ca cervix (combined)

CARCINOMA CERVIXBY : SITI MUNIRAH KAMARUDINNOR ELYA FARHANA BINTI ABDUL RAZAK

OUTLINE INTRODUCTION EPIDEMIOLOGY ETIOLOGY DIAGNOSIS CLASSIFICATION MANAGEMENT PREVENTION

INTRODUCTION Cx ca is the most common gynecologic ca in women

Most of ca cx stem from infection with Human Papilloma Virus (HPV)

Dx : colposcopic examination and histologic evaluation of cervical biopsy

This ca is staged clinically the most important indicator of long term survival

Prevention lies mainly in early detection regular Pap smear screening

EPIDEMIOLOGY

1 million fresh cases/year across the globe

2nd commonest cancer in women (parkin 2005)

Incidence is decreasing in developed countries

Pap smear has reduced incidence by 80%& death by 70%

Most common CA in developing countries

Risk factors Early intercourse(<16yrs) High parity Early age of pregnancy Too many/ too frequent pregnancy Multiple sexual partners OCPills Smoking Lower socioleconomic

Pathogenesis Cx epithelium-> infection->hpv dna

integration to human genome-> up regulation of viral oncogenes-> expression of E6&E7 oncoproteins ->interference with tumor suppressor genes-> host cell immortalization, HPV induced euplastic transformation

HISTOPATHOLOGY Squamous cell carcinoma is the

commonest (80-90%) Well differentiated, moderately

differentiated, poorly differentiated Source- healing erosion, squamous

metaplasia of columnar epithelium, squamous cell rests in ectocx

HISTOPATHOLOGY Adenocarcinoma (10-15%) develops

from endocervical canal- from lining epithelium/glands

Occurs at young age 80% purely endocervical type Others- endometroid, clear,

adenosquamous, or mixed

DIAGNOSISSYMPTOMSEarly stage : watery , blood tinged p/v d/cirregular/continuos bleeding Offensive dischargeLower extremity edemaLow back painBladder, Rectal symptoms , Ureteral obstruction

P/SLesion may appear as

Exophytic or endophytic growth Polypoid mass Papillary tissue Barrel shaped cx Ulceration

invasive cervical cancer originating from the endocervix

Bimanual examination may palpate

indurated, friable, bleeding to touch thick, hard , irregular rectovaginal septum

Rectal examinationParametria involvement

Feel thick, irregular, firm , less mobile

FIGO Staging

• A clinical classification• According to:

– vaginal examination– rectal examination– cystoscopy

* FIGO – International Federation of Gynaecology and Obstetrics

• Stage 0 - CIN III(CIS)

Stage I – confined to the cervix

Ia - Microscopic

1a1 – Stromal invasion ≤ 3mm,

Width ≤ 7 mm

1a2 – stromal invasion 3 – 5 mm,

Width ≤ 7 mm

Ib – Macroscopic

1b1 – Lesion ≤ 4 cm

1b2 – Lesion > 4 cm

Stage II – extend beyond the cervix but not to the pelvic wall and lower third of the vagina

IIa

Extend to the upper two third of the vagina

IIb

Extend to the parametrium

Stage III – Extend to lower one third of vagina or pelvic wall

IIIa

Involvement of the lower one third of the vagina

IIIb

Involvement of the pelvic wall/ hydronephrosis or non-

functioning kidney

Stage IV – extend beyond true pelvis, involve bladder or rectum

IVa

Spread to adjacent organ

(bladder, rectum)

IVb

Spread to distant organ

MANAGEMENTSURGICAL RADIOTHERAPY CHEMOTHERAPY

Pre-invasive (Ca in situ, CIN III)

*** All women who have had CIN before should be followed up with annual smears for a minimum of 10 years.

Wertheim’s hysterectomy

Radical hysterectomy

Bilateral lymph node clearance+

Favoured in :

• Pre-menopausal women• Where the tumour is

small• When the future child bearing is not wished

Complications :• uriteric fistula or stricture

• bladder dysfunction• DVT and PE

Palliative-Pain control

-radioRx - bleeding

Prognosis

• Stage I - > 85%• Stage II – 50%• Stage III – 25%• Stage IV – 5%

• In patients with recurrent disease :– 50 % show recurrence within 1 year– 75% show recurrence within 2 years– 90% show recurrence in 5 years

STAGE SPREAD TREATMENT PROGNOSIS (5-year survival %)

I a

I b

II a

II b

III

IV

Cervix (micro-invasive)

Cervix (macro-invasive)

2/3rd upper vagina

Parametrium

1/3rd lower vagina, pelvic walls

Bladder, rectum or metastases

Local excision

Radical surgery

Radical surgery

Radiotherapy

Radiotherapy

Palliation

100

80

60

50

30

10

PREVENTION STRATEGIES

CERVICAL CYTOLOGY SCREENING

PROGRAMME

PROPHYLACTIC HPV VACCINE

Methods of Screening

• Pap smear• Colposcopy

How to take?

