Cytomorphological
patterns of cervical Papanicolaou smear abnormalities based on 2014 Bethesda
System in North Karnataka region
Zubair A.A.1, Kulkarni S.2, M. Preethi3
1Dr. Ashraf A. Zubair, 2Dr. Shruti Kulkarni, both authors are
Assistant Professor, Department of Pathology, Navodaya Medical College,
Raichur, 3Dr. M. Preethi, Post Graduate, Department of Pathology,
Navodaya Medical College, Raichur, Karnataka, India.
Corresponding Author: Dr. Shruti Kulkarni, Assistant Professor, Department of Pathology,
Navodaya Medical College, Raichur, E-mail: shrutikulkarni1988@gmail.com
Abstract
Introduction:
Cervical PAP smears are a cost effective, out-patient procedure to screen
patients for cervical pathology. Objectives:
To utilize cervical PAP smear examination in categorizing lesions according to the
2014 Bethesda System for cervical cytology, to analyse the spectrum of lesions
andto evaluate its effectiveness as a screening procedure for detection of
epithelial abnormalities in a teaching hospital in North Karnataka. Methods: A prospective one year study
was carried on all conventional PAP smears received in the Department of
Pathology, Navodaya Medical College, Raichur. Reporting was done in accordance
with the 2014 Bethesda System for reporting cervical cytology. Correlation was
done with the clinical findings. Results:
A total of 578 cases were included in the study. The most common presenting
complaint was abdominal pain (28.5%). The most frequent examination finding was
white discharge per vaginum, WDPV (38.9%). 90.8% of PAP smears were categorized
as ‘Negative for intraepithelial Lesion or Malignancy’. Specific infections
were seen in 8.1%, squamous metaplasia in 15.5% and atrophic changes in 3.2%.
Epithelial cell abnormalities comprised 9.2% of cases, of which Atypical
Squamous Cells of Undetermined Significance (ASC-US) was 3.2%, Low grade
Squamous Intraepithelial Lesion (LSIL) was 3.6%, High grade Squamous
Intraepithelial Lesion (HSIL) was 1.9%, Squamous Cell Carcinoma (SCC) was 0.2%
and Atypical Glandular Cells– Not Otherwise Specified (AGC-NOS) was 0.9%. Conclusion: The overall prevalence of
epithelial cell abnormalities concurred with studies done in other parts of
India and constituted9.2% of the total smears screened, LSIL being the most
common lesion.
Keywords: PAP
smear, Screening, Bethesda, Epithelial abnormalities
Author Corrected: 2nd May 2019 Accepted for Publication: 7th May 2019
Introduction
Cancer of the cervix is an increasing
health problem and an important cause of mortality in women worldwide.
According to the World Cancer statistics, >80% of all the cervical cancer
cases are found in developing and low-resource countries, because
of a lack of awareness and difficulty in running cytology-based screening programs. Almost nine in ten (87%) cervical
cancer deaths occur in less developed regions [1]. Cervical cancer is the
fourth most frequent cancer in women with an estimated 570,000 new cases in
2018 representing 6.6% of all female cancers. About 96,922 new
cervical cancer cases are diagnosed annually in India and
ranks as the 2nd leading cause of
female cancer in India [2]. In
India, the peak age for cervical cancer incidence is 55–59 years [3]. Human
Papilloma Virus (HPV) infection prevalence is 87.8%–96.67% among women with
cervical cancer and 9.9% – 36.8% among women with no cancer or other gynaecological
morbidities [3]. Fifty percent of women
diagnosed with cervical cancer have never undergone cervical cytology testing
and another 10% have not received screening in the five years preceding their
diagnosis [4].
In India, unhealthy cervix is a common
finding on per speculum examination in gynaecology Out Patient Department (OPD)
and it is recommended to do the cervical cytology to detect any epithelial cell
abnormality [4]. Early detection and appropriate treatment are possible if
robust screening is implemented [5]. There has been a significant reduction in
mortality from cervical cancer in developed countries, due to widespread
screening programs. The pre-invasive stage of cervical cancer lasts for a long
period, and only a small proportion of cervical intraepithelial neoplasia (CIN)
progresses to an invasive lesion [6]. The appropriate management of CIN can
prevent invasive cervical cancer [7]. The risk of developing cervical cancer
has been associated with a number of socio-epidemiological factors such as age,
parity, religion, socioeconomic status, educational level, and sexual
behaviours [8].
