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FOREWORD
PREFACE
Ho Tew Hong
Clinical Associate Professor
Chairman of Workgroup
CervicalScreen Singapore:
Management Guidelines
for Abnormal Pap Smear and
Preinvasive Disease of the Cervix
iii
CONTENTS
Foreword
Preface
iii
1. CervicalScreen Singapore
9
11
12
17
17
18
20
7.1 HPV
21
7.2 CIN 1
22
23
24
7.5 Adenocarcinoma-in-situ
25
26
27
8. Special Situations
28
29
30
31
32
33
References
34
Acknowledgements
38
iv
CERVICALSCREEN
SINGAPORE
1
CERVICALSCREEN
SINGAPORE
TERMINOLOGY FOR
CERVICAL SMEAR
REPORTING
TERMINOLOGY FOR
CERVICAL SMEAR REPORTING
(B) Definitions
Unsatisfactory
A smear that is unreliable for the detection of cervical epithelial cell
abnormalities.
4
Squamous Lesions
Atypical Squamous Cells
undetermined significance
cannot exclude high grade lesion
There are cells showing cytologic changes suggestive of a dysplastic
squamous lesion that is quantitatively or qualitatively insufficient for a
definitive interpretation.
Undetermined Significance (ASC-US)
Cytologic changes suggestive of a low grade squamous lesion but lack
criteria for definitive interpretation.
Cannot Exclude High Grade Lesion (ASC-H)
Cytologic changes suggestive of a high grade squamous lesion but lack
criteria for definitive interpretation.
Low-Grade Squamous Intraepithelial Lesion (LSIL)
HPV effect
mild dyskaryosis
HPV Effect
Squamous cells present showing stringent criteria of HPV effect ie.
koilocytes in superficial or intermediate squamous cells or sharply
delineated perinuclear halos in parabasal cells.
Mild Dyskaryosis
Cytologic changes indicative of CIN I.
5
TERMINOLOGY FOR
CERVICAL SMEAR REPORTING
If fewer than these are seen because of paucity of cells, poor fixation,
air- drying artefact, thick smearing, or covering of blood, inflammatory
exudate or other contaminants, the smear is considered unsatisfactory.
TERMINOLOGY FOR
CERVICAL SMEAR REPORTING
moderate dyskaryosis
severe dyskaryosis
severe dyskaryosis, cannot rule out invasive carcinoma
Moderate Dyskaryosis
Cytologic changes indicative of CIN 2.
Severe Dyskaryosis
Cytologic changes indicative of CIN 3.
Severe Dyskaryosis, Cannot Rule Out Invasive Carcinoma
Cytologic changes indicative of at least CIN 3, but with features of
possible invasive tumour.
Squamous Cell Carcinoma
Cytologic changes indicative of an invasive squamous cell carcinoma.
Glandular Lesions
Atypical Glandular Cells
undetermined significance
favour neoplastic
There are cells showing cytologic changes suggestive of a dysplastic
glandular lesion that are quantitatively or qualitatively insufficient for a
definitive interpretation. Where possible, these are qualified as to whether
the abnormal cells are of endocervical or endometrial origin.
Undetermined Significance
Cytologic changes which exceed those of a reactive process but lack
criteria for a definitive interpretation of a dysplastic glandular lesion.
Favour Neoplastic
Cytologic changes suggestive of a glandular dysplasia or adenocarcinomain-situ or adenocarcinoma, but lack criteria for definitive interpretation.
Endocervical Adenocarcinoma-in-Situ
Cytologic changes indicative of endocervical adenocarcinoma-in-situ.
Adenocarcarcinoma
Cytologic changes indicative of an invasive adenocarcinoma.
