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Cervical Cancer and HPV

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Cervical Cancer
Module Coordinator:
Dr Valerie Hinch
v.hinch@ulster.ac.uk
Cervical Cancer and HPV
Aims and Learning Outcomes:
after studying this session you should
confidently be able to:
1.
2.
3.
4.
Understand the normal cytology of the cervix
Outline stages of cytology abnormality - Dyskaryosis
Outline stages of Histology abnormality - Cervical Intraepithelial
Neoplasia (CIN)
Describe the role of Human Papilloma Virus in cervical cancer
Glossary
Abnormal: A change in the appearance of epithelial cells (dysplasia) or the appearance of the nucleus (dyskaryosis)
Benign: A tumour that is not cancer. It does not spread to other parts of the body but sometimes it is removed
anyway if it grows too big. Not malignant.
Biopsy: Procedure carried out to extract a sample of tissue so it can be examined.
Borderline: This means that cell changes have been found in the cells from the cervix but they will most likely go
back to normal on their own.
Brush (LBC): Broom like device used to collect cells from the cervix when taking a Liquid Based Cytology
sample.
Call/Recall: The process used to invite people for a screening test
Cervical cancer/carcinoma: Cancer of the neck (cervix) of the uterus. The tumour has spread into surrounding
tissue and may involve adjacent organs (invasion). It may be detected in a precancerous stage of development by a
cervical screening test.
Cervical Intraepithelial Neoplasia (CIN): Cellular changes in the cervix (neck of the womb) preceding the
invasive stages of cervical cancer. The CIN grading system distinguishes three stages, CIN1, CIN2 and CIN3. The
three grades of CIN relate to the thickness of the tissue covering the cervix that is affected. CIN 1 means one third
of the thickness of the tissue covering the cervix has abnormal cells. CIN 3 means the full thickness of the tissue
covering the cervix has abnormal cells. All these results mean that they are pre-cancerous.
Cervix: Neck of the Uterus (Womb)
Colposcopist: Clinician of gynaecological medicine specialising in the use of a colposcope and treatment.
Cytology/Cytopathology: The study of cells under a microscope.
Dyskaryosis: The appearance of abnormal cells whose nuclei show the features characteristic of the earliest stage
of malignancy.
Mild Dyskaryosis Indicates mild or slight cell changes in the cervix
Moderate Dyskaryosis Indicates moderate cell changes in the cervix
Severe Dyskaryosis Indicates severe cell changes in the cervix
Fail Safe System: Procedures built into the computer system to ensure any woman with a not normal result is
followed up.
Human Papilloma Virus: There are over 100 different types of this virus and they cause different epithelial
conditions e.g. HPV 1,2, + 4 cause hand and feet warts; HPV 6 + 11 cause genital warts and HPV 16 +18 cause CIN,
indicated as major risk factor for developing cervical cancer.
Inadequate screening test : A cervical screening test which cannot be properly assessed microscopically due to poor
quality or too few cells/materials This could result in a repeat test. (An inadequate test is also known as an
‘unsatisfactory’ test).
Invasive cancer: Cancer that has spread from its site of origin.
Liquid Based Cytology (LBC) : A technique for taking and preparing slides to be read. A brush is used to gather up
the cells and instead of smearing the cervical cell sample over the slide, it is placed in a preservative liquid for
transportation to a laboratory.
Negative (Normal): A smear result where all cells viewed were normal – no changes in structure of cells or nucleus
were observed.
Referral : The process whereby a patient is transferred from one professional to another, usually for specialist advice
and/or treatment.
Repeat smear: Usually taken three-six months after a positive or abnormal result to check if cells have fixed
themselves or are still not normal
Referral : The process whereby a patient is transferred from one professional to another, usually for specialist advice
and/or treatment.
