1. The Future Control of Cervical Cancer Hazel Lewis Public Health Physician Wellington Cartwright Forum, 7 August 2015

2. NCSP-R centralised 19651990 2000 1988 Cartwright Report NCSP established In 14 AHB 1996 NSU Gisborne Inquiry (CSI) McGoogan review 2001 2004 CCA Legislation amended NCSP-R outsourced 1999 Guidelines 2008 Guidelines incorporating HPV testing, LBC conversion 2008 History of cervical screening in New Zealand 2011 1 st Parliam Review Screening Trials In Thames, Wanganui, Otago, Waikato 2 nd Parliam Review 2015 Policies, stds reviews NCSP research: HPV prevalence, modelling primary HPV, Compass study Lab automation Monitoring indicators reviewed and implemented 146 recs implemented Audits Cancer case audits

3. Global Cervical Cancer Incidence, 2012

4. Global Cervical Cancer Mortality, 2012

5. Cervical cancer incidence trends (ASR (W) per 100,000) Globocan, 2012

6. The next 10 years: Dual Prevention We now have two powerful technologies to dramatically reduce cervical cancer incidence: - Screening for HPV infection - Immunisation against HPV Success will depend on using both technologies together to achieve effective coverage in all groups This will require better technologies, better guidelines, better information systems and better partnerships with all communities -

7. Dual preven tion has its pitfalls In principle, dual prevention should increase effective coverage and reduce gaps Two concerns: - Perception of protection - Impact on cytology screening laboratories Response: - Education - Change screening test from cytology to HPV

8. Challenges to implementing dual prevention Increase cervical screening coverage Co-ordinate components of the screening programme, close gaps ( Who will do what? How much will communities be involved?) Improve quality of the screening programme Increase HPV vaccination coverage (2 doses?) Reduce inequalities between socio-economic and ethnic groups Minimise cost barriers – ‘free’ in primary care Improve co-ordination between screening and immunisation programmes Media involvement (change behaviours, minimise risks) Programmes must be: easily affordable, effective, equitable

9. Screening for HPV infection Cervical cancer is caused by infection with specific “high- risk” types of HPV (hrHPV) 15 hrHPV types identified in cervical cancers (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, 82) Infection is common – only a few of infected women will develop cancer. Persistent infection (>2 years) more likely to lead to cervical cancer Cancer slowly develops over a period of years from precursor lesions – CIN, making screening possible hrHPV testing has been shown to provide a much better protection against CIN3 and cervical cancer than cytology

10. Natural history of HPV infection Schiffman M, Castle P. N Engl J Med 2005, 353:2101-2104

11. Primary HPV screening Screening tests (cervical Pap smear, HPV) identify an existing pre-invasive cervical lesion Pap smear (ie cytology) has been the mainstay of cervical screening for past 60 years However, increased awareness of limitations of cytology: - Interpretation subjective, potential sources of error (lesion not sampled, abnormal cells may not be transferred, preservation of cells may be inadequate, may be reading errors) - Single Pap low sensitivity (44-65%) - Poor in preventing adenocarcinoma - Poor PPV – unnecessary colposcopy - Requires at least 3 yearly repeats Effects of new HPV vaccines Key clinical question that has informed change is the reduction in the burden of CIN3 and cervical cancer incidence and mortality by the combination of hrHPV testing and cytology (60- 70% greater efficacy than cytology alone)

12. Primary HPV screening continued - Impact on inequalities, as can self test with HPV - Extending the screening interval from 3 to 5 years - Education - Effects on laboratories - Transition phase, for safety reasons, given NZ cervical screening, should be considered

13. HPV tests Two types: - those that report pooled hrHPV types - those that report the presence of HPV 16 and 18 HPV can be detected via DNA testing, RNA testing and testing of cellular markers of HPV Specimens can be obtained using a swab, broom, brush or tampon which is then placed in a transport medium Over 100 tests available worldwide but not comparable A test can be falsely negative – important to standardise the quality of test used

14. New clinical guidelines for cervical screening Key clinical questions must inform change: What are the benefits and potential harms of HPV screening with cytology triage? What are the benefits and harms of starting screening at 20, 25 or 30 years and when to stop? What is the best screening interval? Accuracy of self collected specimens?

15. Immunisation against HPV  Introduced on 1 September 2008  Provided for year 8 (11-12 year old girls)  Programme targeted and tailored implementation to achieve equity  Mixed school based and primary care delivery  Vaccine uptake higher when evidence of integration and information sharing across components of the Programme (community engagement, primary care and school based delivery systems)  Improvements should address misinformation about HPV vaccine, integration of delivery systems, possible health equity mechanisms (role of and levers available to primary health organisations locally)

16. HPV vaccine – current issues Full HPV vaccine coverage (3 doses) well below target Coverage falls after 1 st dose Girls only, offered free vaccine Impact on current cytology based screening (high grade lesions) Absence of data linkage - Immunisation Register with NCSP Register, therefore unable to monitor effectively HPV immunised women may not be screened, and will be at risk for cervical cancer Key health education messages (HPV vaccine and screening) should be part of ongoing communication strategy

17. Future developments in HPV immunisation Nonavalent vaccines (CE studies) FDA approved Gardasil 9, Dec 2014 with HPV types 6/11/16/18/31/33/45/52/58 Two dose regimens should be explored Better integration of HPV vaccine with screening - Information systems (data linkage) - Education - Workforce Greater involvement / empowerment of communities

18. Summary: Future Control of Cervical Cancer Dual prevention Better technologies - Screening test (hrHPV) - Vaccine (nonavalent) Better implementation - New clinical guidelines - ‘New’ register for cervical screening (Integrated Data Infrastructure) - Data linkage of two registers (NCSP-R and NIR within IDI) - Community Partnerships Timely analysis and publication