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Addis Ababa University

Addis Ababa Institute of Technology


Center of Biomedical Engineering
A Master Thesis Proposal on
Detection and Classification of Precancerous Cervical Lesions based on Pap
Cytology Image Analysis

In Partial fulfillment of the requirements for the degree of Masters of Science in


Bioinstrumentation and Imaging

Prepared by: Sakata Abera (GSR/0994/08)


Advisor: Dr. Dawit Assefa Haile (PhD)
Co-advisor: Dr. Mesfin Assefa Tola (MD)

Contents
Abbreviations ................................................................................................................................................ ii
Abstract ........................................................................................................................................................ iii
1.

Introduction ........................................................................................................................................... 1

2.

Problem Statement ................................................................................................................................ 3

3.

Literature Review.................................................................................................................................. 4

4.

Objectives ............................................................................................................................................. 5
4.1.

Major objective ............................................................................................................................. 5

4.2.

Specific Objectives ....................................................................................................................... 5

5.

Delimitation .......................................................................................................................................... 5

6.

Methodology ......................................................................................................................................... 5

7.

Proposed Methodology ......................................................................................................................... 6

8.

Materials and Methods .......................................................................................................................... 6


8.1.

Description of the study ................................................................................................................ 6

8.2.

Data Collection ............................................................................................................................. 7

9.

Action Plan and Research Timeline ...................................................................................................... 8

10.

Budget Estimation ............................................................................................................................. 9

11.

Reference ........................................................................................................................................ 10

Abbreviations
CIN Cervical Intraepithelial Neoplasia
SIL Squamous Intraepithelial Lesion
Pap Papanicolaou
HPV Human Papilloma Virus
E6 Early protein 6
E7 Early protein 7
AIDS Acquired Immuno Deficiency Syndrome
EPHI Ethiopian Public Health Institute
SPHMMC St. Paul Hospital Millennium Medical College
VIA Visual Inspection through Acetic Acid
MRI Magnetic Resonance Imaging
ANN Artificial Neural Network
HIV Human Immuno Virus

ii

Abstract
The accurate detection and classification of precancerous cervical image has always a major
challenge for pathologists for screening, diagnosis and treatment planning. The potential risk
factor for cervical cancer is an infection by Human Papilloma virus. The use of manual Pap
cytology image analysis has limited success as it requires repeated testing due to lack trained
man power, poor laboratory and infrastructures. Pathologists simply use stained tissue sample
for visual/manual identification based over a microscope. Such a procedure is subjective and
prone to observer variability. Also it is time consuming as well as non-repetitive to analyze the
best decision. Other factors include lack of specific and accurate quantitative measures to
classify the obtained Pap cytological images as normal or cancerous. The main intent of this
thesis study is development of an automated scheme for use in accurate and effective detection
and classification of cervical cancers based on feature derived from microscopic images of Pap
Cytology image. This will call for the development of algorithmic based automated scheme for
screening of precancerous cervical lesions which can guide for effective detection and
classification of precancerous cervical lesions. Several such algorithms exist in the literature
and it is the intent of this paper to review relevant schemes and develop an effective tool that
could do the thesis purpose thereby improving screening efficiency for early precancerous
cervical lesion so that once the abnormal cells are detected, the patient will be scheduled for
further treatments and cured at an early stage. Microscopic images of cervical tissue samples
taken from patients will be used for testing and validation of the proposed image analysis tool
which will be developed on a Matlab platform. Sensitivity, specificity, and overall accuracy of
the results will be checked during quantitative assessment of the method based on available gold
standards and other schemes already developed in the literature.
Keywords: Cervical Cancer, Human Papilloma Virus, Pap smear Image, Image Processing,
Cytotechnologist, Precancerous lesions.

