CANCER OF THE CERVIX AND ITS PREVENTION: STILL A PUBLIC HEALTH CONCERN:

High lights for both Developed and Developing Countries:

NAMAGEMBE IMELDA:

1) Introduction:

-Definition of Cancer of the cervix.

-What causes cancer of the cervix?

2) The magnitude of cancer of the cervix, its distribution and determinants.

3) Factors associated with cancer of the cervix high lighted.

4) Signs and symptoms of cancer of the cervix.

5) Common complications of cancer of the cervix.

6) Prevention of cancer of the cervix. The Role of Human Papilloma Virus Vaccine and cancer cervix screening programs is mentioned.

7) The magnitude of cancer of the cervix, its distribution and determinants.

8) Comparison of the developed and developing countries.

- The regions to be considered: USA, UK, India, Cuba, and Sub Sahara region).

9) What has been done well and where are the bottle necks.

10) Successful Cancer cervix screening Programs to learn from.

11) The way forward for countries with a big disease burden to reduce the problem basing on lessons learnt from other countries successes and failures.

12) References and additional information.

INTRODUCTION:

Cervical cancer refers to the malignant condition of the cervix (the mouth of the uterus/womb). Despite the known pre-invasive and implementation of cervical screening programs, cervical cancer has remained a major health problem especially in the developing world (1).

The exact cause of cancer of the cervix is not clearly defined but high risk human papilloma virus subtypes are the major ones incriminated (1-5). Human papilloma virus (HPV) is sexually transmitted and thus the linkage between cancer of the cervix and sexually transmitted infections. HPV infects the cells of the cervix and may result into precancerous lesions and invasive cancer (6, 7) The positive rate of high risk HPV increases as the severity of cervical squamous intra-epithelial lesion increases (1,8) The high risk HPV types include 16,18, 31,33 and 35). Most cervical cancers (approximately 80%) are squamous cell carcinomas, with adenocarcinomas and mixed types (adenocarcinomas) accounting for most of the remainder. However the relative and absolute frequencies of adenocarcinomas are rising worldwide, particularly among younger women for reasons that are poorly understood. There may be an association between cancer of the cervix and HIV/AIDS (1, 9).

Who is at risk of developing cancer of the cervix?

Basically every woman who has ever been sexually active can develop cancer of the cervix. Higher rates of cervical cancer have been seen in those at risk of sexually transmitted infections like those with multiple sex partners, having un protected sex before age of 18yrs, presence of other sexually transmitted infections like herpes simplex and Human Immune deficiency Virus infection (HIV) (6,7). The developing countries accounted for 370,000 out of 466000 cases of cervical cancer that were estimated to have occurred in world in the year 2000 (7, 10).Cervical cancer is an important public health problem among adult women in developing countries in South and Central America, Sub Saharan Africa and South Asia and South East Asia where it’s the most common or second commonest cancer among women. About 231,000 or more deaths occur due to cancer of the cervix world wide. More than 80% of those deaths occur in the developing countries (10, 11). A conservative estimate of the global prevalence (based on the number of patients still alive 5 years after the diagnosis) suggests that each year they are 1.4 million cases of clinically diagnosed recognized cancer. It is also likely that 3 to 7 million women worldwide may have high grade dysplasia (pre-cancer lesion). Cancer of the cervix is most common among poor communities with limited facilities for screening for cancer of the cervix (11). Other factors that are associated with cancer of the cervix are low educational status, lack of knowledge about screening, high parity and presence of other sexually transmitted infections like Herpes simplex Virus.

Some developing countries that have data on cancer incidence and / or mortality have registered either a stable or slowly declining trend in cervical cancer incidence, most likely due to sociodemographic changes rather than to early detection/ prevention efforts (12).On the other hand, some regions in sub Saharan Africa have registered an increased incidence in the recent years (13). Despite the declining trends in incidence observed in some regions, the total burden of cancer is rising in developing countries mostly due to increasing populations.

In the developed countries, initiation and sustenance of cervical screening programs involving screening of sexually active women annually, or once in every 2-5 years, have resulted in large declines in cervical cancer incidence and mortality over the last 40-50 years (14-17).

