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Screening for cervical neoplasia during pregnancy
International Journal of Gynecology & Obstetrics 68 Ž2000. 19᎐23
Article
Screening for cervical neoplasia during pregnancy H.S. Cronje ´a,U , E. van Rensburg a , I. Niemanda , B.F. Cooremana , E. Beyer a , P. Divall b a
Departments of Obstetrics and Gynecology, Uni¨ ersity of the Orange Free State, Bloemfontein, South Africa b Department of Cytology, Uni¨ ersity of the Orange Free State, Bloemfontein, South Africa Received 9 April 1999; received in revised form 24 September 1999; accepted 6 October 1999
Abstract Objecti¨ e: To evaluate cytology as a screening method for cervical neoplasia in pregnancy and to compare it with cervicography and the acetic acid test ŽAAT.. Methods: In a large antenatal clinic in South Africa, 842 women were screened utilizing cytology, cervicography and the acetic acid test simultaneously. The proportion of positive results of the different tests were compared and the agreement calculated by the kappa statistic. Results: The mean age of the women was 27 years, and 12.5% smoked. Cytological smears were abnormal Žlow-grade squamous intra-epithelial lesion and higher degrees of abnormality. in 1.4% of cases, cervicography in 6.3% and the AAT in 14.3% Ž Ps 0.5400.. Kappa values were as follows: cytology vs. cervicography 0.01, cytology vs. AAT 0.0 and cervicography vs. AAT 0.2. Conclusions: As a result of cytology’s rather low yield and the small measure of agreement between the tests, cytology should be supplemented by an additional screening test in pregnancy. 䊚 2000 International Federation of Gynecology and Obstetrics. Keywords: Cervical screening; Cytology; Cervicography; Acetic acid test; Pregnancy
U
Corresponding author. Tel.: q27-514053444; fax: q27-514442006. E-mail address: [email protected] ŽH.S. Cronje ´. 0020-7292r00r$20.00 䊚 2000 International Federation of Gynecology and Obstetrics. PII: S 0 0 2 0 - 7 2 9 2 Ž 9 9 . 0 0 1 7 8 - 2
20
H.S. Cronje´ et al. r International Journal of Gynecology & Obstetrics 68 (2000) 19᎐23
1. Introduction Antenatal visits present a unique opportunity of screening for cervical neoplasia. Unfortunately however, the Pap smear Žcytology. has proved to be less sensitive in pregnant patients, resulting in a controversy as to whether cervical screening should be implemented in pregnancy w1x. Pregnancy by itself does not seem to interfere with the natural history of cervical neoplasia and therefore, other factors are responsible for the decreased sensitivity of the Pap smear in pregnancy w2x. This phenomenon may be the result of a number of factors including enlargement of the cervix, increased mucous secretion and increased difficulty in actually viewing the cervix. Sampling errors, responsible for at least 50% of false negative smears, therefore appear to be more pronounced in pregnancy w3x. Due to the problems associated with screening in developing countries, antenatal clinics certainly present the possibility of reaching at least a proportion of the target population. Limitations in the funds available for screening in these countries, however, necessitates critical evaluation of such a policy. It is, therefore, the aim of this study to compare different screening methods in pregnancy with the ultimate goal of formulating a screening policy.
