CERVICAL CANCER

Dr. Vijay Prakash

• Cervical cancer is malignant neoplasm of the
cervix uteri or cervical area. It may present with
vaginal bleeding but symptoms may be absent
until the cancer is in its advanced stages.
• Treatment consists of surgery (including local
excision) in early stages and chemotherapy and
radiotherapy in advanced stages of the disease.
• Pap smear screening can identify potentially
precancerous changes.
• Human papillomavirus (HPV) infection is a
necessary factor in the development of nearly 70%
of cases of cervical cancer.
• HPV vaccine effective against the two strains of
HPV that cause the most cervical cancer has been
licensed in the U.S, Canada, Australia and the EU.
Classification
• The World Health Organization classification system was
descriptive of mild, moderate or severe carcinoma in situ
(CIS). The term, Cervical Intraepithelial Neoplasia (CIN) was
developed to place emphasis on the spectrum of abnormality
in these lesions, and to help standardise treatment. It
classifies
1. mild dysplasia as CIN1,
2. moderate dysplasia as CIN2,
3. severe dysplasia and CIS as CIN3.
• The most recent classification is the Bethesda System,
which divides all cervical epithelial presursor lesions into 2
groups:
1. Low-grade Squamous Intraepithelial Lesion (LSIL) and

2. High grade Squamous Intraepithelial Lesion (HSIL).

LSIL corresponds to CIN1, and
HSIL includes CIN2 and CIN3.
More recently, CIN2 and CIN3 have been combined into
CIN2/3.
Signs and symptoms
• The early stages of cervical cancer may be
completely asymptomatic. Vaginal bleeding, contact
bleeding or (rarely) a vaginal mass may indicate the
presence of malignancy. Also, moderate pain during
sexual intercourse and vaginal discharge are
symptoms of cervical cancer.
• In advanced disease, metastases may be present
in the abdomen, lungs or elsewhere.
Symptoms of advanced cervical cancer may include:
• loss of appetite, weight loss, fatigue, pelvic pain,
back pain, leg pain,
• single swollen leg,
• heavy bleeding from the vagina,
• leaking of urine or feces from the vagina,
• bone fractures.
Causes
Human papillomavirus infection
• Infection with a high-risk strain of human papillomavirus.
The virus cancer link works by triggering alterations in the
cells of the cervix, which can lead to the development of
cervical intraepithelial neoplasia, which can lead to cancer.

• More than 150 types of HPV are acknowledged to exist

(some sources indicate more than 200 subtypes). Of these,
1. Fifteen are classified as high-risk types (16, 18, 31, 33, 35,
39, 45, 51, 52, 56, 58, 59, 68, 73, and 82),
2. Three as probable high-risk (26, 53, and 66), and
3. Twelve as low-risk (6, 11, 40, 42, 43, 44, 54, 61, 70, 72,
81, and CP6108), but even those may cause cancer.
Types 16 and 18 are generally acknowledged to cause about
70% of cervical cancer cases. Together with type 31, they are
the prime risk factors for cervical cancer.
Cofactors
• The American Cancer Society provides the following list of
risk factors for cervical cancer:
human papillomavirus (HPV) infection, smoking, HIV
infection, chlamydia infection, stress and stress-related
disorders, dietary factors, hormonal contraception, multiple
pregnancies, exposure to the hormonal drug diethylstilbestrol
Diagnosis
(DES) and a family history of cervical cancer.
• Visual inspection to detect precancer or cancer
Visual inspection of the cervix, using acetic acid or Lugol’s
iodine to highlight precancerous lesions so they can be
viewed with the “naked eye”, shifts the identification of
precancer from the laboratory to the clinic. Such procedures
eliminate the need for laboratories and transport of
specimens, require very little equipment and provide women
with immediate test results.
Biopsy procedures
While the pap smear is an effective
screening test, confirmation of the diagnosis of
cervical cancer or pre-cancer requires a biopsy of
the cervix. This is often done through colposcopy,
a magnified visual inspection of the cervix aided by
using a dilute acetic acid (e.g. vinegar) solution to
highlight abnormal cells on the surface of the
cervix.

