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Correlation of Cervical Smear and Pathohistological Findings
106 Med Arh. 2014 Apr; 68(2): 106-109
Correlation of Cervical Smear and
Pathohistological Findings
Amir Asotic1
, Suada Taric2
, Jasmina Asotic3
Clinic of Obstetrics and Gynecology, Clinical Center of Sarajevo University, Sarajevo, Bosnia and Herzegovina1
Health center Sarajevo, Sarajevo, Bosnia and Herzegovina2
Cantonal hospital Travnik, Travnik, Bosnia and Herzegovina3
Corresponding author: Amir Asotić, MD, MSc, Clinic of Gynecology and Obstetrics, Clinical Center of Sarajevo University, Jezero, 71000
Sarajevo. Bosnia and Herzegovina, Tel:061/228/550. E-mail: amir.asotic@hotmail.com
ABSTRACT
Introduction: In endeavor to suppress the cervical carcinoma there are several possible approaches including measures of primary and
secondary prevention. So far effects of these measures on the number of cases and mortality rate of cervical carcinoma were modest. Only
exception is organized testing based on cytological exam of the cervical smear – Pap test, which has proven to be highly effective in reduc-
ing the number of cases and mortality of cervical carcinoma in countries with this program. Goal of this research is analysis of correlation
between abnormal cytological test results and pathohistological diagnosis of all patients in the analyzed period. Material and methods:
Research is descriptive, analytical, comparative, and partly epidemiological. Results of cytological and pathohistological diagnostic in the
period between January 1, 2009 and December 31, 2011 were used for analysis. All analyzed patients had colposcopy exam and Pap test,
and patients with abnormal results of this test underwent cervical biopsy for pathohistological diagnostics. Results: We came to follow-
ing results and conclusions: total number of L-SIL and H-SIL (PAPA III) results was 395 (6.20%) in comparison to total sample of 5894
(92.44%) patients. There is a statistically significant difference in relation to PHD result of cervical biopsy after L-SIL and H-SIL (PAPA II
and IV), and highest statistical margin is in relation of CIN II changes to cytological findings, issued at Clinic of Obstetrics and Gynecol-
ogy and other health institutions. We come to conclusion that the highest percentage of patients with L-SIL and H-SIL findings is in age
group between 0-29 years old. Statistical analysis has shown a positive trend in number of younger patients with L-SIL and H-SIL (PAPA
III and IV), with average age of patients in 2011 being 31.12±9.12 years old.
Key words: Pap test, biopsy.
1.	INTRODUCTION
Cytological methods are applied starting from the mid-
19th
century, when the researchers found abnormal cells
in body fluids such as urine, sputum, exudates and gastric
fluid.
Papanicolaou (1928) in New York announced the era of
modern diagnostic cytology, when he published an arti-
cle titled “A new diagnosis of cancer”. Despite skepticism
at the beginning of cytopathological era, the use of this
method that is popularly known as “Pap” test is accepted
as the most appropriate screening test for early detection
of cancer and precancerous states of uterine cancer (1).
Exfoliative cytology analyzes spontaneously exfoliat-
ed cells from the skin, mucous and serous membranes.
Cytodiagnostics of the vaginal-cervical-endocervical
(VCE) smear by volume is the largest in exfoliative cytol-
ogy, since it covers both the healthy and sick women. The
smears include epithelial and non epithelial cells (2,3).
In the universal effort for combating cervical cancer are
available several possible approaches, including measures
of primary and secondary prevention. So far, most of the
effects of these measures on the incidence and mortality
of cervical cancer were modest. The only exception seems
to represents organized screening based on the use of
cytological examinations of the cervix (Pap test), which
proved to be highly effective in reducing the incidence
and mortality of cervical cancer in countries where it is
implemented. Reduction of mortality caused by cervical
cancer in the United States and other developed countries
is significant, and this is due to the successful early di-
agnosis. Squamous intraepithelial lesions are detected in
adolescents, young adults and adults. The peak incidence
is at the age of about 30 years. Similarly, invasive carcino-
ma occurs earlier, in the third decade of life with a peak
frequency at about 40 years, or 10-15 years later (4).
Cytodiagnostics of conventional cervicovaginal smears
or “Pap test” for half of a century is the basic method of
secondary prevention of cervical cancer, which is applied
at the same time as a classic test of choice for the detec-
tion of lesions and a differential-diagnostic method for
predicting the histological diagnosis (5). In an effort to
reduce potential errors and increase the overall sensitivity
of the screening, during the past years has developed sev-
eral new techniques that have been proposed as a comple-
mentary method to conventional “Pap test”. These include
HPV DNA typization (6). There is an assumption that
ORIGINAL ARTICLE doi: 10.5455/medarh.2014.68.106-109
Med Arh. 2014 Apr; 68(2): 106-109
Received: November 21th 2013 | Accepted: March 25th 2014
© AVICENA 2014
Published online: 22/04/2014
Published print: 04/2014
Correlation of Cervical Smear and Pathohistological Findings
107Med Arh. 2014 Apr; 68(2): 106-109
during the last 25-30 years has increased the frequency of
diagnosis of carcinoma in situ, and in part because of the
efficiency of cytologic examination (7).
In the history of medicine, the only case of reduced in-
cidence and mortality, as well as human malignancies is
cervical cancers without medical intervention (8).