2. Patients and methods This study was performed at the antenatal clinic, Pelonomi hospital, Bloemfontein, South Africa. This institution is a secondary referral and training hospital in the Free State province, managing on average, 5500 births per year. The vast majority of these patients are of a lower socio-economic status and for the most part, have never been screened for cervical cancer. This study was approved by the Ethics Committee of the Faculty of Health Sciences, University of the Orange Free State. The sample consisted of 842 patients attending the antenatal clinic for their first visit. Since cervical cytology was a test performed routinely during
the first visit, the enrolment was carried out on a consecutive basis. All vaginal examinations were executed in the dorsal position. After the insertion of a Cusco vaginal speculum, the cervix was examined by a specially trained professional nurse who performed all the screening tests in this study ŽEvR.. Three methods were utilized in the following order: a cytological smear ŽPap smear., cervicography and a macroscopical examination aided by the application of a 5% acetic acid solution Žacetic acid test or AAT.. Excessive vaginal discharge was a commonly encountered problem. In these cases, following visualization of the cervix, it was gently cleansed with a cotton-wool swab, carefully preventing trauma to the cervix as well as the removal of superficial epithelial cells. As soon as the cervix was clear from vaginal discharge and excessive mucous, the smear was taken with an Ayre spatula. The material was smeared across the length of a glass slide and fixated by means of a standard spray fixative. Bleeding of the cervix, caused by this contact, was stopped by gently pressing against the traumatized area with a dry cotton-wool swab. Another cotton-wool swab, drenched in a 5% acetic acid solution, was then gently applied to the cervix for 20᎐30 s. The cervix was left to dry for 20 s whereafter acetic acid was applied a second time. A Cerviscope 䊛 ŽNTL, St. Louis, USA. was then used to take both the first Cervigram 䊛 Žphotograph of the cervix. and after a brief re-application of acetic acid solution, the second. This second photo was indicated for distinguishing mucous from an aceto-white lesion, as well as to expose possible lesions covered by mucous. Thereafter the surface of the cervix was thoroughly examined macroscopically ŽAAT. for the presence of aceto-white lesions, indicative of abnormalities. Upon completion of the examinations, the acetic acid solution that had collected in the posterior fornix was gently swabbed away and the Cusco speculum removed. All the cytological smears were evaluated by the Department of Cytology, Faculty of Health Sciences, University of the Orange Free State. The Cervigrams 䊛 Žtwo photographic slides per patient. were evaluated by two of the authors who
H.S. Cronje´ et al. r International Journal of Gynecology & Obstetrics 68 (2000) 19᎐23
are registered cervicography evaluators ŽHSC and BFC.. They were not informed about the results of the cytological smear or the AAT at the time of evaluating the Cervigrams 䊛 . All patients with low-grade squamous intratepithelial lesions ŽLoSIL. and high-grade squamous intraepithelial lesions ŽHiSIL. diagnosed by cytology, as well as those with aceto-white lesions and possible cancers identified by AAT and all patients with positive Cervigrams 䊛 were referred to a colposcopy clinic for further evaluation and treatment. Cervicography was regarded positive when the diagnosis was P1a Žatypical aceto-white lesion extending into the endocervical canal., P1b ŽLoSIL., P2 ŽHiSIL. or P3 Žcancer.. Although cases with a diagnosis of PO were also referred for colposcopy, we did not use this category in our analysis of positive cases due to the increased vascularity during pregnancy which could lead to false positives.
3. Results The average age of the 842 patients was 27 years Žminimum 15 years and maximum 40 years.. Only one patient had been treated previously by means of a cone biopsy and 12.5% of the women smoked. Only 3.4% of the cervical smears contained both ecto- and endocervical epithelial cells. Of the total number of smears evaluated cytologically, 0.7% were regarded as atypical ŽASCUS.. Cervical intra-epithelial neoplasia ŽLoSIL q HiSIL. was diagnosed in a further 1.5% of cases, whilst no cases of infiltration were reported ŽTable 1.. A cervicography diagnosis of P1 to P3 ŽLoSIL, HiSIL and infiltration. was reported in 6.3% of patients ŽTable 2.. One case had an infiltrating carcinoma. The AAT found 14.3% of cases to be positive ŽTable 3., four of whom were diagnosed with the possibility of infiltrating cancer. The Kappa statistic was used to determine the measure of agreement between the three screening tests. Cervicography vs. cytology produced a Kappa value of 0.01, cervicography vs. the AAT a
21
Table 1 Results utilizing cytology as screening method Ž n s 842. Diagnosis
Number
Negative Atypical squamous cells ŽASCUS. LoSILa HiSILb Infiltration Technically defective
820 6 9 3 0 4
Ž97.4. Ž0.7. Ž1.0. Ž0.4. Ž0. Ž0.5.
Total
842
Ž100.0.
a b
Ž%.
LoSIL, Low-grade squamous intraepithelial lesion. HiSIL, High-grade squamous intraepithelial lesion.
value of 0.2 and cytology vs. and the AAT, a value of 0.01.
4. Discussion In this study 842 patients were included into the study, but only 825 cervicography results and 808 AAT results were analyzed. The reason for these drop-outs is the appearance of the cervix in pregnancy: enlarged Žoften with an extremely large endocervical component. and often hemorTable 2 Results utilizing cervicography as screening method Ž n s 825. Diagnosis
Number
Negative Atypical Positi¨ e (P) 0a lab lb ŽLoSIL.c 2 ŽHiSIL.d 3 ŽCancer.e Technically defective
694 61
Ž84.1. Ž7.4.
5 2 39 9 1 14
Ž0.6. Ž0.3. Ž4.7. Ž1.1. Ž0.1. Ž1.7.
Total
825
Ž100.0.
a
Ž%.