iii

1. Introduction
Cancer is one of the most dangerous diseases of humans that grows in an uncontrolled manner by
spreading abnormally anywhere in the body and later called tumor. More than 100 different
types of cancer diseases are characterized by an uncontrolled cellular growth, local tissue
invasion and distant metastasis (1). Cervical cancer is one of the many types of cancer diseases
that starts in the cells lining the cervix, the lower part of the uterus called uterine cervix that
happens when cells in the cervix area begin to grow out of control and invade nearby tissues (2)
(3). Cervical cancers begin in the cells in transformation zone. These cells do not suddenly
change into cancer; instead the normal cells of the cervix first gradually develop precancerous
changes and later converted into cancer in the transformation zone. Transformation zone is
where Pathologists use several terms to describe these pre-cancerous changes as cervical
intraepithelial neoplasia (CIN1), squamous intraepithelial lesion (SIL/CIN2) which is mild
dysplasia and severe dysplasia (CIN3) (4). Cervical intraepithelial neoplasia (CIN) is a
premalignant lesion that may exist at any one of the three stages above. If left untreated, CIN2 or
CIN3 (collectively called CIN2+) can progress to invasive cervical cancer.
In Ethiopia cervical cancer disease is a public problem and women vulnerable to the disease are
estimated to be more than 35.5 per 100,000 populations (5). The potential risk factor for cervical
cancer is an infection by Human Papilloma virus (HPV) which can transmit when individuals
skin to skin contact, or through sex so that infects cells on the surface of the skin. This infection
produces two proteins called E6 and E7 (Early protein) which turn off a tumor suppressor gene
(p53 called Retinoblastoma). This may allow the cervical lining cells to grow too much and
develop changes in additional genes thereby leads to cervical cancer (2). HPV takes 20 to 50
years to be understood as cancer in once females lifespan. That is why cervical cancer is the
worst in its kind compared to other types of cancer diseases. Women living with HIV are among
the most vulnerable to cervical cancer to develop precancerous lesions because the virus that
causes AIDS damages the immune system and puts women at high risk of HPV infections (6).
Cervical cancer is easier to treat if it is screened and identified early in its precancerous lesions.
It can be screened through conventional Pap cytology test under the microscope. The Pap test
was introduced by Dr. Georges Papanicolaou in 1940s (7). It is the most effective cancer
screening test ever based on obtaining cells from uterine cervix and smearing them onto glass
slides for microscopic examination to detect HPV effects. So it still remains the crucial modality
that leads to automated detection and classification of precancerous cervical tissue.
Pap smear is obtained by collecting cells from the cervix surface (typically using a spatula). The
sample is then stained, screened and analyzed under the microscope by cytotechnologist. The
following method will be employed for the manual identification of cervical cancer.

Figure 1: A pap smear obtained by thinly smearing collected cells onto a glass microscope slide.

Figure 2: Abnormal Cervical Cell

However, its accurate detection and classification has always been a major challenge for
pathologists for screening, diagnosis and treatment planning. Currently, the use of manual Pap
cytology image analysis has limited success as it requires repeated testing due to lack trained
man power, poor laboratory and infrastructures. In Ethiopia there are two institutionalized cancer
centers namely Black Lion Specialized hospital and St. Paul millennium Medical College hosted
by Ethiopian Public Health Institute (EPHI). In both institutions, there is no automated cancer
detection and classification system available and traditionally the screening is done through
visual inspection of the cervix with acetic acid (VIA) so that tissues causing cervical cancer on
the cervix appear as white blotches. Pathologists simply use stained tissue sample for
visual/manual identification based over a microscope. The visual analysis and interpretation of
this microscopic image comes with several challenges. Primarily, such a procedure is subjective
and prone to observer variability. Also it is time consuming as well as non-repetitive to analyze
the best decision. Other factors include lack of specific and accurate quantitative measures to
classify the obtained Pap cytological images as normal or cancerous.
At the end, the research will answer; how can cervical precancerous lesions be identified early in
less developed countries before it develops to invasive cancer? What mathematical algorithms
will be applied? What method is to be employed for cervical precancerous lesion screening
scaling-up than its diagnosis after it occur and is the screening method safe enough than
diagnosis?

Pathologists use 3 ways of pathological image analysis manually. The first one is Pap cytology
image analysis which in this case cervical cells will be analyzed on the Pap smear slide for
screening purpose. This will help us in treatment planning. The second one is biopsy image
analysis of taking tissue sample from the patient and to investigate under a microscope. The third
one is the histopathological image analysis and this is largely used for diagnosis after cervical
cancer cells has been screened and identified. It is sometimes called excisional biopsy as doctors
cut the part affected by cervical cancer. The main intent of this thesis study is development of an
automated scheme for use in accurate and effective detection and classification of cervical
cancers based on feature derived from microscopic images of Pap Cytology image staining.
Quantitative algorithm for automated identification of early cervical precancerous and cancerous
cells from Pap cytology images will be developed which helps in alleviating the manual
interpretation by different pathologists and minimize medical error produced by individual
experts. Mostly this method will be helpful in early screening of cancerous lesions rather than
relying on diagnosis system. Thus, in this study a method for this application would ideally use
quantitative algorithms, decreasing the need for clinical experts and waiting periods for
diagnosis.