2.	GOAL
The aim of the research is to analyze the correlation be-
tween the abnormal cytological findings and histological
diagnosis in all patients during the observed period.
3.	MATERIAL AND METHODS
The study was descriptive-analytical, comparative,
partly epidemiological, and mainly clinical applicative.
The study involved all patients who meet the criteria for
inclusion in the study. Used are the results of cytological
and histological diagnosis in the period from January 1,
2009 to December 31, 2011.
In all subjects had previously done colposcopic exam-
ination and Pap test, and in patients with abnormal find-
ings was also performed cervical biopsy for obtaining his-
topathological diagnosis.
Colposcopy was performed using the Olympus colpo-
scope. The Pap test is taken from the front and rear lip
and cervical canal. From the sample taken is made ​​the cy-
tological smear, which is fixed on a microscopic slide and
stained by the method of Pap-Nikolai. After staining was
performed microscopic analysis of morphological char-
acteristics of the cells in the course of which are detected
signs of cervical inflammation, causes infection, benign
and malignant cells and other pathological changes.
After the punch biopsy changes in the cervix, the sam-
ples were forwarded to the Department of Pathology at
the further processing.
For statistical analysis of the data obtained was used
software package SPSS for Windows. In the analysis of the
results obtained, the following statistical methods were
used: for continuous variables in the study as the first
analysis of symmetry (normality) of their distribution by
Kolmogornov-Smirnov and Shapiro-Wilk test. Since the
distribution of continuous variables significantly deviated
from normal (Gaussian) distribution, mean values ​​and a
measure of dispersion, for their comparison is used the
median and interquartile range and nonparametric test
(ANOVA), normal and ordinal variables in the study were
analyzed by χ2 test and in the lack of expected frequencies
used Fisher’s exact test. The statistical analysis used the
Pearson χ2 test for difference distribution of nominal and
ordinal data.
4.	RESULTS
Table 1 shows the frequency of dysplasia (L-Sil and
H-SIL) in relation to the normal cytological findings.
Mann-Whitney test showed a statistically significant
difference in the frequency of L-SIL and H-SIL (Pap III)
findings in relation to the period covered by this study.
In 2010 was recorded the highest percentage compared
to the total number of L-SIL and H-SIL (Pap III) findings,
Z=-4.913, p=0.004.
Distribution of respondents by age group is displayed
on Tables 2 and 3.
Analysis of respondents by age groups compared to the
period covered by this study has been determined that the
highest percentage of patients was with L-SIL and H-SIL
(Pap III and IV) findings for the age group under 29 years.
The percentage and frequency of L-SIL and H-SIL (Pap
III and IV) findings in women of older age groups linearly
decreases and the lowest is in the age group 60-69 years.
ANOVA test showed that there was no statistically sig-
nificant difference in the average age of patients with L-SIL
and H-SIL (Pap III and IV) findings in relation to the test-
ed year, F=3.86, p=0,21. Statistical analysis showed a pos-
itive trend in terms that younger respondents have L-SIL
and H-SIL (Pap III and IV) cytological findings, so that
the average age of respondents in 2011 was 31.12±9.12
years.
2009 2010 2011 Total
N % N % N % N %
L-SIL; (PAP III) 101 4.34 186 9.50 135 6.46 395 6.20
H-SIL (PAP IV) 25 1.07 20 1.02 15 0.72 27 0.42
Normal cytological findings 2202 94.59 1752 89.48 1940 92.82 5894 92.44
Total 2328 100.00 1958 100.00 2090 100.00 6376 100.00
Table 1. The frequency of the L-SIL and H-SIL (Pap III and Pap IV) findings in relation to other cytological findings (Pap test)
Age groups
2009 2010 2011 Total
N % N % N % N %
≤29 89 45.88 129 55.13 104 51.74 322 51.19
30-59 96 49.48 99 42.31 92 45.77 287 45.63
≥60 9 4.64 6 2.56 5 2.49 20 3.18
Total 194 100.00 234 100.00 201 100.00 629 100.00
Table 2. The age groups of patients with L-SIL and H-SIL (Pap III and IV) cytological findings
Mean SD SEM
95% Confidence
Interval for Mean
Min Max.
Lower
Bound
Upper
Bound
2009 33.85 10.46 0.74 32.39 35.32 19.00 69.00
2010 33.14 10.51 0.68 31.80 34.48 19.00 68.00
2011 31.12 9.12 0.65 29.82 32.42 19.00 66.00
Total 32.75 10.14 0.40 31.95 33.54 19.00 69.00
Table 3. The average age of patients with L-SIL and H-SIL (Pap
III and IV) cytological findings in relation to the period covered
by the survey
Correlation of Cervical Smear and Pathohistological Findings
108 Med Arh. 2014 Apr; 68(2): 106-109
Table 4. Number of the performed biopsies in case of
L-SIL and H-SIL (Pap III and IV) findings, performed at
the Clinic of Obstetrics and Gynecology and in other in-
stitutions, on annual basis.
Pearson Chi square test showed a statistically signifi-
cant difference in the incidence of cytologic findings of
L-SIL and H-SIL (Pap III and IV), set by the cytologist at
the Clinic of Obstetrics and Gynecology and other insti-
tutions, χ2
=93.85, p=0.000.
