening is to be done and desired population coverage. ^[10]

The health policy of the Transitional Government of Ethiopia prioritizes the component of information, education and communication (IEC) to enhance the awareness of health issues. It pays special attention to the needs of women and the poor and the vulnerable. It also emphasizes that appropriate support shall be given to curative and rehabilitative services. However, the word ‘cancer’ is not used at any place in the policy document. The policy talks about communicable diseases but non-communicable and chronic diseases are not mentioned anywhere in the policy document. ^[42]

Cancer is a growing problem in Ethiopia but it is neglected. In Ethiopia there is no national cancer control program and there is no cancer registration process. As a result there is no morbidity and mortality data available to convince policymakers on this issue. ^[43]

Programme level issues

Cervical cancer screening programs are effective in terms of reducing morbidity and mortality. For a program to be successful a lot of resources are required. These are, namely, financial resources and human resources. The screening programs need infrastructure, trained manpower, consumables, follow-up, treatment and a surveillance system for opportunistic as well as non-opportunistic organized programs. Most of the developing countries lack these resources and specially the countries in Sub-Saharan Africa. As a result of this, developing countries cannot follow the successful models of the developed countries where reduction in cervical cancer morbidity and mortality has been achieved.

For the developing countries, targeting the high-risk group and emphasizing on the coverage would be very important. The screening opportunity for women once or twice in a lifetime would be more realistic and also effective. ^[40]

Denny and coworkers reported that screening programs that involve one to two visits to health centers linked with the treatment appear to be effective, safe and feasible. They also reported that the issues involved with the screening programs would vary given the situation of a country and thus country-specific programs would be needed. ^[6]

The quality of the screening programs is critically important. Even in resource-poor settings in the context of developing countries, some additional funds for improving the quality of the programs would be very useful. Follow-up is very important for the success of the screening program. The follow-up can be improved by improving the teamwork and improving the functional linkages between the centers doing the detection and diagnosis of cervical cancer. The issue of time taken between the screening and informing the result of the test is very important. It can be reduced by restoring the linkages between the sampling site and the reading laboratories. Addressing some other issues of the program such as training of the health service provider, outreach workers, identifying the women who are never screened, and facilitating the linkages between the community and the health services would be very useful for the effectiveness of the screening programs in the developing countries. ^[44]

Murillo and coworkers reported that evaluation of the screening program is very important in terms of the impact of the program in reducing morbidity and mortality. They also mentioned that for a program to be effective the follow-up of the positive test and quality control are critical. They discussed the effect of follow-up and coverage on the reduction of cervical cancer. They found that 50% coverage with 100% follow-up is far better than 100% coverage with 50% follow-up in terms of reducing mortality caused by cervical cancer. ^[45]

The control of cancer is a huge challenge, particularly for the poor countries. For these countries, it is extremely important to have a national cancer control program under which specific cancer control programs could run such as cervical cancer or breast cancer. In resource-poor settings optimum utilization of limited resources can be ensured by having a national cancer control program. Sudan presents an example where a carefully planned national cancer control program (NCCP) made a difference in the lives of people in a very resource-poor situation. The Sudan NCCP primarily focused on prevention, early detection, treatment and palliative care. Cervical cancer is one of the cancers that Sudan NCCP focuses upon. The approaches that this program adopted are public awareness through radio because it reaches 80% of the population, education of the medical professionals and the screening programs. They planned to address the facility-level bottleneck and organized programs for skill and knowledge enhancement of the young doctors and postgraduate medical students for the detection of cancers. They also carefully selected the age for cervical cancer screening based upon the situation in their country. For example, they target women of 35 to 50 years of age for screening. ^[46] The World Health Organization (WHO) (2002) recommends that a cervical cancer screening program should be planned in the context of national planning and country-specific priorities. ^[47]

Facility level issues

At the facility level the interaction of the staff with the women should be emphasized. Issues such as privacy of the women, respectful interaction and informed consent are very important for a successful and effective screening program. ^[12]

The health facility should be organized in a manner that women find the services user-friendly. The service organizers should focus on the women as clients and services are organized around the clients. The examination table should be clean and comfortable. There should be adequate light available, the speculum should be sterilized for each woman. If the health facility sends the smears to a centralized laboratory then it should be on a daily basis. The laboratory should be adequately staffed and the staff should be trained. The quality of the laboratory services is very important for the success of the screening programs. ^[48]

It is essential that the women at the health centers receive an appropriate screening test including diagnostic tests if needed. If the diagnostic facility is not available, an immediate referral has to be made. In the event of a positive diagnostic test, appropriate referral has to be made in order to ensure that women receive treatment for abnormalities. Often, poor communication, feedback system and coordination exist between the screening center and treatment centers. ^[12]