Other factors thought to be associated with Cancer of the cervix:

Marital and sexual factors:

The epidemiologists have noted that risk of cervical cancer is strongly influenced by sexual behavior. This has led to discovery of the role of HPV infection. Studies have shown increased risk due to marriage at young age, onset of regular sex at an early age <20yrs, multiple lifetime number of sexual partners (18). These risk factors remain significant especially among those women without apparent human papilloma virus infection (HPV). Frequency of intercourse has not been found to be a risk factor after accounting for the effects of number of sexual partners.

The role of the male sexual partner:

In most studies, the husbands of the cervical cancer patients were found to report more sexual partners, history of various genital infections like venereal warts, gonorrhea and herpes simplex genitalis compared to husbands of control subjects. Frequent use of condoms was associated with a lower risk for cancer of the cervix (19).

Gynecological and obstetric events:

Multiparity with short intervals between pregnancies (<2 yrs) has been consistently shown to increase the risk of SIL (squamous intra-epithelial lesion) and cervical cancer (2). The prevalence of HPV is not increased in multiparous women, thus multiparity could thus be an independent factor. There is little evidence to show that the risk of cervical cancer is affected by age at menarche and menopause, characteristics of menses or personal hygiene (20).

Contraceptive methods:

Recent research is showing that long-term users of oral contraceptives are at excess risk for cervical cancer, even after adjusting for sexual and social factors. The risk may be stronger for adenocarcinoma than squamous cell neoplasm (20).This could possibly explain the surveys showing increasing rates of cervical adenocarcinoma among young women. Some studies found an elevated risk among HPV positive women who used oral contraceptives (19, 20). It’s presumed that oral contraceptives promote the activity of HPV infection. Such findings pose challenges to Health in other areas like family planning, where oral contraceptive use is one of the best methods to prevent pregnancy. There is need for more research in that area. Regular users of barrier methods of contraception (condom or diaphragm) have been found to have lower risk of cervical cancer (21).

Genetic factors:

Although some reports suggest that a familial tendency does exist, but there is still little attention to it (22). Whether this tendency reflects environmental or genetic factors is unknown.

Dietary factors:

Micronutrients (e.g. carotenoids, vitamin C and folate) are thought to have a protective effect to cervical cancer by promoting the regression of low grade squamous intra-epithelial lesion (SIL). Some components of fruits and vegetables have been suggested to be protective too (23).

Smoking:

Some case control studies and a cohort investigation have demonstrated increased risk of cervical cancer and SIL among smokers even after controlling for most other risk factors. However, the smoking effect is restricted to squamous cell carcinoma and not among other histological types (24). Smoking is strongly associated with high risk of cervical HPV infection because of correlation between smoking and sexual behavior (25).Therefore, HPV status can confound studies of smoking and cervical cancer.

Infections other than HPV:

HPV may not be the only agent involved in causation of cervical cancer. Of the other agents examined, most attention has been focused on herpes simplex virus type 2 (HSV-2) and Chlamydia which have been shown to increase the risk (26). One of the studies conducted in Uganda showed an increased risk of cervical cancer with multiple and concurrent infections, thus addressing the hypothesis that chronic cervico vaginal infection may increase the risk of HPV leading to cancer of the cervix (27). HIV infection is another viral infection which has been found to increase the risk of high grade lesions of the cervix and thus increasing risk of cancer of the cervix too. The effect is much higher among patients with both HIV and HPV (possible interaction). This may explain why the younger women are reporting with advanced cancer of the cervix.

Signs and symptoms of cancer of the cervix:

Patients are commonly 30 years and above. In some developing countries like Uganda, It has been noted that younger women are reporting to health facilities with advanced disease of the cervix compared to previous years. This has been attributed to immune suppression from HIV/AIDS. The common symptoms for cancer of the cervix include:

-Intermenstrual bleeding,

-Post coital per vaginal bleeding,

-Abnormal per vaginal discharge which tends to be foul smelling.

-Lower abdominal pain and backache are symptoms for advanced disease due to infiltration of the cancer to involve nerves of the sacral plexus

- Leakage of urine or stool incontinence may occur when the cancer has advanced to stage 4 disease to involve the urinary bladder and rectum respectively (refer to some of the quoted text books for details about staging of the cancer and management0.

NB: It is very important to do a vaginal and speculum examination to be able to look at the cervix. It’s important to have a good source of light when looking at the cervix.