PO, possibly negative, but needs a colposcopically directed biopsy for excluding cancer. b P1a, a typical lesion extending into the canal, warranting a colposcopical examination. c P1b, Low-grade squamous intra-epithelial lesion d P2, High-grade squamous intra-epithelial lesion. e P3, Cancer.
22
H.S. Cronje´ et al. r International Journal of Gynecology & Obstetrics 68 (2000) 19᎐23
Table 3 Results utilizing the acetic acid test as screening method Ž n s 808.
Table 4 Comparison of results in pregnant and non-pregnant women % Positve resultsrindependent sample
Diagnosis
Number
Negative Positive Žaceto-white lesion. Possible cancer Technically defective
686 111 3 8
Ž%. Ž84.9. Ž13.7. Ž0.4. Ž1.0.
Cytology Cervicography AATb
Total
808
Ž100.0.
Pregnant
Non-pregnanta
P-value
12r838 Ž1.4%. 51r811 Ž6.3%. 114r800 Ž14.3%.
214r6147 Ž3.5%. 659r6147 Ž10.7%. 1095r6147 Ž17.8%.
0.0014
U
U
0.0008
U
0.0128
a
Unpublished data from the same institution. AAT, Acetic acid test. U Statistically significant. b
rhagic or infected with excessive amounts of mucous. Subsequently, in a small number of patients cervicography andror the AAT was not possible. We reported only on the proportion of positive outcomes for each test as well as the kappa statistic Žagreement between tests., but not on the sensitivity. The reason being that we have not performed a histological analysis on each patient. During pregnancy, the cervix is extremely vascular and due to the risk of hemorrhage, biopsies were not done. Infection exaggerates this problem, a common phenomenon in our population. In another study, as yet unpublished, we screened 6147 non-pregnant women of a comparable population, utilizing the same three techniques. The results proved 3.5% of smears to be positive ŽLoSIL and HiSIL., as well as 10.7% of cervigrams ŽP1 or more. and 17.8% of AATs Žwhite lesions or possible cancer. ŽTable 4.. Therefore, all three tests significantly performed worse during pregnancy. Cytology decreased by 60% concerning its proportion of positive tests, cervicography by 41% and the acetic acid test by 20%. Generally, the proportion of positive smears, given a non-pregnant population, is approximately 3% but may vary between 1% and 9.7% w4᎐8x. The sensitivity of cytology varies significantly w9᎐13x, but Fahey et al. w14x have published an excellent meta-analysis, concluding that the sensitivity of cytology varies between 20 and 35%. Cervicography in turn, has a reported sensitivity of approximately 55%, whilst that of the AAT is 60% w10,15᎐18x. Unfortunately the AAT tends to overdiagnose since not all visible aceto-white lesions reflect LoSIL or HiSIL.
Why is the sensitivity of cytology decreased in pregnancy? As stated earlier, sampling errors Že.g. the taking of smears in such a way that endocervical cells are not included in the material. are responsible for at least 50% of false negative smears w3x. In pregnancy, the enlargement of the cervix, difficulty in properly visualizing the cervix and excessive mucus on the cervical surface, may increase the problem of false negative smears. In addition, infection, a multiparous cervix and advanced gestational age with more pronounced eversion of the cervix, further complicate cytological smears in pregnancy. In this study only 3.4% of smears contained endocervical cells. Although it is known that the yield is less during pregnancy w19x, our result was unexpectedly low. In a comparable but non-pregnant population, the yield was 34% Žresults still unpublished.. In both cases smears were taken with Ayre spatulas by a single well-trained professional nurse. Bleeding from the cervix caused by the Ayre spatula, may complicate the subsequent preparation of the cervix for cervicography. Therefore, the nurse may have exerted less pressure on the spatula to minimize bleeding resulting in the possibility of less smears containing endocervical cells. In both pregnant and non-pregnant patients, this could have resulted in smaller proportions of adequate smears Žcontaining endocervical cells.. Interesting to note is the significant increase in sensitivity given a combination of screening tests. For example, utilizing cervicography in addition to cytology, results in an increase in sensitivity of
H.S. Cronje´ et al. r International Journal of Gynecology & Obstetrics 68 (2000) 19᎐23
at least 30% and as much as 52% with the further addition of speculoscopy Žspecialized form of AAT. w10,11,16,18x. The reason being the negligibly small measure of agreement between the various methods, a finding supported by this study. Is screening really worthwhile in pregnancy? In developing countries, such an opportunity might be unique. Carter suggested obtaining a smear only if the patient had not recently Žprevious 2᎐3 years. been for cervical screening w1x. But still, this suggestion does not solve the ‘low sensitivity’ problem. We therefore recommend the implementation of a combination of tests. A combination of cytology and cervicography, for example, results in a sensitivity of 50᎐60%, which is significant from a clinical point of view. However, cervicography is not available in most developing countries and it is reasonably expensive. Therefore, the addition of the AAT Žor even speculoscopy. is a reachable alternative in most countries. Although it will overdiagnose to some extent, the sensitivity will be significantly improved. More research is required however, to determine the cost-effectiveness of the various combinations.
