Asia-Oceania J. Obstet. Gynuecol. Vol. 17, No, 7: 1-4 1991
Cervical Cancer Screening Program in a Muslim Country: Three-Year Experience at The Aga Khan University Medical Center, Karachi
Saadiya Rasu1,lf Khalid S. Khan,l) Javaid H. Rizvi,ll Sheema H. Hassan,2) and Siddiqua Maniara) 1) L)epartment of Obstetrics and Gynecology, The Aga Khan University Medical Center, Karachi, Pakistan 2) Department of Pathology, The Aga Khan Uniwersity Medical Center, Karachi, Pakisstan
Abstract A systematic cervical cancer screening program was initiated in January 1987 at The Aga Khan University Medical Center, Karachi, Pakistan. The 8,784 cervical smears obtained in 3 subsequent years from 8,412 consecutive women attending the gynecology and antenatal clinics were reviewed. ‘‘ Positive ” smears were found in 111 (1.3%) patients; 107 (1.27%) smears showed squamous epithelial dysplasia and 4 smears showed adenocarcinoma. The highest incidence of abnormal smears was found in the 45-54 years age group. Colposcopy and biopsy was performed on all patients with “ positive ” smears except on those with atypical or mildly dysplastic ones, in whom only the persistence of the abnormality on repeated smears was considered an indication for tissue evaluation. The histopathologic diagnosis of these biopsy specimens revealed cervical intra-epithelial neoplasia in 60 patients and invasive cervical cancer in 6 patients.
Key words: screening, cervical cancer, Muslim population Introduction Screening with
“
Pap test ” has been shown
to reduce the incidence and mortality from
cervical cancer? However, in developing countries where maternal deaths account for the bulk of mortality in women, cervical cancer screening receives little attention, Moreover, the belief that this cancer is less prevalent in Muslim womec2) has so far delayed the initiation of large scale screening programs in Mus-
lim countries such as Pakistan. Surveys from different centers in Pakistan3~4J have shown that cervical cancer is the third commonest malignant tumor in women accounting for 8.7-11.1% of all cancers in women. Furthermore, the presence of such risk factors as low socioeconomic status, early marriages and multiparity in our population warrants an assessment of the issue. Thus a systematic program for “ Pap testing ” on an institutional basis was initiated at
Received: June 20, 1990 Reprint request to: Dr. Javaid H. Rizvi, Department of Obstetrics and Gynecology, The Aga Khan University Medical Center, P. 0. Box 3500, Karachi 74800,Pakistan
1
S. RASUL ET AL.
The Aga Khan University Medical Center, Karachi in January 1987. The purpose of this paper is to document our experience in the first 3 years of screening.
Subjects and Methods The Aga Khan University Medical Center, Karachi, is a referral center for secondary and tertiary care. Patients are referred by general practitioners, gynecologists in the community or are self referred to out-patient clinics. In the gynecology clinics few patients come for routine checkups. From January 1987 to December 1989, all women attending the obstetrics and gynecology consulting clinics had a cervical smear taken. After insertion of a bivalve vaginal speculum, a cervical scraping was taken from the exocervix and the squamo-columnar junction with an Ayer’s spatula. The smear was fixed with a alcohol fixative (Vale smear fix: Vale laboratories, London, England) and sent for cytopathological assessment. All smears were screened by a single cytotechnologist and all those other than the clearly negative ones were reviewed by one of the cytopathologists. The cytology report incorporated a statement of adequacy and cytodiagnostic terminology introduced by Richart61 including use of squamous atypia, squamous dysplasia (mild, moderate, severe), invasive squamous carcinoma and adenocarcinoma. Grossly abnormal smears were reported to the consultant gynecologist fox immediate action. All other smear reports were available on follow-up clinic visits, where action was taken accordingly. Inadequate smears were repeated. Patients with atypia or mild dysplasia had smears repeated within 3 to 4 months and if the abnormality persisted or became worse, colposcopy and histopathologic evaluation was carried out. Colposcopy directed biopsy was done on all other patients with positive smears. A smear was repeated at the time of colposcopy. Cone biopsy was done if clinically indicated. Some patients with initial normal smears had their smear repeated on follow-up visits after 1 year. Patients with smears showing adenocarcinoma had a fractional curettage in addition to colposcopy. 2
Results A total of 8,784 smears were obtained from 8,412 patients including 3,792 pregnant wommen. I n 85 (1.0%) women an inadequate smear was initially reported, but repeated smears were found adequate. As shown in Table 1, a total of 58 (0.68%) had atypical smears and 107 (1.25%) had squamous epithelial dysplasias of varying degrees. Atypical glandular cells suggesting adenocarcinoma were seen in 4 patients. Those patients with atypical (58) and mildly dysplastic smears (40) were followed up with repeated smears as outlined in the methods. Of these, 7 patients were lost to follow-up, while 14 showed persistence of cytological abnormality and therefore required tissue evaluation. A total of 81 patients underwent tissue biopsy and their histopatholo~icfindings were reviewed. TabIe 1. Results of cervical cytology in 8,412 patients* NO.
