Mohammed I A et al / Int. J. of Res.

in Pharmacology & Pharmacotherapeutics Vol-5(4) 2016 [377-387]

International Journal of Research in

Pharmacology & Pharmacotherapeutics

ISSN Print: 2278-2648 IJRPP |Vol.5 | Issue 4 | Oct - Dec - 2016

ISSN Online: 2278-2656 Journal Home page: www.ijrpp.com

Research article Open Access

A study on colposcopic directed biopsy in early detection of malignant lesions

of cervix
Dr.Mohammed Imran Ali1*
1*
Assistant Professor, Department of Pathology, Kakatiya Medical College, Warangal, Telangana, India.
*Corresponding author: Dr.Mohammed Imran Ali

ABSTRACT
The aim of the study is to determine the outcome of women referred for Colposcopy and directed biopsy with
abnormal pap smears and smears showing persistent inflammation. Cervical cancer is a significant health problem
worldwide among women. Cancer cervix is the most common cancer in developing countries. It is considered as
preventable cancer since there is availability of screening method and effective diagnostic and therapeutic
procedures. Despite the accuracy and efficacy of cervical cytology in detecting and diagnosing cervical neoplasia, it
must remain a screening technique with further evaluation based on histologic diagnosis. The objectives of the study
are To study the Colposcopic features of abnormal pap smears and persistent inflammatory cellular changes on pap
smear, To localize the lesion by Colposcopy and obtain a biopsy, To assess the prevalence of CIN in the study
group. To correlate pap smear findings with colposcopic findings, To study the epithelial cell abnormalities by
colposcopic biopsy of abnormal areas in such cases, To determine the existence of significant cervical intraepithelial
lesion or invasive carcinoma in patients with persistent inflammatory pap smear. The present study is undertaken to
evaluate the role of cytology and Colposcopic guided biopsy in diagnosing neoplastic cervical lesions.
Keywords: Colposcopy, Cervical cancer, Cervical cytology, Histologic diagnosis, Pap smear.

INTRODUCTION for screening of cervical cancer and its precursors.

However, it suffers from low sensitivity and has a
Carcinoma cervix is the commonest cancer
high false negative rate of 9%-40% [6, 7, 8], there is
responsible for about 5% of all cancer deaths in
a possibility that an inflammatory pap smear may
women worldwide. It’s 5th deadliest cancer in
miss the cervical premalignant change. To overcome
women. [1] There are 1.7 million cases in the
this problem many algorithms have been devised to
developing world and as many as 5-13 millions
manage ASCUS or LSIL on Pap smear. These
women have precancerous lesions [2, 3]. It affects
involve HPV DNA testing, colposcopy or both.
about 16 per 10000 women in a year and kills about 9
However, no such algorithm is available for further
per 100000 per year. [4] Approximately 80% of
management of an inflammatory pap smear. Chronic
cervical cancers occur in developing countries [5]
inflammation, either specific or nonspecific, has been
and it is the commonest cancer in these countries.
shown to be associated with malignancy and was
The worldwide Pap smear has been the standard test

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thought to be one of the factors responsible for MATERIALS AND METHODS