Acknowledgments We wish to acknowledge Dr R.H. Bam for her valuable assistance and Mrs I Venter for typing the manuscript. References w1x Carter PM, Coburn TC, Luszczak M. Cost-effectiveness of cervical cytologic examination during pregnancy. J Am Board Fam Pract 1993;6:537᎐545. w2x Guerra B, De Simone P, Gabrielli S, Falco P, Montanari G, Bovicelli L. Combined cytology and colposcopy to screen for cervical cancer in pregnancy. J Reprod Med 1998;43:647᎐653. w3x Shield PW, Daunter B, Wright RG. The Pap smear revisited. Aust N Z J Obstet Gynaecol 1987;27:269᎐282. w4x Szarewski A, Cuzick J, Edwards R, Butler B, Singer A. The use of cervicography in a primary screening service. Br J Obstet Gynaecol 1991;98:313᎐317.
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w5x Omigbodun AO. Management of cervical intraepithelial neoplasia where colposcopy is not available. Cent Afr J Med 1991;37:7᎐10. w6x Mati JK, Mbungua S, Wanderi P. Cervical cancer in Kenya: prospects for early detection at primary level. Int J Gynaecol Obstet 1994;47Ž3.:261᎐267. w7x Bjorge T, Gunbjorud AB, Langmark F, Skare GB, Thoresen SO. Cervical mass screening in Norway ᎏ 510,000 smears a year. Cancer Detect Prev 1994;18: 463᎐470. w8x Ter Meulen J, Eberhardt HC, Luande J, Mgaya HN, Chang-Claude J, Mhina M et al. Human papillomavirus ŽHPV. infection, HIV infection and cervical cancer in Tanzania, East Africa. Int J Cancer 1992;51:515᎐521. w9x Ferenczy A. Viral testing for genital human papillomavirus infections: recent progress and clinical potentials. Int J Gynecol Cancer 1995;5:321᎐328. w10x Baldauf JJ, Dreyfus M, Lehmann M, Ritter J, Philippe E. Cervical cancer screening with cervicography and cytology. Eur J Obstet Gynecol Reprod Biol 1995; 58:33᎐39. w11x Schreider A, Zahm DM, Kirchmayr R, Schneider VL. Screening for cervical intraepithelial neoplasia grade 2r3: validity of cytologic study, cervicography, and human papillomavirus detection. Am J Obstet Gynecol 1996;174:1534᎐1541. w12x Hogenmiller JR, Smith ML, Stephens LC, McIntosh DG. Patterns of Pap smear screening in women diagnosed with invasive cervical cancer. J Gynecol Surg 1994;10:247᎐253. w13x Davidson M, Bulkow LR, Lanier AP, Smith RA, Hawkins I, Jensen H et al. Incidence of invasive cancer preceded by negative screening in high-risk Alaska native women. Int J Epidemiol 1994;23:238᎐245. w14x Fahey MT, Irwing L, Macaskill P. Meta-analysis of Pap test accuracy. Am J Epidemiol 1995;141:680᎐689. w15x Ferris DG, Payne P, Frisch LE. Cervicography: an intermediate triage test for the evaluation of cervical atypia. J Fam Pract 1994;38:332᎐333. w16x McKinnon KJ, Ford RM, Hunter JC. Comparison of cytology and cervicography in screening a high risk Australian population for cervical human papillomavirus and cervical intraepithelial neoplasia. Aust N Z J Obstet Gynaecol 1993;33:176᎐179. w17x Van Le L, Broekhuizen FF, Janzer-Steele R, Behar M, Samter T. Acetic acid visualization of the cervix to detect cervical dysplasia. Obstet Gynecol 1993;81: 293᎐295. w18x Mann W, Lonky N, Massad S, Scotti R, Blanco J, Vasilev S. Papanicolaou smear screening augmented by a magnified chemiluminescent examination. Int J Gynecol Obstet 1993;4:289᎐296. w19x Boon ME. The Pap smear. 2nd ed. Leyden: Coulomb Press, 1993:133᎐134, 244
