Limited Pap screening associated with reduced risk of cervical cancer in South Africa

M Hoffman1, D Cooper1, H Carrara1, L Rosenberg2, J Kelly2, I Stander3, A-L Williamson4, L Denny5, G du Toit6 and S Shapiro7

1 Department of Public Health and Primary Health Care, University of Cape Town, South Africa.
2 Slone Epidemiology Center, Boston University, USA.
3 Medical Research Council of Southern Africa.
4 Division of Virology, University of Cape Town, South Africa.
5 Department of Obstetrics and Gynaecology, University Of Cape Town, South Africa.
6 Department of Obstetrics and Gynaecology, University of Stellenbosch, South Africa.
7 Slone Epidemiology Unit, Boston University, USA.

Professor M Hoffman, Department of Public Health and Primary Health Care, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, 7925, South Africa. E-mail: MH{at}CORMACK.UCT.AC.ZA


    Abstract
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 Abstract
 Methods
 Results
 Discussion
 References
 
Background We investigated the effect of Pap smear screening on the incidence of invasive cancer of the cervix in the Western Cape, South Africa where screening is limited.

Methods Data were derived from a case-control study of the association of hormonal contraceptives and invasive cervical cancer. Incident cases (n = 524) of invasive cervical cancer who presented at two tertiary hospitals and controls (n = 1540) series matched for age, race, and place of residence were interviewed. Information on a wide range of variables was collected including whether the women had previously had a Pap smear taken and the number and timing of smears. Odds ratios (OR) and 95% CI were calculated using multiple logistic regression.

Results The OR of cervical cancer was reduced among women who had ever had a smear (OR = 0.3, 95% CI: 0.3–0.4). The OR declined with increasing number of smears to 0.2 for >=3 smears (trend P = 0.0003). Among women who had a smear <5 years previously the OR was 0.3, but even if the smear was taken >=15 years previously the women remained at reduced risk (OR = 0.5).

Conclusion The data suggest that even limited Pap smear screening reduces the risk of cervical cancer. Should a screening programme be successfully implemented, the incidence of cervical cancer might be reduced by as much as 70%.


Keywords Pap smears, cervical cancer, South Africa

Accepted 5 December 2002

In South Africa, cancer of the cervix is the most common malignancy in African women and the fourth most common in white women, with an overall age standardized incidence rate of 22 per 100 000 per year. The lifetime risk is approximately 1 in 41, and 5000 new cases are reported annually.1 Cervical cancer is a disease of early and late middle age. Isolated cases occur among young women, but incidence rates rise sharply from age 35 with 87% of cases occurring in women over that age.2 In developed countries, cervical cancer has become rare, but it remains a leading cause of cancer death in disadvantaged populations.

Internationally it has been shown that screening for precursors of cervical cancer, most commonly by means of Papanicolou (Pap) smears, substantially reduces the incidence of invasive cancer.3,4 In addition, screening services have been shown to be extremely cost-effective when compared with services that treat cases of invasive disease.5,6 In South Africa there has been much debate as to the most suitable screening policy, particularly with regard to age at commencement and appropriate time intervals between smears. At the present time, opportunistic screening is performed by the public health services of South Africa when women attend family planning and antenatal clinics. Women attending these services are mainly young, and smears are thus being taken in a relatively low risk group. In addition, it has been shown in one study that more than 40% of smears taken in a district of the Western Cape were not satisfactory, and in many of the smears endocervical cells were absent.7

An important question is whether Pap smear screening, as practised in South Africa, is effective in reducing the incidence of invasive cancer of the cervix. This question has not previously been evaluated. In this paper we report on the relation of Pap smear screening to cervical cancer risk among coloured and African women in the Western Cape region of South Africa.


    Methods
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 Abstract
 Methods
 Results
 Discussion
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The data were derived from a case-control study conducted to determine the risk of invasive cancer of the cervix in relation to the use of hormonal contraceptives. The study was conducted among women below the age of 60 years who lived within 150 km of Cape Town, in the Western Cape region of South Africa, for >=6 months of the preceding year. Incident cases of histologically confirmed squamous or adenocarcinoma of the cervix (stages 1b–IV), diagnosed no more than 6 months previously at two tertiary care hospitals, were identified and interviewed. The stage of the cancer, based on clinical and pathological findings, was abstracted from oncology clinic records. Hospital controls were series-matched to the cases in an approximate ratio of 3:1 for decade of age, race, area of residence, and hospital. Women were only included as controls if the diagnosis leading to admission was judged to be independent of cervical cancer risk and of contraception.