Cervical cytology by Papanicolaousmears forms
a simple and effective means of screening for pre-malignant lesions of the
cervix and also to identify reactive conditions and infections. Due to easy
availability, cost effectiveness and reliability, cervical smears became a
valuable tool in screening and diagnosing various pathologies of the cervix
even at peripheral level in rural places [9].
In this study, an attempt is made to analyse
the various findings in conventional PAP smears, categorizing them in
accordance with the 2014 Bethesda Systemfor cervical cytology and correlating
them with clinical details and biopsy findings, wherever available, for
evaluating the efficacy of PAP smears as a screening procedure for neoplastic,
pre-neoplastic and non-neoplastic lesions of cervix.
Materials and Methods
Setting and type of study: A prospective study was carried out over a period of one year (2018) on
all the PAP smears received in the Department of Pathology, NavodayaMedical
College, Raichur. The patient details were obtained from the requisition forms,
case sheets, out-patient slips and enquiry with the patient wherever necessary.
Sampling Methods: Sampling
was done using cytobrush for endocervical component and Ayre’s spatula and both
samples were smeared onto two separate slides and fixed by using a spray
fixative. Each case had a minimum of two slides which were then stained by
using modified PAP stain and examined by the pathologist.
Inclusion Criteria: All
PAP smears which were satisfactory for evaluation based on the 2014 Bethesda
System for cervical cytology were included in the study.
Exclusion Criteria: Patients
who had undergone previous surgical procedures on the cervix, repeat PAP smears
and those which were taken from the vaginal vault were excluded.
Ethical Considerations and permissions: Ethical clearance was obtained from the
institutional ethical committee.
Reporting format: Reporting
was done in accordance with The 2014 Bethesda System for reporting cervical
cytology [10,11]. The findings were correlated with clinical details and
histopathological findings, wherever available, in cases of suspected
epithelial abnormalities.
Results
A total of 578 patients had samples of PAP
smear taken due to various complaints in the calendar year 2018. The age ranged
from 18 to 85 years (Mean = 38.9 years). Majority of the women belonged to age
group between 31-40 years of age. (Figure 1) The mean age for non-neoplastic
lesions was 38 years while that for suspected neoplastic lesions (ASCUS and
beyond) was 49.8 years. The most common presenting complaint was abdominal pain
(28.5%) followed by white discharge per vaginum (WDPV) and abnormal uterine
bleeding (AUB). (Table 1) Eighteen patients were asymptomatic and came for
routine screening PAP smears. Other rare symptoms included low back pain,
itching in perineum, swelling in perineum etc.
Figure-1:
Bar graph representing the age distribution of patients (n=578)
Greater proportion of the patients had
examination findings of WDPV on per vaginal and per speculum examination
comprising 39.8% either as the sole finding or along with others as elaborated
in Table 2, Table 3 and Table 4. Cervical erosions were the most common finding
associated with WDPV (7.6% of total cases).A normal gynaecological examination
was observed in 22.1% of the patients. Other significant findings included UV
prolapsed (10%), bulky uterus (8%), cervical hypertrophy (6.1%) and cervical
erosions (5.5%). Bleeding on touch was a solitary finding in 10 patients and
associated with WDPV in 9 patients. Other less common clinical findings
included cervical pigmentation, cervical stenosis, cervical erythema etc. The
clinical examination findings were not available in 8 cases.
Out of the 578 patients, 555 (96.03%) had PAP
smears which were satisfactory for evaluation. The remaining 23 cases (3.97%)
were unsatisfactory for evaluation due to various reasons as mentioned in Table
5. A minimum of approximately 8,000–12,000 well-preserved and well-visualized
squamous epithelial cells were considered to categorize the conventional PAP
smear as satisfactory for evaluation. Any specimen with abnormal cells [atypical
squamous cells of undetermined significance (ASC-US), atypical glandular cells
(AGC) etc.] was by definition satisfactory for evaluation [10].
Table-1:
Symptoms of women who had cervical PAP smears taken.