The highest percentage of women who underwent cer-
vical biopsy had CIN I findings (n=283), followed by CIN
II (n=165), CIN III (n=152). Histopathologic findings of
CIN II and CIN III were the most frequent in 2010.
Pearson Chi square test showed a statistically significant
difference in the prevalence of histopathological diagnosis
in relation to the total number of the performed biopsies.
The most common finding was CIN I, while there is a
small percentage difference in the incidence of CIN II and
CIN III diagnosis, χ2
=15.68, p=0.016.
5.	DISCUSSION
The incidence of cervical cancer is unacceptably high. It
is believed that about 80% of all cases occur in less devel-
oped countries, because prevention programs are either
non-existent or poorly implemented.
There is a general opinion that organized national
screening programs using Pap test produce the best re-
sults. This is best illustrated by data from Finland, where
organized screening results were exceptional, reducing
the incidence from 14.8/100,000 in 1963 to 2.8/100,000 in
1992, reducing the total incidence by 69.6% (9).
Due to the simplicity of implementation, VCE smear
cytology is considered to be the best technique for screen-
ing. It is important to note that on the basis of cytology
is not made a definitive diagnosis, it is always necessary
to respect the protocol. Results may be false positive and
false negative in range from 10 to 35%. A particular prob-
lem is definitely false negative results (10).
The course of this research led to the following results.
The highest percentage of L-SIL and H-SIL (Pap III)
findings was during 2010 and it was (186) 9.5%, and the
lowest in 2009, where there was (101) 4.34%. In this peri-
od, the total number of L-SIL and H-SIL (Pap III) findings
amounted to 395 (6.20%) compared to other cytological
findings–5894 (92.44%).
Analysis of respondents by age group compared to the
years covered by this study has been determined that the
highest percentage of patients with L-SIL and H-SIL (Pap
III and IV) findings was in the age group under 29 years.
The percentage and frequency of L-SIL and H-SIL (Pap
III and IV) findings in women of older age groups linearly
decreases and is lowest in the age group from 60-69 years.
Brotherton JM. and associates (11), in their study, “Does
HPV type 16 or 18 in the prevalence of cervical intraepi-
thelial neoplasia grade 3 lesions vary by age? An import-
ant issue for postvaccination surveillance”, stated that
among the 317 women who were enrolled in the study,
with diagnosis CIN III, 70% of them aged 16-25 years, was
detected HPV, 16.59% in women age aged 26-35 years and
48% in women older than 36 years.
The study “Gynecologic malignancy in Tuzla Canton”
by Fatusic and colleagues report that in the period from
1993-2006, 27.11% of all women with cervical cancer is
younger than 30 years (12).
This situation can be attributed to insufficient informa-
tion, the motivation of young women for regular gyne-
cological examinations, as well as the absence of national
screening program.
According to the literature, the very frequency of cervi-
cal dysplasia and occurrence of HPV declines in percent-
age with age, so our results do not differ statistically from
the research of other authors.
ANOVA test showed that there was no statistically
significant difference in the average age of patients with
L-SIL and H-SIL (Pap III and IV) findings in relation to
the tested years.
Statistical analysis showed a positive trend that younger
respondents have L-SIL and H-SIL (Pap III and IV) cyto-
logical findings, so that the average age of respondents in
2011 is 31.12±9.12 years.
Year
Total
2009 2010 2011Biopsies
Clinic of Obstetrics
and Gynecology
N 126 206 80 412
% within biopsies 30.6% 50.0% 19.4% 100.0%
% within years 63.6% 86.2% 41.7% 65.5%
Other
N 72 33 112 217
% within biopsies 33.2% 15.2% 51.6% 100.0%
% within years 36.4% 13.8% 58.3% 34.5%
Total
N 198 239 192 629
% within biopsies 31.5% 38.0% 30.5% 100.0%
% within years 100.0% 100.0% 100.0% 100.0%
Table 4 shows the total number of biopsies that are performed in the analyzed period.
Biopsies
Total
CoOaG Other
PHD
CIN I
N 161 122 283
% 56.9 43.1 100.0
CIN II
N 98 67 165
% 59.4 40.61 100.0
CIN III
N 137 15 152
% 90.1 9.87 100.0
Total
N 396 204 600
% 66,00 34.00 100.0
CoOaG=Clinic of Obstetrics and Gynecology
Table 5. Histopathological diagnosis after a biopsy of the cervix
Correlation of Cervical Smear and Pathohistological Findings
109Med Arh. 2014 Apr; 68(2): 106-109
Analyzing the number of the performed biopsies on the
L-SIL and H-SIL (Pap III and IV) findings, set at the Clinic
of Gynecology and Obstetrics and in other institutions on
an annual basis, we came up with the following results.
Of the total number of the performed biopsies on the
Clinic of Gynecology and Obstetrics, University of Sara-
jevo–629, cytological L-SIL and H-SIL (Pap III and IV)
finding was in 412 (65.5%) respondents who directly came
to the Clinic of Gynecology and Obstetrics, and in 217
(35.5%) of respondents cytological L-SIL and H-SIL (Pap
III) finding was set at other medical institutions. The high-
est percentage of cervical biopsy due to L-SIL and H-SIL
(Pap III and IV) findings was made ​​in the 2010, 38% (239),
and approximately the same number was made in 2009
and 2011. The highest percentage of biopsies due to L-SIL
and H-SIL (Pap III and IV) that was set in other medical
institutions was made in 2011–112 (51.6%).
