1. mQlicker This session will utilise the mQlicker interactive audience program Questions will be presented and you will be able to respond electronically through your mobile device Enable the internet on your mobile device Open the web browser Go to https://respond.cchttps://respond.cc When a question is presented, enter the Session Key for that question Select one of the multiple choice answers and Submit

2. The New Cervical Screening Program: Will the pap smear be irrelevant? Dr Shian Miller Obstetrician & Gynaecologist BSc (Hon), MBBS, FRANZCOG

3. Disclaimer This session is not funded by a pharmaceutical nor medical device company Dr Shian Miller is an independent obstetrician and gynaecologist practicing general obstetrics and general gynaecology – with a special interest in colposcopy Dr Shian Miller is not involved in the development nor implementation of the Renewal of the Cervical Screening Program (other than as a practising gynaecologist) and has no association with any committees involved with the Renewal

4. Will the pap smear be irrelevant? Yes

5. Overview Background Why do we need a change? What is going to change? But what about…? Your protests answered! The future (or lack of future) of cervical screening

6. mQlicker This session will utilise the mQlicker interactive audience program Questions will be presented and you will be able to respond electronically through your mobile device Enable the internet on your mobile device Open the web browser Go to https://respond.cchttps://respond.cc When a question is presented, enter the Session Key for that question Select one of the multiple choice answers

7. mQlicker check SESSION KEY: 18401 Q1: I am a: 1. General practitioner 2. Specialist 3. Nurse or nurse practitioner 4. Student 5. Non-medical layperson 6. Other

8. (mQlicker answers)

9. mQlicker Question SESSION KEY: 52769 Q2: My knowledge about the new cervical screening program is: 1. There’s a new cervical screening program? 2. Heard about it but don’t know the details 3. Know a little bit about it 4. Know the main details well and/or you came to my practice and talked about it 5. Confident in all aspects of the new program

10. (mQlicker answers)

11. mQlicker Question SESSION KEY: 52030 Q3: My feelings about the new program are: 1. Angry/annoyed 2. Worried 3. Neutral 4. It’s time for a change; I appreciate the need for a change 5. Excited

12. (mQlicker answers)

13. mQlicker Question SESSION KEY: 59634 Q4: From what I know about the new cervical screening program, I think: 1. We should stay with the current screening program 2. We should delay the release of the new program 3. We should change to the new program as announced 4. I don’t know enough about the new program to say either way 5. I don’t mind either way

14. (mQlicker answers)

15. The History of Cervical Screening George Papanicolaou (1883-1962) Born in Greece, migrated to USA Noticed physiological cellular changes in vaginal fluid over the course of a menstrual cycle One woman in his study had uterine cancer & he discovered that abnormal cancer cells in her vaginal fluid were clearly visible under a microscope Initial presentation at a medical conference in 1928 was met with scepticism Published a paper in 1941 with gynaecologist Herbert Traut on the diagnostic value of vaginal smears in cervical and uterine carcinomas – described technique used today Romanian scientist Aurel Babes independently made similar discoveries in 1927 but used a different collection method

16. Cervical screening in Australia Since 1960s, Australia has been doing pap smears Ad hoc, opportunistic screening National Cervical Screening Program began in 1991 with recommended guidelines and a national register Organised approach to screening with promotion of public awareness Also improved quality control of smear taking, processing, and reporting, as well as standardising the management of screen-detected abnormalities

17. Current Australian screening National Cervical Screening Program (NCSP) Target age 18-69 Pap smear every 2 years If LSIL, repeat in 12 months If LSIL, over 30yo, no negative pap in last 2-3 years, repeat pap in 6 months or refer for colposcopy HSIL, refer for colposcopy

18. mQlicker Question SESSION KEY: 20307 Q5: What is the current participation rate (approx) in the National Cervical Screening Program? 1. 20% 2. 40% 3. 60% 4. 80% 5. Almost 100%

19. (mQlicker answers)

20. Cervical screening participation rates Women aged 20-69 (AIHW)

21. Cervical cancer in Australia 14 th most common cancer diagnosed in females Approx 800 new cases of cervical cancer diagnosed per year in Australia Approx 200-250 women die of cervical cancer per year 5-year survival rate for cervical cancer in Australia is 72% Most cervical cancers (~80%) are SCC, ~15% adenocarcinomas, 5% adenosquamous and ‘other’