No dysplasia 8,243 58 Atypia 107 Squamous epithelial dysplasia Mild 40 Moderate 31 Severe/Invasive cancer 36 Adenocarcinoma 4
*
% 97.9 0.68 I .68 0.47 0.37 0.43 0.05
T h e terminology for reporting the result of cervical cytology is according to the one introduced by Richart (1973).
TabIe 2. Histopathologic diagnosis of 81 patients* with abnormal cervical cytology
No dysplasia Cervical intraepithelial neoplasia (CIN) CIN 1 and 2 CIN 3 Invasive cervical cancer
No.
O/
15 60
18.5 74.1
46 6
56.8 17.3 7.4
81
100
14
/O
~
* 81 patients
underwent colposcopy directed cervical biopsy. As described in the methods, 9 of these patients had a subsequent cone biopsy.
CERVICAL CANCER SCREENING IN MUSLIMS
Table 3. Age distribution of dysplastic cytology, cervical intra-epithelial neoplasia (CIN) and invasive squamous cervical cancer Age group (yrs)
Total patients No.
-
.-
No.
(%I*
No.
(%I*
No.
0.01 0.6 1.5 2.6 2.4
0
16-24 25-34 35-44 45-54 55-64 Over 65
2,699 3,684 1,362 449 165 53
14 30 31 23 6 3
0.5 0.8 2.2 5.1 3.6 5.6
1 23 20 12 4
All ages
8,412
107
1.27
60
* **
Invasive cancer**
CIN**
Dysplastic smear
0
_-
0
1 1 1 1 2
0.71
6
Percentage of patients with dysplastic smears/CIN out of total patients in each age group. Histologic diagnoses.
Colposcopy (in 81 patients) showed abnormalities in most of the patients except in 9 who underwent a subsequent cone biopsy. Histopathologic evaluation revealed no dysplasia in 15 (18.5)%, intra-epithelial neoplasia of varying grades in 60 (74.0%) and invasive cervical cancer in 6 (7.5%) patients as shown in Table 2. Four of the 14 patients with persistent atypical/mild dysplasia were found to have CIN-grade 1 ; none of these patients had CIN-3 or invasive carcinoma. Of all the pregnant women, 4 showed CIN-1 which was treated conservatively; no pregnant woman had CIN-3 or invasive cancer. The ages of the patients with dysplastic cytology ranged from 16 to 81 years. As shown in Table 3, the age specific prevalence of cytological dysplasia (of all types) showed a peak in the 45 to 54 years age group (5.1%). A second peak was seen in the >65 years age group (5.6%). Histopathologically diagnosed cervical intra-epithelial neoplasia was found throughout the age groups between 25 and 64 years; the prevalence increasing with increasing age. Two patients with invasive carcinoma were in >65 years age group, while others were 30, 38,48 and 56 years of age. Two of the 4 patients with a cytological diagnosis of adenocarcinoma had endometrial cancer, one had atypical endometrial hyperplasia and one had no cervical or endometrial pathology confirmed on histopathology of the hysterectomy specimen.