On this basis we can say that there is statistically sig-
nificant difference in the frequency of cytologic findings
of L-SIL and H-SIL (Pap III and IV), set at the Clinic of
Gynecology and Obstetrics and other institutions by the
cytologist. The highest percentage of women who under-
went cervical biopsy had CIN I findings (n=283), followed
by CIN II (n=165), CIN III (n=152). Histopathologic find-
ings of CIN II and CIN III were the most common in 2010.
In relation to the total number of the performed biopsies
there was a statistically significant difference in the inci-
dence of histopathological diagnosis. The most common
finding CIN I, and the difference between CIN II and CIN
III diagnosis was in a small percentage.
In a study conducted by Kirschner et al. is stated that
from the 290 analyzed cervical biopsies diagnosed with
intraepithelial cervical neoplasia, 276 of them were HPV
positive. HPV16 and HPV18 were found in about 75% of
cervical intraepithelial lesions of high-grade in population
of Denmark, and these two genotypes are considered as
causes of at least 61.9% cases (13).
In the study “Correlation of cervical cytology and histol-
ogy” conducted by Saha et al., 2004-2005, which includ-
ed 43 patients, 22 of them with benign lesions, 8 LSIL, 9
HSIL and 1 ASCUS, came to the conclusion that the Pap
test is in a statistically significant correlation with biopsy
results (14). In the course of our research, analyzing the
relationship between histopathologic diagnoses after cer-
vical biopsy in relation to the place of setting the diagno-
sis, we reached the following results.
Of the total number of patients with CIN I (n=283) at
the Clinic of Gynecology and Obstetrics was diagnosed in
56.9%, and with a diagnosis of CIN I diagnosed in other
institutions was 43.1%. With CIN II at the Clinic of Gyne-
cology and Obstetrics was 59.4%, and from other institu-
tions 40.6%. While the total number of women with CIN
III (n=152) at the Clinic of Gynecology and Obstetrics
was 90.1%, and women who were diagnosed at other clin-
ics was 9.9%. This results show that there is a statistically
significant difference compared to the PHD biopsy of the
cervix after L-SIL and H-SIL (Pap III and IV) cytologic
findings, and that the largest statistical difference is in
case CIN III changes in relation to the cytological find-
ings, issued on the Clinic of Gynecology and Obstetrics
and other medical institutions.
6.	CONCLUSION
In this study, which was conducted at the Clinic of
Gynecology and Obstetrics, Clinical Center of Sarajevo
University from January 1, 2009 to December 31, 2012,
were included a total of 2328 patients. We came to the fol-
lowing conclusions: The total number of L-SIL and H-SIL
(Pap III) findings amounted to 395 (6.20%) compared to
other cytological findings–5894 (92.44%). The frequen-
cy of H-SIL (Pap IV) was not statistically different in the
observed period. The highest percentage of women who
underwent cervical biopsy had CIN I findings (n=283).
Histopathologic findings of CIN II and CIN III were the
most common in 2010. There is a statistically significant
difference compared to the PHD biopsy of the cervix after
L-SIL and H-SIL (Pap III and IV) cytologic findings, and
that the largest statistical difference in CIN III changes is
in relation to the cytological findings, issued at the Clinic
of Gynecology and Obstetrics and other health care in-
stitutions. The highest percentage of patients with L-SIL
and H-SIL (Pap III and IV) findings was in the age group
under 29 years. The percentage and frequency of L-SIL
and H-SIL findings in women of older age groups linearly
decreases and is lowest in the age group of 60-69 years.
CONFLICT OF INTEREST: NONE DECLARED
REFERENCES
1.	 Radović M, Veljković M, Pop-Trajković Z, Kristić M, Jančić S, Katić
V. Uloga citopatologije u ranoj dijagnostici cervikalnog karcinoma;
Acta Medica Medianae. 2002; 5: 77-89.
2.	 Audy-Jurković S. Ginekološka citologija. U: Vladimir Šimunić i
saradnici. Ginekologija. Zagreb. Naklada Ljevak, 2001; 151-158.
3.	 Audy-Jurković S i sar. Ginekološka citologija - vrat maternice. Gay-
naecol Perinatol. 2003; 12: 1-9.
4.	 Kumar V, Cotran RS, Robbins SL. Osnove patologije. W.B. Saun-
ders Company, 1989: 158-164.
5.	 Spitzer M. Cervical screening adjunts: recent advances. Am J Ob-
stet Gynecol. 1998; 179: 544-556.
6.	 Nuovo J, Melinkow J, Howell LP. New tests for cervical cancer
screening. Am Fam Physician. 2001; 64: 780-786.
7.	 Niccolai LM, Julian PJ, Bilinski A, Mehta NR, Meek JI, Zelterman
D, Hadler JL, Sosa L.Geographic Poverty and Racial/Ethnic Dis-
parities in Cervical Cancer Precursor Rates in Connecticut. 2008-
2009. Am J Public Health, 2012.
8.	 Anttila A. Pukkala E. Effect of organised screening on cervical
cancer incidence and mortality in Finland, 1963-1995 :recent in-
crease in cervical cancer incidence. Int J Cancer. 1999; 83: 59-65.