Others
Carcinoma
others - specify
not further specified
Other Malignant Tumours
specify
6
MANAGEMENT PROTOCOL
FOR NEGATIVE FOR
MALIGNANT CELLS SMEARS
PAP SMEAR
NEGATIVE SMEARS
Atrophic
changes
No endocervical
cells seen
(without
inflammation)
Repeat in 1 year
(use of an
endocervical
brush in addition
to the cervex
brush/spatula is
recommended)
Specific
micro-organisms
identified
Inflammatory
changes
Endometrial
cells
seen
Treat any
infection
or atrophy
Repeat in
4 6 months
Correlate
with clinical
findings,
patients
age,
hormonal
and
menstrual
status
2nd smear
similar changes
changes
resolve
Treat any
infection
or atrophy
Repeat in
4 6 months
3rd smear
similar changes
Routine
screening
schedule
Routine
screening
schedule
Refer
gynaecologist
Refer
gynaecologist
if necessary
Note : Clinically suspicious looking cervix irrespective of the Pap smear result
must be referred for colposcopy.
8
MANAGEMENT PROTOCOL
FOR UNSATISFACTORY
SMEARS
PAP SMEAR
UNSATISFACTORY
SMEARS
Unsatisfactory
Repeat in 3 months
Note : Clinically suspicious looking cervix irrespective of the Pap smear result
must be referred for colposcopy.
10
MANAGEMENT PROTOCOL
FOR ABNORMAL
SMEARS
11
5.1
PAP SMEAR
Undetermined significance
(ASC-US)
Repeat in 6 months
ABNORMAL
SMEARS
Negative for
malignant cells
Repeat in 6 months
Resume routine
screening if negative
for malignant cells
12
PAP SMEAR
Mild dyskaryosis
or
not otherwise specified
HPV effect
ABNORMAL
SMEARS
Repeat in 6 months
Negative for
malignant cells
HPV effect
and / or more
severe abnormality
Repeat in 1 year
If negative for
malignant cells,
may resume
routine screening
Colposcopy
13
Colposcopy
PAP SMEAR
ABNORMAL
SMEARS
High-grade squamous
intraepithelial lesion
(HSIL)
Moderate
dyskaryosis
or
Severe
dyskaryosis
Severe
dyskaryosis,
cannot rule out
invasive
carcinoma
Colposcopy
Colposcopy
(urgent appointment)
14
Urgent referral
to
gynaecologist
PAP SMEAR
Endocervical
adenocarcinomain-situ
Colposcopy *
Colposcopy
Adenocarcinoma
15
Urgent referral to
gynaecologist
ABNORMAL
SMEARS
Atypical glandular
cells
-Undetermined
significance
-Favour neoplastic
PAP SMEAR
Carcinoma
(specified or not further specified)
ABNORMAL
SMEARS
b.
16
PAP SMEAR
Unsatisfactory
Atypical squamous or
glandular cells,
dyskaryosis
of any degree
Suspicious of invasive
carcinoma or
adenocarcinoma, or
malignant cells seen
Negative for
malignant
cells
Resume follow
up schedule
after treatment
for CIN
ABNORMAL
SMEARS
2nd smear
unsatisfactory
Colposcopy
Colposcopy
Colposcopy
(urgent appointment)
17
PAP SMEARS
AFTER
HYSTERECTOMY
18
1.
Subtotal hysterectomy
Should continue to have Pap smears according to the screening
programme
3.
4.
5.
6.
2.
