Transcript Screening in Gynaecological Cancers

Screening in
Gynaecological Cancers
Prof. HYS Ngan
Department of Obstetrics & Gynaecology
University of Hong Kong
Queen Mary Hospital
Fallopion tube
Endometrium
Ovary
Cervix
Vagina
Uterus
Incidence Rate of the Female Cancer for the year 1993-1996
14
12
10
Ra t e pe r 1 0 0 , 0 0 0
Fe ma l e s
8
Cervix
6
Ovary
4
Corpus
2
0
1993
1994
1995
Year
1996
Mortality Rate of Female Cancers for the year
1993-1996
4.5
4
3.5
3
R at e p er 1 0 0 ,0 0 0 2.5
F emales
2
Cervix
Ovary
1.5
Corpus
1
0.5
0
1993
1994
1995
Year
1996
Screening
• Cervical cancer
• Ovarian cancer
• Endometrial cancer
Screening
To detect disease among
healthy
population
Without symptoms of disease
Purpose: decrease mortality due to the disease
screened
Disease appropriate for screening
• High prevalence of disease
• Known natural history, precursor lesion and
course of progression
• Detection of early stage disease, amenable
to cure
• Method used is simple, cheap, specific and
sensitive, acceptable, risk-free and
accessible
Carcinoma of the cervix
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commonest lower genital tract cancer
about 500 new cases per year in HK
about 140 deaths per year in HK
median age: 50 years
Natural history of low-grade
HPV cervical lesion
• Cervical HPV is very common, related to
sexual behaviour
• High spontaneous remission rate
• lower remission rate in CIN
• LSIL progress to HSIL in 70% in 10 yrs
Natural history of CIN 1-2
regress persist CIN3 Ca
CIN I
57%
32%
11% <1%
CIN2
43%
35%
22%
(100 prospective studies)
5%
Cervical cytology
Sensitivity and Specificity
• Overall sensitivity: 61-64%, cervical
cancer: 82-95%
• Overall specificity : 99 - 99.4%
Quantin.C 1992, Soost.HJ 1991
Cervical cytology
Positive predictive value
• Low-moderate dysplasia: 73-76%
• severe dysplasia : 85-90%
• Invasive cancer: 95%
Quantin.C 1992, Soost.HJ 1991
False negative rate of cervical
cytology in detecting cervical
cancer
• Depends on the quality of the smear taking
and the laboratory
• estimated to be 3-30%
New technology
• automation for cervical cancer screening
• liquid-based cytology - thin layer
preparation
Advantages of LBC
Eliminate
• air-dried artifact
• inflammatory cells
• blood
• mucus
Increase
• detection of abnormal cytology
Cervical cancer screening - new
methods under exploration
• cervicography
• polar probe
• HPV typing
HPV DNA testing - potential use
• HPV based instead of cytology based
screening
• triage of patients with equivocal or ASCUS
• external quality control of cytology
• high risk HPV predicts high grade SIL in
the absence of cytology abnormality
• molecular variant predicts carcinoma
Organized screening vs
Opportunistic screening
• Finland and Sweden
decrease in indicence and mortality of
cervical cancer
concentrate resources
wide coverage
• Policy decision
European and American
recommendation
Age:
• Europe: 35-60 yrs for invasive ca
25-65 yrs for preinvasive lesions
• USA: 18 yrs old
Interval:
• Europe: 3-5 years
• USA: annual
low risk, 3 consecutive negative, space out
Hong Kong College of
Obstetricians and Gynaecologists
• Age: sexually active to 65
• Interval: 2 consecutive annual normal
smears, 3 yearly
How to take a cervical smear?
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•
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Speculum
adequate exposure
light source
sampling device - Ayres’ spatula, brush or
broom
• transformation zone
Speculum
Ayres’ spatula, endocervical
brush
Broom type sampler
When not to take a cervical
smear
• Blood in vagina, on the cervix - usually
because of menstruation
• Obvious or gross growth on the cervix - a
biopsy is more appropriate
• Cervix cannot be seen
How to interpret a cytology
report?