Repeat smear: Usually taken three-six months after a positive or abnormal result to check if cells have fixed
themselves or are still not normal
Definition
•
Cytology (from the Greek word ‘kytos’ means ‘hollow’: Scientific
study of the structure and function of cells
 Non-gynaecology (non cervical) - discuss in next week’s
lecture
 Gynaecology (cervical cytology)
•
Cytopathology: A branch of laboratory medicine concerned with
examination of cells in health and disease
•
Cytopathologist: Clinician whom analysing and diagnoses cytology
cells
•
Cervical Cytology: Study of cervical cells
Histology vs Cytology
• Both valuable diagnostic tools.
• Important to take full advantage of the additional techniques that
can be applied to cytology smears and histopathology tissue
sections to gain maximum clinical information.
• Histology diagnosis may be required for confirmation of Cytology
diagnosis.
Histology
Cytology
Invasive
Minimally-invasive
Tissues
Cells
Formalin fixation
Wet/dry fixation
Paraffin embedded blocks Slide smear preparation
Overnight processing
Same day processing
Diagnosis by Pathologist
Diagnosis by BMS
Costly
Minimum cost
The Female Genital Tract
Surrounding
lymph nodes
Transformation
zone – also
known as the
squamous/
columnar
junction
•
Here you have a schematic diagram of
normal female genital tract illustrating the
transformation zone (squamous/columnar
junction) – note the surrounding lymph
nodes and the Histology representation
Squamous Columnar
cells
cells
Let’s take a journey of a gynaecology
(cervical sample) through the
laboratory,…..it all begins with
cervical screening,..
Why Cervical Screening?
Why Cervical Screening? - To prevent cervical
cancer
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Approximately 3,200 new cervical cancer cases in the UK every year (>8 every
day).
Cervical cancer is the 14th most common cancer
Cervical cancer accounts for 2% of all new cancer cases in females in the UK
Cervical cancer accounts for less than 1% of all new cancer cases in females and
males combined in the UK
Incidence rates for cervical cancer in the UK are highest in females aged 30 to
34 (2015-2017).
Since the early 1990s, cervical cancer incidence rates have decreased by a
quarter (25%) in the UK (2015-2017).
(UK, as at 2017)
,…mortality rates (UK 2016-2018)
• Approximately 850 cervical cancer deaths in the UK every year, (> 2 every
day)
• The 19th most common cause of cancer deaths, with approximately 860
deaths in 2018.
• Accounts for 1% of all cancer deaths in females in the UK (2018).
• Mortality rates are highest in females aged 90+ (2016-2018).
• Each year more than a quarter of all cervical cancer deaths (29%) are aged
75 and over (2016-2018).
• Since the early 1970s, mortality rates have decreased by three-quarters
(75%)
• Over the last decade, mortality rates have decreased by around a sixth (18%)
2020 - Number of NEW CANCER CASES
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Two main forms of cervical cancer:
Squamous Cell Carcinoma ~ 85%
Glandular Cell Carcinoma - Adenocarcinoma ~10-15%
A study by the International Agency for Research on Cancer has
reported an increase in adenocarcinoma and a downward trend in
Squamous Cell Carcinoma in many countries worldwide
• Note the % in comparison to various types of cancers
• Perhaps the screening programme is contributing to the small % of
cervical cancers?
How does a cervical cell become cancerous?
Characteristics common to many cancers:
1. Abnormal signal transduction resulting in uncontrolled cell
proliferation
2. Loss of apoptosis (programmed cell death)
3. Tissue invasion and Metastasis, allowing spread of the cancer
4. Angiogenesis, leading to enhanced blood supply of tumour
Cancer progression
• Most cancers arise as in cervical cells in the epithelial cells
(these are the cells that arise on the surface of tissues and
organs),
• When they begin to proliferate and become out of control, they
are said to become hyperplastic and hyperplasia occurs.
Symptoms and Risk Factors associated with
cervical cancer
•
•
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Cervical cancer characteristically has a long pre-cancerous phase, the
changes take place primarily in the transformation zone
Symptoms:
 Abnormal vaginal bleeding
 Post coital bleeding
 Vaginal discharge
Risk Factors:
 Early age of intercourse
 Smoking
 Number of sexual partners
 HPV
Cervical Screening
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Screening is NOT a test for cancer.
