PAP SMEAR, BENIGN LESIONS

OF THE CERVIX, CIN AND

CARCINOMA OF THE CERVIX
Pap smear
 Used for cervical abnormality screening
 Good sensitivity and specificity, cost effective with
little pain/discomfort
 Screening program (recommended)
 2 smears in 1st year of sexual activity
 then 3 yearly
 Above 50, 5 yearly
 Aim: early malignant changes detection
 Problems: high risk group don’t come
Pap Smear
 Cytological abnormalities can be diagnosed by
taking a cervical smear, fixing it with alcohol and
then examining it applying Papanicolaou's stain
(Pap smear).
 Cells can be obtained by scraping a spatula across
the transformation zone
 Both the ecto- and the endo-cervix must be
included
Pap smear
Pap Smear

Timing of when to take cervical smear

 The optimum time - on days 10-20 of a 28 day cycle

(few polymorphs and mature endocervical cells)
 From day 21 of the cycle (an increase in number of
polymorphs)
 If the woman is menstruating then this can also
obscure the endocervical cells. In high risk subjects it
may be necessary to take a smear whatever period of
their menstrual cycle because of risk of non-
attendence for another appointment
Pap Smear
Management
 Unsatisfactory smears should be repeated

 Inflammatory / inconclusive / borderline smears

 Treat any known causes, repeat smear 4 - 6 months later
 If HPV but no dyskaryosis, repeat 4 months later; if HPV
persists, refer for colposcopy
 If borderline for any other reason, and changes persist, refer
for colposcopy
 Mild dyskaryosis - repeat 3 months later
 Moderate or severe dyskaryosis - refer for colposcopy.
Benign lesion of cervix
 Cervical ectropion/cervicitis
 Excessive but not purulent vaginal d/charge
 Sometimes – post coital bleed
 Due to increase surface area of columnar epithelium
containing mucus – secreting gland
 Rx: Thermal probedestroy epithelium
 Nabothian follicles
 Due to squamous metaplasiaglands within columnar
epithelium roofed over with sq.cells
 Formation of small mucus – filled cyst visible on the
ectocervix
 No treatment neededno pathological significance
 CERVICAL
INTRAEPITHELIAL
NEOPLASIA (CIN)
Cervical intraepithelial neoplasia
(CIN)

 Preinvasive stage of cervical cancer

 Histological diagnosis (biopsy)
 Denotes atypical changes in the transformation
zone/squamo-columnar junction
 Dysplatic features:
 Disorderly maturation
 Lack of differentiation
 Nuclear abnormality
 Increased mitotic activity
Cervical intraepithelial neoplasia(CIN)
 Peak age incident of CIN: 30
 Development to invasive Ca
 But not all cases of CIN progress to invasive Ca
 Progression from low grade to high grade is not
inevitable
 Higher grade of CIN, the higher chance to progress
CIN
Metaplasia is enhanced by:-
 vaginal acidity (most active during adolescence and

the first pregnancy)