Symptoms |
Number (n=578) |
Percentage |
Pain
Abdomen |
165 |
28.5 |
White
discharge per vaginum |
134 |
23.2 |
Abnormal
Uterine Bleeding |
130 |
22.5 |
Mass
per vaginum |
75 |
13.0 |
Urinary
complaints |
24 |
4.2 |
Asymptomatic
(screening) |
18 |
3.1 |
Mass
per abdomen |
12 |
2.1 |
Others |
12 |
2.1 |
Amenorrhoea |
6 |
1.0 |
Post-coital
bleeding |
2 |
0.3 |
Total |
578 |
100 |
Table-2:
Examination findings (per vaginum and per speculum) in patients from whom PAP
smears were taken.
Examination Findings |
Number (n=578) |
Percentage |
WDPV |
147 |
25.4 |
Normal |
128 |
22.1 |
WDPV
+ Associated findings |
83 |
14.3 |
Utero-Vaginal
(UV) Prolapse |
58 |
10.0 |
Bulky
uterus |
46 |
8.0 |
Cervical
hypertrophy |
35 |
6.1 |
Cervical
erosion |
32 |
5.5 |
Others |
11 |
1.9 |
Bleeding
on touch |
10 |
1.7 |
Cervical
polyp |
8 |
1.4 |
Not
available |
8 |
1.4 |
Bleeding
through os |
6 |
1.1 |
Atrophic
cervix |
5 |
0.9 |
Cervical
growth |
1 |
0.2 |
Table-3:
Distribution of cases with isolated finding of WDPV on examination
WDPV |
Number (n=147) |
Percentage |
Serous |
122 |
83 |
Curdy
white |
13 |
8.8 |
Foul
smelling |
8 |
5.4 |
Mucoid |
2 |
1.4 |
Thick |
2 |
1.4 |
Table-4:
Distribution of cases with other findings associated with WDPV on examination
Associated Complaints |
Number (n=83) |
Percentage |
WDPV
+ Cervical erosions |
44 |
53 |
WDPV
+ Bulky uterus |
12 |
14.5 |
WDPV
+ Bleeding on touch |
9 |
10.8 |
WDPV
+ UV Prolapse |
7 |
8.5 |
WDPV
+ Cervical Hypertrophy |
6 |
7.2 |
WDPV
+ Polyp |
3 |
3.6 |
WDPV
+ Labial swelling |
2 |
2.4 |
Table-5:
PAP smear sample adequacy
|
Cases (n=578) |
Percentage |
Satisfactory
for evaluation |
555 |
96.03 |
Unsatisfactory |
23 |
3.97 |
· Low cellularity |
15
(23) |
|
· Obscuration by blood |
06
(23) |
|
· Obscuration by fibrous strands |
01
(23) |
|
· Broken slides |
01
(23) |
|
Out of the 555 PAP smears which were found to
be satisfactory, 504 were reported as “Negative for intra-epithelial lesion or
malignancy” (ie. Non-neoplastic) and 51 were reported as having epithelial cell
abnormality. (Table 6) PAP smears reported as inflammatory smears were 304 and
this was the most common non-neoplastic finding. Among the non-neoplastic
cellular variations, squamous metaplasia was the most often encountered finding
comprising 15.5% of the PAP smears followed by reactive cellular atypia
associated withinflammation and repair (7.9%) and atrophic changes (3.2%).
Among the infectious conditions, 16 cases each of Bacterial Vaginosis and
Candidiasis were reported (2.9% each). Trichomonas infection was seen in 13
cases (2.3%). No cases of actinomycosis or viral infection (Herpes Simplex Virus
or Cytomegalovirus) were noted in our study. Incidental endometrial cells were
seen in a single case of 40 year female presenting with abnormal uterine
bleeding (AUB).
