CARCINOMA OF THE CERVIX

Dr Baidaa abdallah
Cervical cancer is the second most common malignancy
in women worldwide
The median age at diagnosis in North America is 47 years
with nearly half the cases diagnose before the age of 35.
Women over the age of 55 have a disproportionately
higher mortality from this disease as they present with
more advanced disease
In the United States the relative 5-year survival rate for
cervical cancer patients diagnosed with localized disease
is 92% and 70% for all stages respectively.
 Of Cervical carcinoma

• lower socioeconomic status, predominantly because

these individuals have not had good access to health
care and cervical cancer screening programs..
• HIV seropositivity has been identified as a risk factor
for cervical cancers

Other risk factors

• for cervical cancer include early age of first intercourse,
history of multiple sexual partners, smoking, and a large
number of pregnancies, but the single most important
risk factor is a persistent infection with one of the high
risk HPV types.
 Clinical presentation
The clinicalpresentation is variable. Many patients
with small volume microscopic disease are
asymptomatic and are picked up incidentally
following a loop biopsy of the cervix for
preinvasive disease.
Most cervical cancers,however,arefriable,vascular
masses on the cervix and patients present with abnormal
bleeding, typically postcoital (PCB), prolonged, intermenstrual
(IMB) or postmenopausal (PMB) bleeding Any woman with these
symptoms shouldtherefore undergo a pelvic
examination, including visualization of the cervix.
In advanced disease (stagesIII–IV), patients may experience
a number of distressing symptoms including pain (malignant
infiltration of the spinal cord), incontinence (due to
vesicovaginal fistulae), anaemia (from chronic vaginal bleeding)
and renal failure (from ureteric blockage)
 Cervicalcancer diagnosis
• . A pelvicand speculum examination usually
clinches the diagnosis as there is often a cervical
mass that bleeds on contact and if advanced disease, a
hardness and fixity of the tissues.
• A biopsy should be taken in the outpatient setting.
Very occasionally, the diagnosis can be missed as
some tumours are endophytic rather than exophytic
and therefore less clinically revealing. The clinician
thereforeneeds to retain a level of clinical suspicion
in thepresence of unexplained symptomsand
investigate patients with persistent problems.
 Pathophysiology
• The majority (70%) of cervical cancers are squamous cell
carcinomas, with adenocarcinomas making up most of
the remainder. In higher income countries with screening
programmers, there has been a relative fall in the numbers of
squamous tumours and a relative rise in the incidence
of adenocarcinomas. In the UK, 30% of tumours are
adenocarcinomas and are less likely to be picked up on
cervical screening. 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. 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.
 Metastasis of cervical cancer
• Cervical tumours are locally infiltrative in the
pelvic area, but also spread via lymphatic and,
in the late stages, via blood vessels. The
tumour can grow through the cervix to
reach the parametria (anatomical area
lateral to the cervix), bladder, vagina and
rectum. Metastases can occur, therefore,in
pelvic(iliac and obturator)and para-aortic nodes
and, in the later stages, liver and lungs.
 Staging of CA Cervix
• Assessing the stage of the disease is
crucial for:
• planning treatment.
• The stage of disease also correlates with
prognosis.
• Staging for cervical cancer is staged according
to the FIGO system.
• Stage 0 Full thickness involvement of the epithelium without invasion into the
stroma (carcinoma in situ)
• Stage I Limited to the cervix:
• IA – no visible lesion, diagnosed by microscopy
• IA1 – stromal invasion <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 – histologically invasive carcinoma confined to the cervix and greater than stage
1A2.
• IB1 – clinically visible lesions <4 cm in greatest dimension
• IB2 – clinically visible lesion of >4 cm in greatest dimension
• Stage II Carcinoma invades beyond the cervix but not onto the pelvic wall.
Carcinoma involves the vagina but not the lower third:
• IIA – without parametrial invasion IIA1 – clinically visible lesion <4 cm in greatest
dimension
• IIA2 – clinically visible lesion of >4 cm in greatest dimension
• IIB – with obvious parametrial invasion
• Stage III Carcinoma has extended to the pelvic wall/involves the lower third of the
vagina and/or causes hydronephrosis or non-functioning kidney:
•
• IIIA – tumour involves lower third of the vagina, with no extension to the pelvic
wall
• IIIB – extension to the pelvic wall and/or hydronephrosis and or non-functioning
kidney
• Stage IV Carcinoma has extended beyond the true pelvis or has involved the
mucosa of the bladder or rectum. This stage also includes those with metastatic
dissemination:
• IVA – spread of the growth to adjacent organs
• IVB – spread to distant organs
• A biopsy is crucial to confirm malignancy and assess the
tumour type.
• 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.
• An examination under anesthesia may be helpful
when, despite the above tests, the clinician is still
unclear whether the tumour is operable. Doing a
rectovaginal examination under anaesthetic can give
crucial information on the tumour including size of
disease, fixity andvaginal involvement, and a cystoscopy can
help eliminate bladder involvement. Small mobile tumours
favour a surgical approach, whereas larger fixed tumours favour
the use of radiotherapy.
• The FIGO staging includes an intravenous urogram to
ensure the integrity of the ureters; however, this is not
standard practice in higher income countries, where MRI has
superseded such tests.
• The staging of the disease is based on clinical
findings, unlike other gynaecological tumours
where there is a reliance on surgery and
pathology to give the ultimate stage.