The counseling of women before and after the test is important and this is the area where sometimes improvement is needed. In a screening program in Ghana, in most cases the low performance was related to counseling of the women and not to the clinical services. Poor counseling may lead to incorrect informed consent for the test and treatment and also wrong perception of the test result. ^[49]

Another important issue at the facility level is use of standard procedures for tests and treatment. For the success of the program it is essential that protocols are followed. A high performance with respect to the use of protocols for the screening test and treatment in two countries, namely, Ghana and Thailand are observed. ^[49]

Bradley and coworkers reported that there are some barriers in delivering the services from the health facilities in resource-poor settings. They mentioned that sometimes protocols do not exist and at times if protocols do exist they are poorly executed. Monitoring of the process is another important aspect and lack of proper monitoring results in no accountability of the staff. Some other barriers they mentioned were lack of a system to identify the requirement of equipments and supplies, infection control, staff training on screening, treatment, information management and record-keeping. They also mentioned that adequate and designated space for testing is not available and service hours are not convenient to the women. Women are unaware that screening tests are performed at the health centers. One of the important barriers that they mentioned was long delays in getting the reports from the laboratory. They concluded that this affects the confidence of the women regarding the screening services. ^[50]

Perspectives of the service providers and the women

For effective screening programs, it would be important to understand the perspectives of the service providers with respect to the screening program and the issues of cervical cancer. It can give important insights for addressing the barriers to utilization of cervical cancer screening services and responsible for low coverage. Abrahams and coworkers reported that in a study with South African black women, health workers identified several problems in organizing the cervical cancer screening services. Some of the problems mentioned by the health workers were lack of transport facilities, busy clinics, access issues and opposition by the men. But interestingly, the perspectives of the women were different from those of the health workers. The main concerns of the women were related to the behavior of the service providers and delivery of the services at the facility level. So in such a situation the role of the nurses and health workers becomes very important with respect to the services that are being provided by them. This study also emphasizes the importance of taking into account the issues and concerns of women with respect to the procedures. ^[51] Any such study in the context of Ethiopia was not found by the author for this manuscript.

In a study conducted in Nigeria with the heads of the departments of obstetrics and gynecology in public tertiary and secondary care hospitals, Adesina and coworkers reported the perspectives of these heads of the department with respect to cervical cancer screening services. The main concerns of these doctors were lack of financial resources, trained specialists and certified gynecological oncologists. They also mentioned that there is very less utilization of the services available. ^[52]

McFarland conducted a study in Botswana from the perspective of women and reported that the negative attitude of the services providers and limited access to the doctors were among the major barriers to cervical cancer screening services. ^[38]

In Usmanu Danfodiyo University Teaching Hospital Sokoto, Nigeria a study was conducted with doctors, nurses, pharmacists, laboratory scientists and medical social workers. It was assumed that the knowledge of these workers about cervical cancer would be high and they would have taken the screening tests for themselves. However, the results of the study revealed that only 4.4% of the respondents had ever undergone the screening tests themselves. ^[53]

The disease burden of cervical cancer is huge and this is particularly high among the developing countries. The screening tests for early detection of cervical abnormalities followed by treatment provide the most effective strategy to deal with this problem. There are many screening tests available for the purpose with a varying degree of sensitivity and specificity and applicability to different settings.

Cytology-based cervical cancer screening programs have significantly reduced the incidence of and mortality caused by cervical cancer in many developed countries. ^[54] If a screening program is organized well and backed by treatment for the abnormalities detected in the screening, the rate of cervical cancer can be reduced significantly. The experience of developed countries is very encouraging in this direction. ^[50] Screening for cervical cancer is the most accepted and successful strategy for cervical cancer control, the world over. It is a proven strategy in terms of its effectiveness in reducing the incidence and mortality of cervical cancer. It is also a very cost-effective strategy. ^[55]

However, the success story of the developed world is not replicated in the developing world. There are many reasons for this. Some of the reasons are competing health needs of the population, shrinking budget and the prioritization of healthcare needs. Among the other barriers for a successful cervical cancer screening program are human and financial resources, poorly developed healthcare services, low status of women, war and civil unrest and poverty. One of the most important barriers to establishing national-level screening programs in these countries is the nature of the screening test itself. Many of these countries lack the capacity to establish and run cytology-based  Pap smear ^{More Details} test of assured quality backed by the treatment of abnormalities detected. ^[6]

Some other screening tests are also available for cervical cancer apart from Pap smear and these are visual inspection of cervix with acetic acid (VIA), HPV DNA and colposcopy. The applicability of each of them is discussed in the context of developing countries and particularly in the context of Africa.

