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Pap smear accuracy for the diagnosis Article reuse guidelines:
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of cervical precancerous lesions DOI: 10.1177/0049475518798532
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Elie Nkwabong1, Ingrid Laure Bessi Badjan2 and


Zacharie Sando3

Abstract
This cross-sectional descriptive study, aimed at accessing the accuracy of Pap smear in diagnosing cervical precancerous
lesions, was carried out between 3 January and 30 April 2017. All women screened for cervical dysplasia by means of Pap
smear with biopsy done for confirmation were subsequently recruited. Data were analysed using SPSS 20.0. A total of
231 women were screened for cervical dysplasia using Pap smear with 75 biopsies performed. Cervical dysplasia was
noticed in 54 cases. The sensitivity, specificity, positive predictive and negative predictive values of Pap smear were 55.5%,
75%, 88.2% and 33.3%, respectively. The sensitivity of Pap smear remains low. Therefore, biopsy should be done in cases
of macroscopic cervical architectural changes irrespective of the result of the Pap smear. Moreover, to reduce the
number of women with cervical precancerous lesions, the government should make available financial resources to set up
HPV vaccination programmes rather than screening programmes.

Keywords
Cervical precancerous lesions, negative predictive value, Pap smear, positive predictive value, sensitivity, specificity

Introduction The sensitivity of Pap smear is <70% in many stu-


Cervical cancer is the second most frequently diagnosed dies.4–6 Therefore, Pap smear might not be an appro-
gynaecological cancer worldwide.1 An estimated priate test for the diagnosis of cervical precancerous
527,600 new cases of cervical cancer were reported lesions. Consequently, some cases of cervical dysplasia
worldwide in 2012, with around 265,700 deaths. might unknown evolve to cervical cancer, especially
Approximately 90% of cervical cancer deaths occurred when this method has been used for screening. The
in developing parts of the world.2 It is the third leading techniques for diagnosing cervical precancerous lesions
cause of cancer death among women in less developed have improved. Indeed, the liquid medium cytology
countries. The highest incidence and mortality rates are technique has been recently used but with conflicting
reported in Africa.2 results.7,8
The main risk factor for cancer of the cervix is human No recent study evaluated the reliability of Pap
papilloma virus (HPV) infection. Cervical cancer may be smear in the diagnosis of cervical precancerous lesions
prevented, or at least diagnosed at an early stage, given in our environment, hence this study which aimed at
that the cervix is an organ easily accessible to clinical evaluating its accuracy in the diagnosis of cervical
evaluation. Mortality from cancer of the cervix may be
avoided, if not reduced, if precancerous lesions are diag- 1
Associate Professor, Department of Obstetrics & Gynecology,
nosed and treated. Cervical intraepithelial neoplasia
University Teaching Hospital / Faculty of Medicine and Biomedical
(CIN) 1 needs around 10–15 years to evolve to the Sciences, Yaoundé, Cameroon
stage of cervical cancer.3 Immunosuppression may 2
Student, Faculty of Medicine and Biomedical Sciences, Yaoundé,
reduce this time interval. Cameroon
3
Cervical dysplasia may be diagnosed using Pap Associate Professor, Department of Pathology, Faculty of Medicine and
Biomedical Sciences, Yaoundé, Cameroon
smear. All epithelia shed and superficial cells may be
collected and analysed. Pap smear consists of collecting Corresponding author:
shed superficial cells of the transformation zone and Elie Nkwabong, P.O. Box 1364 Yaoundé, Cameroon.
their subsequent examination by a cytopathologist. Email: enkwabong@yahoo.fr
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dysplasia as well as looking at the sociodemographic Of these 30 women, cervical dysplasia was found in
profile of women affected by cervical dysplasia. 23 cases. In seven cases, there was no dysplasia.
All the 45 women with macroscopic cervical archi-
tectural changes (43 erythematous cervices and two
Methods
small polypoid lesions) had colposcopy directed
This cross-sectional descriptive study was carried out in cervical biopsy. Among these women, Pap smear was
two university teaching hospitals between 3 January normal in 35 cases, and revealed the presence of dys-
and 30 April 2017. All women who were screened for plastic cells in 10 cases. Among these 10 women, biopsy
cervical dysplasia by means of Pap smear were showed four cervical dysplasia, two cases without dys-