Article
Screening for cervical neoplasia during pregnancy H.S. Cronje ´a,U , E. van Rensburg a , I. Niemanda , B.F. Cooremana , E. Beyer a , P. Divall b a
Departments of Obstetrics and Gynecology, Uni¨ ersity of the Orange Free State, Bloemfontein, South Africa b Department of Cytology, Uni¨ ersity of the Orange Free State, Bloemfontein, South Africa Received 9 April 1999; received in revised form 24 September 1999; accepted 6 October 1999
Abstract Objecti¨ e: To evaluate cytology as a screening method for cervical neoplasia in pregnancy and to compare it with cervicography and the acetic acid test ŽAAT.. Methods: In a large antenatal clinic in South Africa, 842 women were screened utilizing cytology, cervicography and the acetic acid test simultaneously. The proportion of positive results of the different tests were compared and the agreement calculated by the kappa statistic. Results: The mean age of the women was 27 years, and 12.5% smoked. Cytological smears were abnormal Žlow-grade squamous intra-epithelial lesion and higher degrees of abnormality. in 1.4% of cases, cervicography in 6.3% and the AAT in 14.3% Ž Ps 0.5400.. Kappa values were as follows: cytology vs. cervicography 0.01, cytology vs. AAT 0.0 and cervicography vs. AAT 0.2. Conclusions: As a result of cytology’s rather low yield and the small measure of agreement between the tests, cytology should be supplemented by an additional screening test in pregnancy. 䊚 2000 International Federation of Gynecology and Obstetrics. Keywords: Cervical screening; Cytology; Cervicography; Acetic acid test; Pregnancy
U
Corresponding author. Tel.: q27-514053444; fax: q27-514442006. E-mail address: [email protected] ŽH.S. Cronje ´. 0020-7292r00r$20.00 䊚 2000 International Federation of Gynecology and Obstetrics. PII: S 0 0 2 0 - 7 2 9 2 Ž 9 9 . 0 0 1 7 8 - 2
20
H.S. Cronje´ et al. r International Journal of Gynecology & Obstetrics 68 (2000) 19᎐23
1. Introduction Antenatal visits present a unique opportunity of screening for cervical neoplasia. Unfortunately however, the Pap smear Žcytology. has proved to be less sensitive in pregnant patients, resulting in a controversy as to whether cervical screening should be implemented in pregnancy w1x. Pregnancy by itself does not seem to interfere with the natural history of cervical neoplasia and therefore, other factors are responsible for the decreased sensitivity of the Pap smear in pregnancy w2x. This phenomenon may be the result of a number of factors including enlargement of the cervix, increased mucous secretion and increased difficulty in actually viewing the cervix. Sampling errors, responsible for at least 50% of false negative smears, therefore appear to be more pronounced in pregnancy w3x. Due to the problems associated with screening in developing countries, antenatal clinics certainly present the possibility of reaching at least a proportion of the target population. Limitations in the funds available for screening in these countries, however, necessitates critical evaluation of such a policy. It is, therefore, the aim of this study to compare different screening methods in pregnancy with the ultimate goal of formulating a screening policy.