It is a national recommendation and local policy that females under 25 are
not routinely invited for cervical screening
It is however recommended that all females aged between 25 and 64 years,
who have ever been sexually active, have regular screening tests
Females aged 25-49 are invited every three years
Females aged 50-64 are invited every five years
England, Wales and Scotland use HPV primary screening
Northern Ireland use cell morphology screening following by HPV
detection if required.
Screening aims to prevent cervical cancer by detecting early pre-cancerous
changes in the cells that line the cervix (squamous/columnar)
Test results show abnormal changes in approximately 1 in 10 females
Any abnormal changes can then be treated, preventing them from
potentially developing into cancer
Where does the screening take place?
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All females who fall within the screening age range are automatically
invited to attend for a screening test.
Screening is carried out by a trained clinician
Samples are sourced from:
 GPs
 Health centres
 Hospital Outpatient’s Department
 Sexual and reproductive health (family planning) clinic.
Cervical cells are sampled
A small soft brush is used to gently pick up a sample of cells from your
cervix.
The sample is rinsed in an alcohol based preservative - ThinPrep Vials
e.g. Hologic Ltd (21ml PreservCyt)
How are the cervical cells sampled?
•
Cervical cells are scraped from the squamocolumnar
junction (transformation zone) and screened for
abnormality
Sample rinsed in
alcohol-based
preservative and
sent to laboratory
How are the samples processed by the
clinician?
1
3
5
RECORD the patient's
full name and date of
birth on the vial.
... the patient
information and medical
history on the cytology
requisition form.
RINSE the Cervix Brush
immediately into the
PreservCyt Solution vial
PLACE the vial and
requisition in a specimen
bag for transportation to
the laboratory.
2
4
OBTAIN an
adequate sample
from the cervix
using a Cervix
Brush (broom-like
device)
TIGHTEN
What happens at Cervical Screening: Videohttps://vimeo.com/113916053
Laboratory checks
To ensure samples are suitable for processing
Laboratory checks are important - important
quality control:
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Samples must be accompanied by a request form
No cervix brush should have been left in vial
The vial cap should not be over tightened
Fluid levels should be sufficient
If sample is grossly blood-stained need to treat with Glacial Acetic Acid
(GAA), otherwise cell morphology will be masked
Expiry date of vial should be checked - If the vial is “Out of Date”, this
should be recorded on laboratory error logging system, senior BMS
informed, returned to sender
Samples with any of the following details should be drawn to the
attention of a senior BMS
 Urgent
 Private patients
 Post-menopausal bleeding
 Details of any ongoing therapy e.g. HRT
 Molecular Investigations
 Suspicious
Request form checks:
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Patient and source information must be clearly printed on the request form
Cervical specimen requests received without essential criteria may be returned to
the sender for amendment
 Full Name
Example of essential information recorded for
 Date of Birth
each patient
 Gender
 Patient’s address
 Health & Care Number
 Relevant Clinical history
 Patient’s Location
 Patient’s Consultant/GP
So how is testing performed?
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Thin Prep T5000 Processor (an example)
Fully automated instrument for the preparation of liquid-based
cytology samples
Under negative pressure the sample collects cells which are then
transferred on to a glass microscope slide
The instrument must be kept clean and free from glass particles and
dust
Auto-Loader section allows a batch of up to 160 samples to be
processed
Sample workflow
Processors
PAP
stained
smear
Thin-Prep
vials
Sample workflow
Imaging
system
How could we represent cervical cells in a
practical? Swab our buccal cavity. 
Just like cervical cells, the cells which
line the inside of your cheeks are
 flat sheets of squamous epithelial
cells
 Immature non-keratinized (i.e. they
still contain their nuclei unlike mature
keratinized cells)
Histology view
Squamous
cells
Columnar
cells
Why use PAP stain?