• The reasons for this are that radiotherapy

is used in advanced disease and it
still remains possible to stage patients
in low income countries where
most of the disease occurs.
• Although stromal invasion can be seen in a small
biopsy, the diagnosis of microinvasive cervical
cancer can only be made in a conization or
hysterectomy specimen
• More recently, cervical conization and large loop
excision of the transformation zone (LLETZ) are
considered equally efficacious when the latter is
performed by experienced operators
 Treatment
• Treatment for cervical cancer depends on
the
• Stage of the disease,
• the requirement for future fertility
• and the patient’s performance status.
• Ideally, all cancer patients should be discussed within the
context of a multidisciplinary team (MDT) of doctors
(surgeons, radiotherapists, radiologists and
pathologists)and nurses, so that the most appropriate
treatment can be offered to the patient.
• The fitness of thepatient is crucial before embarking on
treatment as radical surgery may not
be appropriate in an unfit patient.
 Preclinical lesions: stage IA
• These microscopic tumours have a low
volume of cancer and are usually
picked up as incidental findings after
loop excision for precancerous disease.
Small lesions must be removed with a
clear margin of excision, and the
preinvasive disease (CIN) that invariably
coexists should also be completely
excised as the cancer is often
multifocal. If the preinvasive disease is not
completely excised then a repeat loop biopsy or
knife cone biopsy must be carried out. This
allows fertility to be preserved and
a hysterectomy is not necessary.
 Clinical invasivecervical carcinoma
• stages IB–IV The tumour volumes are
much greater in patients with stage 1B
disease and therefore fertility-preserving
treatment for this groupof patients is
more challenging. When small volume
disease is confined to the cervix (stage IB1),
radical hysterectomy and bilateral pelvic node
dissection (Wertheim’s hysterectomy) is standard
of care.
• For young women who have not completed their
families, radical trachelectomy (surgical removal
of the cervixand upper part of the
vagina) and bilateral pelvic node dissection is
an alternative .
• It is important to remember that in
early stage IB disease, pelvic
radiotherapy has similar success
rates to surgery and therefore this
treatment is considered in women who are
too overweight for radical surgery or who
are anaesthetically unfit
• When the disease is beyond the cervix
(stages II–IV disease), radiotherapy
(with or without chemotherapy) becomes
the optimal treatment.
 Surgery
• Surgery The standard surgical operation 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.and
• Pelvic lymph node removal includes the
obturator, internal and external iliac
nodes.
 Advantages of surgery
• The ovaries in premenopausal women can be spared.
• There is higher morbidity with this procedure over the standard total
abdominal hysterectomy.
• Bladder dysfunction (atony), sexual dysfunction (due to vaginal
shortening) and lymphoedema (due to removal of the pelvic lymph
nodes) are not uncommon.
• An atonic bladder is frequent in the immediate postoperative
period due to neuronal damage from the surgery, andintermittent
self-catheterization may be required until the bladder tone
returns. Lymphoedema is variable and is described by patients
as a wooden, heavy feeling to the legs with swelling and
reduced mobility. Management includes leg elevation, good skin
care (e.g. avoid shaving), massage and occasionally
compression stockings. Despite these potential problems, surgery is
the preferred treatment as the cure rate is high, ovarian tissuecan
be preserved and the patient avoids the complications of
radiotherapy
 Radiotherapy
• Radiotherapy The aim of radiotherapy is to deliver a lethal dose