– Reports of cervical smear should be
interpreted together with the clinical
picture of the patient.
– Some physiological or medical
conditions may lead to difficulty in
the interpretation of a smear.
History on request form
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contraceptive history
menopausal status
date of last menstrual period
prior radiotherapy or current chemotherapy
hysterectomy
drugs or hormones
parity
Bethesda System 2001
• Negative
• Squamous cell - ASCUS, ASC-H (cannot
exclude HSIL)
- LSIL
- HSIL, HSIL with features suspicious of
invasion
- SCC
Bethesda System 2001
• Glandular cell
- Atypical : endocervical cells, endometrial
cells, glandular cells
- Atypical, favor neoplastic: endocervical
cells, glandular cells
- Endocervical adenocarcinoma in-situ
- Adenocarcinoma: endocervical,
endometrial, extrauterine, NOS
Cytology screening
Conven
1999
No. Unsat. ASCUS AGUS LG HG Inv
95874 0.44 4.36
0.1
1.24 0.29 0.02
Thin Prep 100420 0.32 4.78
2000
(4800)
0.1
1.6 0.3
(1600)
0.001
A Cheung
How to manage abnormal smear?
Histological grading of preinvasive cervical lesion
• Koilocytes : human papillomaviral changes
• Cervical intraepithelial neoplasia (CIN)
• 1 : dysplastic cells in lower one third of
epithelium
• 2 : lower two third
• 3 : almost the whole thickness
Inflammatory changes with
atypia
– could be due to vaginitis or infection
such as monilia, trichomonas, herpes
or condyloma.
– Treat the cause and repeat the smear
4 to 6 months later to ensure that
dysplastic cells were not masked by
the previous inflammatory cells.
Management of ASCUS
• 5% of smears reported as ASCUS
• Majority of ASCUS turn out to be normal or
of low grade CIN
• Less than 1 % associated with cancer
Management of LSIL
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1.5-2.5 % of smears screened were of LGIL
15-30% associated with HG CIN
about 1% associated with cancer
2 options:
repeat smear 4-6 months interval
refer for colposcopic assessment (HKCOG
guideline)
Management of HSIL
• Gross examination showed a growth biopsy
• Grossly normal - refer colposcopy
Outcome of AGUS
• Normal: 19-34%
• Significant pathology: 15-37%
CIN
16-54%
AIS
3-5%
Ca cervix 2-3%
Ca corpus 1-4%
Recommendation
• AGUS- favor neoplasia, co-existing with
squamous neoplasia, previous hx of cervical
lesion: refer colposcopy, D&C and cone
• AGUS- favor reactive, not otherwise
specified: repeat cytology with adequate
endocervical sampling
Colposcopy services in Hong
Kong
• Department of Obs & Gyn of major
hospitals of the Hospital Authority
• Lady Helen Woo Women’s Diagnostic and
Treatment Centre at Tsan Yuk Hospital
• Private gynaecologist with colposcopy
training
Colposcope
Treatment of high grade CIN
• ablative therapy
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cryotherapy
cold coagulation
diathermy
laser evaporisation
• excision therapy
– cone (knife, laser, loop excision)
• hysterectomy is rarely indicated
Management of abnormal smear
Abn smear
Inflammatory atypia
with
identifiable infection
ASCUS
LSIL/HSIL/
AGUS
Treat infection
repeat 6 mths
if abnormal
colposcopy
repeat 3-6 mths
if abnormal
colposcopy
colposcopy +/biopsy
Invasive
gross tumour
biopsy
normal cervix
colposcopy +/biopsy
Hong Kong College of Obstetricians & Gynaecologists Guidelines on The Management of An Abnormal Cervical Smear
Ovarian Cancer in HK
New Cases
Death
Median age
:
:
:
220
95
51
(1992)
Ovarian cancer
• High mortality due to late diagnosis
• 75% of ca ovary at diagnosis were at late
stage with a 28% 5 yr survival
• Stage I ca ovary has 95% 5 yr survival
Ovarian Cancer
Symptoms of ovarian cancer :
• asymptomatic
• Lower abdominal pain/pressure
• mass
• Abdominal enlargement
• Vaginal bleeding
• Urinary/bowel symptoms
Ovarian Cancer
Risk factors :
1) majority has no risk factor
2) family history 10%
- familial ovarian syndrome
2) nulliparous
3) racial and social
Why screening for ovarian cancer
is so difficult?