9.	 Hakama M. Screening for cervical cancer: experience from the
Nordic countries. U: Franco E, Monsonego J, eds. New develop-
ments in cervical cancer screening and prevention. Oxford: Black-
well Science. 1997; 190-199.
10.	 Bal MS, Goyal R, Suri AK, Mohi MK. Detection of abnormal cer-
vical cytology in Papanicolaou smeras. J Cytol. 2012; 29(1): 45-47.
11.	 Brotherton JM,Tabrizi SN,Garland SM. Does HPV type 16 or 18
prevalence in cervical intraepithelial neoplasia grade 3 lesions vary
by age? An important issue for postvaccination surveillance. Fu-
ture Microbiol. 2012; 7(2):193-199.
12.	 Fatušić Z, Musić A, Sinanović N. Gynecologic malignancy in Tu-
zla Canton. Academy of Science and Arts of Bosina and Herze-
govina, Department of Medical Science, Special Publication, Vol
CXXV, 2007: 6-19.
13.	 Kirschner B,Schledermann D,Holl K,Rosenlund M,Raillard
A,Quint W,Molijn A,Jenkins D,Junge J. HPV-genotypes in high-
grade intraepithelial cervical lesions in Danish women. Acta Ob-
stet Gynecol Scan. 2013; 10.1111/12162.
14.	 Saha R,Thapa M. Correlation of cervicalcytology with cervical his-
tology. Kathmandu Univ Med J. 2005; 3(3): 222-224.

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Coorelacion boznia

  • 1. Correlation of Cervical Smear and Pathohistological Findings 106 Med Arh. 2014 Apr; 68(2): 106-109 Correlation of Cervical Smear and Pathohistological Findings Amir Asotic1 , Suada Taric2 , Jasmina Asotic3 Clinic of Obstetrics and Gynecology, Clinical Center of Sarajevo University, Sarajevo, Bosnia and Herzegovina1 Health center Sarajevo, Sarajevo, Bosnia and Herzegovina2 Cantonal hospital Travnik, Travnik, Bosnia and Herzegovina3 Corresponding author: Amir Asotić, MD, MSc, Clinic of Gynecology and Obstetrics, Clinical Center of Sarajevo University, Jezero, 71000 Sarajevo. Bosnia and Herzegovina, Tel:061/228/550. E-mail: amir.asotic@hotmail.com ABSTRACT Introduction: In endeavor to suppress the cervical carcinoma there are several possible approaches including measures of primary and secondary prevention. So far effects of these measures on the number of cases and mortality rate of cervical carcinoma were modest. Only exception is organized testing based on cytological exam of the cervical smear – Pap test, which has proven to be highly effective in reduc- ing the number of cases and mortality of cervical carcinoma in countries with this program. Goal of this research is analysis of correlation between abnormal cytological test results and pathohistological diagnosis of all patients in the analyzed period. Material and methods: Research is descriptive, analytical, comparative, and partly epidemiological. Results of cytological and pathohistological diagnostic in the period between January 1, 2009 and December 31, 2011 were used for analysis. All analyzed patients had colposcopy exam and Pap test, and patients with abnormal results of this test underwent cervical biopsy for pathohistological diagnostics. Results: We came to follow- ing results and conclusions: total number of L-SIL and H-SIL (PAPA III) results was 395 (6.20%) in comparison to total sample of 5894 (92.44%) patients. There is a statistically significant difference in relation to PHD result of cervical biopsy after L-SIL and H-SIL (PAPA II and IV), and highest statistical margin is in relation of CIN II changes to cytological findings, issued at Clinic of Obstetrics and Gynecol- ogy and other health institutions. We come to conclusion that the highest percentage of patients with L-SIL and H-SIL findings is in age group between 0-29 years old. Statistical analysis has shown a positive trend in number of younger patients with L-SIL and H-SIL (PAPA III and IV), with average age of patients in 2011 being 31.12±9.12 years old. Key words: Pap test, biopsy. 1. INTRODUCTION Cytological methods are applied starting from the mid- 19th century, when the researchers found abnormal cells in body fluids such as urine, sputum, exudates and gastric fluid. Papanicolaou (1928) in New York announced the era of modern diagnostic cytology, when he published an arti- cle titled “A new diagnosis of cancer”. Despite skepticism at the beginning of cytopathological era, the use of this method that is popularly known as “Pap” test is accepted as the most appropriate screening test for early detection of cancer and precancerous states of uterine cancer (1). Exfoliative cytology analyzes spontaneously exfoliat- ed cells from the skin, mucous and serous membranes. Cytodiagnostics of the vaginal-cervical-endocervical (VCE) smear by volume is the largest in exfoliative cytol- ogy, since it covers both the healthy and sick women. The smears include epithelial and non epithelial cells (2,3). In the universal effort for combating cervical cancer are available several possible approaches, including measures of primary and secondary prevention. So far, most of the effects of these measures on the incidence and mortality of cervical cancer were modest. The only exception seems to represents organized screening based on the use of cytological examinations of the cervix (Pap test), which proved to be highly effective in reducing the incidence and mortality of cervical cancer in countries where it is implemented. Reduction of mortality caused by cervical cancer in the United States and other developed countries is significant, and this is due to the successful early di- agnosis. Squamous intraepithelial lesions are detected in adolescents, young adults and adults. The