22. Cervical cancer incidence Women aged 20-69, from 1982 to 2008 (AIHW)

23. Cervical cancer mortality Women aged 20-69, from 1982 to 2007

24. Effects of the NCSP Has resulted in one of the lowest mortality rates from cervical cancer in the world: 1.8 per 100,000 women Incidence of SCCs has halved: 14 per 100,000 in 1982 to 6.9 per 100,000 women in 2011 (although absolute value steady: 963 vs 801) Much more modest reduction in glandular cervical cancers More than 90% of women diagnosed with invasive SCC have either no screening history or an inadequate screening history in the 10 years prior to diagnosis

25. HPV in cervical cancer HPV is detected in >99% of cervical cancers More than 100 types of HPV but only some associated with cervical cell changes – particularly HPV types 16 and 18 Estimated more than 80% of women are infected with HPV in their lifetime – but most clear the infection by on average 12 months It is when HPV infection persists that high-grade cervical changes occur

26. HPV vaccine National HPV Vaccination Program started 2007 Vaccination of 12-13 yo, catch-up program to women up to 26 years for a period of two years Also now vaccinating boys since 2013 Has already reduced the rate of high-grade cervical abnormalities in young women There has been a 90% reduction in genital warts in men & women under 21 years of age Predicted to greatly reduce the incidence of cervical abnormalities and cervical cancer in the future Evidence that two doses of HPV vaccine (Gardasil or Cervarix) are as effective as three doses – change already made in the UK in September 2014

27. mQlicker Question SESSION KEY: 46766 Q6: The uptake of the HPV vaccine in the school cohort is (approx): 1. 10% 2. 30% 3. 50% 4. 70% 5. 90%

28. (mQlicker answers)

29. Why should we change? Balancing the risk of investigation and treatment with the risk of cervical cancer Incidence of cervical cancer 15 per 100,000 compared to abnormal results in 5000 per 100,000 screen Current screening is not having much impact on adenocarcinomas Cervical cancer incidence and mortality has plateaued – can we do better? Incidence of high grade abnormality to fall markedly due to HPV vaccine – will need to ensure screening test still performs well despite low prevalence

30. Cervical cancer rates by histological type Cervical screening is most effective for prevention of SCC but not adenocarcinomas

31. The New Screening Program Scheduled to be implemented in May 2017 Renewal of the NCSP first raised in 2013 Committees formed Over 130 variations of cervical screening models evaluated to ensure a cervical screening program that is safe, acceptable, effective, efficient, and based on current evidence (and of course, cost-effective) Credit to the committees – their comprehensive data analysis can be found at: http://www.msac.gov.au/internet/msac/publishing.nsf /Content/1276-public

32. Old versus new Old NCSPNew cervical screening program Pap smear performed for screening (speculum exam & endocervical swab) With glass slide +/- ThinPrep/Surepath HPV test performed for screening (speculum exam & endocervical swab) With ThinPrep/Surepath Pap every TWO yearsHPV test every FIVE years Age 18-70Age 25-75 Abnormal pap: refer to colposcopyHPV test positive: ‘reflex cytology’ on sample already taken – if cytology abnormal, refer to colposcopy Symptomatic (abnormal bleeding/discharge): refer to colposcopy Poor attendees: no follow-up Poor attendees: offer self-collection for HPV testing

33. mQlicker Question SESSION KEY: 1647 Q7: On hearing about the changes in the new Cervical Screening Program, I am: 1. Angry, annoyed 2. Worried 3. Neutral 4. Starting to come around to the idea 5. Pleased

34. (mQlicker answers)

35. Why HPV? HPV infection is necessary for the development of cervical cancer HPV is positive in 99.7% of cervical cancers HPV testing compared to current screening has a greater negative predictive value and increased detection of high-grade CIN HPV testing (unlike current screening) has been shown to significantly reduce the incidence of adenocarcinomas Low-grade cervical changes may indicate acute HPV infection but it is the persistence of HPV that causes high-grade changes and cervical cancer – HPV testing shows persistence better than cervical cytology