2. Problem Statement
Currently, cervical cancer is the widely emerging disease in Ethiopia and its prevalence was
assumed to be 45% among other types of cancers (8). Even though there was cervical cancer
diagnosis adopted a few years ago it was not effective since it was not linked to precancerous
treatment. Instead, the diagnosis process starts after the disease symptom emerges. Sometimes
patients with abnormal Pap smear will stay so longer until their lesions will become big enough
for an operation and leads patients to radical treatment such as removal of the uterus (9). Thus it
leads patient be suffered. There is no screening and identifying early precancerous lesion from
developing before it is converted to invasive cancer. Also most women have no awareness to
become tested before the disease occurs. Additionally, there is no population based cancer
registry that enhances cancer care and prevention (8) (10). Hence, lack of population based
national cancer registry data on cervical cancer made it not to have attention and raised the
disease burden at its climax.
As a result of traditional Pap smear staining techniques, there may be varied types of cell
properties including overlapped, occluded (obstructed), and grouped cells. Identifying cells of
these properties require different settings in terms of magnification and focus. Pathologists cant
identify tremendous amount of smear slides per day where nuclei and cytoplasm parts are
colored with different staining materials and other artifacts are stained along with cells on the
Pap smear slide which makes analyzing the cells on the slides difficult which simply limits the
mass screening. The staining of cells on the Pap smear slide may be non-homogeneous and the
contrast between nucleus and cytoplasm will become low and this also poses difficulty on the
pathologist in screening and interpreting of the results. This will call for the development of
3

algorithmic based automated scheme for screening of precancerous cervical lesions which can
guide for effective detection and classification of precancerous cervical lesions. Several such
algorithms exist in the literature and it is the intent of this paper to review relevant schemes and
develop an effective tool that could do the thesis purpose thereby improving screening efficiency
for early precancerous cervical lesion so that once the abnormal cells are detected, the patient
will be scheduled for further treatments and cured at an early stage.

3. Literature Review
In recent years many works have been reported in the literature for automated cancer detection
from microscopic images. Soumya et al. (11) for example proposed cervical cancer classification
techniques using Magnetic Resonance Imaging (MRI) to obtain the staging of cervical cancer.
In another study, Zhao et al. (12) presented detailed work on automated screening of cervical
cells using block images. In this system, they divide cervical cancer images into blocks with
certain size instead of segmenting the cells. Lipi B. Mahanta et al. (13) presented cervix cancer
diagnosis from Pap smear images using structure based segmentation and shape analysis. In this
work, they identified cervical smear image based on cell nuclei distribution. Eko Supriyanto et
al. (3) presented classification of cervical cancers based on color image processing of
morphological operators. Asli Genctav et al. (7); also proposed unsupervised segmentation and
classification of cervical cancer images. They used multiscale hierarchical segmentation
algorithm to partition regions based on homogeneity and thresholding to separate the cell regions
from background. This method is not able to delineate (segment) the boundary of each individual
overlapping cytoplasm. Instead it segments the whole cell clump which is insufficient for
subsequent cellular counting and shape analysis. Another study by Hana Sarbortova (14)
reported detection of cervical cancer in Pap smear images using Artificial Neural Network
(ANN) and Fuzzy classification system. Most of the literatures written until now mainly focus on
nuclei segmentation which usually cant be easily used for classification as the cytoplasm has to
be considered too. Another group of researchers used ANN based cervical cancer detection in the
literature that attempt to solve the problem of distinguishing cancer cells from other stained
objects (artifacts) in Pap smear images. Their scheme however was unable to segment individual
cytoplasm regions for each cell (7). Most segmentation algorithms written so far in the area
depend on localization and segmentation of free lying or non-overlapping nucleus and cytoplasm
than overlapping cell.

4. Objectives
4.1.

Major objective

To develop a platform/tool for automated segmentation and classification of precancerous


cervical lesions based on robust feature derived from Pap cytology/Pap smear slide image
analysis.

4.2.
i.
ii.
iii.
iv.
v.
vi.

