Role and Outputs of the Scottish HPV Reference Laboratory

Transcription

1 Role and Outputs of the Scottish HPV Reference Laboratory Kate Cuschieri Scottish HPV Reference Laboratory PRESENTED AT - SCOTTISH ASSOCIATION OF HISTOTECHNOLOGY 37 th SCIENTIFIC MEETING May

2 SHPVRL - How and who.. Established in Built on expertise that had developed in NHS Lothian Team of 3 (2.2 wte) The 13 th Reference Lab.. Close affiliation with HPV Research Group at Uni of Edinburgh Significant Catalyst Immunisation; Scottish Bacterial STI Reference Lab Scottish E coli Reference Lab Scottish HPV Reference Lab Scottish Mycobacteria Reference Lab Scottish Haemophilus, legionella, meningococcus and pneumococcus Reference Lab Scottish MRSA Reference Lab Scottish Parasite Diagnostic and Reference Lab Scottish Cryptosporidium Reference Service Scottish Salmonella, Shigella and Clostridium difficile Reference Lab Scottish Trace Element and Micronutrient Reference Lab West of Scotland Specialist Virology Laboratory/GGC Specialist Virology Centre/Lothian Scottish Toxoplasma Refrence Lab and National Lyme Borreliosis Testing Lab Scottish Reference Laboratory Details NHS Lothian NHS Greater Glasgow and Clyde BBV GGC/Lothian NHS Highland SBSTIRL SERL SHPVRL SMRL SHLMPRL SMRSARL SPDRL SPDRL SSSCdRL STEMRL BBV Glasgow BBV Edinburgh Toxo lab

3 Functions of SHPVRL 1. HPV testing for Epidemiology and Surveillance for the HPV immunisation programme 2. HPV screening / genotyping in individual clinical cases where knowledge of HPV status will inform clinical management 3. Provision of quality assurance and assessment materials for UK-wide HPV testing laboratories and beyond 4. Commitment to a research and development programme Teaching and training of medical, scientific and technical staff 5. Advice and support relating to HPV testing for the Scottish Cervical Screening Programme 6. Consolidation of HPV sample archives to facilitate research, quality assurance, test development, audit and teaching.

4 Scottish HPV immunisation programme and associated surveillance HPV immunisation initiated in September schools based programme year olds girls = routine/ target cohort Three year Catch-up ran for girls 18 years Bivalent vaccine until September 2012, changed to quadrivalent Three dose schedule- changed to two dose in 2014 Partner programme of longitudinal surveillance to determine impact

5 Scottish HPV immunisation surveillance Programme includes Baseline assessments (pre-immunised population) 1,2,3 Monitoring impact of immunisation on disease outcomes over time (histological 4, cytological 5, colposcopic 6 ) Monitoring impact of immunisation on HPV infection In women attending for first smear (yearly) residual LBC 7 In women diagnosed with CIN2/3 -residual biopsy Assessment of < 3 doses of vaccine 1: O'Leary MC, Sinka K, Robertson C, Cuschieri K, Lyman R, Lacey M, Potts A, Cubie HA, Donaghy M. HPV type-specific prevalence using a urine assay in unvaccinated male and female 11- to 18-year olds in Scotland. Br J Cancer Mar 29;104(7): :Cuschieri K, Brewster DH, Williams AR, Millan D, Murray G, Nicoll S, Imrie J, Hardie A, Graham C, Cubie HA. Distribution of HPV types associated with cervical cancers in Scotland and implications for the impact of HPV vaccines. Br J Cancer.2010 Mar 2;102(5): : Kavanagh K, Sinka K, Cuschieri K, Love J, Potts A, Pollock KG, Cubie H, Donaghy M, Robertson C. Estimation of HPV prevalence in young women in Scotland; monitoring of future vaccine impact. BMC Infect Dis Nov 5;13:519. 4: Pollock KG, Kavanagh K, Potts A, Love J, Cuschieri K, Cubie H, Robertson C, Cruickshank M, Palmer TJ, Nicoll S, Donaghy M. Reduction of low- and high-grade cervical abnormalities associated with high uptake of the HPV bivalent vaccine in Scotland. Br J Cancer Oct 28;111(9): : Palmer, T. J., Robertson, C., Cuschieri, K., Nicoll, S. & Pollock, K. G. J. Effect of HR-HPV immunisation on the performance of cervical cytology, presented at EUROGIN 2015 OC12, p206 6: Cruickshank M et al Implications of HPV immunisation on colposcopy services and practice IPV Fri 18/09/15 and Sun 20/09/15 7: Kavanagh K, Pollock KG, Potts A, Love J, Cuschieri K, Cubie H, Robertson C, Donaghy M. Introduction and sustained high coverage of the HPV bivalent vaccine leads to a reduction in prevalence of HPV 16/18 and closely related HPV types. Br J Cancer May 27;110(11):