peak incidence is at the age of about 30 years. Similarly, invasive carcino- ma occurs earlier, in the third decade of life with a peak frequency at about 40 years, or 10-15 years later (4). Cytodiagnostics of conventional cervicovaginal smears or “Pap test” for half of a century is the basic method of secondary prevention of cervical cancer, which is applied at the same time as a classic test of choice for the detec- tion of lesions and a differential-diagnostic method for predicting the histological diagnosis (5). In an effort to reduce potential errors and increase the overall sensitivity of the screening, during the past years has developed sev- eral new techniques that have been proposed as a comple- mentary method to conventional “Pap test”. These include HPV DNA typization (6). There is an assumption that ORIGINAL ARTICLE doi: 10.5455/medarh.2014.68.106-109 Med Arh. 2014 Apr; 68(2): 106-109 Received: November 21th 2013 | Accepted: March 25th 2014 © AVICENA 2014 Published online: 22/04/2014 Published print: 04/2014
  • 2. Correlation of Cervical Smear and Pathohistological Findings 107Med Arh. 2014 Apr; 68(2): 106-109 during the last 25-30 years has increased the frequency of diagnosis of carcinoma in situ, and in part because of the efficiency of cytologic examination (7). In the history of medicine, the only case of reduced in- cidence and mortality, as well as human malignancies is cervical cancers without medical intervention (8). 2. GOAL The aim of the research is to analyze the correlation be- tween the abnormal cytological findings and histological diagnosis in all patients during the observed period. 3. MATERIAL AND METHODS The study was descriptive-analytical, comparative, partly epidemiological, and mainly clinical applicative. The study involved all patients who meet the criteria for inclusion in the study. Used are the results of cytological and histological diagnosis in the period from January 1, 2009 to December 31, 2011. In all subjects had previously done colposcopic exam- ination and Pap test, and in patients with abnormal find- ings was also performed cervical biopsy for obtaining his- topathological diagnosis. Colposcopy was performed using the Olympus colpo- scope. The Pap test is taken from the front and rear lip and cervical canal. From the sample taken is made ​​the cy- tological smear, which is fixed on a microscopic slide and stained by the method of Pap-Nikolai. After staining was performed microscopic analysis of morphological char- acteristics of the cells in the course of which are detected signs of cervical inflammation, causes infection, benign and malignant cells and other pathological changes. After the punch biopsy changes in the cervix, the sam- ples were forwarded to the Department of Pathology at the further processing. For statistical analysis of the data obtained was used software package SPSS for Windows. In the analysis of the results obtained, the following statistical methods were used: for continuous variables in the study as the first analysis of symmetry (normality) of their distribution by Kolmogornov-Smirnov and Shapiro-Wilk test. Since the distribution of continuous variables significantly deviated from normal (Gaussian) distribution, mean values ​​and a measure of dispersion, for their comparison is used the median and interquartile range and nonparametric test (ANOVA), normal and ordinal variables in the study were analyzed by χ2 test and in the lack of expected frequencies used Fisher’s exact test. The statistical analysis used the Pearson χ2 test for difference distribution of nominal and ordinal data. 4. RESULTS Table 1 shows the frequency of dysplasia (L-Sil and H-SIL) in relation to the normal cytological findings. Mann-Whitney test showed a statistically significant difference in the frequency of L-SIL and H-SIL (Pap III) findings in relation to the period covered by this study. In 2010 was recorded the highest percentage compared to the total number of L-SIL and H-SIL (Pap III) findings, Z=-4.913, p=0.004. Distribution of respondents by age group is displayed on Tables 2 and 3. Analysis of respondents by age groups compared to the period covered by this study has been determined that the highest percentage of patients was with L-SIL and H-SIL (Pap III and IV) findings for the age group under 29 years. The percentage and frequency of L-SIL and H-SIL (Pap III and IV) findings in women of older age groups linearly decreases and the lowest is in the age group 60-69 years. ANOVA test showed that there was no statistically sig- nificant difference in the average age of patients with L-SIL and H-SIL (Pap III and IV) findings in relation to the test- ed year, F=3.86, p=0,21. Statistical analysis showed a pos- itive trend in terms that younger respondents have L-SIL and H-SIL (Pap III and IV) cytological findings, so that the average age of respondents in 2011 was 31.12±9.12 years. 2009 2010 2011 Total N % N % N % N % L-SIL; (PAP III) 101 4.34 186 9.50 135 6.46 395 6.20 H-SIL (PAP IV) 25 1.07 20 1.02 15 0.72 27 0.42 Normal cytological findings 2202 94.59 1752 89.48 1940 92.82 5894 92.44 Total 2328 100.00 1958 100.00 2090 100.00 6376 100.00 Table 1. The frequency of the L-SIL and H-SIL (Pap III and Pap IV) findings in relation to other cytological findings (Pap test) Age groups 2009 2010 2011 Total N % N % N % N % ≤29 89 45.88 129 55.13 104 51.74 322 51.19 30-59 96 49.48 99 42.31 92 45.77 287 45.63 ≥60 9 4.64 6 2.56 5 2.49 20 3.18 Total 194 100.00 234 100.00 201 100.00 629 100.00 Table 2. The age groups of patients with L-SIL and H-SIL (Pap III and IV) cytological findings Mean SD SEM 95% Confidence Interval for Mean Min Max. Lower Bound Upper Bound 2009 33.85 10.46 0.74 32.39 35.32 19.00 69.00 2010 33.14 10.51 0.68 31.80 34.48 19.00 68.00 2011 31.12 9.12 0.65 29.82 32.42 19.00 66.00 Total 32.75 10.14 0.40 31.95 33.54 19.00 69.00 Table 3. The average age of patients with L-SIL and H-SIL (Pap III and IV) cytological findings in relation to the period covered by the survey