Further diagnostic procedures are

loop electrical excision procedure (LEEP) and
conization, in which the inner lining of the cervix is
removed to be examined pathologically. These are
carried out if the biopsy confirms severe
cervical intraepithelial neoplasia.
Pathologic types
• Cervical intraepithelial
neoplasia, the precursor to
cervical cancer, is often
diagnosed on examination
of cervical biopsies by a
pathologist. Histologic
subtypes of invasive
cervical carcinoma include
the following:
• Squamous cell carcinoma
(about 80-85%[citation needed])
• Adenocarcinoma (about
15% of cervical cancers in
the UK)
• Adenosquamous
carcinoma
• Small cell carcinoma
• Neuroendocrine carcinoma
• Non-carcinoma malignancies which can rarely
occur in the cervix include
melanoma
lymphoma
Staging
• Cervical cancer is staged by the
International Federation of Gynecology
and Obstetrics (FIGO) staging system, which is
based on clinical examination, rather than surgical
findings. It allows only the following diagnostic
tests to be used in determining the stage:
palpation, inspection, colposcopy, endocervical
curettage, hysteroscopy, cystoscopy, proctoscopy,
intravenous urography, and X-ray examination of
the lungs and skeleton, and cervical conization.
• The TNM Classification of Malignant Tumours (TNM) is a
cancer staging system that describes the extent of cancer in a
patient’s body.
T describes the size of the tumor and whether it has
invaded nearby tissue,
N describes regional lymph nodes that are involved,
M describes distant metastasis (spread of cancer from one
body part to another
• The TNM staging system for cervical cancer is analogous to
the FIGO stage.
Stage 0 - full-thickness involvement of the epithelium
without invasion into the stroma (carcinoma in situ)
Stage I - limited to the cervix
IA - diagnosed only by microscopy; no visible lesions
IA1 - stromal invasion less than 3 mm in depth and
7 mm or less in horizontal spread
IA2 - stromal invasion between 3 and 5 mm with
horizontal spread of 7 mm or less
 IB - visible lesion or a microscopic lesion with more
than 5 mm of depth or horizontal spread of more than
7 mm
IB1 - visible lesion 4 cm or less in greatest dimension
IB2 - visible lesion more than 4 cm
Stage II - invades beyond cervix
IIA - without parametrial invasion, but involve upper
2/3 of vagina
IIB - with parametrial invasion

Stage III - extends to pelvic wall or lower third of the vagina

IIIA - involves lower third of vagina
IIIB - extends to pelvic wall and/or causes
hydronephrosis or non-functioning kidney

StageIVA - invades mucosa of bladder or rectum and/or

extends beyond true pelvis
IVB - distant metastasis
Prevention
• Primary Prevention
Vaccination HPV vaccine
Gardasil, licensed and manufactured a vaccine
against HPV types 6, 11, 16 & 18. Gardasil is up to
98% effective. It is now on the market after
receiving approval from the US Food and Drug
Administration on June 8, 2006.Gardasil has also
been approved in the EU.

GlaxoSmithKline has developed a vaccine called

Cervarix which has been shown to be 92% effective
in preventing HPV strains 16 and 18 and is effective
for more than four years. Cervarix has been
approved some places and is in approval process
elsewhere.
• HPV vaccines are targeted at girls and women of age 9 to
26 because the vaccine only works if given before infection
occurs; therefore, public health workers are targeting girls
before they begin having sex. The use of the vaccine in men
to prevent genital warts and interrupt transmission to women.

Condoms
Condoms offer some protection against cervical cancer.
Evidence on whether condoms protect against HPV infection is
mixed, but they may protect against genital warts and the
precursors to cervical cancer. They also provide protection
against other STDs, such as HIV and Chlamydia, which are
associated with greater risks of developing cervical cancer.

Smoking avoidance
Carcinogens from tobacco increase the risk for many
cancer types, including cervical cancer, and women who
smoke have a much higher chance than a non-smoker to
develop cervical cancer
Nutrition
Fruits and vegetables
• Consumption of papaya at least once a week was inversely
associated with persistent HPV infection.