2. Patients and methods This study was performed at the antenatal clinic, Pelonomi hospital, Bloemfontein, South Africa. This institution is a secondary referral and training hospital in the Free State province, managing on average, 5500 births per year. The vast majority of these patients are of a lower socio-economic status and for the most part, have never been screened for cervical cancer. This study was approved by the Ethics Committee of the Faculty of Health Sciences, University of the Orange Free State. The sample consisted of 842 patients attending the antenatal clinic for their first visit. Since cervical cytology was a test performed routinely during
the first visit, the enrolment was carried out on a consecutive basis. All vaginal examinations were executed in the dorsal position. After the insertion of a Cusco vaginal speculum, the cervix was examined by a specially trained professional nurse who performed all the screening tests in this study ŽEvR.. Three methods were utilized in the following order: a cytological smear ŽPap smear., cervicography and a macroscopical examination aided by the application of a 5% acetic acid solution Žacetic acid test or AAT.. Excessive vaginal discharge was a commonly encountered problem. In these cases, following visualization of the cervix, it was gently cleansed with a cotton-wool swab, carefully preventing trauma to the cervix as well as the removal of superficial epithelial cells. As soon as the cervix was clear from vaginal discharge and excessive mucous, the smear was taken with an Ayre spatula. The material was smeared across the length of a glass slide and fixated by means of a standard spray fixative. Bleeding of the cervix, caused by this contact, was stopped by gently pressing against the traumatized area with a dry cotton-wool swab. Another cotton-wool swab, drenched in a 5% acetic acid solution, was then gently applied to the cervix for 20᎐30 s. The cervix was left to dry for 20 s whereafter acetic acid was applied a second time. A Cerviscope 䊛 ŽNTL, St. Louis, USA. was then used to take both the first Cervigram 䊛 Žphotograph of the cervix. and after a brief re-application of acetic acid solution, the second. This second photo was indicated for distinguishing mucous from an aceto-white lesion, as well as to expose possible lesions covered by mucous. Thereafter the surface of the cervix was thoroughly examined macroscopically ŽAAT. for the presence of aceto-white lesions, indicative of abnormalities. Upon completion of the examinations, the acetic acid solution that had collected in the posterior fornix was gently swabbed away and the Cusco speculum removed. All the cytological smears were evaluated by the Department of Cytology, Faculty of Health Sciences, University of the Orange Free State. The Cervigrams 䊛 Žtwo photographic slides per patient. were evaluated by two of the authors who
H.S. Cronje´ et al. r International Journal of Gynecology & Obstetrics 68 (2000) 19᎐23
are registered cervicography evaluators ŽHSC and BFC.. They were not informed about the results of the cytological smear or the AAT at the time of evaluating the Cervigrams 䊛 . All patients with low-grade squamous intratepithelial lesions ŽLoSIL. and high-grade squamous intraepithelial lesions ŽHiSIL. diagnosed by cytology, as well as those with aceto-white lesions and possible cancers identified by AAT and all patients with positive Cervigrams 䊛 were referred to a colposcopy clinic for further evaluation and treatment. Cervicography was regarded positive when the diagnosis was P1a Žatypical aceto-white lesion extending into the endocervical canal., P1b ŽLoSIL., P2 ŽHiSIL. or P3 Žcancer.. Although cases with a diagnosis of PO were also referred for colposcopy, we did not use this category in our analysis of positive cases due to the increased vascularity during pregnancy which could lead to false positives.
3. Results The average age of the 842 patients was 27 years Žminimum 15 years and maximum 40 years.. Only one patient had been treated previously by means of a cone biopsy and 12.5% of the women smoked. Only 3.4% of the cervical smears contained both ecto- and endocervical epithelial cells. Of the total number of smears evaluated cytologically, 0.7% were regarded as atypical ŽASCUS.. Cervical intra-epithelial neoplasia ŽLoSIL q HiSIL. was diagnosed in a further 1.5% of cases, whilst no cases of infiltration were reported ŽTable 1.. A cervicography diagnosis of P1 to P3 ŽLoSIL, HiSIL and infiltration. was reported in 6.3% of patients ŽTable 2.. One case had an infiltrating carcinoma. The AAT found 14.3% of cases to be positive ŽTable 3., four of whom were diagnosed with the possibility of infiltrating cancer. The Kappa statistic was used to determine the measure of agreement between the three screening tests. Cervicography vs. cytology produced a Kappa value of 0.01, cervicography vs. the AAT a
21
Table 1 Results utilizing cytology as screening method Ž n s 842. Diagnosis
Number
Negative Atypical squamous cells ŽASCUS. LoSILa HiSILb Infiltration Technically defective
820 6 9 3 0 4
Ž97.4. Ž0.7. Ž1.0. Ž0.4. Ž0. Ž0.5.
Total
842
Ž100.0.
a b
Ž%.
LoSIL, Low-grade squamous intraepithelial lesion. HiSIL, High-grade squamous intraepithelial lesion.
value of 0.2 and cytology vs. and the AAT, a value of 0.01.
4. Discussion In this study 842 patients were included into the study, but only 825 cervicography results and 808 AAT results were analyzed. The reason for these drop-outs is the appearance of the cervix in pregnancy: enlarged Žoften with an extremely large endocervical component. and often hemorTable 2 Results utilizing cervicography as screening method Ž n s 825. Diagnosis
Number
Negative Atypical Positi¨ e (P) 0a lab lb ŽLoSIL.c 2 ŽHiSIL.d 3 ŽCancer.e Technically defective
694 61
Ž84.1. Ž7.4.
5 2 39 9 1 14
Ž0.6. Ž0.3. Ž4.7. Ž1.1. Ž0.1. Ž1.7.
Total
825
Ž100.0.
a
Ž%.
