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CARCINOMA OF UTERINE CERVIX : A Case Control Study

VANDANA NIKUMB*, PB SAWANT**, S KARTIKEYAN***
*Lecturer, Department of Preventive and Social Medicine, MGM’s Medical College, Kamothe, Navi Mumbai 410 209. **Associate Professor, Department of Preventive and Social Medicine, Grant Medical College, Byculla. ***Associate Professor, Department of Preventive and Social Medicine, Rajiv Gandhi Medical College, Kalwa.

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A cross-sectional case-control study was conducted on women attending gynaecological out patient department of an urban hospital in Mumbai. Women in study and control group were age matched. The differences in the study group and control group were statistically significant with regards to negative history of PAP smear done in the past and diagnosis of carcinoma in situ.


INTRODUCTION

The proverb that "Prevention is always better than cure" is absolutely valid for the disease of carcinoma of uterine cervix, which was a well known disease in India and Egypt even before the birth of Christ.[1] The disease has gained great importance in last half of the 20th century because of the availability of facilities of its early detection and treatment. Carcinoma of cervix is the second most cancer in women worldwide, today.[2,9] In India, the annual incidence of carcinoma of cervix is estimated to be five lac new cases per year. Carcinoma of cervix accounts for 25-50% of total cancers while for 86-90% of all genital cancers in Indian women.[4] The spectrum of cervical carcinoma is shown in Fig. 1.

Normal cervix

Cervical Dysplasia

Cervical Intra-epithelial Neoplasia (CIN)

Carcinoma In Situ (CIS)

Invasive cacinoma of Uterine Cervix

Fig 1 -- Spectrum of cervical carcinoma[5]

Prognosis of invasive carcinoma of the uterine cervix depends on clinical stage of carcinoma at the time of diagnosis, since pre-invasive cancer is 100% preventable and treatable disease. Cytology is the accepted method for screening of early stages of carcinoma of the uterine cervix all over the world, since it is an easily applicable, economical and effective method.

That Papanicolaou (PAP) smears reduce the frequency of carcinoma of cervix is persuasive, because -

1.In the US, mortality from carcinoma of cervix decreased as the screening rate rose.

2.In Norway, only 5% of the female population undergoes regular screening and in 1980, the incidence of carcinoma of cervix was 115% of that of 1965.

3.In Denmark, about 40% of population is screened every 3-5 years and the incidence of carcinoma of cervix over the same 15 years period fell by about two-thirds.

4.In Iceland, practically 100% of the eligible population is screened every 2-3 years and the incidence of carcinoma of cervix in 1980 had fallen to less than one third of that in 1965.[10,11]

From the above facts, it can be concluded that early diagnosis and prompt specific treatment of pre-invasive or early stages of the disease (mainly in high risk women), reduces the prevalence of invasive carcinoma of uterine cervix. The widespread use of PAP smear permits the identification of patients with cervical dysplasia or ClS, who are at high risk of developing invasive carcinoma of uterine cervix. These patients can then be treated with simple and often non-invasive measures. Due to this diagnostic test, 58% decrease in the incidence of carcinoma of cervix occurred since the mid-1940’s.[6]

The aim and objective of the present study was to find whether the PAP smear examination and cervical biopsy, were the preventive measures for invasive carcinoma of cervix.

MATERIAL AND METHODS

This single observer cross-sectional case-control study was conducted in women attending gynaecological department in JJ group of Hospitals, Mumbai, during the period of 1st December 1992 to 30th March 1994.

The study sample (cases) comprised patients with invasive carcinoma of uterine cervix, all of whom were confirmed by the specialist, and the diagnosis was confirmed by the histopathological examination at every instance. Women attending the same institutions for antenatal check ups, female relatives of patients, women coming for minor gynaecological complaints (like leucorrhoea) formed the control group (controls). Both groups were matched according to age groups.

A standard proforma was prepared and tested. The investigator obtained information by the interview method for following variables like-past history of cervical smear or biopsy done, number of PAP smears done in last five years, past history of ClS detection and its time period from the present study. Also, the results of previous therapeutic or diagnostic procedures were recorded. PAP smear was taken from all women included in the study sample, as per the technique described by Ayre.[7] The smears were sent to the pathology department of the same institute for microscopic examination.

Risk assessment involved the assessment of risk posed to women with carcinoma of cervix by different factors. This was done by finding out the Odds ratio. The Chi-square test was applied to each of the variables to test the significance of difference between two proportions in cases and controls.

RESULTS

There were 99 women in the study group, while the control group comprised 198 women. It was observed that 63.64% of cases as compared to only 15.66% of their age matched controls gave a negative history of smear done in the past, showing statistically highly significant results. 20.20% of cases as compared to 15.66% of controls gave history of biopsy done in the past, but the results were not statistically significant. The risk of developing carcinoma of cervix was about 9.43% times more in women who had no history of smear done in the past compared to women who gave history of smear examination done in the past (Table 1). As compared to controls, the cases had lesser number of smears done in the last five years, showing statistically significant results (Table 2). Only 9.09% of cases and 0.50% of controls were detected to be suffering from ClS prior to the present study, showing a statistically significant difference (Table 3). It was observed that the time period of detection of ClS did not have much impact upon the occurrence of carcinoma of cervix (Table 4).

DISCUSSION

Veechi et al[11] have showed that the proportion of women reporting one or more than one previous screening with PAP smears was less among cases than that among their age matched controls (64% in cases of carcinoma of cervix and 75% in those with ClN). Also, the frequency of the smears in five years before the present study was lower among the cases of carcinoma of cervix than among controls (21% among women with invasive carcinoma of cervix and 50% among controls). The difference between cases and controls in proportion of women smeared was found to decrease with increasing time since last smear.