Specific Objectives
Evaluate current status of cervical cancer burdens in Ethiopia based on data collection
and data analysis to be carried out in selected hospitals in Addis Ababa, Ethiopia.
Revision of existing cervical cancer detection and classification schemes available in the
literature.
To develop image feature based algorithm that could be used to uniquely quantify
precancerous cervical lesion based on rigorous mathematical algorithms.
Check the accuracy and robustness of the developed algorithm by validating with
available ground truth information.
Compare the efficacy (qualitatively and quantitatively) of the developed scheme against
similar other methods proposed in the literature.
Carry out validation procedures and investigate useful clinical implications of the
developed scheme.

5. Delimitation
This research specifically focuses on detection and classification of precancerous cervical lesions
from Pap cytology image analysis. It will consider segmentation of overlapped and occluded
cervical images of nuclear and cytoplasm from Pap cytology images. The work will not consider
segmentation and classification of cervical cancer images taken over other imaging modalities
such as X-ray, MRI or CT-Scan. The works objective clinical implications will thoroughly
discussed, but the actual clinical evaluation of the proposed method is beyond the scope of the
current study. This work will not consider histopathological image analysis as it is used only for
diagnosis purpose only. Before diagnosis, the precancerous lesions must be screened and
detected for diagnosis and treatment planning.

6. Methodology
This study is intended to implement a novel technology to automate cervical cancer screening
system with the objective of optimizing the conventional screening from microscopic Pap smear
analysis by using quantitative and qualitative analysis of cytological images that supports
pathologists on decision about the presence or absence of developed disease and helps in disease

progression evaluation. The system uses efficient analysis of the color Pap cytological
images/Pap Smear slide images using a holistic color image processing tool (15).

7. Proposed Methodology
The proposed methodology was stipulated in the figure below.
Load an Image

Preprocessing (Noise Removal and


Enhancement)

Individual cell

Noise free image

Clustered Image

Segmentation

Feature Extraction

Feature Selection

Classification

Cancerous Cell

Non-cancerous cell

Figure 3: Block diagram of the proposed Image processing Scheme.

8. Materials and Methods


8.1.

Description of the study

This study will use facilities at the St. Paul Hospital Millennium Medical College (SPHMMC) in
joint collaboration with the Ethiopian Public Health Institute (EPHI), Addis Ababa, Ethiopia.
Institute Patholaboratory department of St. Paul Hospital Millennium Medical College is hosted
by Ethiopian Public Health Institute. The laboratory has separate tissue extraction and staining
area. The extracted and stained tissue will be saved and kept in the computer as the dataset for

further analysis and those datasets will be used for developing and testing the image processing
tool in the current study.

8.2.

Data Collection

To systematically study precancerous and cancerous status of the cervix in Ethiopia, the
screening process and patient recording system will be employed. A formal paper based on
standard questionnaire will be distributed to selected pathologists. A one to one interview will be
conducted with volunteer staffs and systematic observation will be incorporated. On the other,
hand there will be exploratory pathology laboratory visit to identify the occurrence of ground
truth datasets and get insight for the questionnaire preparation. Images already available on
hospital databases as well as those taken recently will be used in this study and findings and
delineations by expert pathologists will be used as a gold standard. Normal sample images taken
from non-patients will be used as a control.
Generally, the following materials need to be used for data acquisition.

Staining reagents Hematoxylin and Eosin:


Camera integrated microscope:
USB cable to obtain the captured slide image by microscope camera and transfer image to
laptop/computer desktop
Origin software To trace signal graphs to be visible clearly and to draw as required
Free desktop computer to store/keep processed Pap smear cytological images as image database

The color image analysis tool to be used in this study relies on higher order features extracted
from the sample images taken from both cervical cancer patients as well as controls. A rigorous
mathematical scheme that utilizes holistic color pixel representation and features extraction
techniques will be developed and preceded by a careful pre-processing approach. Testing and
validation of the developed algorithm will be implemented on a Matlab platform while standard
accuracy measures such as sensitivity, specificity and overall accuracy will be utilized to
quantify its robustness.