36. Why ‘reflex cytology’? HPV infection may not be associated with cytological abnormalities HPV testing has high sensitivity and high NPV – so reduces false negatives but has high false positive Reflex cytology to reduce false positive results If partial HPV genotyping performed, refer to colposcopy with HPV 16/18 (45) even if cytology negative (evidence not enough at present to make partial HPV genotyping routine) If reflex cytology is: Negative – repeat HPV testing in 1 year – if HPV still positive, refer for colposcopy regardless of cytology results (means HPV has persisted) Positive for cellular changes – refer for colposcopy

37. Why change from every 2 years to every 5 years? HSIL resolves spontaneously in a large number of women, especially younger women – can also persist for a lifetime without development into SCC At 12 months, LSIL/CIN1 regressed in 80%, progressed in 3.6% CIN2 43% regressed, 35% persist, 22% progress CIN3 33% regressed, 56% persist, 12% progress Average duration from HSIL to progression to cancer is 10 to 15 years Longer screening intervals appropriate due to high NPV of HPV testing – extending screening to every 5 years avoids overdiagnosis of regressive CIN

38. Why change the starting age from 18yo to 25yo? High prevalence of HPV infection but most people spontaneously clear the infection Only in those where HPV infection persists (for generally more than 3 years) do cervical changes occur Less than 0.2% of cervical cancers occur in women under age 25 High incidence of HSIL in younger women (<30) without corresponding incidence of cancer High chance of regression of HSIL in young women – already currently offer conservative management for CIN2 under 25yo Risk of CIN3 progression is age-related

39. Age-specific incidence rates of cervical cancer

40. Incidence of cervical cancer Age Group New cases per 100,000 0-140 15-190.1 20-241.6 25-298.9 30-3410.4 35-3911.7 40-4410.9 Age Group New cases per 100,000 45-4911.4 50-5410.0 55-599.0 60-649.9 65-6911.1 70-7410.2 75-7911.8

41. From 18yo to 25yo (cont) Cervical screening for women 20-24 has had no effect on cancer incidence (10 cases per year) with 0-2 deaths per year over the same period Other countries do not screen under age 25 yet have the same incidence and mortality for cervical cancer Protective effect of vaccination will reduce the benefits of screening in this age group Unnecessary treatment of lesions that have a high chance of regression may impact on future pregnancies

42. What about the early starters? Even if HPV infection occurs, most clear the infection Even if HPV persists, most cervical changes, even HSIL, spontaneously regress So only a small percentage of HPV infection persists and only a small percentage of these persistent infections will have HSIL that progresses Progression of HSIL to cervical cancer averages 10 to 15 years High index of suspicion for referral for further investigation if persistent bleeding or discharge

43. What about the opportunistic screening? Many GPs use pap smears for opportunistic screening of other health disorders and health counselling Some use the speculum exam to also perform endocervical swabs for Chlamydia & Gonorrhoea Opportunistic screening has not been factored in to the new cervical screening program The screening interval is also designed to be ‘cost- effective’ with cost balanced with safety and effectiveness

44. What about the unvaccinated? Too confusing and costly to have one program for vaccinated and one program for unvaccinated Unvaccinated women will benefit from the lowering prevalence of high-risk HPV due to vaccination HPV testing also validated in an unvaccinated population

45. Extending up to 75yo The new cervical program targets women aged 25 to 69yo Then there is an ‘exit’ screen between age 69 and 75 There is still a significant incidence of cervical cancer after 70yo

46. Age-specific incidence rates of cervical cancer

47. Self-collection for HPV testing Patients aware of this method due to media coverage Self-collection is only intended for women who would otherwise not attend for screening Collection kit is sent to the woman who then performs a vaginal swab herself (not endocervical) – results still need to be followed up by GP practice Sensitivity as low as 60% Women who test positive will still need to attend for LBC triage (can’t avoid a speculum exam!)

