CERVICAL CANCER

SCREENING
AND
PREVENTION

Presented by: Dr. Roshan Gachhadar

2nd Year Resident (MD GP & EM )

1
What is Cervical Cancer
 Cervical cancer is a kind of cancer
occurs in the lower part of a cervix with
a development period as long as ten
years.
 The cervix connects the uterus to the
vagina.
 The part of the cervix which is the
closest to uterus is called the endocervix.
The part next to the vagina is the
ectocervix.
 The place where these two parts meet is
called the transformation zone.
 Most cervical cancers start in the transformation zone.
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 Key Facts

Human papilloma virus (HPV) is a group of

viruses that are extremely common worldwide.
There are more than 100 types of HPV, of which
at least 13 are cancer-causing (also known as high
risk type).
HPV is mainly transmitted through sexual
contact and most people are infected with HPV
shortly after the onset of sexual activity.
Cervical cancer is caused by sexually acquired
infection with certain types of HPV.
Two HPV types (16 and 18) cause 70% of cervical
cancers and precancerous cervical lesions.
There is also evidence linking HPV with cancers of
the anus, vulva, vagina and penis.
Cervical cancer is the second most common cancer
in women, with an estimated 5,30,000 new cases
every year.
Every year, more than 2,70,000 women die from
cervical cancer; more than 85% of these deaths are
in low- and middle-income countries.
Vaccines against HPV 16 and 18 have been
approved for use in many countries.
 HUMAN PAPILLOMA VIRUS

Papilloma virus first recognized many years ago as the cause of warts
on the hands and feet or condyloma accuminata on the pubic area

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 HUMAN PAPILLOMA VIRUS

Major capsid protein

(LI)

Viral nucleic acid

(DNA)

HPV is relatively small-just two strands of DNA contained in a

round shell or envelop that looks like a golf ball when enlarged
under an electron microscope
24
 TYPES OF HPV

•HPV 16 and 18 types account for the majority cervical

cancers.

•Non oncogenic types: HPV 6 and 11 are most often

associated with external ano-genital warts.

25
How HPV infection leads to cervical cancer

 Although most HPV infections clear up on their own and

most pre-cancerous lesions resolve spontaneously, there is
a risk for all women that HPV infection may become
chronic and pre-cancerous lesions progress to invasive
cervical cancer.

 Ittakes 15 to 20 years for cervical cancer to develop in

women with normal immune systems. It can take only 5 to
10 years in women with weakened immune systems, such
as those with untreated HIV infection
HOW HPV INDUCES CANCER

 HPV infection is believed to start in the basal cells or

parabasal cells of the metaplastic epithelium.
(Transformation zone)

 If the infection persists, integration of viral genome into

the host cellular genome may occur.

 Then the normal differentiation and maturation of the

immature squamous metaplastic into the mature
squamous metaplastic epithelium is disrupted as a result
of expression of E6/E7 oncoproteins and the loss of
normal growth control.

27
 HOW HPV INDUCES CANCER..contd…

 This may then lead to development of abnormal dysplastic

epithelium-LGL –HGL

 Subsequently the disease may traverse the basement

membrane and become invasive cancer, extending to
surrounding tissues and organs. The invasion may then
affect blood and lymphatic vessels and the disease may
spread to the lymph nodes and distant organs.

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 Spectrum of Changes in Cervical Squamous Epithelium Caused by HPV Infection1

Normal HPV Infection / CIN 2 / CIN 3 /

Cervix CIN* 1 Cervical Cancer

1. Adapted from Goodman A, Wilbur DC. N Engl J Med. 2003;349:1555–1564. Copyright © 2003 Massachusetts Medical Society. All rights reserved. Adapted with permission.
29
 Progression of CIN to malignancy
Time Months Years

Normal HPV infection; CIN I CIN II CIN III Carcinoma

epithelium koilocytosis

Low-grade squamous High-grade squamous

intraepithelial lesions (LSILs) intraepithelial lesions (HSILs)

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 Introduction
To
Cervical Cancer

35
Incidence
Important health problem.

Third most common cancer in women .

Affectsmore than 1.4 million women

worldwide.