carcinogenesis. Persistent inflammation leads to
A prospective study was done for duration of
increased cellular turnover, especially in the
2Years from January 2014 to April 2016 on
epithelium, and provides a selection pressure that
Colposcopic guided biopsy of cervical lesions in the
result in the emergence of cells that are at a high risk
department of pathology, Mahatma Gandhi Memorial
for malignant transformation [9]. Inflammatory pap
Hospital and Government Maternity Hospital
smear is the most common report the gynecologist
Warangal after obtaining clearance from the ethical
receives even where cervix appears normal. Since the
committee.
incidence of inflammation on pap smear is very high
(14%-19%) [10, 11, 12], the cervical screening Exclusion criteria
algorithm for benign cellular changes recommends Pregnant women, known cases of CIN and
treatment of infection if indicated and performing a obvious cervical growth, IUCD users, Diabetes
repeat Pap smear in 4 to 6 months time and, if the mellitus, Women with multiple sexual partners,
inflammatory changes persist, to subject the patient Patients with previous cervical surgery.
to colposcopy [13]. The realization that cervical
intraepithelial neoplasia grade III is present in up to Inclusion criteria
one third of women with mild or moderate Women between 20-65 and above, Women with
dyskaryosis [14, 15, 16] led to the suggestion that all symptoms like vaginal discharge, post coital
women with any degree of dyskaryosis should be bleeding, Inter menstrual /irregular bleeding,
referred for Colposcopic assessment. The advantages Persistent leucorrhoea not responding to treatment,
of this approach are that it enables a prompt Persistent inflammatory changes in pap smear,
histological diagnosis and avoids the possibility of Women having abnormal pap smear (intraepithelial
the patient defaulting on a further smear test. Recent abnormalities), Patients with a report of abnormal
guidelines on the management of women with such pap smear and persistent inflammatory pap smear
smears suggest immediate referral for Colposcopy for were included in the study.
women with a single moderately dyskaryotic smear Those with a clinical diagnosis of chronic pelvic
and referral after two consecutive dyskaryotic smears inflammatory disease and showing inflammatory Pap
for women with mild dykaryosis. [17]. Colposcopy smear were treated with antimicrobial and anti
combined with Colposcopically directed biopsies are inflammatory treatment, according to WHO
the primary modality by which women with guidelines. [18] These patients were given
abnormal pap smears are evaluated. Colposcopic doxycycline and metronidazole orally for 7-14 days
examination consists of viewing the cervix with a and Clotrimazole vaginal pessaries daily for a
long focal length, dissecting type microscope at a minimum of 6 days. A repeat Pap smear was
magnification of about 16x after a solution of dilute performed after a period of 2 weeks. No preparation
acetic acid has been applied to the cervix which of the cervix was undertaken at the time sampling
causes acetiwhitening of abnormal areas. This and women were not menstruating or using any
coloration allows the Colposcopist to identify and vaginal douche or vaginal contraceptives at the time
biopsy epithelial lesions. Colposcopy and of sampling. If the inflammatory cellular changes
appropriately directed biopsy have greatly facilitated were reported again on repeat pap smear, were said to
the management of the patients with pre invasive have a persistent inflammatory smear. These patients
lesions of the cervix. It also allows the clinician to along with abnormal pap smear report were subjected
rule out the invasive cancer and determine the limits to colposcopy and directed biopsy after taking the
of the pre invasive disease. Conservative ablative informed consent.
modalities like cryosurgery, laser ablation, and loop Conventional cytology testing was obtained by
electrosurgical excision procedure can be used to scarping the cervical cells with a cotton swab and the
treat pre invasive disease and obviate the need for a smear was prepared by spreading the specimen
cone biopsy. uniformly across a glass slide, which was
immediately fixed in 95% ethyl alcohol contained in
a Coplin jar. Then smear was stained with

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Papanicolaou stain and cytology results were premalignant and malignant lesions was calculated as
reported, according to the Bethesda system. [19] percentages. [20]

Procedure for Colposcopic guided biopsy

The women were kept in a dorsal position and the RESULTS
cervix was exposed by insetting at Cusco’s speculum. In the study “Colposcopic guided biopsy of
Excess mucous was wiped off with cotton swab cervical lesions”, evaluated 114 patients aged
soaked in saline. Five percent acetic acid was applied between 20-65 years and above age group from
to the cervix and it was visualized with binocular January 2010 to April 2012 in Mahatma Gandhi
Colposcope under 40X magnification. Biopsies were Memorial Hospital Warangal.
taken from the abnormal areas (acetowhite areas and
vascular abnormalities like fine punctuation, coarse Age distribution
punctuations, mosaic and areas showing atypical Out of 114 patients 40 (35.08%) were between
vasculature). A biopsy specimen obtained were fixed 41-50 years, least age group in our study were 65 yrs
in formalin and processed and subjected for and above and all observations shown in both table
histopathological examination. The incidence of and figure number 1.

Table 1 Age distribution

Age No. of cases %
21-30 10 8.77%
31-40 37 32.45%
41-50 40 35.08%
51-60 19 16.66%
61-70 8 7.01%

Age Distribution

7% 9% <30
17%
32% 31-40
41-50
35% 51-60

Figure 1 Age distribution

Clinical Symptoms
Out of 114 patients, 57 patients presented with white discharge results as shown in both table and figure number 2.