recruited. Biopsy of the cervix was performed in all plasia and four cases of microinvasion. Among the
women with abnormal results as well as in women 35 women who presented macroscopic cervical archi-
with normal results, but with macroscopic architectural tectural changes without dysplastic cells found at Pap
cervical changes. Women with cancer at biopsy were smear, biopsy showed 27 cervical dysplasia, seven cases
excluded when analysing the accuracy of screening of without dysplasia and one case of microinvasion
cervical precancerous lesions. When calculating the (Figure 1).
accuracy of Pap smear, women who refused cervical In summary, 75 biopsies were carried out with 54
biopsy because they could not contribute financially showing cervical dysplasia (54/231 or 23.4%), 16 non-
to biopsy too were excluded. Informed consent was dysplastic lesions as well as five micro-invasive lesions
obtained from each patient. This study received (2.1%) that were excluded when analysing the accuracy
approval from the national ethics committee. of screening of cervical precancerous lesions. The socio-
The variables recorded on a questionnaire included demographic and obstetrical variables of the study
the patient’s age, age at first sexual intercourse, age at population is presented in Table 1.
first delivery, number of pregnancies, abortions and Results of Pap smear, presented according to
deliveries, cumulated number of sexual partners and Bethesda system, was abnormal (cells showing abnor-
tobacco consumption. These variables were chosen mal nucleus activity) in 34 cases (14.7%). They included
because we hypothesised that they could influence the 11 (32.3%) high-grade squamous intraepithelial lesions
occurrence of cervical dysplasia. Other variables stu- (HSIL), 13 (38.2%) low-grade squamous intraepithelial
died were the macroscopic appearance of the cervix, lesions (LSIL) and 10 (29.4%) atypical squamous cell
the result of Pap smear and that of cervical biopsy. of undetermined significance (ASCUS). Furthermore,
Our minimal sample size of 44 patients was calcu- 22 with chronic cervicitis were observed. In 14 cases,
lated using the following formula9 for descriptive no abnormality was found. Of the 231 participants, 107
studies women (46.3%) had Pap negative smears a few years
earlier, while 124 women (53.7%) had never been
N ¼ Pð1  PÞZa2 =D2 screened before.
The results of cervical biopsies are presented in Table
where Za ¼ 1.96 corresponds to a confidence level of 2. Biopsy showed 54 cervical intraepithelial neoplasia
0.05, D ¼ 0.08 is the degree of precision and the preva- (CIN) (20 CIN 1, 21 CIN 2 and 13 CIN 3) and no dys-
lence of cervical dysplasia (P) was 7.9% in our milieu.10 plasia in 16 cases (Table 3). Biopsy among the 10 women
The variables of women who presented dysplastic with ASCUS revealed two cervical dysplasia (20%),
lesions were compared to those who did not present including one CIN 1 and one CIN 2. The eight other
any dysplastic lesions. Data were analysed using SPSS women with ASCUS had either chronic inflammation
20.0. The t-test was used to compare continuous vari- (three cases) or normal epithelium (five cases).
ables and Fisher’s exact test to compare categorical Table 3 also shows the accuracy of Pap smear in the
variables. P < 0.05 was considered statistically signifi- diagnosis of cervical dysplasia.
cant. Moreover, the accuracy of cervical Pap smear in All the women screened collected their results
diagnosing cervical dysplasia was assessed. (reports of Pap smear and biopsy). All patients with
cervical precancerous lesions at biopsy had either cryo-
therapy (36 cases) or loop electrosurgical excision pro-
Results cedures (18 cases).
During the study period, 231 women (186 having
macroscopically normal cervices and 45 slight macro-
Discussion
scopic cervical architectural changes) were screened for
cervical dysplasia using Pap smear. Of the 186 women Our prevalence of abnormal Pap smear (14.7%) is
with a macroscopic normal cervix, 79 had cervical dys- higher than the 6.0% found in Thailand among preg-
plastic cells, but only 30 accepted cervical biopsies. nant women.11 The most common abnormal Pap smear
Nkwabong et al. 3

Women screened : n= 231

Macroscopically normal cervices : n=186 Macroscopically abnormal cervices: n= 45

Normal Pap Abnormal


smears: Pap smears :
n=107 n=79

Refusal of Biopsies Abnormal Pap smears: Normal Pap smears:


biopsy: n=49 done: n=30 n=10 (all biopsied) n=35 (all biopsied)

No Dys- No Dys- Micro- Micro- Dys- No


dysplasia plasia dysplasia plasia invasion invasion plasia dysplasia
n=7 n=23 n=2 n=4 n= 4 n=1 n=27 n=7

Figure 1. Flowchart showing screening sequences.