6 Pilot study with the Sandyford Initiative in Glasgow Assess the suitability of urine as a bio-specimen for HPV surveillance Group of young males and females <25 attending drop in services Allowed sensitivity and specificity calculations of urine vs gold standard. Swab - Female Urine testing as a surveillance tool to monitor the impact of HPV surveillance programmes. Cuschieri K(1), Nandwani R, McGough P, Cook F, Hogg L, Robertson C, Cubie H. J Med Virol Nov;83(11): X Urine - Female X

7 The aim is to get a true picture of how many young people in Scotland have human papilloma virus YES? NO? Don t know 2447 urine s What should you bring back? Discuss with your parents (if you re under 16) Return tomorrow at 8:15 to the Medical Suite with the following data form urine sample pot your consent form parent consent form Assess HPV prevalence in year olds, Information leaflet School presentations -

8 Results National HPV Prevalence Study (young males and females) Females Aged HPV prevalence was 1.1% overall; 0.9% for HR-HPV Aged HPV prevalence was 15.2% overall; 12.6% for HR-HPV Males Aged years HPV prevalence was 1.4% overall; 1.0% for HR-HPV Aged years HPV prevalence was 3.9% overall; 2.4% for HR-HPV O'Leary MC, et al Br J Cancer Mar 29;104(7):1221-6

9 Vaccine uptake is high in Scotland Health/publications/data-tables.asp?id=1300#1300

10 As a consequence of vaccination, do we see changes in HPV infection in women attending for first smear? HPV infection in CIN2+? Overall rates of CIN? Less than 3 doses of vaccine?

11 Percentage of women positive for any HPV Significant reduction of HPV 16,18,31,33 and 45 In vaccinated women attending for first smear Unvaccinated (0 dose) Vaccinated (3 doses) Kavanagh et al BJC 2014 HPV type

12 Proportion positive HPV positivity by type and vaccine status in those with CIN2+ (data aggregated from 2011 & 13) HPV positivity by type and vaccine status in those CIN2+ Unknown 0 doses 3 doses Significant decrease in HPV 16 disease is associated with vaccination HPV type

13 .and a reduction in lesions With 3 doses - significant reduction in diagnoses of: CIN 1 (RR 0.71, 95% CI 0.58 to 0.87, p=0.0008) CIN 2 (RR 0.5, 95% CI 0.4, 0.63, p<0.0001) and CIN 3 (RR 0.45, 95% CI 0.35 to 0.58, p< ) for women who received 3 doses of vaccine compared with unvaccinated women adjusting for deprivation and age women received vaccine Pollock et al BJC 2014

14 Even one dose of vaccine is associated with a reduction in HPV 16/18 prevalence Unadjusted P value Adjusted P value No. of VE VE: Doses [%, (95 CI s)] [%, (95 CI s)] HPV 16/ (-5.7,48.0) (16.8,68.9) < (15.3, 52.3) 54.8 (30.7, 70.8) < < (65.0, 74.7) 72.8 (63.8, 80.3) HPV Table 2: Prevalence (unadjusted) of vaccine and cross-reactive HPV types according to number of vaccine doses 31/33/ (-74.6, 25.9) (-85.1, 45.3) (12.1, 62.8) (7.6, 71.8) < < (45.1, 64.1) 55.2 (32.6, 70.2) Cuschieri et al BJC 2016

15 Functions of SHPVRL 1. HPV testing for Epidemiology and Surveillance for the HPV immunisation programme 2. HPV screening / genotyping in individual clinical cases where knowledge of HPV status will inform clinical management 3. Provision of quality assurance and assessment materials for UK-wide HPV testing laboratories and beyond 4. Commitment to a research and development programme Teaching and training of medical, scientific and technical staff 5. Advice and support relating to HPV testing for the Scottish Cervical Screening Programme 6. Consolidation of HPV sample archives to facilitate research, quality assurance, test development, audit and teaching.

16 HPV and cervical cancer Establishing a viral aetiology to cervical cancer has led to 1) cervical disease prevention (vaccination) 2) management beyond traditional cytology screening (HPV testing)

17 HPV (direct) tests in current use for cervical disease management Often: Molecular, frequently based on amplification of HPV sequences Broad spectrum/consensus tests, detect a pool of HR HPV types in aggregate* Consensus tests with limited genotyping Examples: Hybrid Capture 2 (Qiagen), COBAS 4800 HPV test (Roche), RealTime High Risk HPV test (Abbott), Cervista HPV HR Test Assay & the Aptima HPV Test (Hologic). More than 200 others! Very sensitive for detecting disease have a high negative predictive value *Detect a common pool of types: 16,18,31,33,35,39,45,51,52,56,58,59,68,66.