VIA test

In the year 1999 a project of the University of Zimbabwe on visual inspection of cervix with acetic acid (VIA) with naked eye for cervical cancer screening showed that VIA can be used for the detection of precancerous lesions of the cervix. However, concern was expressed over the high number of false-positives and over treatment. ^[56] Sankaranarayanan reported that cytology-based screening programs in developing countries have financial and technological limitations and thus alternative methods such as VIA can be considered. The results from cross-sectional studies from the developing countries showed that VIA has sensitivity similar to that of cytology to detect high-grade cervical dysplasia and invasive cancers. But the specificity of the tests was low. ^[54]

Sankaranarayanan and coworkers reported that VIA has been tested as a screening method in several developing countries and the results from the studies are very promising. It can be concluded that VIA can be used as an alternative screening method in place of cervical cytology in the developing countries. In these studies the sensitivity of this method ranged between 49-96% and specificity between 49-98% in detecting high-grade precancer lesions and invasive cancers. ^[57]

Denny and coworkers reported that one of the main advantages of the VIA method over other methods is that it gives immediate results. This method can be used effectively for treatment without colposcopy and histological sampling in a single visit and thus is known as screen and treat approach. ^[6]

Sankaranarayanan and coworkers reported that a cluster randomized trial was conducted in Tamil Nadu, India with women of the high-risk group to study the effect of VIA in terms of reducing cervical cancer incidence and mortality. In this study it was found that a single round of VIA method has reduced the burden of cervical cancer in the study population in a cost-effective manner. However, they were not sure whether the mortality and incidence can be reduced significantly in a real-life situation. They also reported that the results of this study can be generalized. They mentioned, “We believe that VIA screening, supported by sustained training and quality inputs, should be established in routine health services in India in view of the high burden of disease (120,000 new cases and 80,000 deaths a year) and in other high-risk developing countries and deprived populations.” ^[58]

Several trials conducted in Asia and Africa reveal that VIA is a very effective method of screening. It is also found to be very cost-effective. In resource-poor settings where no screening is available, one screening within a lifetime with VIA is very effective. ^[12]

Pap smear test

The Pap smear test is a cytology-based test that involves collection of cervical cells, preparation of slides, reading and reporting. This method requires at least three categories of health workers. A nurse is required to take a sample of cervical cells, a cytotechnician is required who prepares the slides and does slide readings, and a cytopathologist who is overall responsible for the quality of the process and who supervises the procedure and does final reporting. The entire procedure requires a highly sophisticated lab environment and qualified and trained professionals. ^[57] In the context of the developing countries where resources are competing and infrastructure is not well developed along with shortage of trained manpower, a cytology-based screening test seems to be difficult.

The Pap smear test has been proved to be a very effective method to reduce the burden of cervical cancer in terms of morbidity and mortality. Many developed countries have substantially reduced the incidence through the systematic large-scale programs on screening women with Pap smear. ^[59] In the United States, between the years 1975 and 2000, the incidence of cervical cancer came down from 14.8 to 7.6 per 100,000 women per year. ^[59] A study conducted to assess the effectiveness of Pap smear screening on reduction on cervical cancer mortality in Sweden reveals that this method has brought down the mortality caused by cervical cancer by 53%. This study strongly suggests that Pap smear screening has an important role in reducing mortality caused by cervical cancer. ^[60]

Seeing the success of the cytology-based screening tests, many developing countries started similar tests mainly in Latin America. However, it was noticed that these screening programs were not very successful in reducing mortality caused by cervical cancer. The main reasons for the same were lack of quality control in screening tests. Other factors responsible for poor performance were lack of treatment of the women found positive in the test results and lack of follow-up. ^[61]

Among the various developing countries in the context of resource limitation, the accuracy of the test was found varying. As a result of this varying accuracy of the cytology-based screening tests, the impact of this method in resource-limited settings on reducing the morality and incidence was very limited. It can be concluded that cytology-based screening tests in resource-poor settings were not found effective in controlling cervical cancer. ^[57] Sankaranarayanan et al., reported that the sensitivity of the Pap smear in detecting CIN 2-3 and invasive cancer varies between 48.00-78.00% among the four studies conducted in South Africa. They also reported that the sensitivity of the test was 44.00% in Zimbabwe in detecting CIN 2-3 and invasive cancer. ^[57]