48. mQlicker Question SESSION KEY: 30817 Q8: Now, my feelings about the new Cervical Screening Program are: 1. Angry/annoyed 2. Worried 3. Neutral 4. It’s time for a change; I appreciate the need for a change 5. Excited

49. (mQlicker answers)

50. mQlicker Question SESSION KEY: 68921 Q9: Now that I know about the changes to the Cervical Screening Program and the rationale behind it, I think: 1. We should stay with the current screening program 2. We should delay the release of the new program 3. We should change to the new program as announced 4. I still don’t know enough about the program to say either way 5. I don’t mind either way

51. (mQlicker answers)

52. CASE ONE It is January 2017 20yo woman Previously regular two-yearly pap smears – always normal Last pap smear was two years ago Asks what you recommend now that the screening age doesn’t start until 25yo

53. CASE ONE – mQlicker Question SESSION KEY: 59596 What screening would you recommend? 1. No screening required at present 2. Pap smear 3. Pap smear AND HPV testing 4. HPV testing 5. Colposcopy

54. (mQlicker answers)

55. CASE TWO It is January 2017 20yo woman Never had a pap smear before Asymptomatic Asks what you recommend now that the screening age won’t start until 25yo

56. CASE TWO – mQlicker Question SESSION KEY: 10886 What screening would you recommend? 1. No screening required at present 2. Pap smear 3. Pap smear AND HPV testing 4. HPV testing 5. Colposcopy

57. (mQlicker answers)

58. CASE THREE It is April 2017 19yo woman Persistent intermenstrual bleeding while on the COCP Never had a pap smear Asks what you recommend?

59. CASE THREE – mQlicker Question SESSION KEY: 26985 What screening would you recommend? 1. No screening required at present 2. Pap smear 3. Pap smear AND HPV testing 4. HPV testing 5. Colposcopy

60. (mQlicker answers)

61. CASE FOUR It is the present day (2015) 30yo woman Just had a pap smear and it was negative Asks when her next cervical screening will be..

62. CASE 4 – mQlicker Question SESSION KEY: 27279 What screening would you recommend for her next cervical screening test? 1. Pap smear in 2017 2. Pap smear AND HPV testing in 2017 3. HPV testing in 2017 4. HPV testing in 2020 (five years from now)

63. (mQlicker answers)

64. CASE FIVE It is August 2017 35yo woman Just had HPV testing and it was negative Married, monogamous relationship, “definitely no other partners involved” “HPV is negative – I don’t feel I ever need any other HPV testing”

65. CASE 5 – mQlicker Question SESSION KEY: 98739 What screening would you recommend? 1. Agree that no screening required again as long as no new partners 2. Pap smear two-yearly 3. Pap smear AND HPV testing (any interval) 4. Still need five-yearly HPV testing

66. (mQlicker answers)

67. CASE 6 It is August 2017 71yo woman Last had a pap smear 5 years ago – was told that she never needed another one again Asymptomatic Asks if she needs any cervical screening..

68. CASE 6 – mQlicker Question SESSION KEY: 34325 What screening would you recommend? 1. No screening required 2. Pap smear 3. Pap smear AND HPV testing 4. HPV testing 5. Colposcopy

69. (mQlicker answers)

70. What is being done in the UK Since Sept 2014, only 2 doses of HPV vaccine rather than 3 Since 2008, has been using LBC Since 2003, starting age for screening raised from 20 to 25yo Screening every 3 years from 25-49yo then every 5 years from 50-65yo – no further screening after 65yo Since 2014, if cytology is low-grade or borderline, then HPV triage is used – if HPV positive, then refer to colposcopy, if HPV negative, return to normal screening Currently investigating primary HPV screening

71. The future of cervical screening Incidence of high-grade HPV thus HSIL and cervical cancer predicted to fall due to HPV vaccination Will not be able to go back to cytology screening as there will be a lack of pathologists skilled in cytology HPV testing likely to include HPV genotyping to further refine management Prediction that in the far future, women may need only 2-3 screening tests in their lifetime! Prediction that my colposcope may sit idle in ten years time OR I will be the only expert in colposcopy..

72. Summary The new cervical screening is coming in May 2017 Do not delay pap smears in the meantime Will be a transition period where pap smears will still be able to be done until December 2017 Women of any age who have symptoms (abnormal bleeding, discharge) should be investigated HPV is central to cervical cancer – the natural history of HPV infection and cervical changes have greatly influenced the changes in the new screening program Pap smears will be a thing of the past – HPV testing is the future