Easy to visualise colours from the entire spectrum: red, orange, yellow,
green, blue, and violet (multichromatic)
 Superficial cells are orange to pink
 Intermediate and parabasal cells are turquoise green/blue

Staining results in transparent cells
Cell nuclei are crisp blue to black
Chromatin patterns are visible
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Histology view
Cytology view
Papanicolaou (PAP) stain
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Automated Papanicolaou (PAP) stain
Multichromatic staining histological technique developed by George
Papanikolaou (father of cytopathology)
Most employed for gynaecological specimens
Also employed for some non-gynaecological specimens
This procedure is considered accurate if the prepared, stained specimen
displays a representative subset of the cellularity present
The differential staining pattern permits prolonged periods of microscopy with
minimal eye-strain
The detection of pre-/malignant cells is based upon visual observation, and
does not yield quantitative information
When presenting its composition several dyes, it can reveal different types of
cells.
These characteristics are what make it optimal for cytological type studies.
Papanicolaou (PAP) stain continued,…
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A nuclear stain, haematoxylin, is used to stain cell nuclei
OG-6 counterstain stains keratin
EA (Eosin Azure) counterstain, (Eosin Y ) stains the superficial
epithelial squamous cells, nucleoli, cilia, and red blood cells
Light Green SF yellowish stains the cytoplasm of other cells, including
non-keratinized squamous cells
The stained specimen should display hues from the entire spectrum:
red, orange, yellow, green, blue, and violet
The chromatin patterns are well visible, the cells from
borderline lesions are easier to interpret. The staining results in
transparent cells, so even thicker specimens with overlapping cells can
be interpreted
On a well prepared specimen, the cell nuclei are crisp blue to black
Cells with high content of keratin are yellow. Superficial cells are
orange to pink, and intermediate and parabasal cells are turquoise
green to blue. Metaplastic cells often stain both green and pink at once
Results of
PAP stain
Dye
Structure
Colour
Haematoxylin Nucleus
Blue/Black
Light Green
(Eosin A50)
Immature (Non-keratinized.
intermediate, parabasal, basal,
columnar cells
Blue/Green
Eosin Y
(Eosin A50)
Cytoplasm of superficial cells
Red/Pink/Orange
Orange G
Mature (keratinized),
superficial cells
Orange
A stained PAP smears would then be ready for the Consultant
Pathologist/BMS to screen and diagnose,….
Cytology microscopy
Microscopy Clinicians:
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Primary screening
 All BMS have a daily workload of slides to screen, ‘spotting’
any areas of concern
Rapid Review
 All negative and inadequate smears are reviewed
Checking
 Staff fully re-screen all cases referred commenting on the quality
of the sample and spotting areas
Final medical screening
 Consultant Pathologist produces final report
Cytology results
Results may be as follows:
Infections:
 Fungal hyphae
 Trichomonas
 Actinomyces
 Herpes virus
 Human Papilloma Virus (HPV)
Precancerous changes:
 Negative
 Borderline changes
 Mild dyskaryosis (low grade)
 Moderate dyskaryosis (high grade)
 Severe dyskaryosis (high grade)
 Invasive (high grade)
 Glandular neoplasia
Infections
Candida Albicans
Approximately 20% of
women normally have
Candida in the vagina
without having any
symptoms. PAP show
hyphae and spores.
Trichomonas
Sexually transmitted
infection (STI) caused by
Trichomonas vaginalis
(TV).. Cervix becomes
very inflamed with sores.
PAP show small
perinuclear halo nuclei
Actinomyces
Seen in the vast majority
of patients, usually seen
in patients using an
IUCD (including the
Mirena coil). PAP show
tangled clump clusters of
organisms
Herpes
Genital herpes increases
the risk of cervical
cancer . It causes sores or
blisters to form in or
around the genitals/
HPV Infection – main cause of cancer (this
will be discussed later)
• White area indicates infection
• PAP illustrates nuclear enlargement, multinucleation, anisocytosis,
perinuclear cytoplasmic vacuolization
• Koilocyte is a squamous epithelial cell occur as a result of HPV
Koilocyte
Cytology Morphology
Normal Morphology
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Normal cells are characterised by their morphological uniformity
Nuclear size is proportional to the relative cytopasmic area (cytonuclear index)

Nucleus (N)

Cytoplasm (C)

N:C ratio

Cell size & shape

Nuclear morphology - reflects the state of proliferation, round or ovoid in
shape, smooth nuclear contour, evenly distributed, finely granular
homogeneous chromatin

Cytoplasm - generally provides an indication of origin, functional state &
degree of differentiation
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Small compact
nucleus
Occupying less
than 1/3 of cell
Low N/C ratio
Abnormal cells
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An abnormal cervical screening test result means that you have
changes in the cells covering the neck of your womb (cervix).