 The strong association between the development of

malignancy with early sexual activity, and early age

of first pregnancy thought to be due to exposure of
the transformation zone to carcinogens at times
when it is most active and therefore, most
vulnerable.
CIN - Grading
 Three grades are described
 CIN 1 - dysplasia limited to the basal one third of the
squamous epithelium; previously referred to as "mild
dysplasia"
 CIN 2 - dysplasia extends into the middle third of the
epithelium; previously, "moderate dysplasia"
 CIN 3 - dysplasia extends into the upper third of the
epithelium; previously, "severe dysplasia".
 SIL grading
 Low grade
 High grade
CIN - Screening
 Previously all women aged 20-64 years were
screened at least every 5 years. But, NHS Cervical
Screening programme changed the guidance
regarding timing and age groups of women screened
in October 2003
 sexually active to 50: 3-5 yearly
 above 50: 5 yearly
 women between 25 and 49 years of age - screened every 3
years
 women aged 50-64 years - screened every 5 years
CIN - Screening
 The screening interval influences the rate of
detection of CIN
 5 yearly picks up 82% of CIN
 3 yearly picks up 91% of CIN
 1 yearly picks up 93% of CIN
 Method - based on cervical cytology
 Cons: Screening is not designed to detect
adenocarcinomas which constitute 10% of cervical
tumours
CIN - Management
 CIN1 smear - should be rechecked in 3 months and if
it is persistently abnormal then refer for colposcopy
 CIN2 or CIN3 smear - referred immediately for
colposcopy and biopsy
 Complete removing of abnormal epithelium by:
 Destroying using ablative technique, cryotherapy, laser
 Excisional technique: LLETZ (commonest), cone biopsy,
simple hysterectomy
 Follow up regularly with repeat smears and
colposcopy if necessary
CERVICAL CARCINOMA
Cervical Carcinoma
 Sixth most common malignancy in females
 annual incidence of 16 per 100 000 women. It
accounts for 4% of female malignancy with an
average five year survival of 58%.
 Rare before the age of 20 years. Peak incidence is in
the 45 - 55 year age group but occurs slightly earlier
among those from lower socioeconomic groups
 Mortality has fallen in many developed countries
with the introduction of cervical screening. At
present, 60% of women who develop cervical cancer
have never been screened
Cervical Ca – Risk factors
 Human papilloma virus - types 16, 18, 31 and 33
 Human immunodeficiency virus
 Smoking
 Age of first coitus – the earlier, the higher risk
 Number of sexual partners - increased likelihood to be
exposed to carcinogens
 Young age at first pregnancy - metaplasia most active during
first pregnancy
 Multiple pregnancy
 Low social status - possibly, due to vitamin A deficiency
 Sexual partner with multiple sexual partners
Cervical Ca - Pathology
 75% are squamous cell carcinoma - usually arising from the
squamo-columnar junction
 20-25% are adenocarcinoma - arising from endocervical
glands in the endocervical mucosa - or mixed adenosquamous
carcinoma
 less than 1% are due to melanoma, sarcoma, lymphoma
 The time sequence from pre-invasive cervical carcinoma to
invasive cervical carcinoma is difficult to estimate. An
approximate sequence would be:
 20 years from CIN to invasive carcinoma
 10 years from microinvasive to invasive carcinoma
 Untreated, it is estimated that about 20-30% of patients with
CIN3 would eventually develop invasive carcinoma.
Cervical Ca – Clinical features
 A minority of patients are asymptomatic
 Diagnosis being established after a routine cervical
smear.
 Majority present with:
 postcoital, postmenopausal or intermenstrual bleeding -
occurs in 80-90% of patients; initially, irregular but
later becomes continuous
 blood stained vaginal discharge
 Vaginal bleeding during pregnancy
 Cervical Ca – Clinical features
Features of advanced disease include:
 Heavy bleeding

 Offensive vaginal discharge

 Pain - indicating extension beyond the cervix:

 lower abdominal pain may signify a large pelvic mass

 sciatic pain may signify involvement of lymphatic nodes which have
become adherent to the sacral plexus
 back pain may signify vertebral metastases
 Urinary and/or faecal incontinence - from fistulae formation
 Leg swelling
 Uraemia - from ureteric obstruction or ascending
pyelonephritis
 Cervical Ca – Clinical features
Pelvic examination:-
 May reveal a cervix which is friable and bleeds
easily.
 Early tumours may be seen as a small nodule or ulcer
on the vaginal surface, or as a diffuse patch
resembling an erosion
 Advanced lesions may appear as a crater shaped ulcer
with high everted edges or as a warty-looking mass.
 They may replace the entire cervix.