TABLE1 Past history of investigations
Past history of smear done	No.	Yes	Total	Past history of biopsy done	No	Yes	Total
Cases No. (%)	63 (63.63)	36 (36.36)	99	Cases No. (%)	79 (79.79)	20 (20.20)	99
Controls No. (%)	31 (31.31)	167 (84.34)	198	Controls No. (%)	167 (84.34)	31 (15.66)	198
Total	94	203	297	Total	246	51	297
Chi-square = 70.23, p < 0.001 (Highly significant) OR = 9.43. Chi-square = 0.96, p > 0.05 (Non significant) OR = 1.36

TABLE2 Number of smears done in last five years
No. of smears done in last 5 yrs.	Nil	1	> 1	Total
Cases No. (%)	11 (30.55)	22 (61.11)	3 (8.33)	36
Controls No. (%)	48 (28.74)	74 (44.31)	45 (23.95)	167
Total	59	96	48	203
Chi-square = 6.14, p < 0.05 (significant)

TABLE3 Detection of ClS prior to the present study
ClS detected prior to present study	Yes	No	Total
Cases No. (%)	9 (9.09)	90 (90.91)	99
Controls No. (%)	1 (0.50)	197 (99.50)	198
Total	10	287	297
p < 0.001 (Highly significant) (Fisher exact test).

TABLE4 Time period since detection of ClS
Time period since ClS detection	1-6 mths	6-12 mths	> 12 mths	Total
Cases No. (%)	2 (22.22)	2 (22.22)	5 (55.56)	9
Controls No. (%)	1 (100)	0 (0.00)	0 (0.00)	1
Total	3	2	5	10

p = 0.3 (Non significant) (Fisher exact test).

Estimated crude relative risk of carcinoma of cervix for women who had undergone only one smear examination was 0.44 and 0.20 for those who had undergone two or more smear examination. The difference was statistically significant at p < 0.001. Shy et al[3] have showed that the percentage of women with carcinoma of cervix increased with length of screening interval (chi-square = 13.70, p < 0.001). There was no increased risk for women undergoing screening regularly at three years interval.

Recently, Parazzini et al[8] have showed that multiple PAP smears and a short interval since the last smear strongly decreased the risk of carcinoma of cervix (p < 0.001).

In the present study, it was observed that the degree of protection against carcinoma of cervix increased with the increasing number of previous PAP smears and with decreasing interval since last smear, both trends in risk being highly significant. These results do match with results reported by Parazzini et al.[8] It can be concluded that PAP smears done at regular intervals may be one of the important protective measures against risk of carcinoma of cervix. Previous detection of ClS is one of the important preventive measures, if treated at earlier stages. But, the present study showed that the time period of detection of ClS did not have much impact upon occurrence of carcinoma of cervix. There may be no correlation of development of carcinoma of cervix with the time period of diagnosis of ClS. This finding matches with the fact that duration of development of invasive carcinoma of cervix from its premalignant stages (i.e. ClS) is variable. Since carcinoma of cervix may be of slowly growing form or of rapidly evolving form.[5]

Though the difference between cases and controls with positive history of biopsy was not statistically significant in the present study, the past history of cervical biopsy may have some protective effect in the occurrence of carcinoma of cervix, because prior cervical biopsy can lead to early detection of various early curable lesions. If left undetected and untreated, this may, in future, lead to the development of invasive carcinoma of cervix. It has been recommended that the first PAP smear may be done at 35 years of age and then regularly at every 5-10 years interval upto 65 years of age in countries like India where resources are limited and cost benefits has to be considered.[10] Ideally, screening should be done yearly regularly after women begin sexual life, at whatever age.

REFERENCES

1Ahuja P, Reddy D. Carcinoma of cervix - A statistical study on review of 3081 cases. Indian Journal of Obstetrics and Gynaecology 1963; 13 : 511-20.

2Dass A, Mookerjee G. Statistical survey of cervical cancer. Indian Journal of Obstetrics and Gynaecology 1961; 12 (1) : 51-56.

3.Shy K. Papanicolaou smear screening interval and risk of cervical cancer. Journal of Obstetrics and Gynaecology 1989; 74 (6) : 838-43.

4.Gault EW, Asirvadharam M. Carcinoma of cervix - A review of 525 cases diagnosed by biopsy. Indian Journal of Medical Sciences 1951; 5 (7) : 297-311.

5.Lawson JG. Cancer of uterine cervix-Some factors influencing survival rate. British Journal of Obstetrics and Gynaecology 1957; 64 : 198-91.

6.Mahajan BK, Gupta MC. Textbook of Preventive and Social Medicine, Jaypee Brothers Medical Publishers Pvt. Ltd., New Delhi. 1991; 254-59.

7.Koss. The papanicolaou test for cervical cancer detection. Journal of American Medical Association 1989; 26 (5) : 737-43.

8.Reeves W, Brinton L. Case control study of HIV and carcinoma of cervix. American Journal of Epidemiology 1988; 128 : 939.

9.Shanta V. Carcinoma of uterine cervix. Indian Journal of Cancer 1965; 2 : 142-49.

10.Stjernsward J. Plotting a new course for cervical cancer screening in developing countries, World Health Forum. 1987; 8 (1) : 42-45.

11.Veechi C, Decarli A. PAP smear and risk of cervical cancer. Quantitative estimate from a case control study. Lancet 1984; 2 : 779-82.

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