The fact that cancer cervix is asymptomatic in the early stages can partly explain why most patients have advanced disease at the time of diagnosis especially in countries where the screening services are very rare.

The other problem is that the symptoms for cancer of the cervix mimic infections like vaginitis and pelvic inflammatory disease. It is thus common to get someone with cancer cervix receiving treatment for pelvic inflammatory disease in the hands of general practioners (personal experience). Some patients end up buying medicines from the counter attempting to manage menstrual problems without going for a proper check up. All these factors coupled with poverty, ignorance and lack of nearby services impact on cancer cervix prevention and management.

Complications of Cancer of the cervix:

The common ones include:

- Severe anemia as a result of severe or chronic on and off bleeding from the cervix

- Kidney complications and later kidney failure (Renal failure with hydronephrosis) due to obstruction of the ureters by the infiltrating cancer which continues to spread to the pelvic walls.

- The lymphatic drainage gets blocked too and leads to swelling of the lower limbs (lymphoedema).

- Vesico vaginal fistula (communication between the urinary bladder and vagina) and rectal vaginal fistula (communication between rectum and vagina).

- Severe pain as a result of infiltration of the sacral nerves.

- Mortality is commonly due to anemia and Uremia (due to kidney failure).

PREVENTION OF CANCER OF THE CERVIX:

1) Human Papilloma Virus Vaccine:

Plans are currently in advanced stages about development of a vaccine against the human papillomavirus. That will go a long way in helping prevention of cancer of the cervix. The Medical College of Georgia is a site for the first international study of the vaccine that protects against four strains (6, 11, 16 and 18) of human papilloma virus in men age16-23.Dr Daron G Ferris (the Principal investigator) says. If we do a good job and vaccinate men as well, then it’s less likely that women are going to be at risk.”

2) Screening Programs as a means to prevent cancer of the cervix:

-The aim of these programs is to detect precancerous lesions and treat them before they progress to invasive cancer.

Cancer cervix is one of the few preventable cancers since it has a clear pre-cancer stage. Despite that, it’s still a major public health problem. Regular cytology screening programmes either organized or opportunistic have led to large decline in cervical cancer incidence and mortality in the developed countries. In contrast, cervical cancer remains largely uncontrolled in high risk developing countries because of ineffective or no screening.

Substantial costs are involved in providing the infrastructure, manpower, consumables, follow-up and surveillance for both organized and opportunistic screening programs for cervical cancer. Owing to their limited health resources, developing countries cannot afford the models of frequently repeated screening of women over wide ranges that are used in the developed countries (11). Many low income developing countries, including most in sub-Saharan Africa, have neither the resources nor the capacity for their health services to organize and sustain any kind of screening program. Middle-income developing countries which currently provide inefficient screening, should re-organize in the light of experiences from other countries and lessons from their failures.

Low or middle income countries intending to start a screening program should start with a limited geographical area before considering expansion. It is more realistic and effective to target the screening on high risk women once or twice in their life time using a highly sensitive test, with emphasis on high coverage (>80%) of the targeted population (11). The sensitivity and specificity of the values that are reported for various screening tests correspond to the detection of high grade lesions (cervical intraepithelial neoplasia II and III) and invasive cancer. All these efforts to organize an effective screening program in these countries need adequate financial resources to develop the infrastructure, train the needed manpower and elaborate surveillance mechanisms for screening, investigating, treating and follow up the targeted women. The findings from existing research on the various screening approaches carried out in developing countries and from the available managerial guidelines should be taken into account when reorganizing existing programs and when considering new screening initiatives.

Cervical Screening World wide:

Cervical cancer prevention efforts worldwide have focused on screening sexually active women using cytology smears and treating precancerous lesions. It is thought that cancer of the cervix develops after dysplastic changes within the cervix. These changes tend to progress steadily from mild to moderate and finally to severe dysplasia. The progression to high grade dysplasia occurs in about 30-33% of those who develop dysplasia. The severe dyplasia may progress to cervical cancer over a period of about 10-15 years while most of the low grade dysplasias regress spontaneously (28,29).

