1. Are you prepared for the NEW Cervical Screening Program?
Dr Shian Miller
Obstetrician & Gynaecologist
BSc (Hon), MBBS, FRANZCOG

2. Overview Background: The NEW Cervical Screening Program
History of Cervical Screening
Cervical Screening in Australia
Cervical cancer in Australia
HPV and cervical cancer
HPV vaccination
The NEW Cervical Screening Program
Background
Implementation
Your Questions Answered
But why change?
Why HPV?
Why every 5 years?
Why start at 25 years of age?
Why up to 75 years old?
What is currently done in the UK
Summary
The future of Cervical Screening
Conclusion

3. Background
The Cervical Screening Program

4. The History of Cervical Screening
George Papanicolaou ( )
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 hence ‘Pap’ smear
Romanian scientist Aurel Babes independently made similar discoveries in 1927 but used a different collection method

5. Cervical screening in Australia
Since 1960s, Australia has been doing pap smears
Ad hoc, opportunistic screening
National Cervical Screening Program began in 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

6. Cervical cancer in Australia
14th most common cancer diagnosed in females
Approx 800 new cases of cervical cancer diagnosed per year in Australia
Approx 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’
Since introduction of Cervical Screening Program, significant reduction in cervical cancer incidence and mortality

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

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

9. 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

10. HPV vaccine National HPV Vaccination Program started 2007
Vaccination of 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

11. The NEW Cervical Screening Program

12. 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: g.nsf/Content/1276-public
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

13. The New Screening Program (cont)
The Cancer Council Australia has finalised the clinical management guidelines – but still need endorsement from RACGP, RANZCOG, RCPA and societies, ASCCP and ASGO
Medicare Benefits Schedule Items: working to finalise the item descriptors and fees to support the renewal
Early reports that HPV testing will be covered by MBS (as long as it is within the guidelines eg. done no less than 4.5 years apart)
Pap smears will still be covered by MBS until at least September 2017

14. The New Screening Program (cont.)
Working on:
Supporting workforce and practice change
Resource development for both health care professionals and consumers
Drafting standards for pathology tests
Legislation: The National Cancer Screening Register Bill 2016 and the National Cancer Screening Register (Consequential and Transitional Provisions) Bill 2016 (the Bills) have been included in the new Parliament’s Spring 2016 legislation program
Cancer Council Australia have been contracted to develop the Engaging with under-screened and never-screened women in the National Cervical Screening Program Toolkit for health care professionals
The Quality Framework for the NCSP (protocols for monitoring the safety of the new program) is almost finalised and is likely to be available in February 2017

15. The New Screening Program (cont)
National Cancer Screening Register
Tender awarded to Telstra Health
Also managing the National Bowel Cancer Screening Program
Currently, cervical screening registers are State and Territory based
The National Cancer Screening Register will ‘support’ the current registers ‘at the discretion of individual State & Territory registers’
Will be ready by May 2017 ‘subject to state and territory agreement to migrate data’ and ‘the passage of the National Cancer Screening Register legislation’

16. Old versus new Old NCSP New cervical screening program
Pap smear performed for screening
(speculum exam & endocervical swab)
With glass slide +/- ThinPrep/Surepath
HPV test performed for screening
With ThinPrep/Surepath
Pap every TWO years
HPV test every FIVE years
Age 18-70
Age 25-75
Abnormal pap: refer to colposcopy
HPV 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

17. HPV testing Speculum & endocervical sample with broom
Sample into liquid-based cytology medium
At the Path lab, the sample is processed through a machine – results will be POSITIVE or NEGATIVE
Will also do partial genotyping for HPV 16/18 – if present, refer to colposcopy even if cytology negative
If NEGATIVE, next screen in FIVE years
If POSITIVE, reflex cytology…

18. 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
The initial cytology will be done by a machine – results will be verified by a cytologist ?only if positive ?only if negative
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

19. 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!)

20. Your Questions Answered
The rationale behind the change

21. 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

22. 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

23. 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

24. 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

25. Age-specific incidence rates of cervical cancer

26. From 18yo to 25yo (cont)
Cervical screening for women 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

27. 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

28. 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

29. 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

30. 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

31. Summary

32. 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..

33. Conclusion
The new cervical screening is coming in May 2017 – HPV test every FIVE years for age >25
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