Scottish HPV Investigators' Network (SHINe) - University of Edinburgh

SHINe
Scottish HPV Investigators’ Network (SHINe)
2nd Meeting
24 th November, 2009
Marriott hotel, Edinburgh
Present
Roma Armstrong [CSO]
Simon Beddows [HPA]
Camille Busby-Earle [NHS Lothian]
Christine Campbell [University of Edinburgh]
Seonaidh Cotton [HSRU Aberdeen]
Maggie Cruickshank [Aberdeen]
Heather Cubie – Chair [NHS Lothian/University of Edinburgh]
Kate Cuschieri [NHS Lothian]
Fergus Daly [University of Dundee]
Edward Duvall [University of Edinburgh/NHS Lothian]
Isabel Gavin [NSD]
Sheila Graham [University of Glasgow]
Sarah Howie [University of Edinburgh]
Paul McNamee [HERU Aberdeen]
Catherine Moore [NHS Lothian]
Johanna Pedraza [University of Edinburgh]
Chris Robertson [University of Strathclyde/HPS]
Katie Sinka [Health Protection Scotland]
Frank Sullivan [University of Dundee]
David Weller [University of Edinburgh/ NHS Lothian]
Alistair Williams [University of Edinburgh/ NHS Lothian]
Apologies
Sheila Nicoll [NHS Tayside]
David Harrison [[University of Edinburgh/ NHS Lothian]
Mike Winter [NSD]
HAC outlined the objectives for the day as follows:
• Updates on CSO programmes and funding
• Cohesion of Stakeholders’ group
• Greater understanding of all that is happening in Scotland round HPV
• Some understanding of projects elsewhere which link to SHINe
There was a slight rearrangement of the Programme and the meeting started with the
presentation from invited guest Dr Simon Beddows (Health Protection Agency)
Surveillance and HPV testing in England
SB informed the group of the work going on in England through auspices of HPA.. SB’s
presentation will be available on website. There is overlap with Scottish surveillance (e.g
routine LBC, cancer biopsies and urine testing) with different technology (Luminex) for
genotyping. There was good correlation with other assays for LBC and female urine, while
male urine had proved to be a poor bio-specimen in men. Work on viral load and on
methylation in different disease stages was on-going. KC asked if an English archive was being
established. SB replied that they worked in shared facilities with all samples coming from

surveillance not as clinical samples; experimental work was limited to samples with mono
infections (only 10%) hence HPA’s interest in Scottish archive
Updates on CSO Programmes
HAC reported on progress with the BTRC award in relation to facilities, staffing, samples in
archive, approvals and research. A copy of her presentation slides was circulated
MC updated on position with HSR project and introduced Seonaidh Cotton as Programme coordinator.
She commented that central to the HSR programme was the modelling of future
screening policy and CR explained the model of cost effectiveness which had been developed
with HPA and input from Dublin as a generic model of HPV transmission and vaccine impact,
regionalised according to screening policies. ED commented that cytology was not a stationary
target due to the feasibility studies of automated imaging. After vaccination the sensitivity of
cytology would plummet and the Imager system might help restore this but the timescale of
adoption is unknown. It was pointed out that the feasibility study was to study practicalities of
transporting samples to a few reference centres, not the value of automated reading. The
Scottish report and the HTA Mavaric study report will both become public in the first part of
2010.
MC reminded the group of the research projects in the programme and highlighted that the
REC approval was almost through for HPV genotyping of women aged 20-24 attending
colposcopy as result of abnormal smear. A student in Aberdeen would set up processes during
December with first women enrolled in Aberdeen in January 2010. These samples are an
important contribution to the archive as they will be fully genotyped.
Construction of the National Archive
KC outlined the intention for 50,000 samples or 25,000 with two aliquots and highlighted the
need to populate the archive sensibly rather than simply filling up the bank. Her calculations
showed that with LBC surveillance and HSR projects there would be around 13,800 samples
over 4 years of which 5,500 would have genotyping through surveillance. With two aliquots per
sample this would fill half the archive. If all LBC from 1 st attenders were collected each year
(c3000 pa) this would rise to 22,800. The storage of cell suspensions and NA extracts at -80 0 C
were both reasonable approaches and a small study of LBC samples collected in 2000 and
retested in 2008 gave 91% full or partial concordance for DNA.
CR gave some idea of the sample sizes relevant for adequate powering of research questions
and pointed out that small numbers will be required to show significant changes in HPV 16/18
prevalence due to impact of vaccine while showing changes in any other types will require
large numbers. Having an adequate baseline sample was crucial. SB commented that it
seemed inappropriate to have a large archive when many of the samples would be negative
and the collection should be enriched for positives by concentrating on patients with
recognisable disease. HAC commented that this would be dependent on clinical data available
after sample had been received. It was agreed that the sample collection was dynamic and the
need to cull on a regular basis should be built in to protocols. In the absence of better
information, it was agreed that 2 aliquots (cells and NA extract which could preserve RNA as
well as DNA) should be stored.
In relation to biopsy samples, it was suggested that the 500 collected every second year for
surveillance should be complemented by 500 non-surveillance samples in intervening years.
The two storage samples should be an additional section and NA extract. HAC suggested that
storing an additional section on a glass slide might be preferable to a section in an eppendorf
as it would allow microdissection and/or immunostaining.
In relation to consents, RA commented that use of national archives was an important part of
Better Cancer care and as this archive was at the pre-cancer end it should be considered
similarly to other cancer archives. There is considerable activity through Scottish Academic
Health Sciences Collaboration to have consent which completely covered use of ‘residual or

