Pre Malignant Disease of Cervix

Presented by :
Hafiz M Abdullah
Hafiza Museera
Noor ul ain
 INTRODUCTION
Cervical cancer is caused by persistent high risk HPV infection

 HPV are classified into

 1. High risk( 16, 18,31,33&45) 2. Low risk types (6 and

11)

 HPV spread through sexual intercourse , infections are common following

sexual activity and 80% of adults show serological evidence for previous
infection.

 Smoking reduces immune system efficiency to clear up the virus and hence
increases the risk for the infection.
 Pathophysiology:

Normal HISTOLOGY OF CERVIX :

ECTOCERVIX: stromal tissue composed of squamous
epithelium in the vagina

ENDOCERVIX: composed of columnar epithelium within

cervical canal.They contain deep folds called crypts.

SQUAMOCOLUMNAR JUNCTION:The area where both these

epithelium meet is SCJ.This is usually on ectocervix
TRANSFORMATION ZONE:It is an area
between the original SCJ and the
current SCJ
, where the epithelium changes from
columnar to squamous epithelium over
time.
Sometimes the columnar epithelium is
covered by squamous epithelium
leading to retention of mucus—-
NABOTHIAN FOLLICLE.
 Pathophysiology:
● When HPV infection persists , it triggers the oncogenic process at TZ where metaplasia
occurs.
● Immortalization (incorporation of DNA into the basal epithelium leading to massive
proliferation of the cells)
● Rapid cell turnover …. Disordered immaturity within epithelium.

CERVICAL INTRAEPITHELIAL NEOPLASIA. An intraepithelial condition and cancer is diagnosed

when this process breaks the basement membrane

Immature cells are Hyperchromic, large nuclie , minimal cytoplasm, abnormal mitotic figures

GRADES OF CIN … .CIN 1 &CIN 2

Depends on abnormal cells location , seen on bottom third or top 2/3rd of cervical epithelium
respectfully .
NATURAL HISTORY OF CIN
LOW GRADE CIN HIGH GRADE CIN

Spontaneous regression is Very less likely to regress spontaneously

Uncommon Requires treatment
Cell mediated immunity Risk of progression
Observational followups 20% patients develope cervical cancer
Reason unclear but risk factors play role
And there is a strong association of CIN &
Cancers of cervix .
 Investigations

● The best screening test for premalignant lesions is cytology. Cytologic screening uses
the Pap test.
● This is an outpatient office procedure. It is a screening, not diagnostic, test for
premalignant cervical changes; it allows for early intervention, thus preventing cervical
cancer.
● The diagnostic test for cervical dysplasia or cancer requires a histologic assessment
made on a tissue biopsy specimen.
 Traditional Pap Test

Samples are obtained using a wooden spatula on the ectocervix and a cyto-
brush for the endocervical canal rotating in one direction 360°. The cells from
each area are then smeared evenly onto a glass slide, which is then fixed in
formalin, then stained and examined under a microscope by a cytologist
 Liquid Based Cytology

Specimens can be collected using cervical broom. The broom is rotated 5 times in the
same direction, collecting and sampling both endocervical cells and transformation
zone. The cervical broom is placed in the preservative solution and rotated 10 times
vigorously to release collected material into the solution.
 Interpretation

● For more than 95% of women, cervical cytology is normal and normal squamous cells are
seen.
● Abnormal cervical cytology shows squamous cells at different stages of maturity
(dyskaryosis).
● Like CIN, cervical cytology is classified as low grade (minor cytological abnormalities
showing mild dyskaryosis or borderline change) or high grade (moderate and severe
dyskaryosis)
● Cervical cytology triages patients to the colposcopy clinic for further assessment
 HPV Testing

High-risk HPV testing improves the sensitivity of cervical screening. Its value lies in its
extremely high negative predictive power
● The majority of women (around 95%) have normal cervical cytology and are placed on
routine recall.
● Women with high-grade cytology (2%) are referred urgently for colposcopic
assessment.
 Cervical Screening
• After age 65 if negative cytology and/or HPV tests for
past 10 years AND no history of CIN 2, CIN 3 or cervical
carcinoma.
• Any age if total hysterectomy AND no history of cervical
neoplasia.
 COLPOSCOPY

Definition: Colposcopy is the examination of the magnified cervix using a

light source.

Indications: Abnormal pap smear , warts polyps abnormal bleeding

malignancy suspected

What we see : cervix ( transformation zone , squ col junction ) vagina vulva

Procedure:

1 undress and lithotomy position

2 use speculum and colposcope

3 Apply Acetic acid and iodine ;

4. Abnormal area turns white ; New blood vessels( Angiogenesis) apparent.

W hat We See
TREATMENT OF PRE MALIGNANT DISEASE OF CERVIX

AIMS OF TREATMENT:

● Effective eradication of CIN

● Ensuring that post-treatment cytology is negative
● Minimizing harm to the patient from treatment
 TREATMENT

● Low grade CIN: spontaneous regression in 60% of cases, therefore close follow up
with colposcopy and cytology 6 months after diagnosis
● High Grade CIN: LOOP DIATHERMY / LLETZ
● ADVANTAGE OF LLETZ:
● clinically effective (95% of patient have negative cytology at 6 months)
● cost-effective
● Provides a specimen for pathological assessment
● DISADVANTAGE OF LLETZ:
● mid trimester miscarriage and preterm delivery in subsequent pregnancies in case of
large excision or repeat excisions.
 Other treatment options include:

● COLD COAGULATION: destructive treatment, effective for both high and low grade
CIN but does not provide a specimen. Performed by placing a hot probe on cervix
in outpatients under local anesthesia.
● CONE BIOPSY: cutting away a portion of the cervix under GA, produces a specimen
like LLETZ.
● Patients treated for CIN undergo a test of cure 6 months later
● This includes high risk HPV test and cytological assessment
● If negative then cervical screening in 3 years time
● If positive: repeat colposcopy to identify any residual untreated CIN.
 HPV VACCINATION

● safe and effective at preventing persistent high risk HPV infection CIN.
● Age: 12-13 years girls
● BIVALENT VACCINE : Prevent persistent infection with HPV type 16 and 18- which
are responsible for 70% of cases of cervical cancer.
● QUADRIVALENT VACCINE: protect against HPV type 6,11 , 16 and 18.
● It is expected that vaccination will lead to fewer women being referred for
colposcopy when they reach screening age.
Malignant disease of
Cervix
 Clinical
presentation:
● Many patients asymptomatic
● Abnormal bleeding (PCB, IMB, PMB)

In stage lll-lV distressing symptoms

● Pain. (infiltration of spinal cord)

● Incontinence (vasicovaginal fistulae)
● Anemia (chronic bleeding)
● Renal failure (ureteric blockage)

Pelvic and speculum examination

● Cervical mass that bleeds on contact

● Hardness and fixity of tissues in advanced disease
 Pathophysiology:

1 The majority (70%) of cervical cancers are squamous cell carcinomas, with
adenocarcinomas making up most of the remainder(30%).

2 Precursors of adenocarcinoma, known as cervical glandular intraepithelial

neoplasia (CGIN), can also be detected at colposcopy, although lesions reside
within the endocervical canal and may be difficult to visualize

3 . Often CGIN is found incidentally in loop excision biopsies carried out for high-
grade CIN; it is not uncommon for the two precursors to coexist.
Spread:-

1 -Cervical tumours are locally infiltrative in the

pelvic area, but also spread via lymphatics and, in
the late stages, via blood vessels.

2 -The tumour can grow through the cervix to reach

the parametria (anatomical area lateral to the
cervix), bladder, vagina and rectum.

3 -Metastasis can occur, therefore, in pelvic (iliac and

obturator) and para-aortic nodes and, in the later
stages, liver and lungs.
 Investigations

● History & Pelvic Examination

● Colposcopy
● Cervical Biopsy (Crucial to confirm malignancy and tumor type)
● MRI of the abdomen & pelvis (assess local spread of disease &
lymphadenopathy)
● Cervical Cancer is staged clinically, unlike other gynecologic tumors
which relies on surgery & pathology to give ultimate stage.
 Cervical Biopsy

 Usually done with colposcopy.

 A biopsy is crucial to confirm malignancy and assess the tumour type. The stage of the

disease is crucial for planning treatment.

 The stage of disease also correlates with prognosis. Patients are staged according to

the FIGO system.

Metastatic Work Up

● Full Blood Count

● Urea & Electrolyte
● LFTs
● CXR
● MRI Abdomen Pelvis
● Cystoscopy
● Sigmoidoscopy
 MRI

Magnetic resonance imaging (MRI) of

the abdomen and pelvis will assess the
local spread of the disease in the cervix
and will detect enlarged lymph nodes in
the pelvic area.
 A chest X-ray is vital to exclude lung metastases

 Cystoscopy can help eliminate bladder involvement.

Treatment according to
staging
Preclinical lesions: stage IA
Small volume ,incidental finding on loop excision {leep} for precancerous disease.

1. Small lesions must be removed with a clear margin of excision, and the preinvasive disease
(CIN) that coexists should be completely excised as the cancer is often multifocal.

1. If the preinvasive disease is not completely excised then a repeat loop biopsy or knife cone
biopsy must be carried out.

1. For microscopic lesions (stage IA1), local excision with good clear margins is all that is required.
This allows fertility to be preserved and a hysterectomy is not necessary.
Clinical invasive cervical carcinoma: stages IB–IV

1. Small volume disease is confined to the cervix (stage IB1), radical hysterectomy and bilateral
pelvic node dissection (Wertheim’s hysterectomy).

2. For young women, radical trachelectomy (surgical removal of the cervix and upper part of the
vagina) and bilateral pelvic node dissection is an alternative

3. Early stage IB disease, pelvic radiotherapy for people who are too overweight for radical
surgery.
4. If beyond the cervix (stages II–IV disease), radiotherapy (with or without
chemotherapy)
Surgery
● The standard for stage IB tumours is a radical hysterectomy and pelvic lymph node
dissection.
● This involves removal of the cervix, upper third of the vagina, uterus and the
paracervical tissue.

● Pelvic lymph node removal includes the obturator, internal and external iliac nodes.
● The ovaries in premenopausal women can be spared.

Complications :

1. There is higher morbidity with this procedure over the standard total abdominal
hysterectomy.
2. Bladder dysfunction (atony), sexual dysfunction (due to vaginal shortening) and
lymphoedema (due to removal of the pelvic lymph nodes) are not uncommon
Radiotherapy

Two ways: external beam radiotherapy (as teletherapy) and internal radiotherapy
(brachytherapy).

External beam radiotherapy

●This is given in several treatments or ‘fractions’ as an outpatient over 4 weeks.

●This treatment is given daily, the time of each fraction is no more than 10
minutes.
 Brachytherapy

● Radiation is delivered internally to

the patient.

● Selenium ….. under anaesthesia to

insert the rods into the uterus.

● Delivers a high dose of radiation to

the tumour source and its harmful
effects on the bladder and bowel
are minimized as its effects are
targeted only 5 mm from the rod.
JazakAllah