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CERVICAL CANCER

AND CIN
 Cancer of the cervix has long been recognized as the
commonest malignancy of the female genital tract
However, in the last four decades invasive cancers of the
cervix showed a significant decline in their occurrence
being now nearly as common as endometrial carcinomas.
 One of the key features of cervical cancer is the slow
progression from normal cervical epithelium to precancerous
changes (CIN) to invasive cancer. This slow progression
through numerous precancerous changes provided the
rationale for the preventive and early treatment strategies that
have caused the decline of cervical cancer over the past
decades.
INCIDENCE:
 Cervical intraepithelial neoplasia (CIN), may occur at any
age, however it is commoner in younger age groups 25 – 45
years. It is usually present several years before the occurrence
of preinvasive and invasive disease, and is considered as the
premalignant lesion.
 Pre-invasive carcinoma (carcinoma in situ) occurs mostly
between 35-45 years.
 Invasive carcinoma of the cervix prevails mostly at ages from
40-60 years, with a peak incidence around 50 years, an age
incidence which is nearly 10 years earlier than that for
endometrial carcinoma.
RISK FACTORS:

 Early age at the first sexual intercourse.


 Multiple sexual partners (promiscuous intercourse).
 Viral sexually transmitted diseases (HPV types
16,18,31 & HSV type 2).
 Low socioeconomic standards and poor hygiene
(chronic irritation).
 Smoking. (Chemicals in cigarettes may interact
with cells in the cervix).
HPV AND CIN:

 Forms of HPV, a virus whose different types cause


skin warts, genital warts, and other abnormal skin
and body surface disorders, have been shown to
lead to many changes in cervical tissues that may
eventually lead to cancer.
 Because HPV can be transmitted by sexual contact,
early sexual contact and having multiple sexual
partners have been identified as strong risk factors
for the development of cervical lesions that may
progress to cancer.
 The type of HPV present can affect whether
the CIN develops into a cancer or not. Only
certain HPV types such as 16,18,31 and 33
seem to be associated with the development
of cervical cancers.
 In general, CIN is an asymptomatic condition,
at least in its milder forms, and is usually
diagnosed during screening for cervical
cancer by the PAP smear.
There are three grades of CIN:
 CIN 1 (mild dysplasia): where abnormal cells occupy the
basal one third (1/3) of the thickness of the squamous
epithelium. These cells have high nucleo-cytoplasmic ratio, and
pleomorphic nuclei. Cells of the upper 2/3 show normal
stratification and maturation.
 CIN II (moderate dysplasia): Abnormal dysplastic cells occupy
(2/3) of the thickness of squamous epithelium. Cells of the
upper (1/3) show normal stratification and maturation
 CIN III (severe dysplasia – carcinoma in situ): Abnormal
dysplastic cells occupy the full thickness of the squamous
epithelium, without invasion of the basement membrane.
CIN III & in situ carcinoma are commonly grouped as one
category.
CIN 1 CIN 2 CIN 3
DIAGNOSIS OF CIN:

1) Cervical smears (Pap smear test):


 The smear, or Pap test, is commonly used as a
routine test to detect early cell changes
(dyskaryosis). This is known as cervical screening
and is aimed at women with no symptoms, however
it is sometimes used to help diagnose cancer cervix.
 Scrapings are made from the ectocervix at the
squamo-columnar junction, using a cytobrush, or
from ectocervix using an Ayre wooden spatula. The
cells is spread on a glass slide fixed by ethyl alcohol
and stained by Papanicolau stain.
The Pap smear test result may be either:
 Normal: No inflammation, No CIN.
 Inflammatory without dysplasia. No CIN
 CIN I: mild dysplasia or dyskariosis
 CIN II: moderate dysplasia or dyskariosis
 CIN III: severe dysplasia (In situ carcinoma)
(invasion may be suspected).
Normal Pap Smear Moderate Dyskariosis Severe Dyskariosis
 Advantages of cytological diagnosis include
being; easy, cheap, allows early detection of
malignancy, before symptoms, with an
accuracy exceeding 95%. The test on the
other hand needs a well trained cytologist for
proper interpretation, and has a small
percentage of false positive and false
negative results.
2) Colposcopy:
 A colposcope is like a pair of binoculars with a light
that allows binocular inspection of the ectocervix up
to the squamocolumnar junction within the
transformation zone with magnification of up to 20
times the normal size.
 If the smear test is abnormal, a colposcopic
examination will be useful in visualization of
abnormal areas showing abnormal vascularity by
use of green filters. If the cervix is swabbed with
acetic acid, suspicious areas within the epithelium
will appear as white bleached areas requiring close
attention (aceto-white areas).
 Biopsies may be taken from these suspicious areas
(colposcopically directed biopsy) for histopathologic
examination, and hence the diagnosis of CIN is confirmed,
and the degree of CIN accurately determined.
 Abnormal colposcopic findings include:
 Aceto-white epithelium
 Abnormal vascularity (punctation, mosaic)
 Leukoplakia
 Iodine negative (Schiller +ve) painting with lugol’s iodine
result in brownish staining of the normal epithelium
Colposcope
TREATMENT OF CIN:

 Treatment of CIN depends upon its severity. In


general the management is usually conservative
requiring no or very limited surgical techniques.
 CIN I : Treat infection and repeat the smear test
after 8 – 12 weeks.
 CIN II : Destruction or ablation of abnormal cells.
 CIN III: Excision of a cone of cervical tissue if patient
is young.
 Simple total abdominal hysterectomy, in older
patients.
A) Ablative Techniques:

 All these techniques are meant to destroy


abnormal epithelium within the cervical
tissue. In contrast to excisional methods, no
tissue will be available for histologic
examination. Hence it is essential to exclude
invasive disease by colposcopic directed
biopsies before starting such treatment
techniques.
 Cryosurgery: Allows destruction of affected
epithelium by freezing to a depth of 3-5 mm.
It is quick, sufficiently painless and done
without general anaesthesia.
 Diathermy: Under general anaesthesia,
destroys tissues to a depth of > 7 mm.

 CO2 Laser: Results in tissue vaporization


to a depth of 7-9 mm. with maximum
precision and very minimal trauma.
Cryosurgery
B) Excisional Techniques:

 Excisional techniques have the advantage of


both treating the condition and obtaining
tissue available for histologic examination,
where the original diagnosis may be
confirmed, disease free margin established,
and invasion of basement membrane
excluded.
 Large Loop Electrodiathermy of the Transformation Zone
(LLETZ): A thin wire loop is used to excise the transformation
zone using a blended diathermy current. It is rapid, cheep,
safe, and easy, hence became the most popular technique in
most centres.
 Knife Cone biopsy: Less common nowadays because it is
associated with higher incidence of bleeding, infection,
cervical stenosis and cervical incompetence in subsequent
pregnancies.
 Laser Cone Biopsy: less commonly used as it is more
expensive, needs complicated instruments, done under
general anaesthesia, and requires special training and
experience.
Knife cone biopsy
 Follow Up After Treatment: Despite the
efficacy of the above mentioned techniques
in treating CIN, yet recurrence is still
common and follow up by annual Pap
smears is recommended for a period of up to
10 years.
INVASIVE CARCINOMA OF THE
CERVIX

 PATHOLOGY:
two main histological types
 Squamous cell carcinoma: The commonest type; (> 90%)
develops from the flat cells, which cover the outer surface of
the cervix (ectocervical carcinoma of the portio vaginalis).
However it may rarely arise in the endocervix due to previous
squamous metaplasia. It is easily and early detected with the
Pap smear test.
 B) Adenocarcinoma: Less common; (<10%) develops from
the glandular epithelium, which lines the cervical canal (endo-
cervical carcinoma), but may rarely arise from the columnar
epithelium covering an erosion on the ectocervix,
 Ectocervical carcinomas are almost always
of the squamous type, they usually
present in one of three common varieties
 Hypertrophic type (exophytic)
 Ulcerative type (endophytic)
 Infiltrative type (nodular)
 Endocervical carcinomas are mostly
adenocarcinomas arising from the columnar
epithelium lining the endocervix. It forms a
spherical growth distending the cervix and
giving it a barrel-shaped appearance.
SPREAD OF CANCER CERVIX:

 Direct spread: From the cervix into adjacent


tissues including the corpus uteri. Further spread
to the parametrium induces signs and symptoms
as chronic pelvic inflammation. Significant spread
may result in ureteric obstruction. Spread
downwards into the vaginal wall may later involve
the bladder and rectum. Backwards spread along
the uterosacral ligaments leads to involvement of
the sacral plexus causing intractable sciatic pain.
 Lymphatic spread: Usually follows direct spread,
but may coincide with it. The primary groups
affected include spread from the cervical
lymphatics along the paracervical lymph tract, to
the external iliac nodes. Occasionally the extension
is backwards to the internal iliac group. Secondary
groups affected involve drainage into the common
iliac and lateral sacral groups. Ultimately the
common iliac group drains into the lower lumbar
group of the para-aortic lymph nodes.
 Blood stream spread: Least common,
usually in late or advanced cases.
Metastases may occur to distant organs as
to the liver, lungs, brain and bone.
 Direct implantation: to the peritoneum and
vagina is exceedingly rare.
STAGING OF CERVICAL CARCINOMA

 The FIGO staging classification is based on


findings on examination under anaesthesia
(EUA), intravenous pyelogram (IVP), and
cystoscopy.
 Clinical Staging of Cancer Cervix (FIGO classification):
 Stage 0 : Preinvasive cancer ( Carcinoma in situ or CIN 3 ).
 Stage I A : Microinvasive cancer (invasion depth < 5.0 mm & width
< 7.0 mm)
 Stage I B : Invasive carcinoma confined to the cervix (depth > 5.0
mm & width > 7.0 mm)
 Stage II A: Tumour involving upper 1/3 of the vagina.
 Stage II B: Extension to parametrium (not reaching the lateral
pelvic side wall)
 Stage III A: Tumour extending to lower 1/3 of the vagina
 Stage III B: Extension to parametrium (reaching the pelvic side wall)
 Stage IV A: Tumour involving the bladder or rectum (direct spread)
 Stage IV B: Extrapelvic spread, e.g. liver or lung metastases (blood
borne spread)
Staging of Cervical Carcinoma
CLINICAL PRESENTATION OF
CANCER CERVIX

 Clinical Symptoms:
1. Vaginal Bleeding: is the most common
presenting complaint It may be either;
 Contact bleeding i.e. after coitus or douching
(commonest).
 Intermenstrual bleeding i.e. metrorrhagia.
 Postmenopausal bleeding
 Persistent bleeding during pregnancy (rarest)
 2. Vaginal Discharge: In addition to bleeding, some
patients will complain of profuse, offensive, often
blood stained vaginal discharge, resistant to
conventional treatment.
 3. Other Symptoms, such as pain, are uncommon
until very late disease. Pain may be associated with
infiltration of the parametrium or uterosacral
ligaments, pyometra, or sciatic and obturator nerve
affection.
Clinical Signs:
 General examination: In early cases, most patients are in a
good general condition and relatively young in age. In
advanced stages, chronic blood loss, urinary manifestations
and ureteric obstruction may lead to severe anaemia,
uraemia and cachexia.
 Inspection via a speculum vaginal examination: Invasive
cancer of the cervix presents as a small nodule or ulcer that
bleeds easily on touch. As it advances, it becomes a friable
warty mass that may break into a large ulcer. Later on, the
mass or ulcer will extend to the vaginal walls obliterating the
vaginal fornices.
 Per rectum examination (PR): To evaluate
possible parametrial extension.
DIAGNOSTIC PROCEDURES FOR
CANCER CERVIX:

 1. The Pap Smear Test


 2. Coploscopy
 3. Schiller Iodine Test
In cases where a Pap smear is positive or suspicious, and
in absence of a naked-eye lesion and unavailable
colposcopic examination facilities, the Schiller’s iodine
test will be helpful to locate abnormal cervical epithelium
from which biopsies should be performed. The cervix is
painted with Schiller’s iodine solution. Normal squamous
epithelium takes a deep brown colour, owing to its rich
glycogen content. Abnormal areas of epithelium remain
unstained and retain their normal colour
 4. Cervical Biopsies
Histopathologic examination of a specimen
of cervical tissue containing the abnormal
epithelium is the gold standard for
diagnosis of cervical cancer.
 Knife Biopsies
 Colposcopic Directed Biopsies
 Multiple Punch Biopsies
 Cone Biopsy: Removal of a cone shaped piece of
the cervix with the apex of the cone including the
transformation zone. The procedure is associated
with possible excessive bleeding, and may lead to
scarring, stenosis and later cervical incompetence.
It is indicated in only a few cases:
• with endocervical extension
• when the entire extent of the lesion cannot be
delineated colposcopically
• when a repeatedly positive smear is obtained in
absence of positive colposcopic findings.
 5. Fractional Curettage: Some cases of
endocervical carcinomas will be diagnosed
by obtaining endocervical tissue during a
fractional curettage (FC).
PREVENTION:

 By early diagnosis and proper management


of premalignant lesions (CIN)
PLANNING FOR TREATMENT:

 Before starting treatment, staging of the disease


should be complete. Staging requires thorough
clinical evaluation together with the use of some
special procedures including,
 EUA
 cystoscopy
 IVP
 chest X ray
 abdominal ultrasonography (U.S.)
Treatment Of Carcinoma In Situ (Stage
0)

 Cervical Conization: only in young patients with low-grade


tumours and wide free surgical margin after excision. The aim
is to preserve the uterus for fertility.
 TAH (Total abdominal hysterectomy): In middle age
patients not desirous of fertility. The aim is remove the cancer
and preserve ovarian hormonal production.
 TAH-BSO (TAH + Bilateral salpingo-oophorectomy): In
premenopausal or postmenopausal patients
Lymphadenectomy is not required as there is no invasion of
the basement membrane
Treatment Of Microinvasive Carcinoma
(Stage Ia)

 Total abdominal hysterectomy + bilateral


salpingo-oophorectomy (TAH-BSO). The
patients may be spared a complete
lymphadenectomy, or may be offered only
selective lymph node sampling, to minimize
the extent and morbidity of surgery.
Treatment Of Invasive Cancer

 Choice of treatment, whether surgery,


radiotherapy or both, and the extent of each
of them is based namely on;
 The stage of the disease.
 The grade of the tumour.
 The age and general condition of the patient.
 The availability of well-trained teams for both
surgery and radiotherapy.
 Results of surgery and radiotherapy are
comparable in the early stages of the
disease, however surgery is more preferred
as it allows for complete resection of the
tumour and provides a specimen available
for ensuring the extent of the disease.
 The prognosis in stage I disease is excellent with 5
year survival rates of 80% - 85% whether surgery or
radiotherapy were used.
 The prognosis in stage II drops sharply to a 5
years survival of 50%.
 In stages III and IV, 5 years survival may be as low
as 25% and 5% respectively. The treatment in these
stages is therefore only palliative.
1) SURGERY IN CANCER CERVIX

 Where the disease is confined to the cervix, surgery is usually the


first line of treatment (stage IA& IB). In this situation, radiotherapy is as
effective as surgery but the side effects are greater, and the morbidity
is higher.
 Wertheim’s hysterectomy (Radical hysterectomy), is the
standard surgical procedure for invasive carcinoma of the cervix. It
involves a total hysterectomy and bilateral salpingo-
oophorectomy (TAH-BSO) with removal of the paracervical tissue
surrounding the cervix and 2-3 cm from the upper vagina.
 In addition the pelvic lymph nodes are carefully dissected with
removal of as many of the nodes as possible. The pelvic nodes include
the external iliac, internal iliac, common iliac, obturator and presacral
nodes. If a large number of removed nodes are affected, then it is
usual to offer the patient adjuvant radiotherapy.
 The principal complication seen with surgery
is related to some degree of bladder
dysfunction due to division of the
parasympathetic nerve supply to the bladder
that runs within the uterosacral ligaments.
2) RADIOTHERAPY IN CANCER
CERVIX:

 Ifcancer has spread beyond the cervix


(stage II & III), it will not be curable by
surgery and Radiotherapy becomes the
preferred first line of treatment. It may be
given alone, or in combination with surgery
or chemotherapy
 External beam irradiation: Radical radiotherapy for cervical
carcinoma involves the use of linear accelerator to treat the
whole pelvis with external beam radiotherapy to shrink the
central carcinoma and also to treat possible site of regional
metastases.
 Internal irradiation: Internal sources of irradiation are then
placed in the upper vagina and within the cervical canal to
provide a very high dose to the central tumour. Two internal
applications (tandum & ovoids) are usually inserted within a
week after completing the external beam therapy (which usually
require five weeks).
 Postoperative radiotherapy: Radiotherapy
following surgery is indicated if more than one lymph
node is positive, if tumour margins were very close,
or if the tumour was bulky and has a high chance of
recurrence.
 Palliative radiotherapy: In advanced cancer cervix
(stage III & IV), radiotherapy may be used in
palliative settings to reduce vaginal bleeding and
discharge and to assist in local control of the central
disease.
 Complications of radiotherapy include,
 diarrhoea that often settles after treatment is
finished,
 radiation induced menopause in premenopausal
patients
 variable degrees of vaginal narrowing and fibrosis,
few weeks after treatment is completed.
 Rarely radiation vesico-vaginal fistulas may occur
and are difficult to deal with.
3) CHEMOTHERAPY In Cancer Cervix:

 Recently studies have shown that the addition of


chemotherapy during radiotherapy increases cure
rates by approximately 10%.
 Chemotherapy may also be used in adjuvant
settings prior to surgery to reduce the size of the
primary tumour. In some cases chemotherapy will be
used in adjuvant settings following surgery.
 Chemotherapeutic drugs include cisplatinum,
bleomycin, mitomycin and adriamycin.
CARCINOMA OF THE CERVIX AND
PREGNANCY

 A) In early pregnancy: External irradiation


may be given. Abortion of a dead foetus will
follow and then internal irradiation with
caesium can be given. Medical induction of
abortion using oral and vaginal tablets of
mesoprestol (prostaglandin inhibitor) is also
possible. For early lesions radical
hysterectomy may be performed.
 B) In the 2nd and 3rd trimesters: The
uterus is evacuated surgically, by
hysterotomy or Caesarean section, before
caesium can be inserted.
 Many surgeons will prefer to treat these
cases with Wertheim’s radical hysterectomy
at the time of Caesarean section.
CARCINOMA OF THE CERVICAL
STUMP After Hysterectomy

 The stump of the cervix left after subtotal


hysterectomy is just as prone to the
development of carcinoma as when the
uterus is present.
 The results of treatment of stump carcinoma
are much worse than when the uterus is
intact.
 Internal irradiation is compromised by the absence
of the uterus as a container for intrauterine
applicators, while vaginal irradiation may not deliver
the sufficient dose without risk of damage to the
bladder and rectum.
 Surgery (radical cervicectomy and
lymphadenectomy) is complicated by presence of
adhesions and abnormal anatomic relations induced
by the previous hysterectomy.
RECURRENT CERVICAL CANCER

 A) Recurrence after primary surgery (more


than 6 months); is treated palliatively by
external beam irradiation. The aim is to
control; bleeding, pain, and infection.
Prognosis is poor in all conditions.
 B) Recurrence after radiotherapy;
Palliative surgery through pelvic exentration
may be considered, in order to control pain,
bleeding, and infection.
PALLIATIVE THERAPIES

 Advanced cases of stages III and IV require special


care aiming at amelioration of symptoms, control of
pain, bleeding and infection. Palliative measures
include:
 Palliative medications for pain relief, as pethidine,
morphia
 palliative surgeries for fistulas, colostomies & ileal
bladder
 Palliative radiotherapy
 presacral neurectomy and Nerve block procedures
Colposcopic image of an acetowhite
lesion
Colposcopic image of an acetowhite
lesion
Colposcopic image of an acetowhite
lesion with abnormal vessels ( cancer)
Diagram showing mosaicism and
punctation suggestive of cancer