Screening for the Precursors of Cervical Cancer in the Era of HPV Vaccination. Dr Stella Heley Senior Liaison Physician Victorian Cytology Service

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2 Screening for the Precursors of Cervical Cancer in the Era of HPV Vaccination Dr Stella Heley Senior Liaison Physician Victorian Cytology Service

3 Victorian Cytology Service Dr Stella Heley Dr Siobhan Bourke Dr Lara Roeske

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8 Worldwide cancer Burden among women - incidence Cancer Site Cases Crude Rate ASR (W) Breast Cervix Colorectal Lung GLOBOCAN 2002, IARC

9 Worldwide cancer Burden among women - Mortality Cancer Site Cases Crude Rate ASR (W) Breast Lung Cervix Colorectal GLOBOCAN 2002, IARC

10 Distribution of disease by area of the world 400, , ,000 More developed Less Developed 250, , , ,000 50,000 0 New cases Deaths

11 India accounts for 27% of the new cases and 30% of the deaths

12 Cancer of the cervix Caused by Human papillomavirus (HPV) Prevented by HPV vaccination and Cervical screening

13 Cervical screening in Australia AIHW Cancer Series No 61

14 cases in deaths in Source: AIHW (Australian Institute of Health and Welfare) & AACR (Australasian Association of Cancer Registries) Cancer in Australia: an overview, Cancer series no. 46. Cat. no. CAN 42.Canberra: AIHW.

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16 Screening history of Victorian women diagnosed with an invasive cervical cancer for the period 1 January 2003 and 31 December 2005 Screening History Squamous cell carcinoma Other invasive cervical cancer* Total Number % Number % Number % A. Women never screened 51 23% 73 47% % B. Women with inadequate screening C. Women with some screening history** % 50 32% % 17 8% 33 21% 50 13% Total % % % * Other cervical cancers include small cell carcinoma, mixed adenosquamous and Adenocarcinoma. ** Requires further review

17 Screening history of Victorian women diagnosed with invasive cervical cancer, for the period 1 January 2002 to 31 December 2004.

18 HPV and cancer

19 Schiffman et al Lancet 2007; 370:

20 Human Papillomavirus (HPV) Numerous types Species specific Site specific Multifocal infection at one site ~50 types infect genital epithelium

21 Low- Risk Types Include types 6, % of genital warts 10-20% LSILs

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23 High-Risk Types Mainly types 16 and 18 Less frequently types 31, 33, 35, 52, 58, 67 and 45, 59, 39, & 18: 70% cervical cancer

24 IARC monograph HPV types cause cervical cancer (16,18,31,33,35,39,45,51,52,56,58,59,66)

25 Percent of cancers containing 5 most frequently detected HPV types cervical cancer HPV % HPV % 90% 80% 70% 60% 50% 40% 30% 20% HPV % 0.0% HPV % HPV % HPV % HPV % 0.0% HPV % HPV % 2.3% 0.0% HPV % % 0% Clifford 2003 Australian meta-analysis Clifford HPV 16+18=67.3% Australia HPV 16+18=80.1% NCIRS

26 Monogamous women with first partner are at high risk of HPV 49% at 3 years Winer RL, et al. Risk of female human papillomavirus acquisition associated with first male sex partner. J. Infect. Dis. 2008; 197(2),

27 Percentage Non-Indigenous Females (presenting for routine Pap smears) Age Range HR HPV HPV 16 HPV 18 WHINUR Study (unpublished data, July 2006

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29 2005 Terminology: 4 headings 1. Negative 2. Squamous abnormalities 3. Glandular abnormalities 4. Unsatisfactory

30 Squamous abnormality Possible low-grade Low-grade Repeat cytology at 12 mths Squamous abnormality Possible high-grade High grade Glandular abnormality Atypical cells Possible high-grade High grade Colposcopy

31 Recommendations Negative 2 years LSIL 12 months HSIL/Glandular changes Colposcopy Unsatisfactory Repeat 6-12 weeks

32 LOW-GRADE (definite or possible) If woman is 30+ yrs, and has no negative cytology in previous 2-3 yrs, colposcopy or repeat smear in 6 months Repeat Pap test at 12 months NEGATIVE Repeat Pap test at 12 months LOW-GRADE (definite or possible) COLPOSCOPY HIGH GRADE NEGATIVE ROUTINE SCREENING

