Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02622997 |
| Other study ID # |
10575 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
July 2015 |
| Est. completion date |
December 2015 |
Study information
| Verified date |
January 2016 |
| Source |
Queen Mary University of London |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
60 women from the Colposcopy Clinic at the Royal London Hospital will be recruited, having
been referred following an abnormal cervical screening result.
Aim Human Papillomavirus (HPV) is very common and can cause cervical cancer in some women.
There is interest in HPV testing in place of the smear test currently used for cervical
screening. HPV testing has potential for women to take self-samples.
These self-samples have up to now mostly been placed into liquid to preserve them before
testing. Using liquid however, makes it more difficult to collect samples at home due to
spillage and the logistics of posting. Investigators plan to investigate whether dry samples
are reliable. Investigators would also like to know if samples can still be used if not
tested immediately, particularly in warm temperatures. This would prove useful in the
countries that have found it difficult to set up national cervical screening programmes.
Trial Design Investigators are asking women to take three vaginal self-samples before
patients' colposcopy examination. The samples will be two swabs and a third using the HerSwab
device, designed to make taking a sample easier. Investigators will give women instruction
sheets with illustrations. Samples, taken in a random order so that all samples have an equal
chance, will be sent to the laboratory for testing but under different conditions. Samples
will be either frozen immediately, stored at 25ºC for one week or two weeks and then frozen.
All samples will then undergo HPV testing. Investigators wish to see if all conditions and
swabs provide similar amounts of HPV.
Enrolment is planned to start in May 2015. Sample processing and testing will continue until
enrolment is complete and for a further month. Smear and biopsy results will be collected for
up to 6 months to see if they affect quantities of HPV.
Description:
Background Cervical cancer is caused by persistent infection with high risk human
papillomavirus types (Hr-HPV) but can be prevented if detected at an early stage. Prevention
through routine cervical screening is traditionally done with liquid-based cytology sampling
where the cells collected by clinicians are examined to identify abnormal features. Another
method is HPV testing performed on the same liquid-based samples as for cytology. HPV DNA
testing is more sensitive, but less specific, than cytology for cervical screening and both
tests are broadly acceptable to women (Forrest, McCaffery et al. 2004; Waller, McCaffery et
al. 2006; Szarewski, Cadman et al. 2009). Although clinician-taken samples are the gold
standard, self-sampling may be a useful alternative. HPV DNA testing using self-collected
(SC) samples has been shown to have acceptable sensitivity and specificity for HPV testing
compared to samples taken by clinicians (Petignat, Faltin et al. 2007; Szarewski, Cadman et
al. 2007; Arbyn, Verdoodt et al. 2014). A high level of concordance between self and
clinician sample for HPV DNA detection of 0.87 (95% Confidence Intervals (CI), 0.82-0.91) was
shown in Petignat's systematic review and meta-analysis (Petignat, Faltin et al. 2007). HPV
DNA testing is well established but newer HPV testing technologies are available and
emerging.
HPV DNA testing has most commonly been performed on cervical samples collected in a liquid
medium (generally Specimen Transport Medium (STM) or PreservCyt). However, this is not ideal
for home SC samples because there are often restrictions on postage of biological samples in
liquid, risks (although low) pertaining to the transport medium itself and issues around
refrigeration of the liquid. The removal of the necessity for a liquid transport medium (and
especially any subsequent refrigeration) would greatly improve the accessibility of SC
sampling and reduce costs. This would also increase the potential for cervical screening in
those areas where there may be logistical difficulties such as lack of regular, frequent
postal collections or refrigerated storage facilities.
There have been several studies which have investigated dry sample collection for HPV DNA
detection (Shah, Daniel et al. 2001; Krech, Castriciano et al. 2009; Feng, Cherne et al.
2010; Cerigo, Coutlee et al. 2012; Darlin, Borgfeldt et al. 2013; Eperon, Vassilakos et al.
2013). However, the differing methodologies and requirements for refrigeration have
restricted the generalisability of the results. They have also not addressed the question of
how long the sample on the dry collection device would remain viable, especially under higher
temperatures.
Rationale and Risks/Benefits Evidence increasingly suggests that, at least in temperate
climates, HPV DNA testing from a SC sample using a dry swab provides similar sensitivity to a
wet swab (where the SC sample is placed in liquid specimen transport medium) (Wolfrum,
Koutsky et al. 2012). Dry transport could make HPV DNA testing from SC samples more
accessible and widely available. In the UK for example, postal packaging is simplified when
no liquid is involved. HPV primary screening is being explored in clinical trials and even
being introduced into some screening programmes. In the Netherlands for example SC HPV DNA
testing within the primary screening programme is planned for introduction for non-attenders
in 2016 (Rijksinstituut voor Volksgezondheid en Milieu 2014).