9. Action Plan and Research Timeline


Timeline
March

No.
January

February

April

May

June

Literature review
Pre
Research

Proposal defense

Hospital Visit
- Department visit
- Sample selection

Data
Collection

Data Analysis

- Questionnaire
distribution
- Interview

Data recording
Data Analysis and Discussion

Documentati
on

Presentation
and defense

Progress Documentation
Initial Final Documentation
Final Documentation
Mock defense
Final Defense

Figure 4: Research Timeline

W4

W3

W2

W4
W1

W3

W1
W2

W4

W3

W1
W2

W4

W3

W2

W1

W4

W3

W2

W1

W4

W3

W2

W1

Activities

10.Budget Estimation
Materials description
No
1
2

4
5

Stationary (Paper, pens, pencils, stickers,


notepads)
Print and photocopy prior to final
documentation (Questionnaires, periodic
print, technical diagrams and literature
print
Local travel costs
Man power cost

Detail
Description

For seminar
presentation on
thesis progress

Quantity Unit price Total


cost
3000
-

For data collection


and interviewing

Staining reagents/Chemicals

Tea/coffee
invitation during
launching formal
and informal
interviews
Pack

2 Terabyte External hard disks

#1

5000

2000

1000

1500

#1

5000

5000

#1

2000

4000

Total cost

20,500

Figure 5: Budget Estimation and Cost Analysis

11.Reference
1. Trends of cervical cancer in Ethiopia. Migbaru, Abate Sefinew. 1, Addis Ababa : s.n.,
January 1, 2016, Open Assess Journal, Vol. I, pp. 1-4. CCOA.
2. Cervical Cancer. Society, American cancer. 2016.
3. Automatic Detection System of Cervical Cancer Cells Using Color Intensity Classification.
Eko Supriyanto, Nur Azureen M. Pista, Lukman Hakim Ismail, Bustanur Rosidi, Tati
Latifah Mengko. Johor, Malaysia : Conference Paper, July 2011, Recent Researches in
Computer Sciences. ISBN: 978-1-61804-019-0.
4. Organizations, World Health. WHO Guidelines for Screening and Treatment of
Precancerous Lesions for Cervical cancer Prevention. South Africa : s.n., 2013. pp. 1-38.
5. Risk Factors Associated with invasive cervical carcinoma among women attending Jimma
University Specialized Hopsital, South West Ethiopia: A case control study. Bezabih Mesele,
Fasil Tessema, Hailemariam Segni, Amare Deribew. Jimma : s.n., October 2015, Ethiopian
Journal of Health Science, Vol. 25, pp. 345-352.
6. Ethiopia, Pathfinder International. Combating Cervical cancer in Ethiopia. Addis Ababa :
Pathfinder International Ethiopia, 2010.
7. Unsupervised Segmentation and Classification of Cervical Cell. Asli Genctav, Salim Aksoy,
Sevgen Onder. 45, Ankara, Turkey : Elsevier, May 18, 2012, Elsevier, pp. 4151-4168.
8. Cancer, ICO information Center on HPV. Human Papillomavirus and Related Disease
Report. Oncology, ICO HPV information Center. Barcelona : International Agency for Research
on Cancer (IARC), 2016. pp. 1-64.
9. Knowledge Attitude and practice on cervical Cancer Screening Among Reproductive Health
Service Clients, Addis Ababa, Ethiopia. Getachew, Eyerusalem. 1, Addis Ababa : s.n., June
2015, pp. 1-79.
10. Cancer Care in Sub-Saharn Africa - Urgent need for population based cancer Registries.
Okobia, M.N. Benin : s.n., February 17, 2003, Ethiopian Journal of Health Development, pp.
89-98.
11. Cervical Cancer Detection and Classification uisng Texture Analysis. M.K. Soumya, K.
Sneha, C. Arunvinodh. 2, Calicut : s.n., June 16, 2016, Biomed & Pharmacology Journal, Vol.
9, pp. 663-671.
12. Automatic screening of cervical cells using block image processing. Meng Zhao, Aigou Wu,
Jingjing Song, Xugou Sun, Na Dong. 1, Tianjin - China : Biomedical Engineering Online,
February 4, 2016, Biomed Central, pp. 1-20.
10

13. Cervical Cancer diagnosis from Pap Smear Images Using structure based Segmentation.
Lipi B. Mahanta, Dilip Ch. Narth, Chandan Kr. Narth. 2, Gauhati : s.n., February 2012,
Journal of Emerging trends in Computing and Information Science, Vol. III, pp. 245-249. ISSN
2097-8407.
14. sarbortova, Hana. Detection of Cervical Cancer in Pap smear Images. wisconsin : s.n.,
2013.
15. Recent Advances in Morphological Image Analysis. Shengyong Chen, Mingzhu Zhao,
Guang Wu, Chunyan Yao, Jianwei Zhang. [ed.] Cattani Carlo. Zheijiang : Computational and
Mathematical Methods in Medicine, October 3, 2011, Hindawi Publishing Corporation, pp. 1-10.

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