Discussion In view of its well recognized benefit in detection of preinvasive and invasive cervical disease, “ Pap testing ” was started in the obstetrics and gynecology clinics of The Aga Khan University Medical Center, Karachi, where all patients attending the clinics are screened irrespective of presenting complaints. The available terminology for cytodiagnosis varies and in some instances (e.g., papanicolaou classification) poorly correlates with diagnostic histopathologic terminology. We decided to use Richart’s classification (see Subjects and Methods) which facilitated cytologic-histopathologic correlation and improved effective communication among cytopathologists and referring physicians. The management of patients with moderate and severe squamous dysplasia on cytology has been clearly defined.6) However, controversy prevaih over management of atypical and mildly dysplastic ~mears.7-1~’We elected to use a cost effective and acceptably safe approach7J0) of advising biopsy only upon persistence or worsening of the abnormality in repeated smears as outlined in the methods. The safety of this approach is strengthened in our series, as only 4 of these patients with borderline smears had CIN-1 and none had CIN3 or invasive cancer. The common belief of a low incidence of cervical cancer in Muslim women may be strengthened by our finding of a prevalence of 3
S. RASUL ET AL.
1.27% of dysplastic cytology. This is lower than 2.3% and 1.7% reported for a North Americanll) and for a Jewish popuIation,l2' respectively. This low prevalence, however, may be due to the inherent bias of health awareness in the patients attending our hospital, the majority of whom come from the upper and middle socioeconomic class. The peak age. specific dysplastic cytology rate of 5.1% in the 45-54 years age group (Table 3) is in contrast to peak prevalence in 20-34 years age group in a North American population.11) This difference could be explained by the presumed low prevalence in Pakistan of particular risk factors (Len,multiple sexual partners, veneieal disease including Herpes Simplex Virus and Human Papilloma Virus, smoking and use of oral contraceptives) which are known to contribute significantly to the disease in the West.') The second peak in dysplastic cytology rate in >65 years age group was calculated from small numbers and therefore it is difficult to draw conclusions from it. However, elderly women are known to contribute significantly to the prevalence and mortality of cervical cancer.1) In our series the age specific trends of increasing prevalence of histopathologically diagnosed CIN with advancing age is in contrast to those reported in the Westltll) where its prevalence falls with increasing age. This can possibly be explained by the lack of prior screening in our population which would have allowed treatment at an earlier age. Our findings with a cervical cancer screening program in a selected populations in Karachi cannot be extrapolated to the entire population of Pakistan. Nevertheless the establishment of such a screening program is the first step in the right direction and should lead to a large community-based study to establish more representative figures for use in a public health care setting.
4
References 1.
2.
3.
4.
5.
6. 7.
8.
9.
10.
11.
12.
Mandelblat J. Cervical cancer screening in primary care: Issues and recommendations. Primary Care 1989; 16(1): 133-150 Wynder EL, Cornfield J, Schroff PD, Dorarswarmi KR. A study of environmental risk factors in carcinoma of cervix. A m J Obstet Gynecoll954; 68: 1016-1052 Jafarey NA, Zaidi SHM. Frequency of malignant tumors in Jinnah Postgraduate Medical Centre, Karachi. JPMA 1976; 26: 57-60 Pakistan Medical Research Council Cancer Study Group. Frequency of malignant tumors in seven centres of Pakistan. JPMA 1977; 27: 335-339 Richart RIM. Cervical intra-epithelial neoplasia: A review. In: Sommers SC. ed. Pathology Annual. New York: Appleton Century Crofts, 1973 Singer A. T h e abnormal cervical smear. BY MedJ 1986; 293: 1551-1556 Soutter WP, Wisdom S, Brough AK, Monaghan JM. Should patients with mild atypia in cervical smear be referred for colposcopy? BYJ Obstet Gynaecot 1986; 93: 70-74 Walker EM, Dodgson J, Duncan ID. Does mild atypia on cervical smear warrant further investigations? Lancet 1986; 2(8508): 672-673 Nournoff JS. Atypia in cervical cytology as a risk factor for intraepithelial neoplasia. Am J Obstet Gynecol1987 : 156 : 628-63 1 Robertson JH, Woodend BE, Crozier EH, Hutchinson J. Risk of cervical cancer associated with mild dyskaryosis. BYMed J 1988; 297: 18-21 Sadeghi SB, Hsieh EW, Gunn SW. Prevalence of cervical intraepithelial neoplasia in sexually active teenagers and young adults; Results of data analysis mass Papanicolaou screening of 796,337 women i n the United States in 1981. A m J Obstet GynecoZ1984: 148: 726-729 Baram A, Galon A, Schachter A. Premalignant lesions and microinvasive carcinoma of the cervix in Jewish women; an epidemiological study. Br J Obstet ~ e c o 1985 Z ;92 : 4-8
Cervical Cancer Screening Program in a Muslim Country: Three-Year Experience at The Aga Khan University Medical Center, Karachi