The rationale of this stability study is to ascertain whether SC samples kept under dry
conditions will still be useful if left for a period of time in warm conditions. This would
be of particular use in the many low and middle income countries where cervical cancer
incidence and mortality are highest. These countries have frequently found it very difficult
to set up national cervical screening programmes due to lack of infrastructure, access to
efficient refrigeration and a postal service.
Bart's Health National Health Service (NHS) Trust serves a diverse population from a range of
socio-economic and ethnic backgrounds in inner London. The colposcopy clinic (which was at
Bart's Hospital but relocates to Royal London Hospital in spring 2015) has approximately 1050
new women attending and 1900 women attending for follow-up per year. The participation in
this project will have no implications for the ongoing care of any woman who agrees to
participate. In previous studies and in other United Kingdom (UK) based screening programmes
in the UK, such as for Chlamydia trachomatis, the use of swabs by women themselves has been
shown to be achievable and safe.
Histology and cytology results from within three months prior to the visit and up to six
months post-visit will be collected. There may be a difference in results depending on the
grade of disease and this will be confirmed or excluded with this information.
Trial design This study is a small preparatory project aiming to enrol 60 women from a
colposcopy service and comparing their SC samples taken with two dry flocked swabs and the CE
marked device HerSwabTM (Eve Medical, Toronto, Canada). Each woman will take all three
samples. The swabs will all be refrigerated immediately and then will be either frozen
immediately at -20ºC (SR0) to preserve the sample or incubated at 25ºC for either one (SA1)
or two weeks (SA2). HerSwab samples will be included in the incubation part of the study (HA1
and HA2). The order of sampling will be randomised to remove any bias associated with testing
order and roughly equal numbers of first, second and third swabs will be allocated to each
swab management regimen. The study will precede and inform a multi-phase study with the
overall aim of comparing SC HPV testing using different devices, under different conditions
and using different HPV testing assays.
Feasibility In the period 1st January 2013 to 31st December 2013, 1052 new patients attended
the Bart's colposcopy unit. In the same time period 1930 attended for follow up colposcopy or
treatment, This would mean that over a 12 month period 2982 women attended colposcopy. There
are therefore sufficient numbers of women who can potentially be recruited to the study. The
service will still receive these referrals when it relocates to the Royal London Hospital.
Randomisation Procedures Randomisations will be carried out using an in-house computer
application. The Centre for Cancer Prevention will generate a randomised list linking
participant numbers (PNOs) with a pack number and a code identifying the order of sampling.
The order will be randomised 1:1:1 to dry flocked swab (for freezing on arrival in the
laboratory) (SR0), dry flocked swab (for incubation at 25ºC for one (SA1) or two weeks (SA2)
on arrival in the laboratory), or HerSwab (for incubation at 25ºC for one (HA1) or two weeks
(HA2) on arrival in the laboratory) (please refer to Study Scheme Diagram). PNOs will be
assigned to numbered packs containing three self-sample kits, labelled to show the order in
which the samples should be taken. 60 women consenting to take part will be given the next
pack in sequential order as far as possible as they attend the clinic and consent to the
study. All samples will be immediately refrigerated at 2-8ºC in clinic until transfer to the
laboratory.
Schedule of intervention for each visit Assessment Visit 1 Three self-samples taken x
Study devices Women will be asked to self-collect three vaginal samples using two dry flocked
swabs and the CE marked device HerSwabTM (Eve Medical, Toronto, Canada). HerSwab utilises a
flocked swab contained within a plastic applicator, with the intention of making
self-sampling easier for women.
Procedure for Collecting Data Cervical or vaginal cytology and histology data will be
collected from the referral cytology result, which led to their attending the colposcopy
service, up to six months post appointment date. All study data entry and management will be
undertaken at the Centre for Cancer Prevention.
All HPV, cytology and histology results will be entered onto, or imported into, the study's
ORACLE database by the Centre for Cancer Prevention (CCP) study team. All databases are
protected and only accessible to named staff.
Consent forms will be securely stored at CCP.
Laboratory Assessments Extraction and detection of Human DNA by a quantitative polymerase
chain reaction (qPCR) assay from all samples.
Extraction and detection of HPV DNA (primarily HPV 16) by a qPCR assay from all samples.
Validated HPV test from all samples yielding CT or RLU values.
End of Study Definition The end of study would be defined as when the final histology and
cytology data were collected for the last participant recruited. This would be approximately
eight months after the date of visit of the last recruit. Eight months would allow time for
the data to be entered onto the hospital database.