Table-6:
PAP smear findings – NILM vs Epithelial Cell Abnormaltiy
PAP smear report |
Number (n=555) |
Percentage |
NILM |
504 |
90.8 |
Inflammatory |
307 |
55.3 |
Bacterial
Vaginosis |
16 |
2.9 |
Candidiasis |
16 |
2.9 |
Trichomonas
Vaginitis |
13 |
2.3 |
Squamous
metaplasia |
86 |
15.5 |
Atrophy |
18 |
3.2 |
Keratotic
changes |
2 |
0.4 |
Reactive
atypia |
44 |
7.9 |
Endometrial
cells |
1 |
0.2 |
No
other findings |
1 |
0.2 |
Epithelial Cell Abnormality |
51 |
9.2 |
Table-7:
Distribution of cases with Epithelial Cell Abnormalities
PAP Smear report |
Number (n=51) |
Percentage |
Overall percentage (n=555) |
Age range (years) |
Mean age (years) |
ASCUS |
18 |
35.3 |
3.2 |
30-68 |
43.6 |
LSIL |
20 |
39.2 |
3.6 |
31-77 |
51.5 |
HSIL |
07 |
13.7 |
1.3 |
47-70 |
56.3 |
Squamous Cell Carcinoma |
01 |
2.0 |
0.2 |
- |
50 |
Atypical Glandular cells -NOS |
05 |
9.8 |
0.9 |
38-55 |
47.6 |
Table-8:
Comparison of PAP smear findings with previous studies
Diagnosis |
Elhakeem
et al.19 2005 |
Altaf
et al.20 2012 |
Bal
et al.6 2012 |
Bukhari
et al.22 2012 |
Kulkarni
et al.16 2013 |
Verma
et al.14 2014 |
Maleki
et al.21 2015 |
Nandwani
et al.18 2016 |
Sachan
et al.13 2018 |
Present
study 2019 |
Total
cases (n) |
2100 |
7297 |
300 |
1000 |
350 |
125 |
4274 |
5813 |
1544 |
578 |
NILM |
- |
- |
91% |
- |
83.7% |
68.8% |
- |
86.9% |
48.8% |
90.8% |
Inflammatory |
- |
- |
71.3% |
- |
72.0% |
60.8% |
89.4% |
75.0% |
42.7% |
55.3% |
Organisms |
- |
- |
3% |
- |
1.7% |
4.8% |
2.4% |
6.9% |
- |
8.1% |
Squamous
metaplasia |
- |
- |
- |
- |
25.7% |
- |
4.0% |
- |
- |
15.5% |
Reactive
cellular changes |
- |
- |
- |
- |
- |
- |
0.2% |
64.5% |
- |
7.9% |
Atrophy |
- |
- |
- |
- |
1.4% |
3.2% |
- |
3.5% |
- |
3.2% |
Epithelial
Abnormality |
7.9% |
17.3% |
4.7% |
10.2% |
12.3% |
13.6% |
4.0% |
13.2% |
8.5% |
9.2% |
ASCUS |
2.7% |
9.3% |
0.3% |
0.01% |
0% |
4.8% |
1.9% |
3.6% |
2.9% |
3.2% |
ASC-H |
0.2% |
0.8% |
0% |
0% |
0% |
0% |
0.9% |
0% |
0% |
0% |
LSIL |
1.3% |
2.7% |
2.7% |
4.7% |
7.4% |
5.6% |
1% |
2.6% |
5.1% |
3.6% |
HSIL |
0.7% |
0.9% |
0.7% |
2.2% |
4.3% |
0.8% |
0.1% |
2.8% |
0.5% |
1.3% |
SCC |
0.3% |
0.06% |
1% |
1.4% |
0.6% |
0.8% |
0% |
3.5% |
0% |
0.2% |
AGC
- NOS |
2.6% |
3.2% |
0 |
0.4% |
0.9% |
0.8% |
0.1% |
0.4% |
0% |
0.9% |
Adenocarcinoma |
0% |
0% |
0.3% |
0.6% |
0% |
0.8% |
- |
0.2% |
0% |
0% |
Note: NILM– Negative for intraepithelial lesion or malignancy; ASCUS–
Atypical Squamous Cells of Undetermined Significance; ASC-H– Atypical Squamous
Cells cannot rule out HSIL; LSIL– Low grade Squamous Intraepithelial Lesion;
HSIL- High grade Squamous Intraepithelial Lesion; SCC- Squamous Cell Carcinoma;
AGC– Aypical Glandular Cells– NOS.
Figure-2:
Microscopic images of various PAP smear findings: A – Trichomonas vaginalis
trophozoites;
B– Squamous metaplasia; C - ASCUS; D – LSIL;
E – HSIL; F – SCC
Among the cases with epithelial cell
abnormalities, low-grade squamous intraepithelial lesion (LSIL) was the most
common category comprising 20 of 51 cases followed closely by ASC-US comprising
18 of 51 cases. (Table 5) There were 7 cases of High grade Squamous Intraepithelial
Lesion (HSIL) and one case of squamous cell carcinoma (SCC). Atypical glandular
cells– Not Otherwise Specified (AGC-NOS) was the diagnosis furnished in 5 of 51
cases. No cases of endocervical adenocarcinoma in situ or frank adenocarcinoma
were observed during the study period. The mean age of patients with PAP smears
reported as ASCUS was 43.6 years being at least a decade lower than those
reported as HSIL (Table 7).