PO, possibly negative, but needs a colposcopically directed biopsy for excluding cancer. b P1a, a typical lesion extending into the canal, warranting a colposcopical examination. c P1b, Low-grade squamous intra-epithelial lesion d P2, High-grade squamous intra-epithelial lesion. e P3, Cancer.
22
H.S. Cronje´ et al. r International Journal of Gynecology & Obstetrics 68 (2000) 19᎐23
Table 3 Results utilizing the acetic acid test as screening method Ž n s 808.
Table 4 Comparison of results in pregnant and non-pregnant women % Positve resultsrindependent sample
Diagnosis
Number
Negative Positive Žaceto-white lesion. Possible cancer Technically defective
686 111 3 8
Ž%. Ž84.9. Ž13.7. Ž0.4. Ž1.0.
Cytology Cervicography AATb
Total
808
Ž100.0.
Pregnant
Non-pregnanta
P-value
12r838 Ž1.4%. 51r811 Ž6.3%. 114r800 Ž14.3%.
214r6147 Ž3.5%. 659r6147 Ž10.7%. 1095r6147 Ž17.8%.
0.0014
U
U
0.0008
U
0.0128
a
Unpublished data from the same institution. AAT, Acetic acid test. U Statistically significant. b
rhagic or infected with excessive amounts of mucous. Subsequently, in a small number of patients cervicography andror the AAT was not possible. We reported only on the proportion of positive outcomes for each test as well as the kappa statistic Žagreement between tests., but not on the sensitivity. The reason being that we have not performed a histological analysis on each patient. During pregnancy, the cervix is extremely vascular and due to the risk of hemorrhage, biopsies were not done. Infection exaggerates this problem, a common phenomenon in our population. In another study, as yet unpublished, we screened 6147 non-pregnant women of a comparable population, utilizing the same three techniques. The results proved 3.5% of smears to be positive ŽLoSIL and HiSIL., as well as 10.7% of cervigrams ŽP1 or more. and 17.8% of AATs Žwhite lesions or possible cancer. ŽTable 4.. Therefore, all three tests significantly performed worse during pregnancy. Cytology decreased by 60% concerning its proportion of positive tests, cervicography by 41% and the acetic acid test by 20%. Generally, the proportion of positive smears, given a non-pregnant population, is approximately 3% but may vary between 1% and 9.7% w4᎐8x. The sensitivity of cytology varies significantly w9᎐13x, but Fahey et al. w14x have published an excellent meta-analysis, concluding that the sensitivity of cytology varies between 20 and 35%. Cervicography in turn, has a reported sensitivity of approximately 55%, whilst that of the AAT is 60% w10,15᎐18x. Unfortunately the AAT tends to overdiagnose since not all visible aceto-white lesions reflect LoSIL or HiSIL.
Why is the sensitivity of cytology decreased in pregnancy? As stated earlier, sampling errors Že.g. the taking of smears in such a way that endocervical cells are not included in the material. are responsible for at least 50% of false negative smears w3x. In pregnancy, the enlargement of the cervix, difficulty in properly visualizing the cervix and excessive mucus on the cervical surface, may increase the problem of false negative smears. In addition, infection, a multiparous cervix and advanced gestational age with more pronounced eversion of the cervix, further complicate cytological smears in pregnancy. In this study only 3.4% of smears contained endocervical cells. Although it is known that the yield is less during pregnancy w19x, our result was unexpectedly low. In a comparable but non-pregnant population, the yield was 34% Žresults still unpublished.. In both cases smears were taken with Ayre spatulas by a single well-trained professional nurse. Bleeding from the cervix caused by the Ayre spatula, may complicate the subsequent preparation of the cervix for cervicography. Therefore, the nurse may have exerted less pressure on the spatula to minimize bleeding resulting in the possibility of less smears containing endocervical cells. In both pregnant and non-pregnant patients, this could have resulted in smaller proportions of adequate smears Žcontaining endocervical cells.. Interesting to note is the significant increase in sensitivity given a combination of screening tests. For example, utilizing cervicography in addition to cytology, results in an increase in sensitivity of
H.S. Cronje´ et al. r International Journal of Gynecology & Obstetrics 68 (2000) 19᎐23
at least 30% and as much as 52% with the further addition of speculoscopy Žspecialized form of AAT. w10,11,16,18x. The reason being the negligibly small measure of agreement between the various methods, a finding supported by this study. Is screening really worthwhile in pregnancy? In developing countries, such an opportunity might be unique. Carter suggested obtaining a smear only if the patient had not recently Žprevious 2᎐3 years. been for cervical screening w1x. But still, this suggestion does not solve the ‘low sensitivity’ problem. We therefore recommend the implementation of a combination of tests. A combination of cytology and cervicography, for example, results in a sensitivity of 50᎐60%, which is significant from a clinical point of view. However, cervicography is not available in most developing countries and it is reasonably expensive. Therefore, the addition of the AAT Žor even speculoscopy. is a reachable alternative in most countries. Although it will overdiagnose to some extent, the sensitivity will be significantly improved. More research is required however, to determine the cost-effectiveness of the various combinations.