• Explain to the patient/consent• Not during menstruation• The best time is on D10 - D20• Avoid douching, using spermicidal gel.• Avoid sex 24 hours prior to the procedure

• Patient in dorsal/lithotomy position • using the Cusco’s bivalve speculum to visualize

the cervix • Place the wooden spatula (Ayre’s spatula) on

the cervix and rotate 360° clockwise and make sure cover all the transformation zone

• Immediately smear it on the glass slide • Fix the slide with fixative agent either spray or

ethanol 95%

Speculum

Insert Speculum

• Spread labia• Keep labia apart• Blades remain closed

until fully inserted

Squamo-Columnar Junction

• Junction of pink cervical skin and red endocervical canal

• Inherently unstable • Key portion of the cervix

to sample• Most likely site of

dysplasia

Ayre’s Spatula

Sample Cervix

• Use concave end • Rotate 360 degrees• Don’t use too much force

(bleeding, pain)• Don’t use too little force

(inadequate sample)

How to interpret?

• Dyskaryosis - abnormal nucleus of individual the cell.

• Dysplasia - abnormality in organised growth of the cell.

• CIN – refers to a lesion in epithelium of the cervix

• New technique – Bethesda system

Cervical Intraepithelial Neoplasia

CIN I Mild dysplasiaCIN II Moderate displasia

Severe dysplasiaCIN III

Carcinoma in situ

CIN I

Alterations are limited to the lower third of the cervical epithelium

CIN II

The cell polarity is disturbed in the lower two thirds of the epithelium

CIN III

Dyspolarity is present in more than two-third or all layers of the epithelium.

Natural history of CIN 1-2

**(100 prospective studies)

STAGE/PROGRESS Regress Persist CIN III Cancer

CIN I 57% 32% 11% 1%

CIN II 43% 35% 22% 5%

Bethesda System

• Specimen adequacy– Satisfactory for evaluation– Unsatisfactory for evaluation …… (specify reason)– Specimen rejected/not processed …(specify

reason)– Specimen processed and examined but

unsatisfactory for evaluation … (specify reason)

When to start?• Within 3 years of 1st coitus or by age 21How frequent• Every two years provided the last smear is

normalWhen to stop?• No limit

Colposcopy

• Technique of viewing cervix using binocular microscope with low magnification to determine the source of abnormal cells

• Indication: abnormal finding on Pap smear

Procedure• Position patient in lithotomy position

1. LOOK• Using the speculum to visualize the cervix

2. ACETIC ACID• Apply 3-5% acetic acid for at least 60sec prior to

inspecting for changes• Acetic acid dissolves mucous and accentuates

atypical areas (white epithelium, punctation, mosaic and atypical vessels) by causing cellular dehydration and coagulation of cellular protein.

• The effect of the acetic acid peaks in ~ 2 min and fades in ~ 5 min. Re-apply the acetic acid solution several times.

• Biopsy the acetowhite epithelium

A. Benign surface vessels viewed through a colposcope using usual white light source.

B. Use of a blue-green (red-free) light filter provides higher contrast and definition of vascular patterns.

A. Cervix after application of acetic acid. Several areas of acetowhite change adjacent to the squamocolumnar junction are apparent.

B. Same cervix after application of Lugol iodine solution. Non-staining of the lesions at the 10 to 11 o'clock positions is seen (black arrow) while there is partial iodine uptake of acetowhite areas along the posterior SCJ (white arrow).

3. BLOOD VESSEL PATTERN• Using the green filter to improve the ability to identify the vascular patterns (mosaic, punctation, atypical)

VACCINES

Star – 21st July 2009

Cumulative Incidence of Any HPV InfectionCumulative Incidence of Any HPV Infection

What is HPV ?• HPV is short for human

papillomavirus

• HPVs are a groups of over 100 related viruses

• Each HPV virus in the group is given a number, which is called an HPV type.

American Cancer Society, Inc 2008

Human Papillomavirus Types and Disease Association

nonmucosal/cutaneous(~60 types)

skin warts (hands and

feet)

mucosal/genital(~40 types)

high-risk types16, 18, 31, 45 low-risk types

6, 11

•low grade cervical abnormalities

•cancer precursors•genital cancers

•low grade cervical abnormalities•genital warts

•laryngeal papillomas

How is HPV related to cervical cancer?

53.5

2.3

2.2

1.4

1.3

1.21.0

0.7

0.6

0.50.3

1.24.4

2.6

17.2

6.7

2.9

0 10 20 30 40 50 60 70 80 90 100

XOther

827368395156593558523331451816

Almost all (more than 99 %) cervical cancers are related to HPV. Almost all (more than 99 %) cervical cancers are related to HPV. Of these, about 70% are caused by HPV types 16 or 18.Of these, about 70% are caused by HPV types 16 or 18.

American Cancer Society, Inc 2008American Cancer Society, Inc 2008

Muñoz N et al. Int J Cancer 2004; 111: 278–85.

Vaccine Available

When, Why, HowWHEN can you prescribe CervarixTM?

• Prescribe now for girls and women, as they remain at riskof infection from oncogenic HPV throughout their lives.

WHY prescribe CervarixTM?CervarixTM, with its novel adjuvant AS04, provides strong and

sustained protection against cervical cancer.1,3,4,25-32Induces antibody levels that start high and stay high for both HPV 16/18.

HOW do you administer CervarixTM?Give 3 doses of CervarixTM at 0, 1, 6 months.

Vaccination is by intramuscular injection into the deltoid area.

star– 21st July 2009

THANK YOU

Referrence• Gynaecology companion, Dr Mohd Azhar Mohd Noor• Clinical Practice Guidelines (CPG), Management of Cervical Ca 2003• Gynaecology by Ten Teachers, 18th edition• Quick Management Guide in Gynaecology, Lee Say Fatt, UM 2008