KULLIYYAH OF NURSING

YEAR 1 PROBLEM-BASED LEARNING

TRIGGER 1
CERVICAL CANCER
INSTRUCTOR: DR. Muhammad Lokman Bin Md. Isa

NAME MATRIC NO.

MUHAMMAD FITRI BIN MD ZULKIFLI 1620845
MUHAMAD ASYRAF BIN MAT NASIR 1628313
NURUL NABIHA BINTI ISMAIL 1614590
NOR AMIRA BINTI ABDUL HALIM 1629662
NOR HIKEMAR BINTI A RAHMAN 1629314
 CONTENTS

CONTENTS PAGE

1.0 INTRODUCTION 1

2.0 CONTENT 2-11

a) Anatomy and Physiology of the Cervix
b) Cellular Changes of Cervical Neoplasia
i) Squamous cell carcinoma
ii) Cervical intraepithelial neoplasia
iii) Glandular carcinoma

c) Grading and Staging

d) Signs and Symptoms

e) Treatment and Prevention

3.0 CONCLUSION 12

4.0 REFERENCES 13-15

Introduction

Mrs. Samantha is a 47-year old woman. She is complaining of virginal spotting or bleeding
after intercourse, which she thinks is related to vaginal dryness of pre-menopause. After
investigation was carried out, she was diagnosed with cervical cancer.

The cervix is the lower portion of the uterus that connects the uterus to the vagina.
The opening of the cervix remains small except during labor when it expands to allow the
baby to pass from uterus to the vagina. Cervical cancer occurs when cells in the cervix grow
erratically, multiply out of control (Imaginis, 2017) and invade other area of normal cells
(metastasis). Large collection of cells that grow abnormally are called tumors. Tumors can
differentiate into benign or malignant. Benign tumor does not invade the surrounding tissue
whereas malignant tumor will invade the surrounding tissue. Cervical cancer can be
categorize as malignant tumor because the symptoms will occurs when cancer cells spread to
other area of normal tissue (Oncolink, 2017).

Most common type cervical cancers (80-90 percent) are squamous cell cancer or
squamous cell carcinoma (American Cancer Society, 2016). These cancers arise in the cells
on the outer surface covering of the cervix. Adenocarcinoma is the second most common
type of cervical cancer, accounting for the remaining 10 to 20 percent of cases. This cancer
develops from the glands that produce mucus in the endocervix. The least common type of
cervical cancer is adenosquamous carcinoma which have features both squamous cell
carcinoma and adenocarcinoma.

The Malaysian National Cancer Registry Report found that cervical cancer is the
second highest after breast cancer that frequently occurs in Malaysian women with statistics
about 12.9% of all female cancers (an age standardized incidence rate of 19.7 per 100,000).
This was higher than other Asian and Western countries, and even globally. Death from
cervical cancer are rare amongst young women but increased from the age 30 years and
peaked at 60-69 years. More than half of the cases involved women ages 40-59 years
(Zaridah S, 2014).

A Pap smear, also called a Pap test, is screening procedure to test for the presence of
precancerous or cancerous cells on the cervix. The cells from the cervix are gently scraped
away and then examined for abnormal growth. Detecting cervical cancer at early stage with

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Pap smear is the first step in halting the possible development of cervical cancer thus increase
the chance for cure.

Anatomy and physiology of the cervix

The cervix is part of the female reproductive system, which is made up of internal
organs, including the fallopian tubes, uterus (womb), ovaries and vagina (birth canal). It is
also made up of the external genital organs, including the parts that make up the vulva (the
clitoris, vaginal lips and the opening to the vagina). The cervix, the neck of the uterus,
connects the main body of the uterus to the vagina. It has an outer surface that opens into the
vagina and an inner surface that faces into the uterus. The functions of the cervix include
producing moisture to lubricate the vagina, producing mucus that helps sperm travel up the
fallopian tube to fertilise an egg, holding a developing baby in the uterus and widening to
enable a baby to be born via the vagina ("Anatomy and Physiology of the Cervix", n.d.).

The cervix is made up mostly of connective tissue and muscle, and divided into two
main parts which are endocervix, the inner part of the cervix and ectocervix, the outer part of
the cervix (Figure 1). The cervix is covered by two main types of cells; columnar
cells/glandular cells and squamous cells. Glandular cells line the endocervical canal,
passageway from the uterus to the vagina. They are glandular cells that make mucus.
Meanwhile, squamous cells which is flat and thin cells, line the ectocervix and vagina.