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34 Maria 24 year old woman Presents for Pap test Asymptomatic RSP (female) for 3 years Result: Unsatisfactory Insufficient squamous cells Repeat 6-12 weeks

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39 % smears lacking endocervical component by age, AIHW

40 Increase in Pap smears without endocervical component, Australia

41 Victorian Cervical Cytology Registry, 2010

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43 Joan 63 year old woman Regular Pap test history (negative) Results: Unsatisfactory Evidence of atrophy Repeat 6-12 weeks after course of oestrogen

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45 Kirsty 23 year old woman RSP 4 years Asymptomatic Results: LSIL (Low Grade Squamous Epithelial Lesion) Repeat 12 months

46 Anna 33 year old woman (Kirsty s sister) Last Pap test age 28 (negative) Results: LSIL Repeat 6 months or refer for colposcopy

47 Rebecca 34 yr old woman 2002 treated for something on her cervix; thinks she had laser treatment Told to have annual Pap smears for the rest of her life (thinks she s had a couple since then)

48 Pap smears 2-yearly between lamydia Take adequate specimen Selective HPV DNA testing

49 Post-treatment of histologically-proven high-grade squamous abnormalities (CIN 2, CIN 3)

50 Time since treatment Pap smear Colposcopy HPV typing 4-6 mths 12 mths 24 mths HPV typing has been added to the MBS for this clinical use only ( test of cure : 2 tests in a 2 year period)

51 Time since treatment Pap smear Colposcopy HPV typing 4-6 mths 12 mths Negative Negative 24 mths Negative Negative Return to 2 year screening interval when Pap smear and HPV typing are negative on two consecutive occasions

52 Frequency of positive HPV testing; post-treatment follow-up period

53 When is an HPV test Medicare rebateable? After biopsy-confirmed HSIL (CIN 2; CIN 3) Do first test 12 months after treatment Medicare will pay for 2 tests in an on-going 2 year period Keep doing them until you have Pap and HPV tests negative for 2 years in a row

54 Jennifer 53 year old woman PH HSIL 18 years previously Annual negative Pap tests since then Result: Negative The frequency with which you repeat this test depends on this woman s HPV status

55 A JOINT INITIATIVE OF THE VICTORIAN CYTOLOGY SERVICE AND CANCER COUNCIL NSW

56 Pap smear vs. HPV testing Pap smear Conventional cytology Liquid-based cytology (LBC) Image-read LBC HPV DNA/mRNA testing Plethora of emerging technologies Performance benchmark established (HC2 Qiagen)* *Meijer C et al. Guidelines for human papillomavirus DNA test requirements for primary cervical cancer screening in women 30 years and older. Int J Cancer 2009

57 Key elements Women aged years recruited through primary care practices in Victoria Consenting women will have LBC sample taken, with laboratory-based randomization 6-yearly HPV screening (with safety monitoring) 3-yearly LBC cytology

58 Longitudinal outcomes: HPV and cytology negative women Low risk Dillner, J. et al. Joint European Cohort Analysis. BMJ 2008;337:a1754 Copyright 2008 BMJ Publishing Group Ltd.

59 Barbara 61 year old woman From interstate Hysterectomy 11 years ago for heavy bleeding Pap smears prior to this:? One or two?ok

60 Skye 25 yr old woman Vaccinated & completed course May 2009 Previous smears (2) negative Presented last week for Pap test Result: HSIL How do you explain this?

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62 Amanda Age 53 3 smears in the past 9 months All unsatisfactory; all insufficient squamous cells Most recent smear taken 1 week ago; included a LBC sample (ThinPrep) What next?!

63 Sonia Age 38 March 2000: LSIL May 2000: HSIL/moderate dysplasia Jan 2001: HSIL/severe dysplasia August 2001: negative March 2002: negative June 2005: negative

64 Sonia (cont d) July 2006: negative/+ve HPV October 2007: negative/+ve HPV October 2008: negative/+ve HPV November 2009: negative/+ve HPV November 2010: LSIL/+ve HPV October 2011: negative/+ve HPV What advice would you give?

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