PRE-INVASIVE & INVASIVE CERVICAL DISEASE

Dysplasia lesion in which part of the

epithelium is replaced by cells showing varying
degrees of atypia

Cervical Intraepithelial Neoplasia (CIN):

Intraepithelial dysplastic atypia occurring

within
the metaplastic epithelium of the
transformation
zone.

Dysplasia / CIN System

Mild
Mod.dyspla Severe
CI
Canc
dysplasia
sia
dysplasia
S
er
CIN 1
CIN 2
CIN 3
Cervical neoplasia originates within the TZ.
Low Risk HPV types (6 and 11), are associated lowgrade cervical lesions (condylomata acuminata,
and CIN1).
High Risk HPV types (16, 18, 31,33,or 35), are
associated
with high-grade cervical lesion (CIN2,3) and cervical
cancer.
HPV 16 is the type universally detected with
greatest
frequency in high grade lesion and cervical cancer,
50%
of SCC, 30% of Aden carcinoma, and in over 80% of
preinvasive lesions

Bethesda system
ASCUS:
LSIL: Low
HSIL:High
Cancer:
Atypical
grade
grade
Squamous
squamous
squamous
squamous
cell
cells of
intraepithelia intraepithelia carcinoma
undetermined l lesion
l lesion
significance
Original Squamocolumnar Junction(OSCJ): The junction in fetal
life between the Stratified SE of the vaginal and ectocervix,
and the CE of the end cervical canal.
New Squamocolumnar Junction (NSCJ): The upper margin of
the squamous metaplasia zone determined by the colposcopy
Transformation Zone (TZ): The area lying between the OSCJ
and the NSCJ
Risk factors for Cervical Cancer
1. Persistent HPV infection with high risk types
2. Young age at first coitus(20yr)
3. Multiple sexual partners
4. Sexual partner with multiple sexual partners
5. Young age at first pregnancy
6. High parity
7. Lower socioeconomic status
8. Smoking
9. Oral contraceptives use
10.Genital warts
11.Exogenous/endogenous immunosuppression

At least 35%of patients with CIN3 will develop

invasive
cancer within 10years, whereas lower grades may
spontaneously regress.

Screening of asymptomatic women

Papanicolaou Smear
Colposcopy
Both the end cervical canal and
The colposcope is a
the ectocervix should be sampled
stereoscopic binocular
when taking the Pap smear
microscope of low
In US , the ACOG has
magnification, usually 10x to
recommended that all women,
40x.
Indications for colposcopy:
once they have become sexually
1. Abnormal cervical smear
active, should undergo an annual
2. Abnormal findings on
Pap smear, then 2-5 years
adjunctive screening tests
following two or three normal Pap
such as HPV testing and
smears
cervicography, particularly in
In Australia, once sexually active
cases of ASCUS
till the age of 65 year, routine

BEFORE Colposcopy
A complete medical history and general
examination
should be performed
A clinical and speculum examination of the
cervix, vagina
and vulva should be performed
A 3% to 5%acetic acid solution is liberally
applied to the
cervix using soaked swap
-The abnormal findings are acetowhite epithelium
and
abnormal vascular patterns (mosaicism and

smear every 2 years

The false negative rate for Pap
smear for high grade lesions is
20%
New technologies (Thin prep,
AutoCyte PREP) are automated
liquid based slide preparation
systems to decrease the false
negative rate

3. If the cervix is clinically

abnormal or suspicious on
naked eye examination
4. Abnormal or unexplained IMb
or PCB
5. Persistent vaginal discharge
6. Personal history of in utero
DES exposure, vulvar or
vaginal
neoplasia

Evaluation of a patient with an abnormal Pap smear

Any patient with a grossly abnormal cervix should have a punch
biopsy performed regardless of the results of Pap smear
Patients with ASCUS found in their smear may have a repeat
smear in 6 months or HPV testing
About 6-10% of patients with an ASCUS smear will have highgrade CIN on colposcopy, 90% of these can be detected by HPV
testing for high-risk types
The colposcopic hallmark of CIN is an area of sharply delineated
acetowhite epitheilum, or/and abnormal vascular pattern:
punctuation and mosaicism
Micro invasive carcinoma: extremely irregular puncate and
mosaic patterns are found