Table 2 Clinical Symptoms

Clinical symptoms No . of cases %
White discharge 57 50%
Pelvic pain 21 18.42%
AUB 12 10.52%
Mass per vagina 5 4.38%
Post coital bleeding 8 7.01%
Post menopausal bleeding 5 4.38%
Dysmenorrhoea 6 5.26%

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clinical symptoms

White discharge
5 8 5
pelvic pain
12
57 AUB
21
Mass per vagina

Figure 2 Clinical Symptoms

Colposcopic Findings and vascular abnormalities’ and observations were

shown in both table and figure number 3.
Among 114 patients acetowhite areas were seen
in 44 patients, 27 were having combined acetowhite

Table 3 Colposcopic Findings

Clinical symptoms Normal Erosion AW Vascular AW+Vascular Total
areas abnormality abnormality
Vaginal discharge 3 9 20 9 16 57
Pelvic pain 1 3 10 3 4 21
AUB - - 4 5 3 12
Post coital bleeding - 4 3 - 1 8
Mass per vagina - - 2 1 2 5
Post menopausal - - 3 1 1 5
bleeding
Dysmenorrhea 2 2 2 - - 6
Total 6 18 44 19 27 114

Colposcopic Findings

20
15
Normal
10
5 Erosion

0 AW areas
Vascular abnormality
AW+Vascular abnormality

Figure 3 Colposcopic Findings

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Persistent Inflammation Correlated with in which 11 patients were diagnosed to have CIN I
Histopathology changes and results were shown in both table and
In persistent inflammation group vaginal figure number 4.
discharge was the commonest symptom (25patients)

Table 4 Persistent Inflammation Correlated with Histopathology

Clinical symptom Normal Chronic CINI/HPV CIN CIN Invasive Total
cervix cervicitis II III cancer
Vaginal discharge 4 10 11 - - - 25
Pelvic pain 2 5 4 - 1 - 12
AUB - 3 4 - - - 7
Pot coital bleeding - - 2 1 - - 3
Mass per vagina - 1 1 - - - 2
Post menopausal - - - 1 - - 1
bleeding
Dysmenorrhea 3 2 1 - - - 6

Figure 4 Persistent Inflammation Correlated with Histopathology

Abnormal Pap smear findings: In the 2 Year showed(LSIL) low grade squamous intraepithelial
study period have screened 760 women, out of which lesions,12 showed ASCUS, 8 were having HSIL and
52(7.2%) women were having an abnormal Pap 4 patient were positive for invasive cancer and results
smear, 62 (8.6%) were having persistent shown in both table and figure number 5.
inflammation. Out of 52 abnormal Pap smears 28

Table 5 Abnormal Pap smear findings

Abnormal pap smear finding No. of cases Total %
LSIL 28 3.9%
HSIL 8 1.1%
ASCUS 12 1.6%
Invasive cancer 4 0.6%
Inflammatory smear,atrophic cervix,normal study 668, 92.77%

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Abnormal Pap Findings

LSIL

HSIL

Figure 5 Abnormal Pap smear findings

Abnormal Pap smear Correlated with patients (46.4%) found to have CIN I and 5 patients
Colpohistology were having a high grade disease (17.89%) results as
Out of 28 LSIL cases, 10 were having no shown in both table and figure number 6.
evidence of premalignant or malignant condition.13

Table 6 Abnormal Pap smear Correlated with Colpohistology

Biopsy finding ASCUS LSIL HSIL Invasive cancer Total
Negative 5 (41.66%) 10(35.7%) 1(12.6%) - 16
CIN I 3 (25%) 13 (46.4%) 1 (12.6%) - 17
CIN II 2 (16.66%) 3 (10.75) 2 (25%) 1 (25%) 8
CIN III 1 (8.33%) 2 (7.14%) 3 (37.5%) 2 (50%) 8
Invasive cancer 1 (8.33%) - 1 (12.6%) 1 (25%) 3

14
12
10 ASCUS
8
LSIL
6
4 HSIL
2
Invasive cancer
0
Negative CIN I CIN II CIN III Invasive
cancer

Figure 6 Abnormal Pap smear Correlated with Colpohistology

Persistent Inflammation Correlated with undergone colposcopic directed biopsy. Out of 56

Histology patients 23 were having CIN I changes and 1 case
62 patients had persistent inflammation on Pap diagnosed as CIN III and no invasive cancer was
smear among 720 routine Pap smears.6 patients had found in this study group and observation was shown
normal Colposcopic findings and rest of 56 patients in both table and figure number 7.
who had persistent inflammation on Pap smear have