About 80% of new cervical cancers occur

every year.
36
RISK FACTORS FOR CERVICAL CANCER

RISK FACTORS

Sexual Activity Multiple Sexual

Exposure to STI
(<20 years) Partners

Mother or Sister
With Cervical
Cancer

Previous abnormal
Smoking Immunosupression
Pap Smear

37
Natural History of Cervical Cancer
Normal Cervix

About 60%
regress within HPV Infection
2-3 yrs
HPV-related Changes

Low-Grade SIL (Atypia, CIN I)

Cofactors
High-Risk HPV Types
About 15% progress within 3-4 yrs
(16, 18, 33, etc.)

High-Grade SIL (CIN II, III/CIS)

30%-70% progress within 10 yrs

Invasive Cancer
38
Source: Sherris 1998; Bishop et al 1995.
 HPV Lifecycle in the Cervix
Shedding of virus-
laden epithelial cells

Cervical canal Viral assembly

(L1 & L2)
Mature
squamous
layer
Viral DNA replication
Squamous (E6 & E7)
layer

Episomal viral DNA in

Parabasal cell nucleus
cells (E1 & E2, E6 & E7)

Infection of basal cells

Basal (stem)
(E1 & E2)
cells
Basement membrane

Normal Infected
epithelium epithelium 39
Signs and symptoms
• The majority of HPV infections do not cause symptoms or disease and resolve
spontaneously.
• However, persistent infection with specific types of HPV (most frequently types 16
and 18) may lead to precancerous lesions.
• If untreated, these lesions may progress to cervical cancer, but this progression
usually takes many years.
• Symptoms of cervical cancer tend to appear only after the cancer has reached an
advanced stage and may include:

• Irregular, Intermenstrual (Between Periods) Or Abnormal Vaginal Bleeding

After Sexual Intercourse;
• Back, Leg Or Pelvic Pain;
• Fatigue, Weight Loss, Loss Of Appetite;
• Vaginal Discomfort Or Odourous Discharge; And
• A Single Swollen Leg.

• More severe symptoms may arise at advanced stages.

Cervical Cancer
Screening And
Prevention
Goal Of Screening Programme

To detect pre invasive stage of the

disease(CIN-Cervical intraepithelial lesion)

To treat CIN before it progresses to invasive

forms.

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• Primary Prevention
• Vaccines
• Education to reduce high-risk sexual behavior.
(Promotion of Barrier Methods i.e. Condoms)

• Secondary Prevention
• Identify and treat precancerous lesions before they
progress to cervical cancer.
• Identify and treat early cancer while the Chance of cure is
still good.

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 Effective Secondary Prevention
Safe No one must get hurt

Accurate Test provides reasonable probability of Reasonably Effective

differentiating disease from health. Accurate Treatment
Test
Actionable Test results can be acted upon
immediately.
Affordable Program can be budgeted by private/ Screening
public sector. Coverage

High coverage must be possible even in

Accessible hard to reach areas .

Practical Skill levels must be present at all levels of

the health system to perform, report,
communicate and monitor test and
treatment results.
45
45
Integration of HPV Vaccination and Screening

Modified fromSchiffman, Castle, NEJM 2005 46

46
 Screening For Cervical Cancer

• Cervical cancer screening is testing for pre-cancer and cancer among

women who have no symptoms and may feel perfectly healthy.

• When screening detects pre-cancerous lesions, these can easily be treated

and cancer avoided.

• Screening can also detect cancer at an early stage and treatment has a
high potential for cure.

• Because pre-cancerous lesions take many years to develop, screening is

recommended for every woman from aged 30 to 49 at least once in a
lifetime and ideally more frequently.

• Screening is only effective if a high proportion of women participate.