During the study period, 535 cases and 1668 potential controls were identified; 2 cases and 107 (10%) potential controls refused to participate. Thirty-eight of the control refusals were due to the fact that the women had recently had a Pap smear. Cervical smears were taken from all controls for human papilloma virus (HPV) testing (to be reported on elsewhere); Pap smears were taken at the same time: seven potential controls were found to have cervical cancer, and were excluded. Initially white women were included but since there were only 9 white cases and 14 white controls at the end of the first year of the study they were excluded and the present analysis is confined to coloured and African women. Thus the final series comprises 524 cases (133 African, 391 coloured) and 1540 controls (386 African, 1154 coloured).

A standard questionnaire was administered in the subjects’ preferred language by trained nurses who conducted face-to-face interviews. With regard to the question on Pap smears, we asked the woman if she knew what a Pap smear was, and if it was apparent that she did not understand the term we gave her the following explanation, ‘It is a test to detect abnormal cells on the mouth of the womb that could lead to cancer. When performing this test the doctor or nurse places an instrument (speculum) in the woman’s vagina so that he/she can see the mouth of the womb from which he/she takes some cells to send for testing.’ The woman was asked about the number and the timing of Pap smears that were taken prior to the current illness. Among the 1540 controls, 1123 (73 %) reported that they had undergone screening with one or more Pap smears; the proportions among 485 women admitted for trauma or orthopaedic conditions, 502 admitted for acute conditions (infections or emergency surgery), and 553 admitted for other conditions were 73%, 70%, and 76%, respectively. Seventeen controls were unsure as to the number of smears they had undergone. Adjusted odds ratios (OR) for cervical cancer for women who had had a Pap smear relative to women who had never had a Pap smear were calculated using unconditional logistic regression. Variables included in the models to control possible confounding were age, area of residence (urban/rural), race, years of education, parity, age of first sexual activity, use of injectible contraceptives, use of oral contraceptives, and cigarette smoking.


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The percentages of control women who reported having had a Pap smear, within categories of age and other risk factors, are given in Table 1Go. The proportion screened was highest at ages 30–49 (76%) and lowest at age less than 30 (57%). Smears had been performed among 47% of African controls and 82% of coloured controls. Receipt of a Pap smear was greater among rural residents, more educated women, parous women, users of oral contraceptives or injectable contraceptives, and smokers. The proportion who had had a Pap smear increased according to age at commencement of sexual activity, from 66% for ages <15 to 84% for ages >=23.


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Table 1 Proportion of Pap smears (ever) among 1540 controls according to selected factors
 
Among the 524 cases and 1540 controls, 50% and 73%, respectively, had previously undergone Pap smear screening (Table 2Go). Overall, the adjusted OR for ever having a Pap smear was 0.3 (95% CI: 0.3–0.4). The OR declined from 0.4 among women who only had one Pap smear to 0.2 among those who had >=3 smears (P trend = 0.0003). The results were similar in coloured and African women. The reduction of the risk of cervical cancer became less marked as the interval since last Pap smear increased: the OR was 0.3 (95% CI: 0.2–0.4) for last smear within the previous 5 years and 0.5 (95% CI: 0.4–0.7) for last smear >=15 years previously (trend test, P = 0.0004) (Table 3Go). In all age groups the OR associated with having had a Pap smear was less than 1.0, and except among women under 30 years, the 95% CI excluded 1.0 (Table 4Go). Among 154 women with ‘early’ cancer (stages Ib and II) and 370 with advanced cancer (stages III and IV), 57% and 46%, respectively, reported having been screened by Pap smear. The adjusted OR were 0.5 (95% CI: 0.3–0.7) for stages Ib and II and 0.3 (95% CI: 0.2–0.4) for stages III and IV (Table 5Go).