These changes are not cancer. The cells often return to normal by
themselves, however if not treated, these changes could develop
into cancer in the future.
Depends on characteristics of nucleus and cytoplasm
Screening result may report as being:
low grade (borderline cell changes)
low grade (mild cell changes) CIN1- Histology term
high grade (moderate cell changes) CIN2 - Histology term
high grade (severe cell changes) CIN3 - Histology term
Abnormal nuclear morphology

Nucleus:
 Increase in N/C ratio
 Variation in cell size, shape and staining (anisokaryosisor
anisonucleosis
 Intense nuclear staining (Hyperchromasia)
 Change in chromatin pattern
 Irregular, coarse chromatin clumping
 Condensation of chromatin at nuclear border
 Angularity of nuclear border
 Irregular nuclear outline with grooving, indentation or crenation
 Thickened nuclear envelope –karyotheca
 Increased nuclear DNA content
Abnormal nucleoli morphology

Nucleoli:
 Normal nuclei contain small, discrete nucleoli composed of RNA
and associated proteins
 Both multinucleolation & macronucleolation observed in
proliferative states-both neoplastic& non-neoplastic
 Degenerative chromatin may appear as:
 A dense, contacted mass
 Dense fragments
 Undergo dissolution
Abnormal cytoplasm morphology
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Cytoplasm:
 Variation in size & shape of similar cells –Anisocytosis
 Abnormal cells may have:
 Larger nuclear volume, thus
 Smaller cytoplasmic volume
 Nuclear : Cytoplasmic ratio affected
 Ultrastructural composition of the cytoplasm exerts a major
influence on staining reactions
 Mitochondria, golgi bodies, lipids, carbohydrates & hormones
etc
Cytology has the following stages of
abnormality:
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Cytology terms
Pre-cancerous changes are described as Dyskaryosis
Borderline, Mild, Moderate, Severe Dyskaryosis (Dysplasia)
Histology terms
Cervical Intraepithelial Neoplasia (CIN)
The changes are divided into 3 phases:
 CIN1, CIN2, CIN3
Mild Dyskaryosis
Mild
Dyskaryosis
Normal
cells
•
•
Dyskarytotic nucleus in a
differentiated cell
Less than 1/2 the cell in
the nucleus
Squamous
cells
Basement
membrane
CIN1
Moderate Dyskaryosis
Moderate
Dyskaryosis
Normal
cells
•
•
Less differentiation of
cytoplasm
Dyskaryotic Nucleus
occupies 1/2 - 1/3 cell
Squamous
cells
Basement
membrane
CIN2
Severe Dyskaryosis
Severe
Dyskaryosis
Normal
cells
•
Dyskaryotic nucleus
occupies 3/3 of the cell
Normal
Squamous
cells
Basement
membrane
CIN3
Nuclear abnormality with Koilocytosis
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Nuclear abnormalities due to HPV infection
Nucleus-irregularly enlarged
Nuclear hyperchromatic
Nuclear multinucleation
Cells perinuclear halo
Perinuclear halo
Condensation of cytoplasm
Multinucleation
Condensation
of cytoplasm
Summary of Cervical Intraepithelial Neoplasia
(CIN)
Summary Histology: Normal to CIN3
Squamous
cells
Basement
membrane
Normal
CIN 1
CIN 2
CIN 3
Treatment - abnormal cells
• LLETZ - (large loop excision of the transformation zone). It’s
also known as loop electrosurgical excision (LEEP) or loop
diathermy. This is the most common treatment for abnormal
cervical cells. The colposcopist uses a thin wire loop to remove
the transformation zone of the cervix. The wire has an electrical
current running through it, which cuts the tissue and seals the
wound at the same time.