18 However - HPV is a common virus that often clears Clinical sensitivity of HPV tests often exceeds their clinical specificity i.e. All individuals that have disease that will test HPV positive but not all individuals who are HPV positive will have significant disease Negative predictive value of HPV tests is higher than their positive predictive value i.e. individuals who test HPV negative are unlikely to have the disease but individuals who test HPV positive may not have the disease

19 HPV is common in Scotland 18% HR- HPV in women aged attending for ~280,000 infections routine in screen age cervical women in Scotland. screening

20 What are the indications for HPV testing for the management of cervical disease? Context is key! A As a primary screen With cytology as a triage. Ie START with the more sensitive test and follow-up with a more specific one. B As a triage to refer women with low-grade abnormalities to colposcopy for visual examination of the cervix (and biopsy if indicated). C As a test of cure of treatment of high grade abnormalities To indicate treatment success*

21 Advice and support relating to HPV testing for the Scottish Cervical Screening Programme HPV testing as a Test of Cure of Treatment Major work stream, HPV testing in women treated for cervical lesions as a test of cure. First time HPV testing fully integrated into the Scottish Cervical Screening programme Input into Test of Cure Working Group Design and user acceptance testing of Virology module for IT system (SCCRs) 2010 Since early implementation received 20,000 + Pilot Implementation; Highland, Grampian Lothian Research to investigate/inform optimal test choice for test of cure* 2011 National Roll out 2012 *Cubie HA, Canham M, Moore C, Pedraza J, Graham C, Cuschieri K. Evaluation of commercial HPV assays in the context of posttreatment follow-up: Scottish Test of Cure Study (STOCS-H). J Clin Pathol. 2014

22 Advice and support relating to HPV testing for the Scottish Cervical Screening Programme (2) Further Research to refine and develop Test of Cure processes MAGS* Project: Gathering evidence base to determine whether patients treated with Micro-invasive cancer or Glandular lesions may benefit from HPV-Test of Cure. SHPVRL represented within HPV Reference Group**, Scottish Cytology Steering Group. Primary Screening with HPV a priority issue. Support in the cascade of training, best practice and quality assurance for increased volume of HPV Testing *Microinvasive Glandular and SMILE **Set up to consider the case for HPV Primary Screening

23 - Key phrase: UK Cervical Cancer Screeing Programme should adopt the test for HPV as a primary screening test

24 HPV screening / genotyping in individual clinical cases where knowledge of HPV status will inform clinical management Gynae Non Gyane Year 62 in total In Service Level Agreement originally funded to perform 200 tests per year.

25 HPV screening / genotyping in individual clinical cases where knowledge of HPV status will inform clinical management In Service Level Agreement originally funded to perform 200 tests per year.

26 HPV Testing of Oropharyngeal Cancers can provide insight into prognosis SHPVRL now have core funding to test Oropharyngeal Cancers from Scottish Health Boards since April 2014

27 Research and Development (1) Development and optimisation of new generation of HPV assays through collaboration with basic researchers and industry. Sheila Graham (cellular and viral mrna) Sarah Howie & Juergen Haas (immunological biomarkers ) Mark Bradley (Bio-compatible Polymers) Thomas Wilhem/A Lorincz (Cellular & viral methylation targets) Cepheid, Becton Dickinson, GeneFirst (new generations of HPV tests)

28 Research and Development (2) To inform the development of cervical screening & disease management including in immunised women Partners in Health Services Research programme CI M Cruickshank SHIFT Performance of HPV primary screening in Scottish (young) women attending for screening COHGS Performance of colposcopy in immunised vs non immunised women VALGENT project Assessment and validation of new HPV assays which include a genotyping element SHEVa Performance of HPV testing in immunised populations

29 Research and Development (3) Life beyond the cervix. Further insight into HPV associations and impact in the development of non cervical ano-genital cancers (K Wakeham) AND Head and neck cancers (in addition to oropharynx) hypopharynx, nasopharyx (Ioanna Nixon, Simon Talbot) HOPSCOTCH HPV Oral prevalence study CSO funded feasibility study just completed in dental practices (CI David Conway)

30 Scottish HPV Archive Started in 2009 Archive of cervical samples from women in Scotland Associated data linkage capabilities Can be used for HPV related research Over 27,000 and counting. Multiple aliquots each INTERESTED IN USING THE ARCHIVE? Get in touch Dr Ramya Bhatia - archive manager

31 The Scottish HPV Investigators Network (SHINe, est 2008) Purpose The purpose of SHINe is to act as a multi-disciplinary forum for discussion on HPV and HPV-related diseases, identify emerging research and clinical questions, and implement a series of research programmes/projects relevant to HPV disease prevention and management in the future. The group benefits from the combined expertise of representatives from cervical screening (Primary Care and Cytology), disease management/treatment (Pathology, Gynaecology and Colposcopy) and internationally recognised basic scientists. In addition, representation from the Scottish HPV Reference Laboratory (SHPVRL) and the team at Health Protection Scotland responsible for National Immunisation and surveillance make SHINe a truly relevant and integrated collaboration. Funding has already been obtained from the Chief Scientist Office of the Scottish Government Health Department with two concurrent programme grants, one of which has ensured the development of a National HPV sample archive.

32 Thanks to HPV Surveillance Team at HPS All members of SHPVRL and HPV Research Group All Scottish Pathology Laboratories SHINe