The squamous cells join the columnar cells in an area of the cervix called the
transformation zone, where precancerous changes of the cervix and most cervical cancers
takes place.

Figure 1: Anatomy and physiology of cervix

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Cellular Changes of Cervical Neoplasia

Human papillomavirus (HPV) infection is the major risk factor for cervical cancer.
HPV invades the skin by entering tiny breaks in the surface. Once inside, HPV infects host
epithelial cells causing new viruses to be produced. The infected cells are shed and the viral
particles are released ("How HPV Causes Cancer",n.d.).

According to Kumar, Abul K. Abbas and Aster in their book, Robbins Basic
Pathology (2013), recognized stereotypes of HPV can be classified into high-risk and low-
risk types. High risk HPV strains which contributes to carcinoma development can integrate
viral DNA into the host cell genome. This event can link to progression, that can lead to a
longer infection time, meaning more time there is for cancer to develop

After the integration, two potent oncoproteins encoded in the HPV genome; E6 and
E7, which are responsible for the ability of HPV to cause cancer may be over-expressed.
These proteins prevent the activity of key tumor suppressors by binding and inactivate two
critical tumor suppressors, p53 and retinoblastoma (Rb). E6 inhibits p53, a protein that
controls responses to different types of cellular stress including DNA damage and viral
infection while E7 inhibits Rb, a protein that can prevent cell division by blocking the activity
of transcription factors. These events can cause uncontrolled division of the cells.

The HPV genome contains several genes that encode proteins; E2, E6, and E7, that
can contribute into development of cervical cancer. The E2 blocks the activity of E6 and E7
by binding to both of them. When E6 is not bound to E2, it is free to bind to the p53 tumor
suppressor, causing the p53 to be destroyed. Without p53 protein, a cell may continue to
divide even if it is damaged. The expression of telomerase by E6, maintains the ends of the
chromosomes and helps cancer cells to divide forever.

E7 protein, helps the virus take over control of infected cells by binding to Rb. When
E7 binds to Rb, Rb cannot carry out its normal function. Normally, Rb binds to E2F. The E2F
cannot act as a transcription factor and cannot cause the cell to divide. In essence, E7 inhibits
an inhibitor or cell division. When a cell makes the E7 protein, the E2F transcription factor
causes the cell to divide. The E6 and E7 proteins help HPV hijack cell division and help drive
cancer development ("How HPV Causes Cancer",n.d.).

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Squamous Cell Carcinoma

Cancers are characterized by the cells that they originally form from. The most
common type of cervical cancer; squamous cell carcinoma, comes from abnormal squamous
cells that lie on the surface of the cervix (Dolinsky & Hill-Kayser, 2017).

HPV infection occurs in the most immature squamous cells of the basal layer but the
replication of HPV DNA takes place in more differentiated overlying squamous cells. HPV-
infected squamous cells replicate DNA, because of expression of E6 and E7 and inactivation
of p53 and Rb. Susceptibility to additional mutations increases, will eventually lead to
carcinogenesis

Cervical Intraepithelial Neoplasia (CIN)

HPV-related carcinogenesis begins with the precancerous epithelial change termed

CIN. CIN starts as low-grade dysplasia (CIN 1), progresses to moderate (CIN 2) and then
severe dysplasia (CIN 3) over time. CIN term, also known as squamous intraepithelial
lesions (SIL), can be classified as either low-grade (LSIL), previously as CIN 1 or high-grade
(HSIL), the combination of CIN 2 and CIN 3.

CIN 1 or LSIL, only affects cells on or close to the surface of the cervical lining. CIN
1 is characterized by dyplastic changes in the lower third of the squamous epithelium and
koilocytotic change in the superficial layers of the epithelium. The early changes to the cells
make them slightly different from normal cells and considered mildly abnormal
("Precancerous conditions of the cervix", n.d.).

In CIN 2, dysplasia extends to the middle third of the epithelium and takes the form of
delayed keratinocyte maturation. Some variations in the cell and nuclear size, heterogeneity
of the chromatin, and presence of mitoses above the basal layer extends into the middle third
of the epithelium. The superficial layer of cells shows some differentiation and occasionally
demonstrates the koilocytotic changes. CIN 3 stage is marked by almost complete loss of
maturation. The variation in cell, nuclear size, chromatin heterogeneity, normal and abnormal
mitoses, becomes even greater and there are more severe changes to cells deeper in the
cervical lining. At this stage, the cells are considered abnormal and different from normal

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cells. The changes to cells are linked with a higher risk of becoming cancer or may mean that
there is an underlying cancer (Kumar, Abul K. Abbas & Aster, 2013).