Saadiya Rasu1,lf Khalid S. Khan,l) Javaid H. Rizvi,ll Sheema H. Hassan,2) and Siddiqua Maniara) 1) L)epartment of Obstetrics and Gynecology, The Aga Khan University Medical Center, Karachi, Pakistan 2) Department of Pathology, The Aga Khan Uniwersity Medical Center, Karachi, Pakisstan
Abstract A systematic cervical cancer screening program was initiated in January 1987 at The Aga Khan University Medical Center, Karachi, Pakistan. The 8,784 cervical smears obtained in 3 subsequent years from 8,412 consecutive women attending the gynecology and antenatal clinics were reviewed. ‘‘ Positive ” smears were found in 111 (1.3%) patients; 107 (1.27%) smears showed squamous epithelial dysplasia and 4 smears showed adenocarcinoma. The highest incidence of abnormal smears was found in the 45-54 years age group. Colposcopy and biopsy was performed on all patients with “ positive ” smears except on those with atypical or mildly dysplastic ones, in whom only the persistence of the abnormality on repeated smears was considered an indication for tissue evaluation. The histopathologic diagnosis of these biopsy specimens revealed cervical intra-epithelial neoplasia in 60 patients and invasive cervical cancer in 6 patients.
Key words: screening, cervical cancer, Muslim population Introduction Screening with
“
Pap test ” has been shown
to reduce the incidence and mortality from
cervical cancer? However, in developing countries where maternal deaths account for the bulk of mortality in women, cervical cancer screening receives little attention, Moreover, the belief that this cancer is less prevalent in Muslim womec2) has so far delayed the initiation of large scale screening programs in Mus-
lim countries such as Pakistan. Surveys from different centers in Pakistan3~4J have shown that cervical cancer is the third commonest malignant tumor in women accounting for 8.7-11.1% of all cancers in women. Furthermore, the presence of such risk factors as low socioeconomic status, early marriages and multiparity in our population warrants an assessment of the issue. Thus a systematic program for “ Pap testing ” on an institutional basis was initiated at
Received: June 20, 1990 Reprint request to: Dr. Javaid H. Rizvi, Department of Obstetrics and Gynecology, The Aga Khan University Medical Center, P. 0. Box 3500, Karachi 74800,Pakistan
1
S. RASUL ET AL.
The Aga Khan University Medical Center, Karachi in January 1987. The purpose of this paper is to document our experience in the first 3 years of screening.
Subjects and Methods The Aga Khan University Medical Center, Karachi, is a referral center for secondary and tertiary care. Patients are referred by general practitioners, gynecologists in the community or are self referred to out-patient clinics. In the gynecology clinics few patients come for routine checkups. From January 1987 to December 1989, all women attending the obstetrics and gynecology consulting clinics had a cervical smear taken. After insertion of a bivalve vaginal speculum, a cervical scraping was taken from the exocervix and the squamo-columnar junction with an Ayer’s spatula. The smear was fixed with a alcohol fixative (Vale smear fix: Vale laboratories, London, England) and sent for cytopathological assessment. All smears were screened by a single cytotechnologist and all those other than the clearly negative ones were reviewed by one of the cytopathologists. The cytology report incorporated a statement of adequacy and cytodiagnostic terminology introduced by Richart61 including use of squamous atypia, squamous dysplasia (mild, moderate, severe), invasive squamous carcinoma and adenocarcinoma. Grossly abnormal smears were reported to the consultant gynecologist fox immediate action. All other smear reports were available on follow-up clinic visits, where action was taken accordingly. Inadequate smears were repeated. Patients with atypia or mild dysplasia had smears repeated within 3 to 4 months and if the abnormality persisted or became worse, colposcopy and histopathologic evaluation was carried out. Colposcopy directed biopsy was done on all other patients with positive smears. A smear was repeated at the time of colposcopy. Cone biopsy was done if clinically indicated. Some patients with initial normal smears had their smear repeated on follow-up visits after 1 year. Patients with smears showing adenocarcinoma had a fractional curettage in addition to colposcopy. 2
Results A total of 8,784 smears were obtained from 8,412 patients including 3,792 pregnant wommen. I n 85 (1.0%) women an inadequate smear was initially reported, but repeated smears were found adequate. As shown in Table 1, a total of 58 (0.68%) had atypical smears and 107 (1.25%) had squamous epithelial dysplasias of varying degrees. Atypical glandular cells suggesting adenocarcinoma were seen in 4 patients. Those patients with atypical (58) and mildly dysplastic smears (40) were followed up with repeated smears as outlined in the methods. Of these, 7 patients were lost to follow-up, while 14 showed persistence of cytological abnormality and therefore required tissue evaluation. A total of 81 patients underwent tissue biopsy and their histopatholo~icfindings were reviewed. TabIe 1. Results of cervical cytology in 8,412 patients* NO.
