1. Screening in Gynaecological Cancers
Prof. HYS Ngan
Department of Obstetrics & Gynaecology University of Hong Kong
Queen Mary Hospital

2. Fallopion tube
Uterus
Endometrium
Ovary
Cervix
Vagina

5. Screening
Cervical cancer
Ovarian cancer
Endometrial cancer

6. Screening To detect disease among healthy population
Without symptoms of disease
Purpose: decrease mortality due to the disease screened

7. 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

8. Carcinoma of the cervix
commonest lower genital tract cancer
about 500 new cases per year in HK
about 140 deaths per year in HK
median age: 50 years

9. 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

10. Natural history of CIN 1-2
regress persist CIN3 Ca
CIN I 57% % % <1%
CIN2 43% % % 5%
(100 prospective studies)

11. Cervical cytology Sensitivity and Specificity
Overall sensitivity: %, cervical cancer: %
Overall specificity : %
Quantin.C 1992, Soost.HJ 1991

12. Cervical cytology Positive predictive value
Low-moderate dysplasia: 73-76%
severe dysplasia : %
Invasive cancer: 95%
Quantin.C 1992, Soost.HJ 1991

13. 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%

14. New technology automation for cervical cancer screening
liquid-based cytology - thin layer preparation

15. Advantages of LBC Eliminate air-dried artifact inflammatory cells
blood
mucus
Increase
detection of abnormal cytology

16. Cervical cancer screening - new methods under exploration
cervicography
polar probe
HPV typing

17. 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

18. Organized screening vs Opportunistic screening
Finland and Sweden
decrease in indicence and mortality of cervical cancer
concentrate resources
wide coverage
Policy decision

19. European and American recommendation
Age:
Europe: 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

20. Hong Kong College of Obstetricians and Gynaecologists
Age: sexually active to 65
Interval: 2 consecutive annual normal smears, 3 yearly

21. How to take a cervical smear?
Speculum
adequate exposure
light source
sampling device - Ayres’ spatula, brush or broom
transformation zone

22. Speculum

23. Ayres’ spatula, endocervical brush

24. Broom type sampler

25. 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

26. How to interpret a cytology report?

27. 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.

28. History on request form
contraceptive history
menopausal status
date of last menstrual period
prior radiotherapy or current chemotherapy
hysterectomy
drugs or hormones
parity

29. Bethesda System 2001 Negative
Squamous cell - ASCUS, ASC-H (cannot exclude HSIL)
- LSIL
- HSIL, HSIL with features suspicious of invasion
- SCC

30. 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

31. Cytology screening Conven 95874 0.44 4.36 0.1 1.24 0.29 0.02 1999
No. Unsat. ASCUS AGUS LG HG Inv
Conven
1999
Thin Prep
(4800) (1600)
A Cheung

32. How to manage abnormal smear?

33. Histological grading of pre-invasive 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

34. 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.

35. 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

36. Management of LSIL 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)

37. Management of HSIL Gross examination showed a growth - biopsy
Grossly normal - refer colposcopy

38. Outcome of AGUS Normal: 19-34% Significant pathology: 15-37%
CIN %
AIS 3-5%
Ca cervix 2-3%
Ca corpus 1-4%

39. 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

40. 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

41. Colposcope

42. Treatment of high grade CIN
ablative therapy
cryotherapy
cold coagulation
diathermy
laser evaporisation
excision therapy
cone (knife, laser, loop excision)
hysterectomy is rarely indicated

43. Management of abnormal smear
Hong Kong College of Obstetricians & Gynaecologists -
Guidelines on The Management of An Abnormal Cervical Smear

44. Ovarian Cancer in HK
New Cases : 220
Death : 95
Median age : 51
(1992)

45. 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

46. Ovarian Cancer Symptoms of ovarian cancer : asymptomatic
Lower abdominal pain/pressure
mass
Abdominal enlargement
Vaginal bleeding
Urinary/bowel symptoms

47. Ovarian Cancer Risk factors : 1) majority has no risk factor
2) family history 10%
- familial ovarian syndrome
2) nulliparous
3) racial and social

48. 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

49. Methods used for ovarian cancer screening
Serum CA125
Transvaginal ultrasonogram
Multimodal
New method under investigation - lysophosphatidic acid

50. 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)

51. 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%

52. Ovarian cancer screening
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%

53. Ovarian screening Not cost-effective
May be considered in high risk population
No place for population screening yet

54. Carcinoma of Endometrium
Incidence : third commonest malignant tumour of genital tract
Age : 58

55. Endometrial Cancer in H.K.
New cases : 200
Death : 50
Median age :
(1992)

56. Risk factors nulliparity, anovulation, late menopause
exogenous estrogen
endogenous estrogen
DM, HT, obesity
smoking, white
tamoxifen
familial history

57. Postmenopausal Bleeding
1) carcinoma of endometrium 14%
2) other gynecological malignancy 14%
3) atrophic endometritis 20%
4) endometrial hyperplasia 12%
5) cervicitis/erosion %
6) endometrial polyp 8%
7) cervical polyp %

58. Diagnosis of Carcinoma of Endometrium
(f) D&C near 100%
uterine aspirate %
endocervical aspirate + vaginal % aspirate
vaginal aspirate + cervical smear %
cervical smear %

59. 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

60. Endometrial Cancer Screening
Tools explored
pelvic ultrasound (>8mm endometrial thickness in postmenopausal women) Karlsson 1995
endometrial aspirate (inadequate sampling in menopausal women)

61. Endometrial aspirator

62. Endometrial aspirator

63. 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

64. 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)

65. Endometrial cancer screening
Not justified in population screening
excellent prognosis of majority of ca endometrium unlikely will result in decreased mortality rates

66. 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