 Rectal examination is essential to ascertain the extent

of spread
Cervical Ca - Staging
 The International Federation of Obstetricians and
Gynaecologists (FIGO) system
 Histological staging:
 0 - CIN III (carcinoma in situ)
 IA - Microinvasive carcinoma
 Clinical staging:
 IB - invasive carcinoma confined to the cervix
 IIA - invasion into the upper one third of the vagina
 IIB - extension to the parametria but not to the pelvic side wall
 IIIA - extension to the lower one third of the vagina
 IIIB - extension to the pelvic side wall
 IVA - tumour involving the bladder or rectum
 IVB - extrapelvic spread, e.g. liver or lung metastases
Cervical Ca - Spread
 Local spread:
 vagina, bladder, bowel, transverse cervical ligaments,
arteries, uterus
 Lymphatics:
 outwards in the pelvic fascia to internal iliac nodes, then to
common iliac nodes, and para-aortic nodes
 Haematogenous - relatively uncommon; the patient
often dies from the effects of local invasion before
metastases to distant sites are clinically apparent:
 principally, to the lung, bone, and brain
Cervical Ca - Investigations
 FBC's - for anaemia
 U+E's - ureteral obstruction occurs in 30% of stage III, 50% of
stage IV
 Calcium - hypercalcaemia may occur in advanced disease, but
not always due to bone involvement
 Liver function tests - abnormal if liver metastases
 Cone biopsy - a smear is pointless with a gross lesion
 Chest Xray - lung metastases seen in 5% of patients with
advanced disease
 Cystoscopy and sigmoidoscopy - rarely reveal mucosal
invasion except in advanced disease
 Intravenous pyelogram
 CT scan
Cervical Ca - Surgical
 Stage O - usually by ablative techniques (e.g. cryosurgery),
cone biopsy or hysterectomy - future child bearing is not
wished.
 Stage IA - cone biopsy or hysterectomy.
 Stage IB and IIA tumours - radical hysterectomy and bilateral
pelvic lymph node clearance
 Radical hysterectomy in these patients if favoured:
 in premenopausal women - as the ovaries can be preserved and
complications of vaginal irradiation
 where the tumour is small
 where future child bearing is not wished
 where radiotherapy would be undesirable – e.g. existing colonic
diverticular disease or chronic PID; those with a fear of radiation
Cervical Ca - Radiotherapy

 Treatment of choice in patients with stage IIB, III and

IV disease, and most patients with stage IIA disease.
 Stage IB tumors may be treated by radiotherapy if the
lesion is of sufficient size that extensive surgical
resection is required, with consequent increased risk
of postoperative bladder dysfunction.
 Stage IV is treated by external radiotherapy if the
disease is confined to the pelvis. Spread outside the
pelvis is an indication for chemotherapy.
Cervical Ca - Radiotherapy
 Also used in an adjuvant setting following surgery
 Also used in palliative care to reduce vaginal
bleeding and discharge
Cervical Ca - Chemotherapy
 Chemotherapy may be indicated in:
 advanced disease - with extra pelvic spread
 recurrent disease
 As neo-adjuvant prior to surgery
 where radiotherapy has been ineffective
 Most treatments are based on cytotoxics based on cisplatin.
 Chemotherapy is not a first choice treatment because:
 cervical carcinoma is relatively radiosensitive
 large, bulky tumours may have necrotic centres which are never reached
 tissue vascularity is reduced following radiotherapy so drug uptake is
sub-optimal
Cervical Ca - Prognosis
 The prognosis of invasive carcinoma will vary according to the
skill of the surgeon or radiotherapist, and to the exact method
chosen.
 Illustrative values for 5 year survival would be:
 stage I - 80% or more
 stage II - 60%
 stage III - 30%
 stage IV - 10%
 Stages IA and IIB show little difference between surgically
treated disease and ones treated by radiotherapy.
 In patients with recurrent disease:
 50% show recurrence within one year
 75% show recurrence within two years
 90% show recurrence within five years
Palliative treatment
 Pain control
 Codine, pethidine, analgesic
 Opium and its derivatives
 Nerve-blocking procedure
 Surgical division of spinothalamic tract