CERVICAL CANCER

•	Epidemiology.
•	Clinical presentation. 
•	Investigations.
•	Staging and prognosis.
•	Management.

Epidemiology

1.	The most common gynaecological cancer in Singapore, it accounts for 7.2% of all cancers in the female.

2.	ASR: 14.2 / 100,000 / yr.

3.	Histology:

a.	Squamous cell: 78.0%.

b.	Adenocarcinoma: 14.4%.

c.	Adenosquamous: 2.3%.

d.	Others: 5.6%.

4.	Risk factors:

a.	Oncogenic HPV infection, types 16, 18.

b.	Early age of sexual intercourse.

c.	Multiple sexual partners.

d.	OCP usage: slight increase in risk.

e.	Smoking.

f.	Immunosuppression.

Clinical presentation

1.	Tumor:

a.	Post-coital bleeding.

b.	Inter-menstrual bleeding.

c.	Post-menopausal bleeding.

d.	Menorrhagia.

e.	Foul-smelling discharge.

2.	Local invasion:

a.	Bladder: pneumaturia, haematuria, urine PV.

b.	Colon: hematochezia, feces PV.

c.	Ureters causing hydronephrosis: loin to groin pain, fever, chills and rigors. 

3.	Spread of disease:

a.	Lateral spread through cardinal ligament into parametrium.

b.	Anterior extension through vesicovaginal septum.

c.	Lymphatic spread in decreasing incidence: obturator, external iliac, hypogastric lymph nodes.

d.	Metastasis to lumbosacral nerve roots causing lumbosacral back pain.

4.	Neoplastic: LOA, LOW, anaemia, jaundice, shortness of breath, lymphadenopathy.

Investigations

1.	Pap smear

a.	Using a cytobrush to scrap the cervix directly to collect the cells.

b.	The cells are spread on a glass slide and fix immediately with alcohol.

c.	They are then seen under a microscope for cytological abnormalities.

d.	An abnormal Pap smear:

i.	dysplastic changes.

ii.	inadequacy.

iii.	inflammation.

iv.	infection.

v.	presence of endometrial cells.

e.	Follow-up:

i.	ASCUS: treat present infections and repeat smear.

ii.	LSIL: excision or ablation or regular surveillance with Pap every 4 – 6 months for 2 years until 3 consecutive negative Pap.

iii.	HSIL: referred for colposcopy, excision or ablation.

2.	Colposcopy

a.	The colposcope is a binocular operating microscope with magnification of between five to 20 times used to examine the cervix in detail to identify dysplastic abnormalities on the ectocervix.

b.	Indications:

i.	abnormal Pap smear: CIN I, II, III and AGUS.

ii.	exclude invasive disease.

iii.	identify site, size and extent of any abnormality.

iv.	decide between targeted or excisional biopsy to obtain reliable histological diagnosis.

c.	Procedure:

i.	magnified examination with green filter or saline.

ii.	apply acetic acid 3 – 5% precipitate nuclear proteins.

iii.	Lugol’s iodine stains glycogenated epithelium (Schiller’s test).

d.	Features of abnormal epithelium:

i.	acetowhite change: spread of uptake and intensity.

ii.	punctation: stippled vascular pattern within a well demarcated area.

iii.	alterations in surface contour: raised, peeling edges, contact bleeding.

iv.	variations in blood vessel patterns: mosaicism. 

3.	Cone biopsy:

a.	Use of scalpel, laser or loop diathermy to obtain cervical tissue.

b.	Indications:

i.	CIN II or III with a lesion extending beyond view into the endocervical canal.

ii.	cytologic or colposcopic suggestion of microinvasive or invasive disease.

iii.	discordance between Pap and colposcopy findings.

iv.	persistent LSIL > 12 months.

v.	suspicion of adenocarcinoma.

Staging and Prognosis

1.	FIGO staging

Stage	Clinical features	
0	CIN III	
I	Confined to the cervix.	
IA	IAI: depth < 3mm, diameter < 7mm.
IA2: depth < 5mm, diameter < 7mm.	
IB	Clinical lesions confined to the cervix or preclinical lesions greater than IA:
IB1: lesions < 4mm in size.
IB2: lesions > 4mm in size. 	
II	Beyond cervix, no pelvic wall or lower 1/3 vaginal involvement:
IIA: no parametrial involvement.
IIB: parametrial involvement.	
III	IIIA: lower 1/3 of vagina involved.
IIIB: pelvic side wall or hydronephrosis.	
IV	IVA: involves mucosa of bladder or rectum.
IVB: distant spread beyond pelvis. 	