Cytology screening has been shown to be effective in reducing the incidence and mortality from cervical cancer in the developed countries (14-17). The incidence of cervical cancer can be reduced by as much as 80% if the quality, coverage and follow up of screening are high. In most developing countries, women are advised to have their first smear test soon after becoming sexually active and subsequently once every 1-5 years. A number of National guidelines are currently moving towards less frequent smear tests (once every 3-5 years) since the cervical lesions develop fairly slowly after several years. Women with high grade lesions of the cervix are further evaluated using colposcopy, biopsy and subsequent treatment of confirmed lesions. The women with low grade lesions are generally advised to return for routine follow up smears. Organized programs with systematic call, recall and follow up showed greatest effect in Finland and Iceland using fewer resources compared to USA where they are successful but more resources used.

Though cervical cytology (Papanicolao Smear or PAP smear) is considered to be a very specific test for high grade precancerous lesions or cancer, its sensitivity is only moderate even if the quality of other factors is good. I.e. with good collection and spreading of cells, fixation and staining of smears, reporting by well trained technicians and cytopathologists. Cytological screening was shown to have a wide range of sensitivity to detect lesions

(30, 31). Results of meta-analyses estimated the mean sensitivity of cytological smears as 58% (probability that a positive test will detect disease) and specificity of 69% (probability that a negative test will truly imply that no disease (30). It’s possible that the observed decrease in risk of cervical cancer in the developed world may be a result of high screening frequency. Since progression to cervical cancer occurs after several years and the low grade lesions tend to regress spontaneously or may not progress, high frequency of screening would help in detection of previously missed high-grade lesion of the cervix. Current procedures that involve screening women once every 1-5yrs have considerable cost and resource implications. The limited health care budgets in most developing countries preclude initiating and sustaining such programs even in a small geographic setting (11)

Cervical cancer screening programs in the developing countries:

Cytology-based screening programs for cervical cancer have been introduced in some developing countries, particularly in South and Central America, over the last 30 years, but generally have achieved very limited success. In contrast, a comparison of the performance of conventional cytology and its potential alternatives in detecting cervical cancer and its precursors is ongoing in Asia, Africa, and Latin America. Both these approaches are briefly reviewed below since they provide potentially useful information for directing public health policy on introducing new and effective programs in low-resource settings and for reorganizing existing programs.

South and Central America

Since the 1970s, there have been efforts to organize cervical cytology screening programs nationally or regionally in selected Latin American countries.

Chile. In Chile the cervical cancer screening program has been in operation since the early 1970s. Cervical cancer mortality rates did not change much in the period from 1970 to 1985 after the introduction of the program (Fig.2). A recent evaluation of the program indicated that more than 80% of the married women in Chile have been screened at least once. The program was reorganized in the early 1990s, and mortality from cervical cancer has subsequently begun to decline.

Colombia. In Colombia, the Colombian National League against Cancer (a part of the public health system) and private organizations such as PROFAMILIA have been offering cytology screening since the 1970s (32). Subsequently, the cervical cancer mortality rate in the country has, however, remained stable (Fig.2). Nevertheless, there has been a steady and substantial decline in the incidence of cervical cancer in the city of Cali (Fig. 1), possibly as a result of the ongoing screening activities carried out there since 1967, including educational and early detection campaigns. In 1990, a 5-year nationwide cervical cancer control program was initiated to provide cytology smears to more than 60% of women aged 25¾69 years over a 3-year period and to provide follow-up to over 90% of the women screened. The program trained over 4000 nurses, 40 gynecologists, and 36 pathologists. Cytology services were centralized and extensive community information and education campaigns were launched. Midway through the project, the centralized national health care system was reorganized and several services were decentralized to encourage the creation of efficient networks of services and surveillance. However, 5 years after the initiation of the program, cervical cancer mortality data suggested that the situation had remained unchanged.

Costa Rica. In Costa Rica nationwide cytology services have been available to women aged ³15 years since 1970. Information/education campaigns have been used to encourage sexually active women to have annual cytology smears. Invariably in all pelvic examinations a Pap smear is also obtained (33). In Costa Rica, they perform ~250 000 smears annually. Coverage varies according to region, with coverage of rural areas being inadequate in each given round of screening. Despite of this, it seems that more than 85% of eligible women have been screened at least once. Though cervical cancer incidence remained virtually unchanged from 1983 to 1991, a significant decline has been observed more recently (i.e. a 3.6% decrease in annual incidence in 1993- 97 compared with that in 1988-92) (Fig.1). However, the cervical cancer mortality rates have remained unchanged over the last 25 years (Fig. 2) (34, 35). In an ongoing cohort study of more than 9000 women in Guanacaste Province, the cross-sectional sensitivity of HPV testing was found to be higher than that of conventional cytology (88% versus 78%) but the specificity was lower (89% versus 94%) (36).

