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 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 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? 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 Conven 95874 0.44 4.36 0.1 1.24 0.29 0.02 1999 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

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

Ovarian Cancer in HK New 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 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 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 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% 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