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Table 7 Persistent Inflammation Correlated with Histology

Biopsy finding No. of cases Total %
Normal cervix 9 16.07%
Chronic cervicitis 21 37.50%
CIN I/HPV changes 23 41.07%
CIN II 2 3.57%
CIN III 1 1.78%
Invasive cancer - -

3.57 1.78 16.07

41.07
37.5

Normal cervix Chronic cervicitis CIN I/HPV changes

CIN II CIN III

Figure 7 Persistent Inflammation Correlated with Histology

Final Histopathology Reports of both Abnormal and Persistent Inflammatory Pap smears
In abnormal Pap smear group out of 52 patients, 17 were CIN I group and 3 patients were diagnosed to have
invasive cancer. In persistent inflammation group out of 62 patients 6 did not underdone biopsy since colposcopy
was normal in these patients. So out of 56 patients 30 were having chronic cervicitis and 23 were diagnosed to have
CIN I lesions and results were shown in both table and figure number 8.

Table 8 Final Histopathology Reports of both Abnormal and Persistent Inflammatory Pap smears
Biopsy report Abnormal pap smear Persistent inflammatory smear
Chronic cervicitis 16 (30.76%) 30 (53.57%)
CIN I 17 (32.69%) 23 (41.07%)
CIN II 8 (15.38%) 2 ( 3.57%)
CIN II 8 (15.38%) 1 ( 1.78%)
Invasive cancer 3 (5.76%) 0

35
30
25
20
Abnormal pap mear
15
persistent inflammation
10
5
0
Chronic cervicitisCIN I CIN II CIN IIIInvasive cancer
Figure 8 Final Histopathology Reports of both Abnormal and Persistent Inflammatory Pap smears

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Pap smear finding-age distribution age group 51-60 Years, 10 patients between age
group <30 Years,8 patients between age group >60
Among 114 patients Pap smears seen in 40
Years results were shown in both table and figure
patients between age group 41-50 Years, 37 patients
number 9.
between age group 31-40 Years, 19 patients between

Table 9 Pap smear finding-age distribution

Age Inflammatory smear LSIL HSIL ASCUS Invasive cancer Total
<30 yr 8 2 - - - 10
31-40yr 22 8 1 5 1 37
41-50yr 18 10 6 4 2 40
51-60yr 9 6 1 3 - 19
>60 yr 5 2 - - 1 8

25
20 <30
15
10 31-40
5
0 41-50
51-60
>60

Figure 9 Pap smear finding-age distribution

Histopathology findings-age distribution age group 51-60 Years, 10 patients between age
group <30 Years,8 patients between age group >60
Among 114 patients, Negative for malignancy,
Years results were shown in both table and figure
Invasive cancer, CIN I, II and III etc seen in 40
number 10.
patients between age group 41-50 Years, 37 patients
between age group 31-40 Years, 19 patients between

Table 10 Histopathology findings-age distribution

Age Negative for malignancy CIN I CIN II CIN III Invasive cancer Biopsy not done Total
<30 yrs 6 3 - - - 1 10
31-40yr 16 11 2 4 - 4 37
41-50yr 12 17 6 2 2 1 40
51-60yr 9 8 1 1 - - 19
>60yr 3 1 1 2 1 - 8

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18
16
14
12 <30
10 31-40
8
6 41-50
4 51-60
2
0 >60
Negative CIN I CIN II CIN III Invasive Biopsy not
for cancer done
malignancy