 Different types of screening tests are:

1. Conventional (Pap) test and liquid-based cytology (LBC).

2. Visual inspection with Acetic Acid (VIA) and Lugol’s Iodine.

3. HPV - DNA testing for high-risk HPV types.

Dealing With Test Results
Conventional Cervical Cancer Prevention
Laboratory backup not available,
not reliable or expensive
Pap Test Colposcopes expensive and fragile
The pathologist is one of the rarest
of medical species
Negative Positive Poor records, difficulty In tracking
patients
Patients unable to return for
multiple visits
Colposcopy
Follow up 1- 5 years
Biopsy

Negative CIN 1 (low grade SIL) CIN 2 & 3(High Grade SIL)

Follow up
Follow up or treat Treat
yearly

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 Screening Strategies Of Nepal

Family Health Division (FHD) should be the focal

point for placing the developed protocol into the
national policy and action for implementation.
Once the Screening program is adopted into the
MoHP Systematically it will go into Schedule in
Health care of government as TB and other
programs.
 Strategies For Cervical Cancer Screening
Objective of Cervical Cancer Screening and Prevention (CCSP) is to provide cervical
cancer screening services to the target population who attend the health or are invited for
screening at the nearest possible vicinity in a nation wide scale.

Table 1. Age-Specific Female Population of Nepal, Eligible for Cervical Cancer Screening

Age Group 2006 2011 2016 2021

30 - 34 930,564 1,075,404 1,223,906 1,378,645

35 - 39 777,905 915,024 1,059,865 1,208,446

40 - 44 643,984 761,304 897,527 1,041,809

45 - 49 530,011 625,001 740,921 876,053

50 - 54 429,381 507,772 601,181 715,049

Total 3,313,851 3,886,246 4,525,416 5,222,023

Source: Central Bureau of Statistics (CBS)/UNFPA Population Statistics of Nepal,

CLIENT ASSESMENT
AND
VIA TESTING
 Counseling Prior To Via Testing

 The nature of cervical cancer as a disease and

consequence of HPV infection.

 Availability of HPV vaccines and who can benefit most

from them.

 Risk factors for the disease.

 The role and importance of VIA testing.

 Consequences of not being tested.

 Treatment options if the VIA test is abnormal.

 Counseling Prior To Cryotherapy

Cryotherapy procedure, it's risks, benefits,

likelihood of success and alternatives:

Expected side effects:

Cramps
Vaginal Discharge (Profuse watery)
Spotting/light bleeding
 Single Visit Approach (SVA)
Screen And Treatment Approach
Provided at the lowest levels of the health care
system where majority of women at risk are
located.

Take place during the same visit.

Provide by doctors, nurses and healthcare workers.

Offers excellent cure rates with good cost-benefit

ratio for treatment of lesions that have a low
likelihood of being cancerous.
 TE D
E T ES
LD B
H O U
WH OS
Screening Interval:
Once in Five years

Coverage Goal
50% of the target population within a span of Five years.

Documentation of the screened Population:

National Citizenship card should be used for the documentation. It can
be a Consistent source of identification for re Screening and Follow-up.
When To Perform VIA ???
Anytime in the menstrual cycle including
during menses.
During Pregnancy.
Postpartum.
Post abortion follow-up
 Screening Methods:

1. Visual Inspection with Acetic Acid (VIA).

2. VIA and Treatment by Cryotherapy as a

Single Visit Approach ( SVA ).

3. Cytology / Pap smear.

Instruments and materials required
 Examination table
 Good light source (preferably a bright halogen lamp);
 Sterile bivalve speculum: Cusco's, Grave's or Collin's
 Pair of gloves
 Cotton swabs, cotton-tipped buds, gauze
 Ring forceps, pickup forceps
 5% freshly prepared acetic acid or vinegar and lugol’s
iodine
 A steel/plastic container with 0.5% chlorine solution in
which to immerse the gloves and instruments
Preparation of 5% acetic acid

 5% acetic acid is prepared by adding 5 ml of glacial

acetic acid into 95 ml of distilled water.

 If vinegar bought from a store is used, check the

strength to ensure that it is 5%.
How 5% Acetic Acid Works?

Application – reversible coagulation or

precipitation of cellular proteins.

Effect of Acetic acid depends on the amount

of proteins present in the epithelium
 Test provider skills

Good knowledge of the anatomy, physiology

and pathology of the cervix.

Clinical features of benign conditions,

inflammation, precancerous lesions and
invasive cancer of the cervix.
Procedure

 Written informed consent.