Cuba. In Cuba a cervical cytology screening program, offering smears every two years to women aged ³20 years, was implemented through the primary health care services in 1968 (37). Pap smears are taken by a nurse in the family doctor's office and are processed in one of the 36 regional cytology laboratories. It has been suggested that more than 80% of Cuban women aged 20¾60 years have been screened at least once. However, no reduction in cervical cancer incidence and mortality (Fig. 2) has been observed since the introduction of the program.

Mexico: A national cervical cancer screening program was initiated in Mexico in 1974 (38, 39) and now operates in the Federal District and all 31 states of the country. Cytology smears are offered annually to women aged 25¾65 years and the program is integrated with the existing health care services. Mexico reportedly had 463 cytotechnologists, 251 reading centers, 70 dysplasia clinics, and 540 gynecological oncology units in 1996. However, the infrastructure and resources were sufficient to carry out only 3.5 million smears annually for a target population of 16.5 million women (data for 1996); annual screening was nevertheless the "norm" for the program. Realistically, this infrastructure is sufficient to screen the targeted women only once every 5 years. The Ministry of Health (MOH) has a total of 120 cervical cancer screening centers (CCSCs) where 230 cytotechnologists are employed. These screening canters are intended to carry out cytology screening of 6.5 million women who are not covered by social security. The Mexican Institute for Social Security (IMSS) is responsible for screening women covered by social security. In 1992, the MOH's screening centers carried out 1.02 million smears and the IMSS 1.3 million smears. There is a wide variation in the coverage of women on the national level. Studies indicate that less than 30% of the women in rural areas have been screened so far. There is no systematic effort to coordinate the program through a central organization for call, recall, and follow-up of screened women.

An evaluation of the cervical cytology tests provided within the Mexican program indicated that the validity and reproducibility varied greatly within and between the screening carried out by the MOH and the IMSS (40). Among the CCSCs the sensitivity to detect high-grade lesions varied from 46% to 90% and that of the specificity from 48% to 96%. The false-negative rate varied from 10% to 54%, with an average false-negative rate of 35%. Review of a random sample of 6011 negative smears indicated that 64.0% of the smears were of insufficient quality. There has been no decline in mortality from cervical cancer in Mexico since the initiation of the screening program (Fig. 2) (41).

Brazil, Peru, and Puerto Rico: There are no organized cervical cancer screening programs in Brazil. A high-risk of the disease (incidence >40 per 100 000 women) is reported from the north-east region. Low-level sporadic screening with opportunistic cytology smears is carried out in different regions.

Peru has also recorded a high incidence of cervical cancer; there are no organized screening programs in the country. A large demonstration project of cervical cancer screening with visual inspection with acetic acid (VIA) is currently on- going in San Martin region of Peru.

An early detection program for cervical cancer was established in Puerto Rico in the 1960s. This covered the metropolitan areas until 1962, and was later expanded to all health regions of the island. Cytology smears are offered to women aged ³15 years and about 150 000 smears are processed annually. The incidence and mortality from cervical cancer have declined steadily over the last three decades (Fig. 1 and Fig. 2). The average, annual age- standardized incidence dropped from 38 per 100 000 women during 1950¾54 to 19.9 per 100 000 women in 1990, and the mortality rate dropped from 19.1 per 100 000 women to 5.2 per 100 000 women in the same period.

Sub-Saharan Africa

There are no organized or opportunistic screening programs for cervical cancer in any of the high- risk sub-Saharan African countries. While data from Uganda indicate that, at least in some areas of the country, substantial increases in the incidence of cervical cancer may have occurred (13), there is no evidence of an increase in incidence over time in Zimbabwe (42). Studies in Zimbabwe and South Africa have assessed the performance characteristics of potentially alternative screening tests such as visual inspection with acetic acid (VIA) and HPV testing. A cross-sectional screening study in Zimbabwe reported that the sensitivity and specificity to detect high-grade dysplasias and cancer was 77% and 64%, respectively for VIA compared to 43% and 91% for cytology (43). The sensitivity and specificity of HPV testing using Hybrid Capture II assay (Digene Corporation, Gaithersburg, USA) were 81% and 62%, respectively (44); the sensitivity and specificity of HPV testing was, respectively, 91% and 41% for HIV-infected women and 62% and 75%, respectively, for HIV-negative women (45). It is also reported that the sensitivity and specificity of VIA and HPV testing, when used sequentially, was 64% and 82%, respectively (46).