Table 1. Sociodemographic and obstetrical variables among the population under study.

Women with Women without


cervical dysplasia cervical dysplasia
Variables (n ¼ 54) (n ¼ 16) P value

Patient age (years) 43.5  9.8 (24–63) 43.0  11.0 (26–63) 0.862
Age at 1st intercourse 16.7  2.7 (11–25) 16.0  3.1 (12–23) 0.381
Age at 1st delivery 20.0  4.3 (14–28) 19.1  2.1 (16–23) 0.423
Abortions (n) 1.3  1.3 (0–7) 2.0  1.0 (0–4) 0.051
Deliveries (n) 4.9  2.3 (0–10) 6.1  3.2 (2–12) 0.099
Sexual partners (n) 7.2  2.6 (1–12) 6.0  2.1 (1–10) 0.096
Tobacco consumption* (n (%)) 3/54 (5.6) 0 (0) 0.581
Previous cancer screening (n (%)) 25/54 (46.3) 7/16 (43.7) 1
Values are presented as mean  SD (range) unless specified otherwise.
*One active and two passive tobacco consumptions.

was LSIL in our study (38.2%). LSIL was also the most Pakistan.12 This can be explained by the fact that their
common Pap smear abnormality observed in Thailand youngest patient was 19 years old, while the youngest
(44%).11 Our data showed that cervical dysplasia is fre- patient in our study was 24 years old. According to
quent among women screened for cervical precancerous some societies, screening should concern women aged
lesions. Our hospital-based prevalence of cervical dys- 25–69 years.13,14 Our patient aged 24 years first had
plasia (23.4%) is higher than that of 7.9% observed in sexual intercourse at the age of 11 years. She might
our environment in a previous study.10 Our high preva- have presented cervical dysplasia many months
lence might be attributed to the fact that it is the preva- before, given that it was the first time she was screened.
lence among women who consulted in our unit and not We think that screening should start earlier, for
among the general population. instance at 21 years, as done by Ryu et al. in the
The mean age of patients observed in our study (43.5 Korea University Medical Center, Seoul, Republic of
years) was higher than that of 35.7 years observed in Korea,15 especially among women whose first sexual
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Table 2. Cervical non-dysplastic abnormalities after biopsy. The sensitivity, for women who had also a biopsy, of
a Pap smear in our study (55.5%) was similar to that of
Abnormality n %
52% found by Bhattacharyya et al. in India,4 but
Inflammation 13 81.2 higher than the 18.2% observed in Iran6 and lower
Polyp 3 18.8 than the 63.2% found by Bobdey et al. in India.5
Total 16 100 This shows that biopsy should be preferred in certain
cases such as those with macroscopic cervical architec-
tural changes. This low sensitivity also reveals that Pap
smear is ineffective in reducing mortality from cancer of
Table 3. Accuracy of Pap smear in diagnosing cervical dysplasia. cervix. The government should look for financial
resources to put an emphasis on HPV vaccination
Cervical dysplasia on biopsy specimen
rather than on screening.
Pap smear Present Absent Total The specificity of Pap smear noticed in our study
(75%) was similar to the 76% observed in Turkey.19
Positive 30 (a) 4 (b) 34 (a þ b) The negative predictive value of Pap smear observed
Negative 24 (c) 12 (d) 36 (c þ d) in our series (33.3%) was lower than the 71.3% found
Total 54 (a þ c) 16 (b þ d) 70 (a þ b þ c þ d) in Iran6 and the 92% noticed in Turkey.19
Sensitivity: a/a þ c ¼ 30/54 ¼ 55.5%; specificity: d/b þ d ¼ 12/16 ¼ 75%; For cases with slight macroscopic cervical architec-
positive predictive value: a/a þ b ¼ 30/34 ¼ 88.2%; negative predictive tural changes, colposcopy-directed biopsy might be
value: d/c þ d ¼ 12/36 ¼ 33.3%. associated or substituted to Pap smear to reduce the
false-negative rate, as suggested by some authors.19
Moreover, this attitude shortens the proceedings.
intercourse occurred before the age of 12 years. In our The presence of ASCUS was observed in 10 women
study, another patient first had sexual intercourse at the in our series. Some societies believe that women with
age of 12 years. Age at first intercourse is decreasing, ASCUS or LSIL could just be observed and followed
with some adolescents abusing children at the age of up every six months, and colposcopy-directed biopsy is
eight or nine years.16,17 advised after three consecutive abnormal smears.14,20 In