  • 3. Correlation of Cervical Smear and Pathohistological Findings 108 Med Arh. 2014 Apr; 68(2): 106-109 Table 4. Number of the performed biopsies in case of L-SIL and H-SIL (Pap III and IV) findings, performed at the Clinic of Obstetrics and Gynecology and in other in- stitutions, on annual basis. Pearson Chi square test showed a statistically signifi- cant difference in the incidence of cytologic findings of L-SIL and H-SIL (Pap III and IV), set by the cytologist at the Clinic of Obstetrics and Gynecology and other insti- tutions, χ2 =93.85, p=0.000. The highest percentage of women who underwent cer- vical biopsy had CIN I findings (n=283), followed by CIN II (n=165), CIN III (n=152). Histopathologic findings of CIN II and CIN III were the most frequent in 2010. Pearson Chi square test showed a statistically significant difference in the prevalence of histopathological diagnosis in relation to the total number of the performed biopsies. The most common finding was CIN I, while there is a small percentage difference in the incidence of CIN II and CIN III diagnosis, χ2 =15.68, p=0.016. 5. DISCUSSION The incidence of cervical cancer is unacceptably high. It is believed that about 80% of all cases occur in less devel- oped countries, because prevention programs are either non-existent or poorly implemented. There is a general opinion that organized national screening programs using Pap test produce the best re- sults. This is best illustrated by data from Finland, where organized screening results were exceptional, reducing the incidence from 14.8/100,000 in 1963 to 2.8/100,000 in 1992, reducing the total incidence by 69.6% (9). Due to the simplicity of implementation, VCE smear cytology is considered to be the best technique for screen- ing. It is important to note that on the basis of cytology is not made a definitive diagnosis, it is always necessary to respect the protocol. Results may be false positive and false negative in range from 10 to 35%. A particular prob- lem is definitely false negative results (10). The course of this research led to the following results. The highest percentage of L-SIL and H-SIL (Pap III) findings was during 2010 and it was (186) 9.5%, and the lowest in 2009, where there was (101) 4.34%. In this peri- od, the total number of L-SIL and H-SIL (Pap III) findings amounted to 395 (6.20%) compared to other cytological findings–5894 (92.44%). Analysis of respondents by age group compared to the years covered by this study has been determined that the highest percentage of patients with L-SIL and H-SIL (Pap III and IV) findings was in the age group under 29 years. The percentage and frequency of L-SIL and H-SIL (Pap III and IV) findings in women of older age groups linearly decreases and is lowest in the age group from 60-69 years. Brotherton JM. and associates (11), in their study, “Does HPV type 16 or 18 in the prevalence of cervical intraepi- thelial neoplasia grade 3 lesions vary by age? An import- ant issue for postvaccination surveillance”, stated that among the 317 women who were enrolled in the study, with diagnosis CIN III, 70% of them aged 16-25 years, was detected HPV, 16.59% in women age aged 26-35 years and 48% in women older than 36 years. The study “Gynecologic malignancy in Tuzla Canton” by Fatusic and colleagues report that in the period from 1993-2006, 27.11% of all women with cervical cancer is younger than 30 years (12). This situation can be attributed to insufficient informa- tion, the motivation of young women for regular gyne- cological examinations, as well as the absence of national screening program. According to the literature, the very frequency of cervi- cal dysplasia and occurrence of HPV declines in percent- age with age, so our results do not differ statistically from the research of other authors. ANOVA test showed that there was no statistically significant difference in the average age of patients with L-SIL and H-SIL (Pap III and IV) findings in relation to the tested years. Statistical analysis showed a positive trend that younger respondents have L-SIL and H-SIL (Pap III and IV) cyto- logical findings, so that the average age of respondents in 2011 is 31.12±9.12 years. Year Total 2009 2010 2011Biopsies Clinic of Obstetrics and Gynecology N 126 206 80 412 % within biopsies 30.6% 50.0% 19.4% 100.0% % within years 63.6% 86.2% 41.7% 65.5% Other N 72 33 112 217 % within biopsies 33.2% 15.2% 51.6% 100.0% % within years 36.4% 13.8% 58.3% 34.5% Total N 198 239 192 629 % within biopsies 31.5% 38.0% 30.5% 100.0% % within years 100.0% 100.0% 100.0% 100.0% Table 4 shows the total number of biopsies that are performed in the analyzed period. Biopsies Total CoOaG Other PHD CIN I N 161 122 283 % 56.9 43.1 100.0 CIN II N 98 67 165 % 59.4 40.61 100.0 CIN III N 137 15 152 % 90.1 9.87 100.0 Total N 396 204 600 % 66,00 34.00 100.0 CoOaG=Clinic of Obstetrics and Gynecology Table 5. Histopathological diagnosis after a biopsy of the cervix