• Anatomic location of the ovary, not easily
accesible
• Lack well defined precursor lesion and has
poorly defined natural history
• Low prevalence, need exquisite specificity
to avoid unnecessary intervention
• Lack of a good method
Methods used for ovarian cancer
screening
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Serum CA125
Transvaginal ultrasonogram
Multimodal
New method under investigation lysophosphatidic acid
Serum CA125
• Elevated in 82% of ovarian cancer and <1%
of healthy women
• rising pattern over time preceded ovarian
cancer
• limitations: lack of sensitivity in Stage I
disease, poor specificity (elevated in benign
and other malignant conditions)
TVS in ov ca screening
Kentucky study 2000
• 14,468 postmenopausal women
• annual TVS
• total 57,214 scans
• 180 laparotomies: 17 ov ca (stage I=11,
stage II=3, stage III=3)
• sensitivity 81% specificity 98.9% PPV
9.4% NPV 99.97%
• Survival at 2 yr 92.9% and at 5 yr 83.6%
Ovarian cancer screening
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Jacobs et al. 1993
22000 women over 45 yrs
CA125 and transvaginal ultrasound
125 elevated CA125, FU with CA125 and
TVS
41 laparotomies: 11 ovarian ca vs 8 in
control gp
specificity = 99.9%
sensitivity = 78.6%
positive predictive value = 26.8%
Ovarian screening
• Not cost-effective
• May be considered in high risk population
• No place for population screening yet
Carcinoma of Endometrium
Incidence : third commonest
malignant tumour of
genital tract
Age
: 58
Endometrial Cancer in H.K.
New cases
Death
Median age
:
:
:
200
50
60
(1992)
Risk factors
• nulliparity, anovulation, late
menopause
• exogenous estrogen
• endogenous estrogen
• DM, HT, obesity
• smoking, white
• tamoxifen
• familial history
Postmenopausal Bleeding
1) carcinoma of endometrium
2) other gynecological malignancy
3) atrophic endometritis
4) endometrial hyperplasia
5) cervicitis/erosion
6) endometrial polyp
7) cervical polyp
14%
14%
20%
12%
8%
8%
8%
Diagnosis of Carcinoma of
Endometrium
(f) D&C
near 100%
uterine aspirate
90%
endocervical aspirate + vaginal
65%
aspirate
vaginal aspirate + cervical smear
40%
cervical smear
15%
Should endometrial cancer be
screened?
• High prevalence in the West, low (same as
ovarian ca) in Hong Kong
• precursor lesion, atypical endometrial
hyperplasia
• accessibility of endometrium to sampling
• high cure rate for early disease
Cons: majority detected at early stage because
of abnormal bleeding esp PMB
Endometrial Cancer Screening
• Tools explored
– pelvic ultrasound (>8mm endometrial thickness
in postmenopausal women) Karlsson 1995
– endometrial aspirate (inadequate sampling in
menopausal women)
Endometrial aspirator
Endometrial aspirator
Endometrial aspiration
• Sensitivity for endometrial ca 94% in
patient with symptoms
• sensitivity for hyperplasia 31%
Cons: discomfort to patient
lack of known efficiency in
asymtomatic patients
TVS in endometrial ca screening
• Croatia study (Kurjak 1994)
• 5013 asymptomatic women
• ca endometrium 6 and hyperplasia 18, no
false positive
(low prevalence of ca endometrium in
asymptomatic patients, ? Advantage)
Endometrial cancer screening
• Not justified in population screening
• excellent prognosis of majority of ca
endometrium unlikely will result in
decreased mortality rates
Conclusions
• Cervical cancer screening is the most
successful programme in gynaecological
cancers
• Ovarian cancer screening is not proven to
be cost-effective yet, may be considered in
high risk groups
• Endometrial cancer screening may be
consider in high risk groups