Figure 2 : Cervical cancer progression

Glandular Carcinoma

Besides, the glandular cells of the endocervix also undergo some changes. But usually
these abnormalities are quite difficult to be interpreted compare to changes occurred at
squamous cells. According to Cancer Council Australia (2017), the percentage of it
occurrences only about 25%. When normal glandular cells are exposed towards the factors
that can induce its growth, cells will undergo some abnormalities. The changes are called as
precancerous condition which is the cells are easily become cancer cells. The degree of
abnormality and severity of the glandular cells will determine which group are they from.

For atypical glandular cells (AGC), the cells look a little bit different from normal
cells. Some cells are crowding in sheet and their nuclear membranes are overlapping with
each other (Figure 3). As stated by Aysun Uguz (2016), the changes of the cells including
slight hyperchromasia, nuclear membranes enlarged, distinct cells border, nucleoli may be
present or not and mitotic figures are rare. Besides, adenocarcinoma in situ (AIS) is another
group of cellular changes. The cells are nuclear stratification, losing the normal nuclear
polarity, increasing in nuclear size, hyperchromasia, changing in chromatin pattern and
mitotic activity (Aysun Uguz, 2016) (Figure 4). After many years past and no action taken to
cure AIS, the cells will enter cancerous phase which they are called as adenocarcinoma. This
occurs as metastasis begin and the cells start to invade the surrounding cells and tissues. The
abnormal cells will produce extended papillary projections from surface of endocervix are
produced. Besides, the changes of the cells as mentioned by Aysun Uguz (2016) are
including pleomorphic nuclei with coarse chromatin, macro nucleoli, thin vacuolated

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cytoplasm and atypical squamous cells are spotted because of squamous adenocarcinoma
differentiation (Figure 5).

Figure 3: Atypical Glandular Cells Figure 4: Adenocarcinoma In Situ Cells

Figure 5 : Adenocarcinoma cells

Grading and Staging

For grading of cervical cancer, it divides into two which are low-grade and high-grade
of cellular changes (Prevention of Cervical Cancer: A Guide for Women in New Zealand,
n.d) (Figure 6). Low-grade is mild changes of cells and they are usually become normal
again. While high-grade is quite risky which it can differentiate and become cancerous if it is
not treated early. Besides, as remarked by Cervical Cancer: Stages (2017) cervical cancer
also has different stages. In each stage, the cancer cells will show different abnormalities and
characteristics based on their severity. Cervical cancer is consisting of four stages (Figure 7).

Stage Ⅰ : The cancerous areas are still in the uterus which they are from the cervix lining into
the deeper tissue. The cancer is not spreading to lymph nodes and no distant spread. This can
only diagnose by microscopy.

Stage IA Diagnosed only by microscopy

Stage IA1 Depth: 3mm, Length: ≤7mm
Stage IA2 Depth:3-5 mm, Length: <7mm

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 Stage IB Doctor can see the lesion
Stage IB1 ≤ 4 cm
Stage IB2 > 4 cm

Stage Ⅱ : It spreads to nearby areas inside pelvic(vagina or tissue near the cervix). It has not
spread to lymph nodes or other parts of the body.

Stage IIA Not spread to the nearby tissue

Stage IIA1 ≤4 cm
Stage IIA2 > 4 cm
Stage IIB Spread to the parametrial area

Stage Ⅲ : The tumor has spread to the pelvic wall, and/or involves the lower third of the
vagina, and/or causes swelling of the kidney, called hydronephrosis, or stops a kidney from
functioning. No lymph nodes are involved, and there is no distant spread.

Stage IIIA Involves the lower third of the vagina

Stage IIIB grown into the pelvic wall and/or affects the kidneys,
cancer has/has not spread to lymph nodes in the pelvis

Stage IVA : The cancer has spread to the bladder or rectum and may or may not have spread
to the lymph nodes, but it has not spread to other parts of the body.

Stage IVB : The cancer has spread to other parts of the body.