Treatment of intraepithelial neoplasia CIN

punctuation)
Lugols iodine application to the cervix is called
shillers
test
-Normal ectocervix and vaginal squamous
epithelium
contains glycogen and stains mahogany-brown
-Normal columnar and squamous metaplasia
and neoplastic epithelium do not contain
glycogen, and appear mustard yellow
Satisfactory Colposcopic Examination: If the
new SCJ
and the entire TZ are seen

If colposcopic examination is satisfactory, punch

biopsy
from the suspicious area with end cervical curettage
specimen
Diagnostic cone biopsy of the cervix is indicated if:
1. colposcopic examination is unsatisfactory
2. Endocervical curettings show a high-grade lesion
3. Pap smear shows a high-grade lesion that is not
confirmed on punch biopsy
4. Pap smear indicates Adenocarcinoma in situ
5. Microinvasion is present on punch biopsy

Low grade lesions (CIN1) repeat smear in 6 month interval 4. Electrocoagulation, Requires general anesthesia, cervical
stenosis may occur, success rates up to 97%.
until normal then back to the normal screening program
5. Cervical conization: (cold knife or laser)
High grade lesions (CIN 2,3):
-mainly diagnostic but it may be used for treatment, cure
1. Loop Excision of The Transformation Zone
rates are as high as with hysterectomy for high grade lesions.
(LLETZ),relatively cheap, it can be performed on an
-Major complications: Bleeding, infection, cervical stenosis
outpatient basis under local anesthesia, and tissue is
and incompetence.
obtained for histologic evaluation.
2. LASER, destruction of the TZ by CO2 laser, ablation can be Simple hysterectomy is rarely necessary, it may be
performed as an outpatient procedure with local anaesthesia, applicable when sterilization is desired in a patient with CIN III
or when there is concomitant uterine or adnexal disease.
expensive.
3. Cryosurgery, relatively painless outpatient procedure
without anaesthesia, cheap, high failure rate for large lesions,
copious vaginal discharge for several weeks.
CERVICAL CANCER
Symptoms
Physical findings
Worldwide, cervical cancer is the most
1. Abnormal vaginal bleeding is the 1. Usually normal general
common cause of death from cancer in
most common presenting
examination
women.
2. In advanced disease, enlarged
symptom.
In developed countries, regular screening
2.
Postcoital
bleeding
in
sexually
inguinal or supraclavicular lymph
with Pap smear has markedly decreased the
active women, IMB, and PMB
nodes, edema of the legs, ascites,
incidence of the disease.
3.
Asymptomatic
until
quite
pleural effusion or hepatomegaly.
In US, cervical cancer now ranks only
advanced in women who are not 3. The Pap smear may be normal in
eleventh among cancers in women.
sexually active (unlike
up to 50% of cases (false-negative
The mean age for cervical cancer is 51.4
endometrial cancer who bleed
rate)
years, with the number of patients fairly
4.
Pelvic examination in early
early)
evenly divided
4. Persistent vaginal discharge,
disease may be normal, especially
between the age groups 30 to 39 and 60 to
pelvic pain, leg swelling, and
if the lesion is endocervical.
69 years
5. Visible disease may be, ulcerative,
urinary
frequency
are
usually
The most common type is SCC up to 80%,
exophytic ornecrotic
seen with advanced disease
adenocarcinoma and adenosquamous
5. Vesico-vaginal/recto-vaginal
account for 20% to 25%, other cell types
symptoms

are rare.

Pattern of spread
1.Direct invasion into the
cervical stroma, corpus, vagina,
and parametrium
2. Lymphatic permeation and
metastasis
3. Hematogenous dissemination

CERVICAL CANCER
Investigations
1. CBC, LFT, KFT
2. Chest X-ray
3. Pelvic-abdominal CT Scan
4. Biopsy of the lesion
5. Cystoscopy and proctoscopy for clinical staging
6. PET Scan (positron-emission tomography) new technique has the potential more
accurately to delineate the extent of disease at the primary site and in lymph nodes.