surplus’ diagnostic sample for research. In GGHB a new policy will apply to all tissues/ samples
including blood with information going to SCI store to be shared for research purposes. These
are dramatic changes and she agreed to pass on information. FS offered to send appropriate
wording from UK Biobank collection.
HPV Surveillance in Scotland
KS reported on the HPS strategy for surveillance starting with vaccine uptake data which
showed that school programme had reached over 90% in all age groups with out-of school less
than half of that. However it was noted that latter started later, had a large back-log of data
entry and had been more affected by H1N1. In schools uptake was over 80% across all
deprivation index quintiles and across the age range. She reported on the HPV positivity in all
surveillance arms with urine prevalence study in teenagers showing 25% positivity in 17-18
year old girls and 5% in males (c/f HPA results of 40% in urine in women and 10% in men
check)
KS also talked of approval for the linkage of CHI numbers to both CHSP-S vaccine data and in
time SCCRS cytology data. This approval was obtained not through PAC but through the CHI
Advisory group (Caldicott guardians plus others). No group would have all data on named
individuals. The link would be made once per year, probably in March with first linkage in March
2011 after a small number of the girls entering screening would have been vaccinated.
Current/Near Future of Cervical screening
Isabel Gavin provided an extremely useful insight into the position and potential changes to the
screening programme. She outlined the Test of Cure Early Implementers project using
‘PreQuot’ LBC sample and HPV testing at 6,12 and 24 months. NHS Highland had informally
agreed and NHS Lothian formally responded but as process was again to test transport this
would not happen by using Lothian! However it will also test the HPV Module of SCCRS which
is essential for future changes to the programme. This specification for the module has been
written and funding found for the software development which will take approx 6 months from
unknown starting point.
IG talked of activity in the Information Advisory Group following exploration of attitudes to low
uptake and the need to improve communication strategy in relation to screening. New leaflets
are in development and both SGPC and SHPVRL would be co-opted to comment before
publication. SG asked how the information will be linked to websites and comments were made
by several present that an easy source of information which is first hit on Google (Just as
www.fightcervicalcancer.org.uk was) is required.
Finally IG reported on the position with age of screening. When England increased the starting
age of programme from 20 to 25, Scotland’s NAG decided that no changes would be made in
Scotland until LBC evaluation, full SCCRS implementation and more evidence on value of HPV
testing had been published and agreed to review the situation in 2010 with decision within 1
year. The draft scope had already gone to NAG, noting that Peter Sasieni had said there was
insufficient evidence in England to lower starting age and no evidence in Scotland to increase
it! ED asked what other evidence was required not to consider HPV first instead of cytology. IG
replied that the draft scope did not contain any reference to this, nor to impact of HPV
vaccination on the decision, nor to awareness of impact of any age changes on the surveillance
strategy in place and the consequent programmes of research, also funded by Scottish
Government. The group was particularly concerned with this lack of joined-up thinking and it
was agreed that IG would feed back on all of these concerns.
HPV late mRNA expression
SG reported on the CSO project grant she had which was the first to use samples which could
be part of the archive. A pilot study of 8 HPV 16 LBC samples had suggested that late mRNA
expression was preferentially detected in low grade disease with E6/E7 oncogene expression
found at higher levels in high grade disease. Her group was extending this to 60 HPV16 mono-

infections in the hope of developing an L1/E6&7 dual test. She outlined plans for further
research projects involving samples from the archive including work on transcriptomics and
cellular profiling. SH suggested there was opportunity for collaboration in this area
Outcome and Actions
HAC posed a series of questions as a result of all the discussions
1. How best can we ensure ‘linkage’ to Scottish Government and Policy Makers It was
agreed that
a. IG would feed back concerns of SHINe member to NAG and suggest wider
consultation was required
b. MC would speak to National Colposcopy Group
c. ED would discuss with Sheila Nicoll as Chair of Lab QA group
d. KS would contact Andrew Riley at SG in relation to HPS interaction with NAG
and to Tracy McKen re interaction with SCSP
2. Have any research ideas/projects arisen as a consequence of recent or the day’s
discussions The following were identified
a. SG and SH to discuss collaboration over cellular responses to HPV infection
b. SH to report back on outcome of MRC Chlamydia network funding application
( due next week) as this could lead to further opportunities and research
questions
c. MC asked which test should be considered for screening in the HSR projects.
HAC suggested that a comparison already done of Abbott rt PCR which
detects HPV 16,18 and ’X’ separately suggests it could be valuable for this
and TOC but there was a slight resource issue
d. CC suggested that if successful wit the Wellbeing of Women application (due
February) it would be good to extend qualitative ideas to collaborations in
England and Wales
3. What difficulties might there be in asking Cytology Laboratories to send more residual
LBC samples from 1 st attenders in 2010 compared with 2009
a. ED to discuss with Sheila Nicoll and Lab QA Group what the impact would be,
what resource might be needed
b. KS suggested that HPS could work out how many samples this might be from
each lab over the year and make suggestions on what documentation could be
reduced for archive samples compared with surveillance. HAC suggested
SCCRS number and CHI were only things needed
c. IG suggested a corporate report could be produced from SCCRS to give lists
to labs
4. What would researchers like the archive to hold/produce as far as they know at this
time
a. SG would like access to residual LBC as cytospins. HAC considered this
would be possible
b. SH would be keen for blood samples (stored as sera) for future micro array
work
Next Meetings
The spring 2010 meeting will be held in Aberdeen (to be organised by MC and SC)
Autumn 2010 will be a Research Day in Edinburgh
Spring 2011 meeting potentially in Dundee