MANAGEMENT OF
PREINVASIVE DISEASE
OF THE CERVIX
20
7.1 HPV
HPV on Biopsy
Treat :
i. If any associated CIN,
according to guidelines
for CIN
ii. If condylomas present
HPV
No CIN
MANAGEMENT OF
PREINVASIVE DISEASE
If negative for
malignant cells,
may return to routine
3 yearly screening
21
7.2 CIN 1
CIN 1 on Biopsy
Observation
Treatment
Ablation *
or
Excision
Persistent CIN I
- cytology
(ASC-US / LSIL)
- colposcopy +
biopsy
Treatment
Or
Observation
Normal
Follow-up
Pap smear at
3 6 months
MANAGEMENT OF
PREINVASIVE DISEASE
Progression
- cytology
(ASC-H / HSIL)
- colposcopy +
biopsy
Return to routine 3
yearly screening
Treat
Excision
- LEEP / LLETZ
- Laser cone
- Cold knife cone
Follow-up
23
MANAGEMENT OF
PREINVASIVE DISEASE
Ablation
- The upper limit of the lesion is completely
visualised
- The whole transformation zone is seen on
colposcopy
- There is no discrepancy of more than one grade
between cytology, colposcopy or biopsy
- There is no suspicion of microinvasive / invasive
disease on cytology, colposcopy or biopsy
- There is no suspicion of any glandular
lesion on cytology, colposcopy or biopsy
- The patient will be compliant to follow up
SUSPICION OF MICROINVASION
on Biopsy
MANAGEMENT OF
PREINVASIVE DISEASE
Subsequent management
according to histology of
cone biopsy
24
7.5 Adenocarcinoma-in-situ
ADENOCARCINOMA-IN-SITU
on Biopsy
Invasion present
Manage according to
guidelines for
cervical cancer
No invasion
Margins involved
Adequate specimen
and margins clear
If fertility desired
or desire
to preserve uterus
Total
hysterectomy
Follow patient
closely
25
MANAGEMENT OF
PREINVASIVE DISEASE
Completed
family
Recommend
expert opinion
2.
3.
4.
MANAGEMENT OF
PREINVASIVE DISEASE
26
Margin positive
for CIN I
Margin positive
for CIN 2 or 3
Repeat excision
or hysterectomy
Biopsy
Follow up
according to
schedule for CIN
CIN I
CIN 2 / CIN 3
Individualise
treatment
Ablation*
or
excision
Excision
or
hysterectomy
Consider
expert
opinion
27
MANAGEMENT OF
PREINVASIVE DISEASE
SPECIAL
SITUATIONS
Note:
Management should be individualised.
Consider expert opinion including pathology review.
28
Colposcopy unsatisfactory
vulva / vagina normal
Do ECC
Pap smear
abnormal
colposcopy
normal
ECC
positive
Repeat Pap
smear in
6 months
ASC-US
or LSIL
Negative
for
malignant
cells
ASC-H/
HSIL
ECC
negative
Abnormal
Normal
Repeat Pap
smear in
6 months
Yearly Pap
smear x 2
Negative for
malignant cells
If negative
for malignant
cells, resume
3 yearly
screening
Yearly Pap
smear x 2
Legend : ECC
Note :
Pap smear
abnormal
colposcopy
unsatisfactory
Cone biopsy
or LEEP
Endocervical currettage
Cone
biopsy
or LEEP
Estrogen treatment if
post-menopausal. Repeat Pap
smear & colposcopy in 3 months
SPECIAL
SITUATIONS
Colposcopy unsatisfactory
Vulva / vagina normal
Not conclusive
for ASC-H / HSIL
ASC-H / HSIL
SPECIAL
SITUATIONS
Repeat Pap
smear in 6 months
If negative for
malignant cells,
yearly Pap
smear x 2
ASC-H / HSIL
Not conclusive
for ASC-H / HSIL
ASC-US
or LSIL
ASC-H / HSIL
If negative for
malignant cells,
to resume
3 yearly screening
30
Cone biopsy or
LEEP
Follow
algorithm
as in 8.1
Abnormal
Biopsy
Normal or unsatisfactory
AIS / SIL
High suspicion of
neoplastic lesion
Manage according
to guidelines
for cervical cancer
Low suspicion of
neoplastic lesion
Normal
Normal
Manage according
to histology of lesion
AGUS
SPECIAL
SITUATIONS
Carcinoma
Colposcopy
No lesion on cervix
Lesion on cervix
SPECIAL
SITUATIONS
Squamous intraepithelial
lesion
Cone biopsy
+ ECC
D&C if risk factors
for Ca endometrium
present,
symptomatic or
>40 years
Legend: ECC
Cone biopsy
+ ECC
D&C if risk factors
for Ca endometrium
present,
symptomatic or
>40 years
AIS
biopsy
Adenocarcinoma
Cone biopsy
+ ECC
Manage
according to
guidelines for
cervical cancer
Endocervical currettage
Lesion on cervix
No lesion on cervix
Colposcopy normal
AIS
Manage according
to guidelines
for cervical cancer
Cone biopsy
+ ECC
and D&C
SPECIAL
SITUATIONS
Adenocarcinoma
D&C + hysteroscopy
Cone biopsy of cervix
Squamous
intraepithelial lesion
or no dysplasia
Biopsy
33
REFERENCES
34
2.