  • 4. Correlation of Cervical Smear and Pathohistological Findings 109Med Arh. 2014 Apr; 68(2): 106-109 Analyzing the number of the performed biopsies on the L-SIL and H-SIL (Pap III and IV) findings, set at the Clinic of Gynecology and Obstetrics and in other institutions on an annual basis, we came up with the following results. Of the total number of the performed biopsies on the Clinic of Gynecology and Obstetrics, University of Sara- jevo–629, cytological L-SIL and H-SIL (Pap III and IV) finding was in 412 (65.5%) respondents who directly came to the Clinic of Gynecology and Obstetrics, and in 217 (35.5%) of respondents cytological L-SIL and H-SIL (Pap III) finding was set at other medical institutions. The high- est percentage of cervical biopsy due to L-SIL and H-SIL (Pap III and IV) findings was made ​​in the 2010, 38% (239), and approximately the same number was made in 2009 and 2011. The highest percentage of biopsies due to L-SIL and H-SIL (Pap III and IV) that was set in other medical institutions was made in 2011–112 (51.6%). On this basis we can say that there is statistically sig- nificant difference in the frequency of cytologic findings of L-SIL and H-SIL (Pap III and IV), set at the Clinic of Gynecology and Obstetrics and other institutions by the cytologist. The highest percentage of women who under- went cervical biopsy had CIN I findings (n=283), followed by CIN II (n=165), CIN III (n=152). Histopathologic find- ings of CIN II and CIN III were the most common in 2010. In relation to the total number of the performed biopsies there was a statistically significant difference in the inci- dence of histopathological diagnosis. The most common finding CIN I, and the difference between CIN II and CIN III diagnosis was in a small percentage. In a study conducted by Kirschner et al. is stated that from the 290 analyzed cervical biopsies diagnosed with intraepithelial cervical neoplasia, 276 of them were HPV positive. HPV16 and HPV18 were found in about 75% of cervical intraepithelial lesions of high-grade in population of Denmark, and these two genotypes are considered as causes of at least 61.9% cases (13). In the study “Correlation of cervical cytology and histol- ogy” conducted by Saha et al., 2004-2005, which includ- ed 43 patients, 22 of them with benign lesions, 8 LSIL, 9 HSIL and 1 ASCUS, came to the conclusion that the Pap test is in a statistically significant correlation with biopsy results (14). In the course of our research, analyzing the relationship between histopathologic diagnoses after cer- vical biopsy in relation to the place of setting the diagno- sis, we reached the following results. Of the total number of patients with CIN I (n=283) at the Clinic of Gynecology and Obstetrics was diagnosed in 56.9%, and with a diagnosis of CIN I diagnosed in other institutions was 43.1%. With CIN II at the Clinic of Gyne- cology and Obstetrics was 59.4%, and from other institu- tions 40.6%. While the total number of women with CIN III (n=152) at the Clinic of Gynecology and Obstetrics was 90.1%, and women who were diagnosed at other clin- ics was 9.9%. This results show that there is a statistically significant difference compared to the PHD biopsy of the cervix after L-SIL and H-SIL (Pap III and IV) cytologic findings, and that the largest statistical difference is in case CIN III changes in relation to the cytological find- ings, issued on the Clinic of Gynecology and Obstetrics and other medical institutions. 6. CONCLUSION In this study, which was conducted at the Clinic of Gynecology and Obstetrics, Clinical Center of Sarajevo University from January 1, 2009 to December 31, 2012, were included a total of 2328 patients. We came to the fol- lowing conclusions: The total number of L-SIL and H-SIL (Pap III) findings amounted to 395 (6.20%) compared to other cytological findings–5894 (92.44%). The frequen- cy of H-SIL (Pap IV) was not statistically different in the observed period. The highest percentage of women who underwent cervical biopsy had CIN I findings (n=283). Histopathologic findings of CIN II and CIN III were the most common in 2010. There is a statistically significant difference compared to the PHD biopsy of the cervix after L-SIL and H-SIL (Pap III and IV) cytologic findings, and that the largest statistical difference in CIN III changes is in relation to the cytological findings, issued at the Clinic of Gynecology and Obstetrics and other health care in- stitutions. The highest percentage of patients with L-SIL and H-SIL (Pap III and IV) findings was in the age group under 29 years. The percentage and frequency of L-SIL and H-SIL findings in women of older age groups linearly decreases and is lowest in the age group of 60-69 years. CONFLICT OF INTEREST: NONE DECLARED REFERENCES 1. Radović M, Veljković M, Pop-Trajković Z, Kristić M, Jančić S, Katić V. Uloga citopatologije u ranoj dijagnostici cervikalnog karcinoma; Acta Medica Medianae. 2002; 5: 77-89. 2. Audy-Jurković S. Ginekološka citologija. U: Vladimir Šimunić i saradnici. Ginekologija. Zagreb. Naklada Ljevak, 2001; 151-158. 3. Audy-Jurković S i sar. Ginekološka citologija - vrat maternice. Gay- naecol Perinatol. 2003; 12: 1-9. 4. Kumar V, Cotran RS, Robbins SL. Osnove patologije. W.B. Saun- ders Company, 1989: 158-164. 5. Spitzer M. Cervical screening adjunts: recent advances. Am J Ob- stet Gynecol. 1998; 179: 544-556. 6. Nuovo J, Melinkow J, Howell LP. 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