No dysplasia 8,243 58 Atypia 107 Squamous epithelial dysplasia Mild 40 Moderate 31 Severe/Invasive cancer 36 Adenocarcinoma 4
*
% 97.9 0.68 I .68 0.47 0.37 0.43 0.05
T h e terminology for reporting the result of cervical cytology is according to the one introduced by Richart (1973).
TabIe 2. Histopathologic diagnosis of 81 patients* with abnormal cervical cytology
No dysplasia Cervical intraepithelial neoplasia (CIN) CIN 1 and 2 CIN 3 Invasive cervical cancer
No.
O/
15 60
18.5 74.1
46 6
56.8 17.3 7.4
81
100
14
/O
~
* 81 patients
underwent colposcopy directed cervical biopsy. As described in the methods, 9 of these patients had a subsequent cone biopsy.
CERVICAL CANCER SCREENING IN MUSLIMS
Table 3. Age distribution of dysplastic cytology, cervical intra-epithelial neoplasia (CIN) and invasive squamous cervical cancer Age group (yrs)
Total patients No.
-
.-
No.
(%I*
No.
(%I*
No.
0.01 0.6 1.5 2.6 2.4
0
16-24 25-34 35-44 45-54 55-64 Over 65
2,699 3,684 1,362 449 165 53
14 30 31 23 6 3
0.5 0.8 2.2 5.1 3.6 5.6
1 23 20 12 4
All ages
8,412
107
1.27
60
* **
Invasive cancer**
CIN**
Dysplastic smear
0
_-
0
1 1 1 1 2
0.71
6
Percentage of patients with dysplastic smears/CIN out of total patients in each age group. Histologic diagnoses.
Colposcopy (in 81 patients) showed abnormalities in most of the patients except in 9 who underwent a subsequent cone biopsy. Histopathologic evaluation revealed no dysplasia in 15 (18.5)%, intra-epithelial neoplasia of varying grades in 60 (74.0%) and invasive cervical cancer in 6 (7.5%) patients as shown in Table 2. Four of the 14 patients with persistent atypical/mild dysplasia were found to have CIN-grade 1 ; none of these patients had CIN-3 or invasive carcinoma. Of all the pregnant women, 4 showed CIN-1 which was treated conservatively; no pregnant woman had CIN-3 or invasive cancer. The ages of the patients with dysplastic cytology ranged from 16 to 81 years. As shown in Table 3, the age specific prevalence of cytological dysplasia (of all types) showed a peak in the 45 to 54 years age group (5.1%). A second peak was seen in the >65 years age group (5.6%). Histopathologically diagnosed cervical intra-epithelial neoplasia was found throughout the age groups between 25 and 64 years; the prevalence increasing with increasing age. Two patients with invasive carcinoma were in >65 years age group, while others were 30, 38,48 and 56 years of age. Two of the 4 patients with a cytological diagnosis of adenocarcinoma had endometrial cancer, one had atypical endometrial hyperplasia and one had no cervical or endometrial pathology confirmed on histopathology of the hysterectomy specimen.