Acknowledgments We wish to acknowledge Dr R.H. Bam for her valuable assistance and Mrs I Venter for typing the manuscript. References w1x Carter PM, Coburn TC, Luszczak M. Cost-effectiveness of cervical cytologic examination during pregnancy. J Am Board Fam Pract 1993;6:537᎐545. w2x Guerra B, De Simone P, Gabrielli S, Falco P, Montanari G, Bovicelli L. Combined cytology and colposcopy to screen for cervical cancer in pregnancy. J Reprod Med 1998;43:647᎐653. w3x Shield PW, Daunter B, Wright RG. The Pap smear revisited. Aust N Z J Obstet Gynaecol 1987;27:269᎐282. w4x Szarewski A, Cuzick J, Edwards R, Butler B, Singer A. The use of cervicography in a primary screening service. Br J Obstet Gynaecol 1991;98:313᎐317.
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w5x Omigbodun AO. Management of cervical intraepithelial neoplasia where colposcopy is not available. Cent Afr J Med 1991;37:7᎐10. w6x Mati JK, Mbungua S, Wanderi P. Cervical cancer in Kenya: prospects for early detection at primary level. Int J Gynaecol Obstet 1994;47Ž3.:261᎐267. w7x Bjorge T, Gunbjorud AB, Langmark F, Skare GB, Thoresen SO. Cervical mass screening in Norway ᎏ 510,000 smears a year. Cancer Detect Prev 1994;18: 463᎐470. w8x Ter Meulen J, Eberhardt HC, Luande J, Mgaya HN, Chang-Claude J, Mhina M et al. Human papillomavirus ŽHPV. infection, HIV infection and cervical cancer in Tanzania, East Africa. Int J Cancer 1992;51:515᎐521. w9x Ferenczy A. Viral testing for genital human papillomavirus infections: recent progress and clinical potentials. Int J Gynecol Cancer 1995;5:321᎐328. w10x Baldauf JJ, Dreyfus M, Lehmann M, Ritter J, Philippe E. Cervical cancer screening with cervicography and cytology. Eur J Obstet Gynecol Reprod Biol 1995; 58:33᎐39. w11x Schreider A, Zahm DM, Kirchmayr R, Schneider VL. Screening for cervical intraepithelial neoplasia grade 2r3: validity of cytologic study, cervicography, and human papillomavirus detection. Am J Obstet Gynecol 1996;174:1534᎐1541. w12x Hogenmiller JR, Smith ML, Stephens LC, McIntosh DG. Patterns of Pap smear screening in women diagnosed with invasive cervical cancer. J Gynecol Surg 1994;10:247᎐253. w13x Davidson M, Bulkow LR, Lanier AP, Smith RA, Hawkins I, Jensen H et al. Incidence of invasive cancer preceded by negative screening in high-risk Alaska native women. Int J Epidemiol 1994;23:238᎐245. w14x Fahey MT, Irwing L, Macaskill P. Meta-analysis of Pap test accuracy. Am J Epidemiol 1995;141:680᎐689. w15x Ferris DG, Payne P, Frisch LE. Cervicography: an intermediate triage test for the evaluation of cervical atypia. J Fam Pract 1994;38:332᎐333. w16x McKinnon KJ, Ford RM, Hunter JC. Comparison of cytology and cervicography in screening a high risk Australian population for cervical human papillomavirus and cervical intraepithelial neoplasia. Aust N Z J Obstet Gynaecol 1993;33:176᎐179. w17x Van Le L, Broekhuizen FF, Janzer-Steele R, Behar M, Samter T. Acetic acid visualization of the cervix to detect cervical dysplasia. Obstet Gynecol 1993;81: 293᎐295. w18x Mann W, Lonky N, Massad S, Scotti R, Blanco J, Vasilev S. Papanicolaou smear screening augmented by a magnified chemiluminescent examination. Int J Gynecol Obstet 1993;4:289᎐296. w19x Boon ME. The Pap smear. 2nd ed. Leyden: Coulomb Press, 1993:133᎐134, 244