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Cervical Cancer
What is Cancer?
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Hippocrates was the first to use the word “cancer” to describe tumors
Cancer is derived from the Greek word “karkinos” which means crab
It is thought Hippocrates was referring to the appearance of tumors.
The main portion of the tumor being the crabs body and the various
extensions of the tumor appear as the legs and claws of the crab.
What is Cancer?
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Changes to the DNA of a cell (mutations)
lead to cellular damage
Mutations enable cancer cells to divide
continuously, without the
need for normal signals
In some cancers the unchecked growth
results in a mass, called a tumor
Cancerous cells may invade other parts of
the body interfering with normal body
functions
What is Cancer?
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Although cancer is often referred to as if it
were a single disease, it is really a diverse
group of diseases that affects many
different organs and cell types
The likelihood of developing any particular
cancer depends on an individual’s
genetics, environment, and lifestyle.
The occurrence of some cancers may be
prevented/reduced by wise lifestyle
choices.
What Causes Cancer?

Some known cancer causing agents
(carcinogens) with which you might
interact:

How to reduce your cancer risk:
DON’T:
Smoke
UV Radiation (sun, tanning bed)
DO: use sunscreen
DON’T: excessively exposure
yourself to UV radiation
(tanning beds, sun)
DO: get available
vaccines
Tobacco (cigarettes
and smokeless)
Viruses (HPV, EBV)
DO: make healthy
lifestyle choices
What is Cervical Cancer?
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Cervical cancer is a slow developing cancer that starts in the interior lining of
the cervix. Almost all cases begin with changes caused by the human
papillomavirus (HPV), a sexually transmitted infection.
Over time the changes caused by HPV build up and a pre-cancerous condition
called cervical intraepithelial neoplasia (CIN) develops.
CIN can progress to cervical cancer, but this is not always the case.
Image Courtesy of QIAGEN
www.qiagen.com
What is a Cervix?
1
1. Fallopian (uterine) Tubes - location of
fertilization of an egg by a sperm cell
2. Ovaries - produce and store gametes (eggs)
and produce the female sex hormones,
estrogen and progesterone
3. Uterus (womb) - location where fertilized
egg develops into a fetus and is nourished
until birth. Note that the walls of the uterus
are thick and lined with muscles
4. Cervix - region connecting the uterus to
the vagina
5. Vagina - passageway for menstrual blood
and babies during childbirth
1
3
2
2
4
5
More About the Cervix
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The cervix is the lower portion of the uterus
and it plays an important role in reproduction
The narrow cervical canal connects the uterus
to the vagina and allows passage of menstrual
fluid
During pregnancy the muscles of the cervix
support the weight of the fetus
During childbirth the muscles relax and the
opening widens (dilates) allowing the fetus to
pass through the cervical canal and out of the
vagina
Note: Cervical abnormalities can result in
miscarriage
uterus
Endocervix
cervix
Ectocervix
vagina
More About Cervical Cancer
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Cervical cancer is most often diagnosed in middle-aged women, with half of those
diagnosed between the ages of 35 and 55. It is rarely seen in women younger than 20
and approximately 20% of cases are in women over the age of 65.
Cervical cancer is not often diagnosed in young women, but this does not mean young
women are not at risk.
Cervical cancers that develop in older
women frequently result from HPV
infections that occurred many years
earlier.
HPV infection, which can occur at any
age, greatly increases the risk for
cervical cancer.
How Common is Cervical Cancer?
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Cervical Cancer Statistics 2007 (estimated)
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Worldwide cases: 555, 094
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Worldwide deaths: 309,808
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US cases: 11,150
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US deaths: 3,670
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In 2007 cervical cancer was second only to breast
cancer as the most commonly diagnosed cancer in
women worldwide
In the US the estimated yearly costs of cervical
Human Papillomavirus (HPV) related disease is at
least $2.25 billion and may be as high as $4.6
billion.
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cervical cancer is a global issue
and does not discriminate
What Kinds of Cervical Cancer Are There?
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There are two main types of cervical cancer:
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Squamous cell carcinoma
The majority of cervical cancer cases (8090%) are of this type. This cancer type
often originates where the ectocervix
joins the endocervix

Adenocarcinoma
This type constitutes the other 10-20% of
cervical cancer and develops in the
mucous producing glands of the
endocervix
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In rare cases, cervical cancer can be a mix
of both adenocarcinoma and squamous
cell carcinoma
cervical squamous cell carcinoma
Does Cervical Cancer Have Any Symptoms?
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Precancerous changes and early stage cancer usually have no
symptoms (are asymptomatic)
Symptoms of later stage disease
may include:
- pain, if lymph nodes are involved
- bleeding, caused by the tumor
- vaginal discharge
- pelvic or back pain
cervical cancer viewed with colposcope
How Does Cervical Cancer Develop?
