Screening in gynaecological cancers
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Screening in Gynaecological Cancers. Prof. HYS Ngan Department of Obstetrics & Gynaecology University of Hong Kong Queen Mary Hospital. Fallopion tube. Uterus. Endometrium. Ovary. Cervix. Vagina. Screening. Cervical cancer Ovarian cancer Endometrial cancer. Screening.

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Screening in gynaecological cancers l.jpg

Screening in Gynaecological Cancers

Prof. HYS Ngan

Department of Obstetrics & Gynaecology University of Hong Kong

Queen Mary Hospital


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Fallopion tube

Uterus

Endometrium

Ovary

Cervix

Vagina


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Screening

  • Cervical cancer

  • Ovarian cancer

  • Endometrial cancer


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Screening

To detect disease among

healthy

population

Without symptoms of disease

Purpose: decrease mortality due to the disease screened


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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


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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


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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


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Natural history of CIN 1-2

regress persist CIN3 Ca

CIN I 57% 32% 11% <1%

CIN2 43% 35% 22% 5%

(100 prospective studies)


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Cervical cytologySensitivity and Specificity

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

  • Overall specificity : 99 - 99.4%

    Quantin.C 1992, Soost.HJ 1991


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Cervical cytologyPositive predictive value

  • Low-moderate dysplasia: 73-76%

  • severe dysplasia : 85-90%

  • Invasive cancer: 95%

    Quantin.C 1992, Soost.HJ 1991


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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%


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New technology cervical cancer

  • automation for cervical cancer screening

  • liquid-based cytology - thin layer preparation


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Advantages of LBC cervical cancer

Eliminate

  • air-dried artifact

  • inflammatory cells

  • blood

  • mucus

    Increase

  • detection of abnormal cytology


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Cervical cancer screening - new methods under exploration cervical cancer

  • cervicography

  • polar probe

  • HPV typing


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HPV DNA testing - potential use cervical cancer

  • 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


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Organized screening vs Opportunistic screening cervical cancer

  • Finland and Sweden

    decrease in indicence and mortality of cervical cancer

    concentrate resources

    wide coverage

  • Policy decision


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European and American recommendation cervical cancer

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


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Hong Kong College of Obstetricians and Gynaecologists cervical cancer

  • Age: sexually active to 65

  • Interval: 2 consecutive annual normal smears, 3 yearly


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How to take a cervical smear? cervical cancer

  • Speculum

  • adequate exposure

  • light source

  • sampling device - Ayres’ spatula, brush or broom

  • transformation zone


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Speculum cervical cancer



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Broom type sampler cervical cancer


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When not to take a cervical smear cervical cancer

  • 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



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History on request form with the clinical picture of the patient

  • contraceptive history

  • menopausal status

  • date of last menstrual period

  • prior radiotherapy or current chemotherapy

  • hysterectomy

  • drugs or hormones

  • parity


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Bethesda System 2001 with the clinical picture of the patient

  • Negative

  • Squamous cell - ASCUS, ASC-H (cannot exclude HSIL)

    - LSIL

    - HSIL, HSIL with features suspicious of invasion

    - SCC


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Bethesda System 2001 with the clinical picture of the patient

  • 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


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Cytology screening with the clinical picture of the patient

No. Unsat. ASCUS AGUS LG HG Inv

Conven 95874 0.44 4.36 0.1 1.24 0.29 0.02

1999

Thin Prep 100420 0.32 4.78 0.1 1.6 0.3 0.001

2000 (4800) (1600)

A Cheung


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How to manage abnormal smear? with the clinical picture of the patient


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Histological grading of pre-invasive cervical lesion with the clinical picture of the patient

  • 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


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Inflammatory changes with atypia with the clinical picture of the patient

  • 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.


