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

Screening in Gynaecological Cancers

Prof. HYS Ngan

Department of Obstetrics & Gynaecology University of Hong Kong

Queen Mary Hospital

Fallopion tube

OvaryEndometrium

Cervix

Vagina

Uterus

0

2

4

6

8

10

12

14

Rate per 100,000

Females

1993 1994 1995 1996

Year

Incidence Rate of the Female Cancer for the year 1993-1996

Cervix

Ovary

Corpus

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

Rate per 100,000 Females

1993 1994 1995 1996

Year

Mortality Rate of Female Cancers for the year 1993-1996

Cervix

Ovary

Corpus

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

• 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% 5%

(100 prospective studies)

Cervical cytologySensitivity and Specificity

• Overall sensitivity: 61-64%, cervical cancer: 82-95%

• Overall specificity : 99 - 99.4%

Quantin.C 1992, Soost.HJ 1991

Cervical cytologyPositive 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?

• 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

– 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

No. Unsat. ASCUS AGUS LG HG InvConven 95874 0.44 4.36 0.1 1.24 0.29 0.021999

Thin Prep 100420 0.32 4.78 0.1 1.6 0.3 0.0012000 (4800) (1600)

A Cheung

How to manage abnormal smear?

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

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

• 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– cryotherapy– cold coagulation– diathermy– laser evaporisation

• excision therapy– cone (knife, laser, loop excision)

• hysterectomy is rarely indicated

Management of abnormal smear

Trea t in fec tionrep eat 6 m th s

if ab n orm a lco lp oscop y

In flam m atory a typ iaw ith

id en tifiab le in fec tion

rep eat 3 -6 m th sif ab n orm a lco lp oscop y

A S C U S

co lp oscop y + /-b iop sy

L S IL /H S IL /A G U S

g ross tu m ou rb iop sy

n orm a l ce rvixco lp oscop y + /-

b iop sy

In vas ive

A b n sm ear

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

Ovarian Cancer in HKNew Cases : 220

Death : 95

Median age : 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 CancerSymptoms 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

• 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 screeningKentucky 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• 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 : 200

Death : 50

Median age : 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 14%2) other gynecological malignancy 14%3) atrophic endometritis 20%4) endometrial hyperplasia 12%5) cervicitis/erosion 8%6) endometrial polyp 8%7) cervical polyp 8%

Diagnosis of Carcinoma of Endometrium

(f) D&C near 100%uterine aspirate 90%endocervical aspirate + vaginal 65%

aspiratevaginal 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