Vitamin A
• There is weak evidence to suggest a significant deficiency
of retinol can increase chances of cervical cancer

Vitamin C
• Risk of type-specific, persistent HPV infection was lower
among women reporting intake values of vitamin c

Vitamin E
• A statistically significantly lower level of alpha-tocopherol
was observed in the blood serum of HPV-positive patients
with cervical intraepithelial neoplasia
 Folic acid
Higher folate status was inversely associated with becoming HPV
test-positive. Women with higher folate status were significantly less
likely to be repeatedly HPV test-positive

CoQ10
Women who had either CIN or cervical cancer had markedly
lower levels of CoQ10 in their blood

Secondary Prevention
Awareness
• According to the US National Cancer Institute's 2005 Health
Information National Trends survey, only 40% of American
women surveyed had heard of human papillomavirus (HPV)
infection and only 20% had heard of its link to cervical cancer.
Screening
• The widespread introduction of the Papanicolaou test, or Pap
smear for cervical cancer screening has been credited with
dramatically reducing the incidence and mortality of cervical cancer
in developed countries.
• Abnormal Pap smear results may suggest the presence of
cervical intraepithelial neoplasia before a cancer has developed,
allowing examination and possible preventive treatment.
• The HPV test is a newer technique for cervical cancer triage which
detects the presence of human papillomavirus infection in the cervix.
It is more sensitive than the pap smear
Treatment
• Stage IA is usually treated by hysterectomy (removal of the whole
uterus including part of the vagina).
• Stage IA2, the lymph nodes are removed as well.

An alternative for patients who desire to remain fertile is a local

surgical procedure such as a loop electrical excision procedure (LEEP)
or cone biopsy.
If a cone biopsy does not produce clear margins, one more possible
treatment option for patients who want to preserve their fertility is a
trachelectomy.This attempts to surgically remove the cancer while
preserving the ovaries and uterus, providing for a more conservative
operation than a hysterectomy
• Early stages (IB1 and IIA less than 4 cm) can be treated with radical
hysterectomy with removal of the lymph nodes or radiation therapy

• Larger early stage tumors (IB2 and IIA more than 4 cm) may be
treated with radiation therapy and cisplatin-based chemotherapy,
hysterectomy (which then usually requires adjuvant radiation
therapy), or cisplatin chemotherapy followed by hysterectomy
• Advanced stage tumors (IIB-IVA) are treated with radiation therapy
and cisplatin-based chemotherapy.
On June 15, 2006, the US Food and Drug Administration approved
the use of a combination of two chemotherapy drugs, hycamtin and
cisplatin for women with late-stage (IVB) cervical cancer
treatment.Combination treatment has significant risk of neutropenia,
anemia, and thrombocytopenia side effects.
Prognosis
• With treatment, 80 to 90% of women with stage I cancer and 50 to
65% of those with stage II cancer are alive 5 years after diagnosis.
• Only 25 to 35% of women with stage III cancer and 15% or fewer of
those with stage IV cancer are alive after 5 years.

According to the International Federation of Gynecology and

Obstetrics, survival improves when radiotherapy is combined with
cisplatin-based chemotherapy.
As the cancer metastasizes to other parts of the body, prognosis
drops dramatically because treatment of local lesions is generally
more effective than whole body treatments such as chemotherapy

Epidemiology
• Worldwide, cervical cancer is the fifth most deadly cancer in
women. It affects about 16 per 100,000 women per year and kills
about 9 per 100,000 per year. Approximately 80% of cervical cancers
occur in developing countries
• Epidemiologists working in the early 20th century noted
that cervical cancer behaved like a sexually transmitted
disease. In summary:
• Cervical cancer was common in female sex workers.
• It was rare in nuns,
• It was more common in the second wives of men whose
first wives had died from cervical cancer
• It was not until the 1980s that human papillomavirus (HPV)
was identified in cervical cancer tissue. A description by
electron microscopy was given earlier in 1949 and HPV-DNA
was identified in 1963. It has since been demonstrated that
HPV is implicated in virtually all cervical cancers. Specific viral
subtypes implicated are HPV 16, 18, 31, 45 and others.

Pap test
The Papanicolau test (also called Pap smear, Pap test, cervical
smear, or smear test) is a screening test used in gynecology
to detect premalignant and malignant (cancerous) processes
in the ectocervix. Significant changes can be treated, thus
preventing cervical cancer
• In taking a
Pap smear, a
tool is used to
gather cells from
the outer
opening of the
cervix of the
uterus and the
endocervix. The
cells are
examined under
a microscope to
look for
abnormalities.
• The test remains an effective, widely used method for early
detection of pre-cancer and cervical cancer. The test may also
detect infections and abnormalities in the endocervix and
endometrium.

• In general, it is recommended that females who have had

sex. seek regular Pap smear testing. Guidelines on frequency
vary, from annually to every three years. If results are
abnormal, and depending on the nature of the abnormality,
the test may need to be repeated in six to twelve months

• The patient may also be referred for HPV DNA testing,

which can serve as an adjunct to Pap testing.
THANKS