Discussion
Cervical cancer is on the declining trend in
India according to the population-based registries; yet, it continues to be a
major public health problem for women in India [3]. Cervical cancer is the
third largest cause of cancer mortality in India accounting for nearly 10% of
all cancer-related deaths in the country [12] most cases of cervical cancer in
India are diagnosed at later and more serious stages which will reduce the
survival rate of women with cervical cancer. The prime reason for late stage
diagnosis of disease is a lack of awareness about screening and preventive methods
of cervical cancer. Screening would not only help to evaluate women without any
obvious presenting symptoms but detect pre-malignant lesions of the cervix when
are still amenable to curative therapy. PAP smears using standardized reporting
criteria [10,11] (Bethesda System 2014) would greatly aid in identifying
precursor lesions at an early stage and directing appropriate management.
The mean age of the women included in the
study was 38.9 years. Majority of the women belonged to age group between 31-40
years of age. The mean age of women with epithelial abnormalities detected in
their PAP smear was 49.8 years as opposed to those without epithelial
abnormalities which was 38 years. This correlates with the studies of Verma et
al. and Sachan et al [13,14].
As per the recommendations of American Cancer
Society, cervical cancer screening should begin at age 21 years. For women
21–29 years of age, screening with cytology alone every 3 years is recommended.Women
agedbetween30–65 years should be screened with cytology and HPV testing
(“cotesting”) every 5 years (preferred) or cytology alone every 3 years
(acceptable) [15].
The most frequent presenting complaints in
this study was abdominal pain (28.5%) followed by WDPV (23.2%) and AUB (22.5%).
However, the most common clinical finding on per vaginal and per speculum
examination was WDPV (43.08%) followed by normal findings in 22.1% of the
cases. This correlates well with other studies conducted previously
[4,13,14,16].
Among the smears obtained, 96.03% were found
satisfactory for evaluation and 3.97% were unsatisfactory due to various
reasons as mentioned in Table 3. This correlates with studies conducted by Bal
et al [5]. A slightly higher percentage of unsatisfactory smears was observed
in studies conducted by Vaghela el al. (4.8%), Sachan et al (6.42%) and
Nandwani et al. (5.73%). [13,17,18]. The marginally lower rate of
unsatisfactory smears could be due to better coordination between Obstetrics
& Gynaecology and cytopathology departments in our institution and
mandatory screening by the pathologist of all the PAP smears rather than by
technologists.
The distribution of various PAP smear findings
in comparison to other previous studies is displayed in Table 6.
Among the various findings, the category
“Negative for intraepithelial lesion or malignancy (NILM)” constituted the most
common with 90.8% cases. This correlates with most of the previous studies
except Sachan et al [13]. Who classified the cases separately as NILM and
inflammatory whereas the other studies included inflammatory smears as a
sub-category of NILM.
Micro-organisms encountered in PAP smears
(Trichomonas, Candida, Gardenella etc.) comprised around 8% of the smears in
the present study and this fact correlated well with the study conducted by
Nandwaniet al [18]. The incidence of micro-organisms was less in other studies
(Table 8) and this could be due to a more vigorous search for epithelial
abnormality rather than presence of micro-organisms presence of which could
easily be overlooked.
The occurrence of atrophic features in PAP
smears comprising a predominance of parabasal cells was noted in 3.2% of the
smears in the present study and this correlated well with other studies [14-18]
Squamous metaplasia was seen as an additional finding in 15.5% of the cases.
However, this finding was not adequately reported in many previous studies as
it was an optional non-neoplastic finding [10].
The occurrence of epithelial cell
abnormalities varied from 4% to 17.3% in various studies (Table 8). In the
present study, the occurrence of epithelial cell abnormality was 9.2%. The
differences may be due to different geographical areas and ethnicities as the
studies were done in different parts of India and the world. LSIL was the most
common lesion among the epithelial abnormalities in the present study
contributing to 3.6% of the cases followed by ASCUS (3.2%). This fact
correlated well with many of the Indian studies [5,13, 14, 16]. However, the
studies conducted in other countries [19-21] and some Indian studies [18]
showed greater occurrence of AS-CUS as compared to LSIL. ASC-H was not
encountered in our study and probably contributes to a very negligible
proportion (0.2-0.9%) of cases as observed in previous studies [19-21] with a larger
sample size.