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Table 2 Odds ratio (OR) for cervical cancer in relation to number of Pap smears
 

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Table 3 Odds ratios (OR) for cervical cancer in relation to recency of Pap smear
 

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Table 4 Odds ratios (OR) for cervical cancer in relation to Pap smears in various age categoriesa
 

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Table 5 Odds ratios (OR) for cervical cancer in relation to Pap smears according to stage of cancer
 
Finally, since it is possible that women with pre-existing but undiagnosed cervical cancer may selectively have undergone screening or that some smears reported by cases may have been for diagnostic purposes, the analyses were repeated after excluding all women who had had a Pap smear performed within a year of enrolment in the study (6 cases and 46 controls). The findings were unchanged (data not shown).


    Discussion
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The present findings suggest that in the Western Cape region of South Africa the use of Pap smears to screen for precursor lesions of cervical cancer reduces the incidence of invasive disease. Assuming the validity of the results, if all women had been screened under the conditions in the present study, an estimated 70% of cases of cervical cancer would have been prevented. Using the prevalences of Pap smear screening, which was 81% in coloured women and 46% in African women, we estimate that in the study population Pap smears reduced the incidence by 57% in coloured women and 37% in African women. The reductions in the present study occurred despite the acknowledged limitations in both quality and quantity of the screening programmes. Improved standards in the performance of Pap smears as well as widespread use of Pap smears directed at appropriate age groups should result in an even greater reduction in the incidence of cervical cancer.

The risk reduction appeared to be greatest for more recent smears, but even smears done >=15 years previously were associated with a reduced risk of cervical cancer. More frequent screening was associated with a greater reduction in risk. The reduction was present at all ages beyond 30 years; among women under 30 years the OR was reduced but was not statistically significant. In addition, the risk reduction was present for both early and advanced stage cancer but was most marked in the latter.

It is unlikely that the selection of cases or controls biased the findings. Refusal rates were low both among the cases (<1%) and the controls (10%). Other sources of selection bias are also unlikely. The enrolment of cases was deliberately confined to stages lb–lV in order to minimize detection bias due to screening associated with lifestyle factors such as health consciousness. Such a bias could conceivably have applied to cancers that were not yet clinically evident (such as cancer in situ or stage 1a tumours). Invasive cancer of the cervix, on the other hand, would inevitably have come to diagnosis, irrespective of lifestyle. The controls in this analysis were admitted for conditions that were unrelated to the likelihood of having a Pap smear or of developing cervical cancer, and the similar rates of Pap smears among the major diagnostic categories supports the likelihood that the selection was unbiased. Since the findings were unchanged when Pap smears performed in the preceding year were omitted, it is unlikely that diagnostic Pap smears were included which could have introduced bias.

The possibility of information bias cannot be excluded. However, it is likely that the loss of recall for having undergone a Pap smear would, if anything, have been greater among the controls than among the cases. If so, the reduction in the OR could have been even greater than was estimated. Potential confounding from multiple sources was controlled in the logistic regression analyses, but there may have been some distortion from uncontrolled residual confounding. For example, use of Pap smears was inversely associated with early sexual activity. Failure to completely control for sexual activity due to not having reliable information would have resulted in overestimation of the reduction in the OR associated with Pap smears. However, the crude OR in our study were similar to the multivariate OR derived with control for important cervical cancer risk factors that were related to acceptance of Pap smears. This suggests that better control with more precise data on risk factors would have little effect on the OR.

Cases and controls in this study were treated in public institutions in the Western Cape that serve women who have no medical insurance, or only limited coverage. An unknown number of women who were fully insured (membership of a medical aid society) were not enrolled because they would have been treated in private hospitals. Thus the findings are only generalizable to women attending public institutions in the Western Cape. Yet, even though the cases and controls were from disadvantaged communities, in which the screening programmes were presumably of variable quality, Pap screening nevertheless appeared to be effective. Furthermore, even when the time since last having had a Pap smear was >10 years previously there was still an apparent reduction in cervical cancer risk in all age categories. These findings are in accord with those from a study in Mexico.8 The two studies suggest that developing countries’ screening programmes, conducted at a much lower intensity than those practised in the West, can substantially reduce incidence from a preventable disease.