Treatment
Stage IA ( Micro invasive
carcinoma)
A preoperative diagnosis can be
made only on the basis of a cone
biopsy of the cervix
Stage 1A1 :
Total abdominal / vaginal
hysterectomy
Cone biopsy alone may suffice if
the patient desires to preserve her
fertility, as long as the cone
margins are free of disease and the
endocervical curetting are negative.
Stage 1A2:
Modified radical hysterectomy

Stage 1B

Radiation Therapy

May be treated by either radical

hysterectomy and bilateral pelvic
lymphadenectomy or radiation therapy.
The results of treatment by either method
are similar.
The advantages of surgery is that the
ovaries may be spared in young women,
surgical staging may be carried out, and
chronic radiation therapy may be avoided.
Radical Hysterectomy: Removal of the
uterus along with the adjacent portions of
the vagina, cardinal ligaments , uterosacral
ligaments, and bladder pillars.

For patients with stage 1b2, most

centers use primary chemo radiation,
using weekly cisplatin as the radiation
sensitizer
Therapy usually begins with external
radiation to shrink the central tumor
and subsequent intracavitary therapy.
External radiotherapy may also be
used postoperatively for patients with
lymph node mets, or inadequate
surgical margins
The addition of chemotherapy to
radiotherapy has been shown to

and pelvic lymph node dissection.

If childbearing is desired, largecone biopsy or radical
trachelectomy and pelvic lymph
node dissection may be offered

The most common complication of

Rad/Hys is bladder dysfunction, 1% to 2%
have permanent dysfunction.
The most serious complication of Rad/Hys
is ureteric fistula or stricture, which occurs
in 1% to 2% of cases
Lower limb lymphodema, 15% to 20%
due to pelvic
lymphadenectomy

improve survival.

CERVICAL CANCER
Complications of radiotherapy
Acute
Chronic

Stage IIa with minimal involvement of

the vaginal fornix, radical surgery or
chemo radiation may be employed.
Stage IIa to stage IVa: Pelvic chemo
radiation is the treatment of choice
Stage IVb Palliative radiotherapy or
palliative
chemotherapy

1. Acute cystitis: hematuria,

urgency and frequency.
2. Proctosigmoiditis:
manifested as tenesmus ,
diarrhea, and passage of
blood and mucus in the
stool
3. Enteritis: manifested by
nausea, vomiting,
diarrhea, and colicky
abdominal pain
4. Bone marrow depression

Radiation Enteropathy:
1. Proctosigmoiditis: pelvic pain, tenesmus,
diarrhea, and
rectal bleeding
2. Ulceration: manifested by rectal bleeding
and tenesmus
3. Rectovaginal fistula: manifested by
passage of stool
through the vagina
4. Rectum or sigmoid stenosis manifested by
progressive
large bowel obstruction
5. Small bowel injury usually present with
cramping
abdominal pain and vomiting with alternating
diarrhea
and constipation

Recurrent or Metastatic Disease

Chemotherapy: the effectiveness is limited, the most
active drug is the cisplatin
Pelvic exenteration: Reserved for patients who have
central recurrence following irradiation.
Total exenteration involves removal of the pelvic
viscera,
including the uterus, tubes, ovaries, bladder and
rectum
Radiotherapy if the initial disease treated with surgery
alone

Vaginal vault necrosis: associated with

severe pain
and tenderness of the vaginal vault and a
profuse
discharge.
Urologic Injuries:
1. Hemorrhagic cystitis which may need
frequent
blood transfusion and urinary diversion
2. Vesicovaginal fistula manifested by the
constant
leakage of urine demonstrable by cystoscopy
3. Ureterovaginal fistula which is manifested
by
constant leakage of urine and is
demonstrable by IVU
4. Ureteric stenosis which is manifested by
progressive hydronephrosis.

Prognosis
Prognosis is directly related to clinical stage
With higher stage , the frequency of nodal mets escalate,
and the 5-year survival rate diminishes.
Adenocarcinoma and adenosquamous carcinoma have a
somewhat lower 5-year survival rate than do SCC, stage for
stage