South Africa. The South African Institute of Medical Research organized the infrastructure for mass screening of the female population of Soweto (Project Screen Soweto) so that 90 000 cytology smears could be tested annually (47). However, the lack of a planned population education and motivation program resulted in poor participation of the target population in the program. In a cross- sectional study that addressed the comparative performance of cytology, VIA, cervicography, and HPV testing in South Africa, the sensitivity was found to be 78%, 67%, 53%, and 73%, respectively; the specificity was 94%, 83%, 89%, and 86%, respectively (48). In another study in South Africa, HPV testing using self-collected vaginal samples was found to be more sensitive than cytology (66% versus 61%), but less specific (83% versus 88%) (49). In an earlier study in South Africa, the sensitivity of VIA was found to be 65% (50). A recent study of the cost- effectiveness of several cervical cancer screening strategies, based on the South African experience, indicated that strategies using VIA or HPV DNA testing may offer attractive alternatives to cytology- based screening programmes in low-resource settings (51). When all the strategies were analyzed on the basis of a single lifetime screening at age 35 years compared with no screening, it was found that HPV testing, followed by treatment of screen-positive women at a second visit, cost US$ 39 per year of life saved (27% reduction in cancer incidence); VIA, coupled with immediate treatment of screen-positive women at the first visit, was the next most cost- effective (26% reduction in cancer incidence) and was cost saving; cytology, followed by treatment of screen-positive women at a second visit, was the least effective (19% reduction in cancer incidence) at a cost of US$ 81 per year of life saved (51).

Currently, cytology smears are provided on demand in antenatal, postnatal, gynecology, and family planning clinics in South Africa. Work to develop a cervical screening policy for South Africa, based on the models of natural history, and has been ongoing for some time. It is proposed to initiate screening at the age of 30 years with three smears being carried out in a woman's lifetime. However, there has been debate about both whether this policy should be implemented and how. A pilot project to set up screening services using the health systems development approach is currently being undertaken by three provincial departments of health (Western Cape, Northern Cape, and Gauteng) in cooperation with nongovernmental organizations. This approach seeks to set up programme components such as reaching the target population, providing a competent screening service, relaying the results, and organizing referral, investigation, treatment and follow-up of screening-positive women. It is expected that these tested methods will be applied in the provinces and then nationally.

A three-arm, prospective randomized intervention trial in South Africa is currently addressing the comparative safety, acceptability and efficacy of screening women with VIA and HPV DNA testing and immediately treating screen-positive women with cryotherapy performed by nurses in a primary health care setting. Outcome measures include reduction of high-grade cervical cancer precursors in treated versus untreated women, followed over a 12-month period.

Other countries: Cross-sectional/randomized screening intervention studies are currently ongoing in several African countries ¾ Burkina Faso, Congo (Brazzaville), Ghana, Guinea (Conakry), Kenya, Mali, Niger, and Nigeria ¾ to address the accuracy of various screening approaches such as cytology, HPV testing, VIA, and visual inspection with Lugol's iodine (VILI) as well as the detection rates associated with them.

South Asia

India. India accounts for one-fifth of the world burden of cervical cancer. There are no organized or high-level opportunistic screening programmes for cervical cancer in any of the provincial states. Data from population-based cancer registries in different regions indicate a slow, but steady, decline in the incidence of cervical cancer. However, the rates are still too high, particularly in the rural areas, and the absolute number of cases is on the increase due to population growth. Efforts to improve awareness of the population have resulted in early detection of and improved survival from cervical cancer in a backward rural region in western India (52, 53). Also in two sub districts of western India where the literacy among women is less than 20% there have been attempts to evaluate the role of improved awareness in the early detection and control of cervical cancer (54). Person-to-person and group health education on cervical cancer were provided to 97 000 women in Madha Tehsil, Solapur district, Maharashtra State, in western India; 79 000 women in Karmala Tehsil served as the control population. This program was initiated in 1995 and the preliminary results for 1995-99 indicate that, compared with the control area, in the intervention sub district a substantially higher proportion of women presented with cervical cancer in earlier stages with significantly reduced case fatality (Table 1).