 Obstetric and gynecological history.
 Modified lithotomy position.
 Vaginal discharge if any observe.
 Gently introduce a sterile vaginal speculum.
 Observe the size and shape of the cervix.
 Identify :
◦ The external os,
◦ Columnar epithelium (red in colour),
◦ Squamous epithelium (pink) and
◦ The squamocolumnar junction.
Contd…
 Identify the transformation zone.
 Look for ectropion, cervical polyp, nabothian cysts, healed
laceration, leukoplakia, condylomata and signs of cervicitis.
 Post menopausal women, the cervix appears pale and brittle.

then

 Apply 5% acetic acid using a cotton swab soaked in acetic acid.

( wait for 1 minute)

 Carefully look at the cervix to see whether any white lesions

appears .
Observation

 The intensity of white colour of the acetowhite lesion.

 The borders and demarcations of the white lesion:

 Uniformity of white colour.

 Location of the lesion.

 Size and number of the lesions.

VIA CLASSIFIICATION RELATIVE TO CLINICAL FINDINGS

Via Classification Clinical finding

Test Positive Raised and thick white plaque or

acetowhite epithelium, usually near the
SCJ
Test Negative Smooth pink, uniform and featureless;
ectropion, polyp, cervicitis,
inflammation, Nabothian cysts.

Cancer Cauliflower like growth or ulcer,

fungating mass
 Visualization of cervix after application of Acetic Acid

Normal Cervix VIA Positive Invasive Cancer

TREATMENT
AND
FOLLOW- UP
Different methods of ablative treatment of CIN

 Cryotherapy

 Electrocoagulation

 Cold coagulation
 Laser ablation
 The loop electrosurgical excision procedure (LEEP), using thin wire loop
electrodes of out-patient excisional treatment of CIN.
 Cone biopsy
 Hysterectomy
 TREATMENT

 Basically all the treatments aim to remove or destroy the

abnormal cells, just the part of the cervix contains abnormal
cells.  This allows normal cells to grow back in their place. 

 All of the treatments are usually very successful in removing

the abnormal cells.
 Of all available and effective treatments of CIN, Cryotherapy
and LEEP are appropriate for both high- and low-resource
settings for several reasons.
Treatment Options for Dysplasia/CIS
Characteristic Cryotherapy Diathermy Loop
Excision (LEEP)
Effectiveness 80–90% 90–95%
Side effects watery discharge; bleeding
infection risk
Anesthesia required no yes
Tissue sample no yes
Power required no yes
Cost relatively low relatively high

Source: Gaffikin L, Blumenthal P, Davis C, Brechin SJG (eds). 1997. Alternatives for Cervical Cancer
Screening and Treatment in Low-Resource Settings.

75
Cryotherapy :

This is also an out

patient treatment, the
aim is to ablate the
abnormal cells in the
lesions and the
transformation zone.
 
The cryotherapy technique uses a cryoprobe with a
tip that makes direct surface contact with the
ectocervical lesion . Nitrous oxide (N2O) or carbon
dioxide (CO2) are the refrigerants of choice.

Cryotherapy should consist of two sequential freeze-

thaw cycles, each cycle consisting of 3 minutes of
freezing followed by 5 minutes of thawing (3 minutes
freeze-5 minutes thaw-3 minutes freeze-thaw).
Healing takes place during the first six weeks after
cryotherapy.

Granulation tissue is present in the wound during

the first 2-3 weeks after cryotherapy followed by
re-epithelialization of the surface.

Normally, the wound is totally healed within 6-8

weeks of treatment.
Women should receive instructions on self-care and symptoms to expect after
treatment.

some mild cramps.

Clear or lightly blood-stained watery discharge for up to 4-

6 weeks after treatment.

Women should be advised not to use a vaginal douche or

tampons or to have sexual intercourse for one month
after treatment.
 Criteria for Cryotherapy
 VIA positive, including woman who are less than 20 weeks
pregnant if lesions

 Not suspicious of cancer.

 Occupies less than 75% of the cervix.

 Does not extend onto the vaginal walls or into the cervical
canal beyond the reach of the cryoprobe

 The entire lesion is visible.