3.
4.
From the Centres for Disease Control and Prevention. Incidence of Pap test
abnormalities within 3 years of a normal Pap test - United States,
1991 - 1998. JAMA 2000; 284 (21): 2714-5.
5.
6.
7.
8.
9.
35
REFERENCES
1.
10. Kim TJ, Kim HS, Park CT, Park IS, Hong SR, Park JS, Shim JU. Clinical evaluation
of follow-up methods and results of atypical glandular cells of undetermined
significance (AGUS) detected on cervicovaginal Pap smears. Gynecol Oncol
1999; 73 (2): 292-8.
11. McIndoe WA, McLean MR, Jones RW, Mullins PR. The invasive potential of
carcinoma in situ of the cervix. Obstet Gynecol 1984; 64 (4) : 451-8.
12. Cox JT. Management of cervical intraepithelial neoplasia. Lancet 1999; 353
(9156): 857-9.
13. Shafi MI, Luesley DM. Management of low grade lesions: Follow-up or treat?
Ballieres Clin Obstet Gynaecol 1995; 9 (1): 121-31.
14. G Flannelly, D Anderson, HC Kitchener, E M F Mann, M Campbell, P Fisher, F
Walker. Management of women with mild and moderate cervical dyskaryosis.
BMJ; 308: 1399-403.
15. Martin-Hirsch PL, Paraskevaidis E, Kitchener H. Surgery for cervical
intraepithelial neoplasia. Cochrane Database Syst Rev 2, CD001318, 2000.
16. Duggan BD, Felix JC, Muderspach LI, Gebhardt JA, Groshen S, Morrow CP,
Roman LD. Cold-knife conization versus conization by the loop electrosurgical
excision procedure: a randomized, prospective study. Am J Obstet Gynecol
1999; 180 (2 Pt 1): 276-82.
17. Narducci F, Occelli B, Boman F, Vinatier D, Leroy JL. Positive margins after
conization and risk of persistent lesion. Gynecol Oncol 2000; 76 (3): 311-4.
REFERENCES
18. Dobbs SP, Asmussen T, Nunns D, Hollingworth J, Brown LJ, Ireland D. Does
histological incomplete excision of cervical intraepithelial neoplasia following
large loop excision of transformation zone increase recurrence rates? A six
year cytological follow up. Br J Obstet Gynaecol 2000; 107 (10) : 1298-301.
19. K Mohamed-Noor, MA Quinn, J Tan. Outcomes after cervical cold knife
conization with complete and incomplete excision of abnormal epithelium:
A review of 699 cases. Gynecologic Oncology 1997; 67: 34-8.
20. Grainne Flannelly, Heather Langhan, Lata Jandial, Evelyn Mann, Marion
Campbell, Henry Kitchener. A study of treatment failures following large
loop excision of the transformation zone for the treatment of cervical
intraepithelial neoplasia. British Journal of O&G 1997; 104: 718-22.
36
30. Law KS, Chang TC, Hsueh S, Jung SM, Tseng CJ, Lai CH. High prevalence of
high grade squamous intraepithelial lesions and microinvasive carcinoma in
women with a cytologic diagnosis of low grade squamous intraepithelial
lesions. J Reprod Med 2001; 46 (1): 61-4.
37
REFERENCES
ACKNOWLEDGEMENTS
38
Workgroup Members
Chairperson
Clinical Assoc Prof Ho Tew Hong
Dr Lee I Wuen
Raffles Hospital
Dr Jeffrey Low
Dr Pritam Singh
39
ACKNOWLEGEMENTS
Members