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There are 3 steps necessary for cervical cancer development
1. HPV infection
2. Progression to cervical intraepithelial neoplasia (CIN)
3. Invasion
HPV infection
must persist for
more than one year
Normal
Cervix
HPV Infection
HPV Clearance
Infected
Cervix
Progression
Invasion
CIN
Regression
Cancer
Tell Me More About CIN
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Cervical Intraepithelial Neoplasia (CIN)
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Long term HPV infection can lead to abnormal cellular changes. If these
changes accumulate a condition called Cervical Intraepithelial Neoplasia (CIN)
develops.
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There are 3 stages (grades) of CIN:
CIN 1, CIN 2, CIN 3.
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Some, but NOT ALL, cases of CIN can
progress to cervical cancer.
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CIN can also regress, returning the
cervix to normal
high grade CIN 3
What are the Stages of CIN?
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CIN1
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CIN 2
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Rarely (~1%) develops into invasive cervical cancer, about 20% will progress to CIN2
About 30% of CIN2 will progress to CIN 3
CIN3
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About 40% will progress to cancer; usually develops after long term HPV 16 or 18 infection
Can Cervical Cancer be Detected?
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Detection Types
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Because early cervical cancer is generally asymptomatic, regular screening is the
best way to detect precancerous lesions.
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Pap Test
 Recommended yearly for women over 21 or within 3 years of
becoming sexually active.
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HPV Test
 HPV tests are not normally recommended for women under 30. After
age 30, HPV tests are recommended with a Pap test
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Colposcopy
 Used when abnormal findings are present on Pap test and a positive
HPV test
Tell Me More About the Pap Test
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Pap Test
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A doctor or a specially trained healthcare professional inserts a cervical brush or
spatula though the vagina and cells are wiped from the surface of the cervix and
placed on a slide or in a vial.
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The cells are then examined under a microscope for abnormalities that could
indicate pre-cancerous or cancerous conditions.
brush
Tell Me More About the HPV Test
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HPV Test
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A sample of cells is taken from the cervix during a pelvic examination, using a
brush or spatula. The sample is placed into a preservative and sent to a lab for
testing. The lab tests the sample for the presence of HPV DNA.
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A positive test indicates HPV infection, but a positive result does not indicate
CIN or cervical cancer. Follow up procedures (pap test and colposcopy) are
recommended.
The test detects
HPV DNA
If an HPV infection is present in the cervix,
HPV DNA will be detectable
Tell Me More About Colposcopy
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Colposcopy
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A colposcopy is done using an instrument called a colposcope. A colposcope is a
special microscope that can magnify the cervix up to 16 times its actual size. It
allows the physician to examine the linings and other structures of the cervix.
Colposcope
View of Cervix with Colposcope
Are There Cervical Cancer Risk Factors?
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The Main Risk Factor
 Human papillomavirus (HPV)
HPV has been found in over 95% of cervical cancer cases. But, most cases
of HPV infection will clear within 1 to 2 years and will NOT cause cervical
cancer.
Co-Factors
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Co-factors increase the ability of HPV to cause cervical cancer.
These include:
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Smoking
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Other sexually transmitted infections (STI), including the human
immunodeficiency virus (HIV) , chlamydia, and the herpes virus
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Additional risk factors, including genetics and diet, are being actively
researched
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So HPV is the Main Cause?
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The Main Risk Factor
 Human papillomavirus (HPV)
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HPV has been found in over 95% of cervical cancer cases. But, most cases
of HPV infection will clear within 1 to 2 years and will NOT cause cervical
cancer.
Human papillomavirus is one of the most common sexually transmitted
infections (STI) in the United States. Recent studies have shown that over
25% of all women are infected. Infection rates among women aged 20-24
may be as high as 44%.
Men can also be infected by HPV and transmit it to women. In fact
prevalence may be higher in men than women.
More on HPV later
Cervical Cancer, HPV, and Smoking
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Nicotine (the addictive compound found in cigarettes)
has been found in the cervical secretions of women that
smoke. This indicates other cancer causing compounds
found in cigarettes also may collect in the cervix.
A recent study of 346 US women aged 18-35 found a
correlation between cigarette smoking and cervical
cancer. Women who are current or previous smokers
had significantly longer HPV infections than women who
never smoked1.
The Human Papillo…What?
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The Human Papillomavirus
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What’s a Virus?
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The human papillomavirus is a group of over 200 genetically different viruses. It
is a sexually transmitted infection (STI) and is the main cause of cervical cancer
worldwide.
Viruses are very small infectious particles, responsible for diseases that include
the common cold, the flu, AIDS, and chicken pox.
The smallest known virus is 20 nanometers across (a nanometer is about
35-millionths of an inch). For comparison, a human hair is about 65,000
nanometers in diameter or about 4,000 times larger.
What’s a papillomavirus
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Papillomaviruses were first discovered in the early 20th century and named for
their ability to cause papillomas (warts).
Tell Me More About Viruses
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What Exactly is a Virus?