Visual inspection-based approaches to cervical cancer screening have been extensively investigated in India. The performance characteristics of unaided visual inspection (without acetic acid), also known as "downstaging", has been addressed in several studies (55). The unaided approach suffers from low sensitivity and specificity to detect cervical dysplasia Currently there are several ongoing, cross-sectional studies being carried out on other screening approaches such as VIA, VIA with magnification (VIAM), and HPV testing as alternative screening approaches. Results from two reported studies indicate that the sensitivity of VIA to detect high-grade lesions was similar or higher than that of conventional cytology but that its specificity was lower (56,57).

There are three large, ongoing cluster-randomized intervention trials in India ¾ in Dindigul district (Tamil Nadu), in Mumbai, and in Osmanabad district (Maharashtra) ¾ to evaluate the effectiveness of VIA, in reducing cervical cancer incidence and mortality. The intervention programme in Osmanabad district aims to address the comparative efficacy and cost-effectiveness of three different primary screening approaches in reducing the incidence and mortality: VIA, conventional cervical cytology, and HPV testing. The results of these studies are likely to provide valuable leads to the development of public health policies to control cervical cancer in developing countries. A recently held national workshop on control of cervical cancer in India reviewed the various methodologies for the early detection of cervical neoplasia and considered both good quality conventional cytology and VIA as suitable tests for early clinical diagnosis (58-62). In view of the inadequately developed cytology services, VIA was recommended as the immediate option for the introduction of cervical cancer control initiatives as part of the district cancer control programs in 54 districts in India.

South-east Asia

In Singapore, a high level of opportunistic screening for cervical cancer has been operating over the last few years, but has had only minimal impact on the overall incidence and mortality from cervical cancer (12). However, a substantial decline in cervical cancer incidence and mortality has been observed among the Singapore Indian community, with stable trends among the Chinese and Malay communities. Efforts are currently underway to provide an organized screening program by restructuring the existing opportunistic program. A test-and-treat approach following VIA is currently being evaluated in Thailand. A cytology-based demonstration program on screening is currently being implemented by the MOH in Nakornpanam Province in north-east Thailand. The comparative performance of VIA and VILI in detecting cervical neoplasia is being addressed in Vientiane, Lao People's Democratic Republic. Ongoing studies in rural China are addressing the accuracy of cytology and non- cytology-based screening approaches.

Situation in Uganda:

From the Ugandan experience, cervical cancer is the commonest malignancy among women (13). Over 80% of patients diagnosed with cancer at Mulago hospital present with advanced disease (63, 64). Cancer cervix patients on palliative radiotherapy account for ~20 to 30% of the patients on the gynecological wards at Mulago hospital. There are no organized screening programs in Uganda, same as in most of the developing countries. The only available activity has been to use opportunistic screening of those women who come to health units for other reasons. Screening of women becomes a responsibility of medical workers who should have the necessary skills and should have functional units to be able to perform cervical screening (63). From a study conducted at Mulago, the authors noted that knowledge about risks for cervical cancers was low among finalists in nursing and medical schools (40 %), but 93% considered it a Public health problem. Most of those final students did not feel confident enough to perform a pap smear (63). Recent research work from a population survey in Uganda on Predictors of High Risk papilloma Virus showed that ~17% of the studied women had high risk HPV types (self collected vaginal samples wee used). Presence of HIV infection was highly associated with HPV. This shows that high risk HPV is highly prevent in Uganda and yet screening services are still poor (65).

Way Forward:

Effective screening programs in developing countries:

To organize effective cervical cancer screening programs, developing countries will have to;

-find adequate financial resources, develop the infrastructure, train the needed manpower, and elaborate surveillance mechanisms for screening, investigating, treating, and follow-up of the targeted women.

- There is considerable discussion focused on which screening test to use ¾ cytology or alternatives to cytology, such as VIA or HPV testing ¾ or which combinations/sequence of screening tests should be used for screening in developing countries. Choosing a suitable screening test is only one aspect of a screening program.