Figure 6: Grading of cervix cancer Figure 7: Staging of cervix cancer

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Signs and Symptoms

Basically, in early-stage of cervical cancer produce no signs or symptoms. In women

with advanced and metastatic cancers, the symptoms may be more severe depending on the
tissues and organs to which the disease has spread. The first most common sign of cervical
cancer is Vaginal bleeding after intercourse which is correlated to vaginal dryness of Mrs
Smith. Next, watery or bloody vaginal discharge and have a foul odor. The last one is
unexplained, persistent pelvic and/or back pain. When one of the above signs appeared, it
should be reported to the doctor. The earlier precancerous cells or cancer is found and treated,
the better the chance that the cancer can be prevented or cured.

Factors that commonly contributing to cervical cancer are infection by the human
papillomavirus (HPV). This is the core factors of the cervical cancer. HPV can infect cells on
the surface of the skin, and those lining the genitals, anus, mouth and throat, but not the blood
or internal organs such as the heart or lungs. To add, HPV can spread from one person to
another during skin-to-skin contact. One way HPV spreads is through sexual activity,
including vaginal, anal, and even oral sex.

Next is smoking. Women who smoke are about twice as likely as non-smokers to get
cervical cancer. Tobacco by-products have been found in the cervical mucus of women who
smoke. Scholars believe that these chemical substances damage the DNA of cervix cells and
may contribute to the development of cervical cancer. Smoking also can lower the immune
system of the body to fight against HPV infections.

Next, women with lowered immune systems also have a higher risk of developing
cervical cancer. A lowered immune system can be caused by immune suppression from
corticosteroid medications, organ transplantation, treatments for other types of cancer, or
from the human immunodeficiency virus (HIV), which is the virus that causes acquired
immune deficiency syndrome (AIDS). When a woman has HIV, her immune system is less
able to fight off early cancer. Last, the lowest possibility that may be the factors of cervical
cancer is age.

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 So, in case of Mrs Samantha Smith, the factor that can be related to Mrs Smith is
having a multiple partner that can increase the chances to get HPV. To add, she also may get
this HPV from other person maybe from his husband that carried this virus which also due to
multiple partner. Next, Mrs Smith have higher chances to be infected by HPV because she
already having 6 children and she is in the stage of pre-menopause. Due to her age which
cause the immune weakness, her body have low immune system which make her prone to get
HPV infection.

Preventions and Treatments

In some cases, cervical cancer can be prevented. The best way to prevent from
cervical cancer is to do Pap test every 3 years from age 21 to detect any abnormality at the
cervix at an early stage. Pap test or Pap smear is a test where a part of cervical tissue is
brushed off and taken as a sample by using a cotton swab, cytobrush or a small spatula.

Taking HPV (Human Papiloma Virus) vaccine can also be used to avoid from the
infection or growth of HPV which is the common factor in cervical cancer. This vaccine can
be given from starting from age 9 to 26. Gardasil 9, the vaccine however is only effective
against HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58, which may be ineffective against
other types of HPV. Markowitz et al. (2014), reported that some cases of adverse events
occurred within 7 days of the vaccination in females aged 9 to 25 such as swelling, fever,
fatigue, rashes, arthralgia (pain in a joint) and myalgia (pain in a muscle). Precautions such as
allergy should be considered as well to avoid anaphylaxis reaction.

The other ways to decrease the risk of cervical cancer are avoiding long term use of
contraceptive pills, giving birth to lesser children, avoiding having multiple partner
intercourse and avoiding from smoking. Women who gave birth to more ha three children
and have shorter latency period (period between two births) are shown to have higher risk
than women with lower number of pregnancy and women with larger latency period.
According to Marzi et al, 1996; Giannini et al, 1998; 2002; Jacobs et al, 2003, (as cited in
Louje, 2009), pregnant women have higher estrogen level and higher estrogen receptors
density. The hormonal raise in estrogen triggers HPV oncoproteins, which increase the HPV

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presistance and may cause decrease in levels of cytokines that regulates the cervical cell-
mediated immune response, which increase the risk of HPV. Cigarette is well-known for its
nicotine content that has euphoric and carcinogenic effects on human body. The nicotine
metabolites can be upheld inside the body and in the cervical mucus of a smoking woman
which later will cause neoplasia (abnormal cell growth) in the cervical tissue. Avoding a long
term use or discontinuing oral contraceptives can lower the risk of cervical cancer of the user.
The estrogen and progestin content in the oral contraceptives cause genetic mutation in the
BRCA1 and BRCA2 gene. (Franco, E. L., Duarte-Franco, E. & Ferenczy, A., 2001)

Up to stage III, cervical cancer can be treated by large loop excision of the
transformation zone (LLETZ), a type of conization which is cutting away the abnormal tissue
using a fine wire with electrical current, undergoing chemotherapy, surgery, radiation therapy
and targeted therapy.