• Cone - biopsy where a cone shaped wedge of tissue from the
cervix is removed.
• Cold coagulation - this uses a hot probe to burn away abnormal
cells.
• Cryotherapy - The colposcopist uses a cold probe to freeze away
the abnormal cells.
• Laser ablation - A laser beam is a very strong, hot beam of light.
It burns away the abnormal area.
If cancer arises
Summary:
Normal - Invasive carcinoma
Cervical Squamous Carcinoma
Normal Cervix
Cervical Squamous Carcinoma
Invasive carcinoma
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Nucleoli irregular in shape and size, vary in number
Irregular clearing in chromatin (windowing)
Cytoplasmic keratinisation
Cancer Stages
Cervical Cancer - Stage 1
Stage 1A1 means the cancer has grown less than 3
mm into the tissues of the cervix.
Stage 1A2 means the cancer has grown between 3
and 5 mm into the cervical tissues.
Stage 1B2 the cancer is at least 2cm but not
bigger than 4cm in size.
Stage 1B1 the cancer is deeper than
5mm but no more than 2cm in size.
Stage 1B3 the cancer is at least 4cm but
is still only in the cervix.
Cervical Cancer - Stage 2
Stage 2A1 means the cancer is 4
cm or less.
Stage 2A2 means the cancer is
more than 4 cm.
Stage 2B the cancer has spread up
into the tissues around the cervix.
Cervical Cancer - Stage 3
Stage 3A is when the cancer has
spread to the lower third of the
vagina but not the pelvic wall.
Stage 3B means the tumour has grown Stage 3C1 means cancer is in the
through to the pelvic wall or is blocking nearby pelvic lymph nodes. Stage 3C2
means cancer is in the para-aortic lymph
1 or both of the tubes that drain the
nodes (in the abdomen).
kidneys (the ureters).
Cervical Cancer - Stage 4
Stage 4A is when the cancer
has spread to nearby organs
such as the bladder or back
passage (rectum).
Stage 4B is when the cancer has
spread to organs further away,
such as the lungs. Your doctor
might call this secondary or
metastatic cancer.
Cervical Cancer Treatment
• The stage of cancer helps the clinician decide which treatment
is required.
• Treatment depends on the type of cancer (the primary source)
• Where the cancer is located
• Other health conditions
• Surgery
• Combined chemotherapy and radiotherapy
(chemoradiotherapy)
Cervical Cancer survival rates
Survival statistics for people diagnosed between 2013 and 2017. These
statistics are non-age-standardized.
Stage 1
Around 95 out of 100 people (around 95%) will survive their cancer for 5 years
or more after diagnosis.
Stage 2
Almost 70 out of 100 people (almost 70%) will survive their cancer for 5 years
or more after diagnosis.
Stage 3
More than 40 out of 100 people (more than 40%) will survive their cancer for 5
years or more after diagnosis.
Stage 4
Around 15 out of 100 people (around 15%) will survive their cancer for 5 years
or more after being diagnosed.
Human Papilloma Virus (HPV)
and Cervical Cancer
HPV
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In humans viruses contribute to ~ 15% of all malignancies
Viruses are the second most important risk factor for developing
cancer in humans after cigarette smoking!