- A more fundamental and challenging issue is the organization of the program in its totality. Whichever screening test is to be used, the challenges in organizing a screening program are more or less the same.

- However, screening tests (e.g. cytology, HPV testing) that require additional recalls and revisits for diagnostic evaluation and treatment may pose added logistic difficulties and these may emerge as another barrier for participation in low-resource settings.

-The choice of screening test in countries/ regions that plan to initiate new programs should be based on the comparative performance characteristics of cytology and its potential alternatives such as VIA, their relative costs, technical requirements, the level of development of laboratory infrastructure, and the feasibility in a given country/region.

-A highly sensitive test should be provided. If cytology is chosen, considerable attention should be given to obtaining good quality smears, staining, and reporting so that a moderately high sensitivity to detect lesions is ensured.

- If VIA is chosen for screening, considerable attention should be given to the proper monitoring and evaluation of the program inputs and outcomes before further expansion, since VIA is still an experimental option for cervical cancer screening and it remains to be demonstrated whether VIA-based screening programs are associated with a reduction in cervical cancer incidence and mortality.

- In developing countries, existing ineffective cytology- based programs should be urgently reorganized and monitored.

Quantitative studies have shown that after two or more negative cytology smears, even screening once every 10 years yields a 64% reduction in the incidence of invasive cervical cancer, assuming 100% compliance (15, 59). Further studies based on this model indicate that once-in-a-lifetime screening may yield around 25-30% reduction in the incidence of cervical cancer (60, 61,).

To have an impact on cervical cancer incidence and mortality, efforts must be focused on the following:

1) Increasing the awareness of women about cervical cancer and preventive health-seeking behavior; screening all women aged 35¾50 years at least once, before expanding the services and providing repeated screening (11). In South Africa, it’s proposed that cancer cervix screening should start at 30 yrs, with 3 pap smears to be done in a woman’s life. (Age of onset of screening is still a controversy). Person to person and group health education on cancer cervix can attract people to go for screening as long as the infrastructure is functional.

2) Providing a screening test with high sensitivity (since women have less frequent opportunities for repeated screening);

3) Treating women with high-grade dysplasia and cancer;

4) Monitoring program inputs and evaluating the outcomes should part of the package.

5) Strengthening training of service providers on how to perform cancer cervix screening is mandatory plus to training cytopathologists and cytotechnicians to ensure quality specimens and interpretation of results.

References:

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More information can be obtained from the following websites:

1) http://www.ahrq.gov/clinic/uspstf/uspscerv.html.

U.S. Preventive Services Task Force: Screening for Cervical cancer:

Release Date: January 2003 (Summary of Recommendations / Supporting Documents)

2)http://www.sciencedaily.com/releases/2004/1/041123162300.html

HPV Vaccine Studied For First Time In Men:Source: Medical College of Georgia (Posted November 2004

3) Cancer screening web sit.htm. (bbc.co.uk) BBC Health Condition Screening Programmes.

4) Health Promotion Lifestyle. (http://www.patient.co.uk/showdoc/16/#can.

5)New scientist.com .Will the cancer Vaccine get to al lwomen? http://www.newscientist.com/channel/sex/mg18624954.500.

6)Websiteteforsymptomsfrocancerofthecervix.(http://www.wrongdiagnosis.com/c/cervical_cancer/symptoms.htm)

7)http://www.fpahealth.org.au/news/20021128_papvirus.html: Human Papilloma Virus(HPV) Vaccine.

8)The interested reader is referred to common text books about details of examination of a patient with cancer of the cervix and for details about staging of the cancer and management).

à) Cervical Cancer and Preinvasive Neoplasia (Hardcover)
by Stephen C., M.D. Rubin (Editor), William J. Hoskins (Editor)

à) Clinical Gynecologic Oncology (Hardcover)
by Philip J. Disaia, William T. Creasman

à Te Linde's Operative Gynecology (Hardcover)
by Howard W. Jones (Editor), John A. Rock (Editor), Richard W. Te Linde (Editor)

NB To read about Programmes that have worked: Most of the section on Cervical Cancer Screening from developing countries is from a “WHO Bulletin” where I found good information regarding experience from developing countries”.

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