 The lesion extends less than 2 mm beyond the cryoprobe.

Cervical Cancer Screening,Treatment And Follow-up(Step -1 approach)

VIA
SCREENING

POSITIVE NEGATIVE

F/U at 1,3,12 Repeat after 5

Cryotherapy months years

Larger lesions
> Refer
81
 Danger sign

Instruct to come if they have any of following symptoms

within the six weeks after treatment:

 Fever for more than two days,

 Severe lower abdominal pain

 Foul-smelling- pus colored discharge,

 Bleeding with clots or bleeding for over two days.

 Treatment failure is detected in about 5-10% of women
during the follow-up in the first year

 These persistent, local or multifocal lesions are more likely

to occur if the original lesion was large.

 To rule out the presence of unsuspected invasive

carcinoma, it is advisable to do biopsy all persistent lesions

 Re-treatwith cryotherapy, LEEP, or cold- knife conization,

as appropriate.
 Follow-up:
 Follow-up evaluation may be carried out after 12 months in
which screening examinations such as VIA, cytology and/or
colposcopy should be carried out.
 Those negative for neoplasia - advise to undergo follow-up after
three or five years.

Referral:
 Ifany of the above conditions are not met.
 Who request to be treated using a procedure other than Cryo.
 One Who request further testing not offered at the site.
 Test positive women declining any treatment.
 HIV patient who have dysplastic changes.
 Prevention
 Vaccine is an effective way to prevent cervical cancer;
 There are two HPV vaccines currently available.
 Highly effective in preventing persistent infections caused by HPV 6, 11, 16 and
18
 100 % effective in preventing from CIN grades 2/3 and warts.
 99 % effective against external genital lesion including warts.
Gardasil, licensed and manufactured by Merck & Co.
is a vaccine against HPV types 6, 11, 16 & 18. up to 98% effective.
Received approval from the US FDA June 8, 2006
Cervarix, manufactured by GlaxoSmithKline,
has been shown to be 92% effective in preventing HPV strains 16 and 18 and
is effective for more than four years.
approved in the US on 16 October 2009vaccine.
 The vaccine's key developmental steps are claimed by the
National Cancer Institute in the US, the University of Rochester in New York,
Georgetown University in Washington, DC, Dartmouth College in Hanover,
Who should get the vaccine?

 The FDA has recommended the following groups of

women get vaccinated:

◦ Girls 11–12: Recommended Age Group (can

be started as young as age 9).

◦ Women 13–26: the benefit of the vaccine may

be lower depending on prior HPV exposure.
Most appropriate age in Nepal, 12 to 13 years.

Minimum age 9 and maximum age up to 26.

Lactating mother within the age group.

‧ Vaccination Schedule

3 doses of vaccination should be given intramuscularly within 6 months

The 1st dose: Any date

The 2nd dose: One or two months after the first dose
The 3rd dose: Six months after the first dose

Side Effects of the vaccine

The most common side effects are fever and local reaction like pain,
swelling, rash and itching. The effectiveness of the vaccine may be affected if
the woman is on immuno-suppressive medication. Advice from your family
doctor is needed if you consider receiving simultaneous injection of other
vaccine.
Who Should not get the HPV vaccine ?

 Pregnant women.

 Allergic / hypersensitive to yeast and any of the

vaccine components.

 Women who get allergic reaction to first dose /

should discontinue.
 Side Effects

1. Mild to moderate pain.

2. Redness or swelling at the injection site.
3. Some headache, fever and nausea.
4. For pain relieve, Paracetamol can be served and by
placing a cool, moist cloth over the injection site.
‧ Healthy lifestyles

HPV infection is the most important factor causing cervical cancer. Since it is
transmitted through sexual intercourse, women should have safe sex, for
example:

 Have single sexual partner

 Avoid having multiple sexual partner
 Use a condom
 Avoid sex before 18

Leading a healthy life enhances the immune system:

Avoid smoking: The chance smokers develop cervical cancer is 3
times higher than non-smokers
Balanced diet: more vegetables, water intake, grains and beans;
less meat and greasy food, with appropriate
exercises and regular daily routines.