of radiation to the tumour and minimize
damage to the surrounding tissues.
• Treatment is overseen by a radiotherapist and team.
Treatment is delivered in two ways: external beam
radiotherapy (as teletherapy)and internal
radiotherapy (brachytherapy).In external beam radiotherapy,
the source of the radiation is from a machine called a
linear accelerator, and radiation is delivered to the
pelvis a distance from the patient .
• The dose of radiotherapy is carefully calculated according to
the patient weight and the tumour, and is
usuallyadministered as 45 Gy in total. This is given
in several treatments or ‘fractions’ as an
outpatient over 4 weeks. Although this
treatment is given daily, then time of each fraction
is no more than 10 minutes.
• Brachytherapy is a radiotherapy technique where the radiation is
delivered internally to the patient. The source of
the radiation is usually selenium and patients generally
have to undergo an examination under anaesthetic
to insert the rods into the uterus. These rods are
then attached to the radiotherapy source; the
patient receives this internal treatment in
isolation to protect the staff. Brachytherapy 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. Patients frequently
suffer lethargy with treatment and may experience both
bowel and bladder urgency, which is due to the initial
inflammatory effects of the radiation. Skin erythema-
like sunburn is not uncommon after external beam
radiotherapy. Symptomatic treatment is usuallyrequired,
such as antiinflammatory creams for skin. Around
5% of patients experience a serious side-effect
that might interrupt treatment, for example bowel perforation.
• There aremany long-term complications of
radiotherapy that affect only a minority
of patients but do have a significant
impact on patients’ quality of life.
The initial inflammatory process is
replaced by fibrosis in the long
term. Vaginal stenosis can causesexual
pain, bladder damage can lead to
cystitis-like symptoms, haematuria and bowel
damage lead to malabsorption and
mucous diarrhoea. None of these
complications can be managed easily.
Patients who are premenopausal will
undergo a radiotherapy-induced
menopauseas the ovaries are very
sensitive to small doses of irradiation.
 Chemotherapy
• Chemotherapy (cisplatin) is ideally givenin
conjunction with the radiotherapy, as this
combination increases cure rates morethan
when radiotherapy is used in isolation.It
probably works by enhancing the effects of
radiotherapy and might also address
micrometastases that are outside the
radiotherapy field
 Palliative treatment
• Palliative treatment When it is not possible to offer
curative treatment, palliation of symptoms
becomes important and early involvement of
the palliative care teamis essential for symptom
control. The disease can be hidden from family and
friends even in the late stages of the
disease; patients may be experiencing a number
of symptomsfrom local infiltration of the
pelvis by the cancer. Malignant pain, recto
and/or vesicovaginal fistulae andbleeding may occur.
Distant spread is often a very late stage of the
disease. Radiotherapy may be consideredwith a
palliative intent; for example, a one-off treatment
may be used for symptomatic bone metastases.
 KEY LEARNING POINTS
• • Cervical cancer affects young women who may
not have completed their families.
• • Many cervical tumours are picked up when
they are microscopic or very small
volume, making fertility-sparing treatment a
possibility.
• • Cone biopsy or radical trachelectomy with
bilateral pelviclymphadenectomy allows
preservation of the ovaries and uterus,
permitting pregnancy in the future.
• • The long-term cure rate of radical
trachelectomy is lesswell established than
radical(Wertheim’s) hysterectomy.
Stage 1a
Linear accelerator for teletherapy
FIGO classification