 “a kind of borrowed life”
 Viruses don’t fit neatly into a category of living or non-living. They have
some characteristics of living things, but they are not made of cells and
lack equipment for self reproduction. Because of this, they can only
reproduce within a host cell.
Human Immunodeficiency Virus (HIV)
Human Papillomavirus (HPV)
Tell Me More About Viruses
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Virus Structure
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Viruses come in all shapes and sizes, but
they are usually composed of a genome and
a surrounding shell (capsid)
Viral Capsid
protein shell that surrounds
and protects the viral genome
made up of various protein
subunits called capsomeres
Viral Genome
Contains genetic
information; DNA or RNA
that may be either double or
single stranded
Organized as either linear
or circular molecules
Circular Genome
How do Viruses Reproduce?
1
1.
2.
2
3.
3
Virus binds host cell and inserts
genome
Host cellular machinery begins
to replicate the viral genome
and produce viral proteins.
Viral molecules self-assemble
into new viruses (virions) and
exit the cell
A single infecting virus can produce
many copies of itself, often hundreds
or thousands at a time. When the
viruses exit the host cell they are
capable of infecting other cells,
spreading the infection.
Are There Different Types of HPV?
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There are over 200 described genetically different types of HPV
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Some HPV types are responsible for
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common warts
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plantar warts
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Other types infect the genital tract; these are divided into high risk and low risk
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High risk – responsible for the majority of cervical cancer
•
Types 16 and 18 cause ~70% of cervical cancer cases
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Low risk – not thought to cause cancer
•
Types 6 and 11 cause a large percentage of genital warts
Add images of plantar and genital warts
How Can I Reduce My Risk?
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Prevention of HPV
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Abstinence (not having sex), is the only completely effective method of
HPV prevention
HPV can be transmitted by oral and anal sex as well as vaginal intercourse
Ways for sexually active individulals to reduce risk
•
Use a condom! Condoms will not provide complete protection
against HPV, but they will reduce the chance of getting it.
Remember: condoms also help reduce the risk of unwanted
pregnancy and other STI’s, including: HIV, gonorrhea, Chlamydia,
herpes, hepatitis, syphilis, among others.
•
Reduce number of sexual partners! The chances of getting HPV
increase with number of sexual partners. Studies have shown that
women with multiple (>1) sexual partners have an increased risk for
HPV and for CIN .
How is HPV Transmitted
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Ways HPV is Passed From Person to Person:
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Skin to skin sexual contact with a partner
who is infected with HPV is the most
common way HPV is passed. Sexual contact
includes:
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intercourse
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oral sex
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genital to genital contact
Not passed through:
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toilet seats
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doorknobs
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water fountains
How Does HPV Cause Cervical Cancer?
HPV
E7
E6
Two of the proteins made by the
human papillomavirus are strongly
associated with the development of
cervical cancer
E6 inhibits the
function of p53
E7 inhibits the
function of Rb
p53
Rb
p53 is a protein that controls
response to cellular stress
including DNA damage and
viral infection.
Rb is a protein that can
prevent cell division by
blocking the activity of
transcription factors
Of Great Importance…
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HPV Vaccines
Gardasil ®
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What is it?
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Gardasil ® is a vaccine approved by the Food and Drug Administration
(FDA) to protect against four types of HPV: 6, 11, 16, and 18
Who can get it?
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The CDC and FDA recommends girls and women aged 9-26 should get the
vaccine.
Why 6, 11, 16, and 18?
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Types 6 and 11 cause most cases of genital warts
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Types 16 and 18 are high-risk types that can cause cervical cancer (~70%)
How effective is it?
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Studies have shown the vaccine to be almost 100% effective in preventing
diseases caused by the 4 types of HPV it covers
Of Great Importance…
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HPV Vaccines
Cervarix™
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What is it?
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Cervarix™ is an HPV vaccine produced by GlaxoSmithKline that has not
yet been approved by the Food and Drug Administration (FDA). It has
been approved in Australia and Europe.
What does it protect against?
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Cervarix™ protects against types 16 and 18. These are high-risk types that
cause cervical cancer over 70% of all cervical cancer cases.
A Closer Look: Vaccines
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The human immune system is a complex
collection of cells and proteins that
function to protect the body from foreign
matter, both living and nonliving.
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Two types of immune cells involved in
protection against viruses are T cells and B
cells. Both cell types are activated when they
encounter viral proteins (antigens)..
A Closer Look: Vaccines
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Upon Activation:
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B cells - produce large amounts of
proteins called antibodies which move
throughout the circulatory system
binding the specific antigen for which
they were created.
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T cells - reproduce thousands of times
and enter the bloodstream searching
for their corresponding antigen.
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When antibodies and T cells encounter
the antigen, they begin a process that
leads to the destruction and removal of
the antigen.
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The presence of antibodies against HPV
in a vaccinated person prevents
infection by the virus.