No significant difference was observed between low-resource countries, for financial or cultural rea-
women with cervical dysplasia and those with non- sons, many women do not routinely attend hospital.
dysplastic lesions as concerns maternal age If they do, some of them are lost to follow-up.13 We
(P ¼ 0.862), tobacco consumption (P ¼ 0.581), age at think that women from low-resource countries with
first sexual intercourse (P ¼ 0.381), abortion number ASCUS should be immediately investigated (colpo-
(whether spontaneous or induced) (P ¼ 0.051), age at scopy-directed biopsy), as it has been associated in
first delivery (P ¼ 0.423), delivery number (P ¼ 0.099) our study with 20% of cervical dysplasia. This point
and number of sexual partners (P ¼ 0.096). This sug- of view is shared by some authors in Japan who
gests that the previously described risk factors for cer- observed cases of CIN 3 and carcinoma in-situ among
vical dysplasia are only co-factors.18 The main risk women diagnosed with ASCUS.20 Screen-and-treat
factor, not investigated in this series, is HPV infection approaches for cervical cancer prevention have been
that is mostly spread by sexual intercourse. proven effective in low-resource settings.21 World
The presence of cervical invasion or micro-invasion Health Organization (WHO) guidelines for screening
among some women is explained by the fact that the and treatment of precancerous lesions for cervical
majority of our women (53.7%) never had cervical cancer prevention recommend colposcopy with or with-
screening combined with adequate treatment. out biopsy among women with ASCUS living in high
Moreover, the diagnosis might have been missed in a HIV endemic regions.22
previous screening among women who had a prior Pap The limitation of our study is the absence of tests for
smear. Indeed, 107 women (46.3%) were screened nega- diagnosing HPV as this might have shown its associ-
tive for Pap smear a few years before. Women should ation with cervical dysplasia. Moreover, we could not
be encouraged to perform Pap smear or other screening be certain of the reliability of the answers given by
methods more often. They should also be prepared for women, especially when it concerned the number of
immediate treatment of positive cases. sexual partners. Finally, cervical biopsies were not per-
The presence of dysplasia and cancer among women formed in all cases with abnormal Pap smear, because
with macroscopic cervical architectural changes nega- some women could not contribute financially to both
tive for Pap smear reminds us that biopsy should be Pap smear and biopsy, as biopsies might have increased
directly carried out in such cases, i.e. when the cervix the size of our population with cervical dysplasia.
looks abnormal.
Nkwabong et al. 5

Indeed, women with low socioeconomic status are at 8. Latsuzbaia A, Hebette G, Fischer M, et al. Introduction
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low, the authors think that after two normal Pap smear pital. Asian Pac J Cancer Prev 2016; 17: 4163–4167.
results, it could be repeated yearly or every two years 12. Khan M, Sultana SS, Jabeen N, et al. Visual inspection of
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Pak Med Assoc 2015; 65: 192–195.
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limited countries, as it will be more cost-effective in cancer screening in rural Madagascar: Feasibility, cover-
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Declaration of conflicting interests cancer screening programme in Norway, 1992–2000:
changes in Pap smear coverage and incidence of cervical
The authors declare that there is no conflict of interest. cancer. J Med Screen 2002; 9: 86–91.
15. Ryu KJ, Lee S, Min KJ, et al. Management of atypical
Funding squamous cells of undetermined significance or low-grade
This research received no specific grant from any funding squamous intraepithelial lesions of the uterine cervix with
agency in the public, commercial, or not-for-profit sectors. human papilloma virus infection among young women
aged less than 25 years. Diagn Cytopathol 2016; 44:
959–963.
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