A study was conducted in Nairobi, Kenya to evaluate the quality and usability of various cervical cancer screening methods. In this study the Pap smear method, VIA method, cervicography and HPV DNA methods were used. The study concluded that the Pap smear had the highest specificity (94.4%) and HPV DNA had highest sensitivity (94.6%). The study also concluded that the specificity of the visual method was low, however, in the acceptable range. The author reported that this study was conducted in a training center so the results of this study cannot be generalized in field settings. ^[62]

HPV DNA test

The HPV DNA test has the ability to detect the DNA of the HPV in the sample of cervical cells. The technology can find the HPV DNA in almost 100% of the invasive cervical cancer cases, 75-100% of precancer lesions and 50% of borderline lesions’ samples. In many studies in which HPV DNA test method was used, the sensitivity of the test was found to be 10% more than the sensitivity of the cytology-based screening tests. However, Sankaranarayanan et al., reported that the sensitivity of the HPV DNA test was found to be lower when performed in developing countries. In four African countries it ranged from 50-80%. ^[57]

The research conducted to assess the sensitivity of the HPV DNA test in detecting high-risk carcinogenic HPV in developed countries led to the conclusion that the HPV DNA test is more sensitive than cytology-based screening tests. This is also true for developing countries such as Mexico and South Africa. There is consensus among various experts that the HPV DNA test can be used as a primary screening test for detecting women with CIN 2 and 3. Some experts have concerns related to the use of this test as a primary test method as many young women below the age of 30 years would have the infection of HPV but not necessarily the precancer abnormalities. Another issue concerning the use of this test is – should it be used alone or should it be used in combination with cytology. ^[63]

Nevertheless, the HPV DNA test is a good quality test and the variability of the results can be minimized by it. However, it is a very costly test and it needs a molecular diagnostic laboratory. This test presents an opportunity for getting combined with the cytology test where first test shows abnormality in the countries where the cytology based screening tests is performed. However, in the countries where cytology-based tests are not performed the HPV DNA test may be used as a primary screening test. But, for this more evidences from the field settings are required. ^[12]

Thomas (2006) also reported that the HPV DNA test can be used as a primary cervical cancer screening method. He also reported that this method can be used as an effective method for some resource-limited settings. He mentioned that if the HPV DNA test is used for screening, then cytology-based tests would be useful in determining the treatment for the women who are found positive in the HPV tests. However, financial and technical resources would be needed for this combination. ^[63]

Colposcopy

Colposcopy is often used for low-power magnification and illumination. The purpose of the colposcopy is to assess further if some abnormalities are found in smear tests. One of the main objectives of the colposcopy is to make sure that invasive cancer is present or not. It is also used in the treatment and management of cases with precancer lesions and in the follow-up of the cases. Colposcopic assessment is subjective in nature. It requires long training and accurate reading largely depends upon the quality of training and duration of internship under the supervision of an expert. The variability of colposcopic assessment among various observers is high. ^[64] When colposcopy is combined with cytology, it gives a more reliable diagnosis of cervical lesions. A study conducted with 1564 patients in Nigeria reveals that diagnosis of cervical intraepithelial neoplasia with smear tests combined with colposcopy became more reliable. ^[65]

Colposcopy is generally used in the routine examination of women in whom gynecological problems are indicated. It is also combined with cytological testing. Colposcopy is not used as a primary screening method for cervical cancer anywhere. There are no evidences available for the use of colposcopy in primary screening for cervical cancer. ^[6]

Use of a speculum for visual inspection in detection of cervical abnormalities

A speculum is increasingly being used for vaginal examination across many developing countries. Studies reveal that the use of a speculum is acceptable to women in situations where adequate privacy is maintained. There are concerns of women regarding who is performing the vaginal examination. The acceptance of the use of a speculum is more if examination is performed by female health workers.

A speculum is used for detecting cervical abnormalities by visual inspection without any aid in Bangladesh and in other parts of the developing world. It is often done at places where formal population-based cervical cancer screening programs such as Pap smear or VIA are not in existence. ^[66]

A speculum is used for visual inspection of the cervix. The aim of such an inspection is to detect cervical abnormalities at an early stage before the women become symptomatic. This approach can help detect early cervical abnormalities and treatment can be provided. But this approach has limitations. The incidence of cervical cancer cannot be reduced by this but the morbidity and early mortality can be averted. This strategy was proposed by WHO and is known as down-staging. The strategy is particularly important in many developing countries where the disease burden is high and nationwide cytology-based screening programs do not exist. The down-staging strategy involves visual inspection of the cervix using a speculum to detect early stages of cervical cancer. This strategy needs backup treatment services to treat the cases with cervical abnormalities. ^[67]

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1755-6783.92871