80% of viruses-associated cancers include
 Carcinoma of the cervix
Since the advent of recombinant DNA technology and the cloning of
human papillomaviruses (HPV), the association between HPV, CIN
and cancer has been confirmed
Compelling evidence both epidemiological and molecular tests
demonstrate that persistent HPV infection is a pivotal step in the
development of cervical cancer
HPV
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Small DNA viruses
55nm in diameter
A non-enveloped icosahedral outer coat
Surrounding a circular genome of double stranded DNA
The genome of ~ 8000bp
Divided into
 Early genes: E1, E2, E4, E5, E6 & E7
 Late genes: L1 & L2
Over 30 HPV types infect the cervical mucosa
HPV genes
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Early genes are responsible for:
 DNA replication
 Transcriptional regulation and transformation
The early gene products E6 and E7 encode the major transforming
proteins:
 Capable of inducing cell proliferation and immortalisation
 By binding to the tumour-suppressor gene products p53 & pRB
 P16-associated with cervical cancer (IHC)
Late genes control:
 Formation of the capsid coat
HPV Infection
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Initiated when the virus gains access to the basal epithelial cells
Stages include:
 infection of metaplastic epithelium at the cervical
transformation zone
 viral persistence
 progression of persistently infected epithelium to cervical
precancer
 invasion through the basement membrane of the epithelium
Minor trauma (during sexual intercourse) allows access to the target
cells:
 Near or at the cervical transformation zone
The viral life cycle is linked to keratinocyte differentiation
Viral replication leads to:
 Koilocytosis (indication of HPV), nuclear enlargement,
multinucleation, dyskaryosis and CIN
HPV sub-types
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Approximately 200 types of HPV are acknowledged to exist
15 are classified as high-risk types: 16, 18, 31, 33, 35, 39, 45, 51, 52,
56, 58, 59, 68, 73, and 82
3 as probable high-risk: 26, 53, and 66
12 as low-risk: 6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, and CP6108
HPV 16 and 18 associated with 70% cases of cervical cancer
HPV 6 and 11 associated with 90% of benign lesions such as genital
warts
Together with type 31, they are the prime risk factors for cervical
cancer
HPV Mode of Transmission
Detection of HPV
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
Morphological
 Electron Microscopy
 Immunohistochemistry (p16, Ki-67, P53)
 In Situ Hybridisation (ISH)
Non-Morphological
 PCR
 Hybrid Capture
Popular Testing Methods
1. Roche: Cobas 4800 (most popular)
2. Hologic Aptima
3. Abbott Real-Time
Detection
HPV16, HPV18 and 12 ‘other HR-HPV’ genotypes
but doesn’t have the specificity to provide their
genotypes.
-70% of cervical cancers are due to HPV 16 & 18
HPV16, HPV18 & HPV 45 (3rd most common HPV
genotype)
-12% of cervical adenocarcinomas caused by HPV45 thus this method of testing could help to identify
more women at risk of cervical cancer
14 HR-HPV genotypes including HPV 16 & 18
Similar to Roche: Cobas 4800, HPV 16 and HPV 18
are specifically identified
HPV Vaccines
What are HPV vaccines?
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Vaccines which produce antibodies to protect against infection
with HPV
Three vaccines approved by the Food and Drug Administration
(FDA)
Gardasil, Gardasil 9 and Cervarix
All three prevent infection with HPV 16 and 18
Gardasil also prevents infection with HPV 6 and 11
Gardasil 9 prevents infection with HPV 16, 18, 6, 11 plus
31,33,45,52 and 58
Administered to children aged 11-12 years old in two doses six
months after the other
Trials have proved that these vaccines have found to provide
almost 100% protection against HPV16 and 18 associated HPV
infections
Vaccine - with/without
Abnormal cervical result - what next?
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Borderline change (low-grade dyskaryosis)
 Laboratory will perform a reflex high-risk human papillomavirus
(HR-HPV) test on the cytology sample
 If the HPV test is positive the female will be referred
for colposcopy for an appointment within 6 weeks
 If HPV test is negative, the female will be returned to routine
screening (3 years)
High-grade dyskaryosis (moderate or severe)
 referral to colposcopy for an appointment within 2 weeks
Suspected invasive cancer or glandular neoplasia
 referred to colposcopy for an appointment within 2 weeks
Cervical
Screening
Programme
HPV triage and
test of cure
protocol
It has to be noted that HPV causes more
than cervical cancer,…..
You should now be able to:
1.
2.
3.
4.
5.
Understand the normal cytology of the cervix
Outline stages of Dyskaryosis
Outline stages of Cervical Intraepithelial Neoplasia (CIN)
Describe the role of Human Papilloma Virus in cervical cancer
Be aware of the various types of treatment.
End of Lecture
Thank you for listening - any questions?
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