Figure 10 Histopathology findings-age distributions

DISCUSSION frank malignancy. In the study LSIL was diagnosed

in 28 patients, further Colpocopic guided biopsy CIN
Cervical cancer screening was proved to be an
I was diagnosed in 13 (46.4%) and CIN II &III
important part of preventive health care of women.
constitutes 5 (17.84%) cases. And 10 (35.7%) cases
Attempts are being made to improve efficacy of the
were negative for malignancy and no invasive cancer
screening program to decrease the morbidity and
was reported in LSIL group and LSIL group shows
mortality due to cervical cancer. Cytologic atypia
17.84% women have high grade lesion who were
reported on a routine Pap smear of the cervix
under diagnosed by Pap smear were missed if not
frequently present a dilemma for the physician. Steps
further investigations done and ASCUS was seen in
to evaluate of this entity depend on multiple factors,
12 cases. Among, them 49.9% women had CIN
most important being whether the presence of
lesions and high grade CIN lesions were 24.93%. A
underlying cervical neoplasia is suspect. Cervical
more common approach is to repeat the smear after a
cytological abnormalities are of concern because in a
course of antibiotic or after an arbitrarily determined
small but important number their reflex the presence
time interval, then performs Colposcopy if atypical
of high grade CIN. The cervical cancer screening
persist on repeat Pap smear. This “treat and repeat”
algorithm for benign cellular changes on Pap smear
or “wait and repeat” approach is possible in highly
recommends treatment of infection and repeat Pap
motivated people and aggressive protocol may be
smear in 6-9 weeks if inflammatory changes persist
required if the sexual history and socioeconomic
to subject the patient to Colposcopy. In developing
profile of the target population is a high risk
countries where proper screening protocols are not
category. A significant number of CIN cases were
followed a good number of patients with
missed if atypia on Pap smear is not investigated
premalignant stage are being missed. Most
further. HSIL was diagnosed in 8 patients, among
Gynecologists do not review the pap smear result
them CIN II & III were diagnosed in 5 (62.5%) by
with cytologist and 41% do nothing when the
biopsy and invasive cancer in 1 (12.6%). The
inflammatory Pap smear is reported. Only 11% treat
detection rate of CIN II & III in the study is similar to
the infection and repeat Pap smear and 24% treat
chomet et al study and Booonlikit et al study which
infection and do not repeat pap smear.21 The detection
shows 67.8%. Women with HSIL can harbor high
rate of premalignant and malignant lesions of the
grade cervical lesion and prevalence of invasive
cervix by guided biopsy of lesions in an abnormal
carcinoma is also high. So immediate Colposcopy
pap smear group in the present study is as follows: In
and Colposcopically directed biopsy is mandatory.
LSIL group CIN I constituted 46.4%, while CIN II,
Among 720 routine pap smears 4(0.6%) were
CIN III combined to have17.84% In HSIL group CIN
positive for malignancy ,these cases are followed
I constituted 12.6%, while CIN II and III combined to
with Colposcopically guided biopsy and results
have 62.5%. Among 4 cases of invasive cancer CIN
shows 3 cases(75%) proved to be CIN II & III and 1
II, CIN III was reported in 75% cases and one case

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case(25%) invasive cancer, it shows smear positive in 41-50 age group with a mean age of 42.6.Pap
for malignancy are inconsistent predictor of high smears studied among 720 patients in the outpatient
grade premalignant lesions and invasive cancer. department, majority are negative for intraepithelial
Persistent inflammation was seen in 62(8.2%) women lesion or malignancy (92.77%) and abnormal Pap
among 760 routine pap smears. Histological smears constitutes 7.2% (52cases.) Among these 52
diagnosis showed 21 (38.3%), 9(16.07) cases, cases LSIL, HSIL, ASCUS and Invasive cancer
chronic cervicitis and negative for any premalignant constitutes 3.9%, 1.1%, 1.6%, 0.6% respectively.
and malignancy respectively. Premalignant lesions Among 720 cases, 114 cases (52 cases of abnormal
26(46.42%) were present in persistent inflammatory pap smears and 62 of persistent inflammation) were
smear which were missed if not Colposcopic directed followed by Colposcopy and directed biopsy. Biopsy
biopsy was not done. Most cases were in CIN I group was not done 6 patients with persistent inflammation
(41.07%) and 3 cases (5.35%) of CIN II & III. And showing normal Colposcopic finding commonest
no invasive cancer was seen in this group. finding in Colposcopy in the study was acetowhite
areas(44 Cases out of 114) 56 of these persistent
CONCLUSION inflammation group CINI, II, and III were seen in
41.07%,3.57%,and 1.78% respectively. Among 52
A prospective study was done on “Colposcopic
abnormal pap smear followed by Colposcopic guided
directed biopsy in early detection of premalignant
biopsy CIN I in 32.69%, CIN II & III in 30.76% and
and malignant lesion of cervix” in MGM Hospital
invasive cancer in 5.7% of patients.
Warangal for duration of 2 years. In the study group
majority of premalignant and malignant lesions seen

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