2.	Cervical cancer staging

a.	Examination under anaesthesia:

i.	tumor volume estimation.

ii.	vaginal assessment.

iii.	parametrium assessment.

b.	Cystoscopy.

c.	Rectal examination with / without sigmoidoscopy.

d.	IVU or CT scan or MRI. 

3.	Prognostic factors

a.	Age.

b.	Performance status.

c.	Stage.

d.	Volume of tumor.

e.	Histologic type. 

f.	Grade of tumor.

g.	Lymphatic spread, especially to para-aortic chain.

h.	Vascular invasion.

4.	Prognosis

Stage	5-year survival %	
IA	> 99	
IB1	85	
IB2	70	
IIA	75	
IIB	79	
IIIA	50	
IIIB	40	
IVA	10	
IVB	< 1	

Management

1.	Overview:

Stage	I	II	III	IV	
Treatment	A	B	A	B	A	B	A	B	
Conization	√								
Radical trachelectomy	√	√							
Total hysterectomy	√								
Radical total hysterectomy		√	√						
Radiotherapy	√	√							
Concurrent chemotherapy		√	√	√	√	√	√		
Chemotherapy								√	

2.	Preclinical lesions

a.	Patients who have preclinical disease that invades to a depth of less than 3mm and a width of 7mm can safely be treated by complete local excision -  this is usually in the form of a colposcopically-directed cone biopsy.

b.	Patients with disease invading to a depth of between 3 – 5 mm may have a risk of nodal disease of about 5 percent and should be offered radical treatment.

c.	Endocervical lesions require laser or cold knife excision.

d.	Types of ablative therapy:

i.	hot cautery.

ii.	electrocoagulation diathermy.

iii.	radical diathermy.

iv.	cold coagulation.

v.	cryotherapy.

vi.	laser ablation.

vii.	Loop electro-excision procedure (LEEP).

3.	Invasive cervical carcinoma:

a.	If the disease is confined to the cervix, then either surgery or radiotherapy may be offered.

b.	Once the disease has spread outside the cervix, radiotherapy is usually the mainstay of treatment.

4.	Surgery:

a.	Radical trachelectomy:

i.	excision of cervix up to internal os and parametrium.

ii.	indicated for younger women who desire family.

b.	Wertheim’s hysterectomy:

i.	removal of the uterus and paracervical tissue surrounding the cervix and upper vagina.

ii.	the pelvic lymph nodes are dissected

c.	Complications:

i.	Acute: hemorrhage, infection, atelectasis, UTI, DVT and PE.

ii.	Fistula formation: uretero-vaginal, vesico-vaginal, recto-vaginal.

iii.	Chronic: bladder dysfunction due to partial denervation of detrusor muscle and lower lymphadenoma.

5.	Radiotherapy:

a.	Involves the use of a linear accelerator to treat the whole pelvis with external beam therapy to shrink the central carcinoma and also to treat possible sites of regional metastasis.

b.	The external beam therapy is usually given in 25 fractions over a 4-week period, followed by two internal treatments the following weak.

c.	In advanced cancer of the cervix, radiotherapy may be used in a palliative setting to reduce vaginal bleeding and discharge and to assist in local control of the disease. 

d.	Complications:

i.	intracavity therapy: uterine perforation, hemorrhage and peritonitis.

ii.	vaginal stenosis and fistula formation.

iii.	bladder: ureteric stricture, hemorrhagic cystitis.

iv.	rectum: proctosigmoiditis, small bowel obstruction. 

v.	ovaries: premature ovarian failure. 

6.	Chemotherapy with combined cytotoxic drugs, including cisplatin are used in extensive recurrent disease.

7.	Recurrent cervical cancer:

a.	Anterior exenteration: radical hysterectomy, vaginectomy and cystectomy.

b.	Posterior exenteration: AP resection, radical hysterectomy and vaginectomy.

c.	Total pelvic exenteration:

i.	en bloc excision of bladder, uterus, rectum and vagina.

ii.	urinary diversion with neoileobladder and pouch.