The mean age for non-neoplastic lesions was
38 years while that for epithelial cell abnormality (ASCUS and beyond) was 49.8
years. This correlates well with study conducted by Sachen et al [13] where the
mean age for epithelial cell abnormality was 49 years. The mean age for HSIL
category was approximately 5 years greater than the LSIL category in our study.
The LSIL to HSIL ratio was near equal to 2 or
greater than 2 in most of the studies. Our study showed an LSIL to HSIL ratio
of 2.77, asserting that LSIL is more than twice as commonly encountered as HSIL
in PAP smears. This fact also correlates well with most other studies. (Table 8)Nandwani
et al [18], however, reported an LSIL to HSIL ratio lesser than 1 in their
study and the proportion of squamous cell carcinoma cases was more than the
HSILcases. The reason could be that this study was conducted in a tertiary care
setup receiving greater proportion of referred cases from the periphery.
One case of squamous cell carcinoma (SCC) was
reported in our study contributing to 0.2%, correlating with studies done by
other authors [16,19,20]. A greater proportion of SCC in other studies [18, 22]
may be due to a greater sample size and the study institute being a referral
centre for malignancies. No case of adenocarcinoma was encountered in our
study. This also correlates with other studies (Table 8) and may be due to a
smaller sample size and a relatively lower occurrence of adenocarcinoma of
cervix as compared to SCC.
Atypical glandular cells were seen to a
lesser extent in our study comprising around 0.9%, which is consistent with
other studies detailed in Table 6. In studies conducted by Elhakeem et al [19]
and Altaf et al [20], the proportion of atypical glandular cells was higher.
This could be attributed to the increased sample size and probably increased
prevalence of endocervical lesions in these areas as both these studies were
conducted in different provinces of Saudi Arabia.
We observed that the PAP smear is a cost
effective, simple and reliable method for screening women presenting to OBG
department with complaints related to the genitor-urinary tract. Though a
majority of the cases (90.8%) were reported as Negative for Intraepithelial Lesion
or Malignancy, the remaining cases were advised regular follow-up with repeat
PAP smears or colposcopic biopsy to evaluate them further. Nearly 5% of the
examined cases had a Squamous Intraepithelial Lesion (LSIL or HSIL) which mandated
a biopsy.
The limitations of this study were a smaller
sample size (n=578) and a study duration of 1 year. HPV testing which is an
important adjunctive method for screening was not utilized in this study due to
the cost constraints and availability issues. Histopathological correlation could
not be done satisfactorily as many of the cases diagnosed with epithelial cell
abnormalities were referred to specialist centres for follow up. Of the other
cases, in which either a cervical biopsy or hysterectomy was done in our
institute, two cases of HSIL had moderate and mild cervical dysplasia
respectively and a case of SCC was confirmed on histopathological examination.
Conclusion
Our study highlights conventional PAP smears with
2014 Bethesda System of reporting as an important screening tool for cervical
lesions especially in the under-resourced countries where facilities for HPV
testing and liquid based cytology techniques are of limited availability. Cost
incurred by the patient also limits utility of more sophisticated screening
techniques. In such situations, conventional PAP smears play an important role
in filtering out a greater proportion of patients with a non-neoplastic cytological
findings and identifying patients with epithelial abnormalities so that
appropriate management can be instituted at the earliest. In addition,
specificinfections (trichomonas, candida etc.) can also be identified by
optimal examination of PAP smears which help reduce patient morbidity due to
these conditions.
Contributions
of Authors
·
Ashraf A. Zubair– Played a major role is designing the study,
collecting data, organising data and preparing the manuscript.
·
Shruti Kulkarni– Contributed to organising the data,
comparisons with other studies and preparing manuscript.
·
M. Preethi– Contributed to data compilation and organisation.
What
this study adds to the existing knowledge?
Systematic reporting of cervical PAP smears
based on the 2014 Bethesda System aids in effective screening of patients for
epithelial abnormalities, provides uniform terminology for clinicians and
pathologists and caters to appropriate and better patient management to reduce
mortality and morbidity.
References