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Management of ASCUS with the clinical picture of the patient

  • 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


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Management of LSIL with the clinical picture of the patient

  • 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)


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Management of HSIL with the clinical picture of the patient

  • Gross examination showed a growth - biopsy

  • Grossly normal - refer colposcopy


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Outcome of AGUS with the clinical picture of the patient

  • Normal: 19-34%

  • Significant pathology: 15-37%

    CIN 16-54%

    AIS 3-5%

    Ca cervix 2-3%

    Ca corpus 1-4%


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Recommendation with the clinical picture of the patient

  • 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


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Colposcopy services in Hong Kong with the clinical picture of the patient

  • 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


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Colposcope with the clinical picture of the patient


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Treatment of high grade CIN with the clinical picture of the patient

  • ablative therapy

    • cryotherapy

    • cold coagulation

    • diathermy

    • laser evaporisation

  • excision therapy

    • cone (knife, laser, loop excision)

  • hysterectomy is rarely indicated


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Management of abnormal smear with the clinical picture of the patient

Hong Kong College of Obstetricians & Gynaecologists -

Guidelines on The Management of An Abnormal Cervical Smear


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Ovarian Cancer in HK with the clinical picture of the patient

New Cases : 220

Death : 95

Median age : 51

(1992)


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Ovarian cancer with the clinical picture of the patient

  • 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


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Ovarian Cancer with the clinical picture of the patient

Symptoms of ovarian cancer :

  • asymptomatic

  • Lower abdominal pain/pressure

  • mass

  • Abdominal enlargement

  • Vaginal bleeding

  • Urinary/bowel symptoms


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Ovarian Cancer with the clinical picture of the patient

Risk factors :

1) majority has no risk factor

2) family history 10%

- familial ovarian syndrome

2) nulliparous

3) racial and social


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Why screening for ovarian cancer is so difficult? with the clinical picture of the patient

  • 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


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Methods used for ovarian cancer screening with the clinical picture of the patient

  • Serum CA125

  • Transvaginal ultrasonogram

  • Multimodal

  • New method under investigation - lysophosphatidic acid


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Serum CA125 with the clinical picture of the patient

  • 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)


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TVS in ov ca screening with the clinical picture of the patient

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%


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Ovarian cancer screening with the clinical picture of the patient

  • 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%


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Ovarian screening with the clinical picture of the patient

  • Not cost-effective

  • May be considered in high risk population

  • No place for population screening yet


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Carcinoma of Endometrium with the clinical picture of the patient

Incidence : third commonest malignant tumour of genital tract

Age : 58


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Endometrial Cancer in H.K. with the clinical picture of the patient

New cases : 200

Death : 50

Median age : 60

(1992)


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Risk factors with the clinical picture of the patient

  • nulliparity, anovulation, late menopause

  • exogenous estrogen

  • endogenous estrogen

  • DM, HT, obesity

  • smoking, white

  • tamoxifen

  • familial history


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Postmenopausal Bleeding with the clinical picture of the patient

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%


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Diagnosis of Carcinoma of Endometrium with the clinical picture of the patient

(f) D&C near 100%

uterine aspirate 90%

endocervical aspirate + vaginal 65% aspirate

vaginal aspirate + cervical smear 40%

cervical smear 15%


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Should endometrial cancer be screened? with the clinical picture of the patient

  • 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


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Endometrial Cancer Screening with the clinical picture of the patient

  • Tools explored

    • pelvic ultrasound (>8mm endometrial thickness in postmenopausal women) Karlsson 1995

    • endometrial aspirate (inadequate sampling in menopausal women)


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Endometrial aspirator with the clinical picture of the patient


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Endometrial aspirator with the clinical picture of the patient


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Endometrial aspiration with the clinical picture of the patient

  • Sensitivity for endometrial ca 94% in patient with symptoms

  • sensitivity for hyperplasia 31%

    Cons: discomfort to patient

    lack of known efficiency in asymtomatic patients


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TVS in endometrial ca screening with the clinical picture of the patient

  • 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)


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Endometrial cancer screening with the clinical picture of the patient

  • Not justified in population screening

  • excellent prognosis of majority of ca endometrium unlikely will result in decreased mortality rates


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Conclusions with the clinical picture of the patient

  • 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


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