Discussion In view of its well recognized benefit in detection of preinvasive and invasive cervical disease, “ Pap testing ” was started in the obstetrics and gynecology clinics of The Aga Khan University Medical Center, Karachi, where all patients attending the clinics are screened irrespective of presenting complaints. The available terminology for cytodiagnosis varies and in some instances (e.g., papanicolaou classification) poorly correlates with diagnostic histopathologic terminology. We decided to use Richart’s classification (see Subjects and Methods) which facilitated cytologic-histopathologic correlation and improved effective communication among cytopathologists and referring physicians. The management of patients with moderate and severe squamous dysplasia on cytology has been clearly defined.6) However, controversy prevaih over management of atypical and mildly dysplastic ~mears.7-1~’We elected to use a cost effective and acceptably safe approach7J0) of advising biopsy only upon persistence or worsening of the abnormality in repeated smears as outlined in the methods. The safety of this approach is strengthened in our series, as only 4 of these patients with borderline smears had CIN-1 and none had CIN3 or invasive cancer. The common belief of a low incidence of cervical cancer in Muslim women may be strengthened by our finding of a prevalence of 3
S. RASUL ET AL.
1.27% of dysplastic cytology. This is lower than 2.3% and 1.7% reported for a North Americanll) and for a Jewish popuIation,l2' respectively. This low prevalence, however, may be due to the inherent bias of health awareness in the patients attending our hospital, the majority of whom come from the upper and middle socioeconomic class. The peak age. specific dysplastic cytology rate of 5.1% in the 45-54 years age group (Table 3) is in contrast to peak prevalence in 20-34 years age group in a North American population.11) This difference could be explained by the presumed low prevalence in Pakistan of particular risk factors (Len,multiple sexual partners, veneieal disease including Herpes Simplex Virus and Human Papilloma Virus, smoking and use of oral contraceptives) which are known to contribute significantly to the disease in the West.') The second peak in dysplastic cytology rate in >65 years age group was calculated from small numbers and therefore it is difficult to draw conclusions from it. However, elderly women are known to contribute significantly to the prevalence and mortality of cervical cancer.1) In our series the age specific trends of increasing prevalence of histopathologically diagnosed CIN with advancing age is in contrast to those reported in the Westltll) where its prevalence falls with increasing age. This can possibly be explained by the lack of prior screening in our population which would have allowed treatment at an earlier age. Our findings with a cervical cancer screening program in a selected populations in Karachi cannot be extrapolated to the entire population of Pakistan. Nevertheless the establishment of such a screening program is the first step in the right direction and should lead to a large community-based study to establish more representative figures for use in a public health care setting.
4
References 1.
2.
3.
4.
5.
6. 7.
8.
9.
10.
11.
12.
Mandelblat J. Cervical cancer screening in primary care: Issues and recommendations. Primary Care 1989; 16(1): 133-150 Wynder EL, Cornfield J, Schroff PD, Dorarswarmi KR. A study of environmental risk factors in carcinoma of cervix. A m J Obstet Gynecoll954; 68: 1016-1052 Jafarey NA, Zaidi SHM. Frequency of malignant tumors in Jinnah Postgraduate Medical Centre, Karachi. JPMA 1976; 26: 57-60 Pakistan Medical Research Council Cancer Study Group. Frequency of malignant tumors in seven centres of Pakistan. JPMA 1977; 27: 335-339 Richart RIM. Cervical intra-epithelial neoplasia: A review. In: Sommers SC. ed. Pathology Annual. New York: Appleton Century Crofts, 1973 Singer A. T h e abnormal cervical smear. BY MedJ 1986; 293: 1551-1556 Soutter WP, Wisdom S, Brough AK, Monaghan JM. Should patients with mild atypia in cervical smear be referred for colposcopy? BYJ Obstet Gynaecot 1986; 93: 70-74 Walker EM, Dodgson J, Duncan ID. Does mild atypia on cervical smear warrant further investigations? Lancet 1986; 2(8508): 672-673 Nournoff JS. Atypia in cervical cytology as a risk factor for intraepithelial neoplasia. Am J Obstet Gynecol1987 : 156 : 628-63 1 Robertson JH, Woodend BE, Crozier EH, Hutchinson J. Risk of cervical cancer associated with mild dyskaryosis. BYMed J 1988; 297: 18-21 Sadeghi SB, Hsieh EW, Gunn SW. Prevalence of cervical intraepithelial neoplasia in sexually active teenagers and young adults; Results of data analysis mass Papanicolaou screening of 796,337 women i n the United States in 1981. A m J Obstet GynecoZ1984: 148: 726-729 Baram A, Galon A, Schachter A. Premalignant lesions and microinvasive carcinoma of the cervix in Jewish women; an epidemiological study. Br J Obstet ~ e c o 1985 Z ;92 : 4-8