According to American Cancer Society, one of the treatments for cervical cancer is by
prescribing the patient with chemotherapy drugs. Chemotherapy medication can be given
orally or through injection. The chemotherapy medicine kills the cancer cells and reduces the
risk of recurrence. The therapy is given in sessions for a few months depending on the
severity and malignancy of the cancer cells. This therapy however, can cause hair loss due to
the its effect killing cells that undergo mitosis non-selectively which includes both cancer
cells and normal cells that undergo mitosis. The other adverse effects of chemotherapy are
nausea, vomiting, diarrhea, dry skin and mouth and lethargy. There are a few types of
chemotherapy drugs such as alkylating agents (Cisplatin, Carboplatin). This type of drug
inhibits cell proliferation by damaging its DNA and because of this mechanism they can
affect bone marrow and cause leukemia. Anti metabolites (Gemcitabine) interfere with the
cell DNA and RNA by substituting the arrangement in DNA and RNA of the cell during S
phase of cell growth cycle. Mitotic inhibitors chemotherapy drugs (Paclitaxel) inhibits cell
mitosis by keeping enzymes from making proteins for cell reproduction, and eventually
inhibits metastasis of the tumor cell. (How Chemotherapy Drugs Work, 2016)

Radiotherapy or radiation therapy is a treatment using radiation to kill cancer cells.

This treatment is normally delivered up to eight weeks. Radiotherapy can be delivered
externally and internally to treat cervical cancer. External radiotherapy is using a machine
beams high-energy waves into pelvis to destroy neoplastic cells while internal radiotherapy or
bracytherapy is a treatment by implanting a piece of radioactive metal near or at the cancer

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spot in the vagina or at the cervix and the neoplastic cells are killed by the radiation emitted
by the metal. This treatment however, like chemotherapy, may cause adverse effects such as
nausea, vomiting, diarrhea, painful urination, damage to ovaries, bowel and bladder, skin
burning sensation and even infertility. (Radiation Therapy for Cervical Cancer, 2016)

The cancer cells can also be removed surgerically. There are few types of surgery for
cervical cancer; cryosurgery, laser, hysterectomy, and pelvic exenteration. Cryosurgery or
ceyotherapy is a treatment by using an extreme cold produced by liquid nitrogen (or argon
gas) to freeze and destroy abnormal tissue. Laser surgery is burning the abnormal cells with
laser beam focused on the cancer spot (directed through vagina). Hysterectomy can be
classified as total hysterectomy (removing the uterus alone), radical hysterectomy (removing
the uterus along with nearby tissue) and total+salpingoophorectomy (removing the uterus
along with the fallopian tube and ovary). Radical tracholectomy is removing the cervix with
the nearby tissue, the nearby lymph node and upper part of the vagina. (Surgery for Cervical
Cancer, 2016).

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Conclusion

In conclusion, cervical cancer screening remains an important part of a woman's

health care maintenance plan. While Pap smears were once synonymous with a woman's
annual wellness visit, and they will recognize that annual Pap smears are no longer needed.
Thus, we should use these annual encounters as an opportunity to educate patients on the
current screening recommendations and the pitfalls that come with excessive screening.
These wellness visits can also serve as educational opportunities to review risk reducing
behavior, HPV vaccination, contraceptive counseling, and so on.

As with any screening tool, it is important to evaluate the pros and cons of cervical
cancer screening and its impact on patients. While the Pap smear has drastically reduced the
number of cases of cervical cancer and mortality from this disease, we must recognize the
potential harm and expense that can come from overscreening. Utilization of the guidelines
should allow health care providers to adequately screen patients and detect premalignant and
treatable invasive disease while reducing the number of unnecessary procedures that can be
harmful and costly to patients.

In Islam, we believe that everything happens for a reason, we can refer to the Quran
as our guidelines and take the hints to health and diseases. A verse for the Quran states that:

“Everything good that happens to you (O Man) is from God, everything bad that
happens to you is from your own actions”. (Quran 4:79)

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