There were insufficient data to analyse the effects of Pap smears in white women. However, since Pap smear services are more readily accessible to them, the more common use of Pap smears among white women may partly or wholly account for the lower incidence of invasive cervical cancer in this race group.1

A number of attempts were made in the past to introduce cervical screening programmes at national, provincial, and local levels in South Africa. In the 1970s the Department of Health suggested that a Pap smear should be taken only if the cervix appeared abnormal.9 This suggestion was criticized because by the time the cervical abnormality is visible a biopsy, rather than a smear, is indicated. In the 1980s, in an urban African area, a well-organized programme failed: attendance of women at the health service was poor because the community education programme that was intended to accompany introduction of the service was delayed.10 In 1995, in the Western Cape, a new policy was introduced: three Paps were recommended at 10-year intervals commencing at about 30 years of age. This policy was not implemented effectively, and its introduction saw an overall decline in screening, as smears were no longer taken regularly at the family planning and ante-natal services. Studies revealed that health personnel did not understand the rationale for the policy and became less motivated. In addition, no effort was made to educate women in the community.7,11

At the national level, there has been extensive debate as to whether cervical screening is a priority service that should be provided by the public health sector in South Africa, and whether a national policy should be introduced.12–16 There have also been discussions regarding the most appropriate programme, in terms of age at first smear and frequency of screening. Some have suggested that a cervical screening policy for South Africa would be inappropriate because the poor health infrastructure, particularly in rural areas, makes a universal service unfeasible; in the interest of equity a national programme should therefore not be introduced. It was also suggested that the country needs to focus its efforts on more cost-effective interventions such as immunization, tuberculosis, sexually transmitted disease, and human immunodeficiency virus (HIV) control. More recently, however, the government has shown a commitment to reform based on a primary health care approach, and has acknowledged the need to provide comprehensive reproductive health services. In recognition of the fact that cancer of the cervix is a major cause of preventable morbidity and mortality, a national cervical screening policy has recently been approved. It again states that women aged >=30 years should have a Pap smear three times in succession at about 10-year intervals.17 This policy is analogous to that recommended by the World Health Organization for less-resourced settings. The appropriateness of the policy is supported by findings of a South African multicentre study on the prevalence of precancerous lesions and cervical cancer.18 The programme will be introduced incrementally. Challenges that are posed by the introduction of the new policy include the development of ways to increase coverage, to reach older women and African women, and to ensure high-quality Pap smears. In addition, it is recognized that the HIV/AIDS epidemic may have a major effect on the incidence and prevalence of cancer of the cervix.19

The present findings provide quantitative evidence to suggest that the newly formulated policy, if successfully implemented, could bring about a material reduction in the incidence of invasive cancer of the cervix in South Africa. In addition, the evidence from many studies suggests that death and morbidity from this disease could be substantially reduced by Pap smear screening programmes in other disadvantaged populations.


KEY MESSAGES

  • Pap smear screening in the Western Cape, South Africa is limited.
  • The limited Pap smear screening programme reduces the risk of cervical cancer.
  • The risk of cancer of the cervix declines with increasing number of smears.
  • An organized screening programme might reduce incidence of cervical cancer by 70%.

 


    Acknowledgments
 
This study was supported by a grant from the National Institutes of Health, USA—Grant No. R01 CA 73985–01. We are indebted to our clinical colleagues at provincial hospitals in the Western Cape for their co-operation and support. We would also like to acknowledge the fieldworkers for their contributions.


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 Discussion
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16 Cruse P, Martin A. Cervical Smears in South Africa—too little, too late. S Afr Med J 1997;87 :1423–25.

17 Guidelines for Cervical Screening Programme. Pretoria Department of Health, 2000.

18 Fonn S, Bloch B, Mabena M et al. Prevalence of precancerous lesions and cervical cancer in South Africa—A multicentre study. S Afr Med J 2002;92 :148–56.[Medline]

19 Wallace SV, Carlin EM. HIV in cervical cancer. Int J STD AIDS 2001; 12 :283–85.[CrossRef][ISI][Medline]