Screening in Gynaecological Cancers

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% 32% 11% <1% CIN2 43% 35% 22% 5% (100 prospective studies)

11. Cervical cytologySensitivity and Specificity • Overall sensitivity: 61-64%, cervical cancer: 82-95% • Overall specificity : 99 - 99.4% Quantin.C 1992, Soost.HJ 1991

12. Cervical cytologyPositive predictive value • Low-moderate dysplasia: 73-76% • severe dysplasia : 85-90% • 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: 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

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 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

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 16-54% 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)