Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000714684
Ethics application status
Approved
Date submitted
24/06/2014
Date registered
7/07/2014
Date last updated
6/05/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
The use of primary Human Papillomavirus (HPV) testing for cervical screening in New Zealand
(A service evaluation project)
Scientific title
A service evaluation project for a trial in Human Papillomavirus (HPV) vaccinated and unvaccinated women presenting for cervical screening of 3 to 5 years HPV screening versus 3-yearly cytology screening to assess feasibility via participant acceptability, promote GP and Nurse and colposcopist education, and facilitate laboratory implementation
Secondary ID [1] 284845 0
Nil
Universal Trial Number (UTN)
Trial acronym
Compass study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cervical cancer 292237 0
Human Papillomavirus (HPV) 292238 0
Condition category
Condition code
Cancer 292574 292574 0 0
Cervical (cervix)
Infection 292697 292697 0 0
Sexually transmitted infections
Public Health 292698 292698 0 0
Health promotion/education

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention (Arm 2): The HPV test will be the primary test performed on a cervical smear sample that is taken in the usual manner and stored in the Thin-Prep liquid-based storage fluid. If the participant tests positive for oncogenic HPV other than types 16/18, a cytology test is the triage. (The HPV test will be undertaken only once in each patient and the test duration is around 15 minutes)

Intervention (Arm 3): HPV screening with types 16/18 genotyping and dual-stained (DS) cytology triage of intermediate risk women with other oncogenic HPV infection. The HPV test will be the primary test performed on a cervical smear sample that is taken in the usual manner and stored in the Thin-Prep liquid-based storage fluid. The triage for other oncogenic HPV positive women is a dual-stained cytology sample for the detection of more advanced HPV infection. (The HPV test will be undertaken only once in each patient and the test duration is around 15 minutes)
Intervention code [1] 289641 0
Early detection / Screening
Comparator / control treatment
Arm 1: Three-yearly image read cytology screening with reflex HPV triage testing for low grade smears (ASCUS/LSIL), as in the existing National Cervical Screening Program (NCSP) screening process. The sample collected from participants in Arm 1 will be a Liquid Based Cytology (LBC) Pap test and collection should take 15 minutes/single occasion only.
Control group
Active

Outcomes
Primary outcome [1] 292434 0
1.To assess the understanding of women in regard to HPV as the primary screening test and acceptability of this change to women using a study specific questionnaire.
Timepoint [1] 292434 0
At end of recruitment (estimated 12 months)
Primary outcome [2] 292435 0
2). Education of General Practitioners and nurses about HPV testing, including interpreting the results, when to refer to colposcopy and, when to recall women for further testing using a study specific questionnaire.
Timepoint [2] 292435 0
Ongoing for up to 2 years.
Primary outcome [3] 292436 0
3). Education of providers of colposcopy services with respect to appropriate management of screen positive women using a study specific questionnaire.
Timepoint [3] 292436 0
Ongoing for up to 2 years.
Secondary outcome [1] 308937 0
4). Laboratory processing of specimens, including the handling of large volume HPV testing, manpower and cost requirements including the time and motion studies.

The Time and Motion study will be assessed using several measures, including total laboratory processing times (TLT), total sample processing times (TPT) and hands-on processing times particularly for the dual-stained cytology samples (HOT).
Timepoint [1] 308937 0
Baseline
Secondary outcome [2] 308938 0
5). In the context of laboratory requirements, the sensitivity and specificity of dual-stained cytology as an adjunctive test in HPV positive women will also be assessed.
Timepoint [2] 308938 0
Ongoing for up to 2 years.
Secondary outcome [3] 308939 0
6). Requirements for associated IT changes in regard to format of reporting to test referrers and the NCSP Register, the latter for the purposes of maintaining a repository of data to enable adequate follow-up of women.
Timepoint [3] 308939 0
Ongoing for up to 2 years.
Secondary outcome [4] 308940 0
7). Test positivity rates. To assess positivity rates for the primary screening test in each arm in women <30 years and 30+ years, and to perform preliminary cross-sectional analyses to estimate the sensitivity and specificity in the baseline screening round for histologically-confirmed CIN 3 in each arm.
Timepoint [4] 308940 0
Ongoing for up to 2 years.

Eligibility
Key inclusion criteria
1. Eligible women attending for routine cervical screening who have their smears collected in primary care and sent to DML for assessment

2. Women between the ages of 25 to 64 years
Minimum age
25 Years
Maximum age
64 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. who have had a total hysterectomy

2. with signs and symptoms suggestive of cervical cancer

3. currently undergoing treatment for cervical pre-cancer or cancer

4. attending follow-up of a prior cervical abnormality and have not yet been discharged to routine screening

5. known to be pregnant

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Practitioners will approach patients during regular cervical screening visits, confirm eligibility and seek consent from women.

Prior to performing the cervical screening examination, the practitioner will assess patient eligibility and, where appropriate, seek consent for participation in the study. The practitioner will be provided with study information sheets to provide to participants. A separate consent form will be presented to the patient for perusal and signature. The randomization procedures will be carried out using an appropriate software.

Women who provide consent will have a cervical smear collected using a ThinPrepPreservCyt vial which is routinely used for cervical smears reported by Diagnostic Medlab. The LBC sample vial will be labelled with the woman’s name and date of birth, placed in a sample bag, along with the consent form, and submitted to Diagnostic Medlab via the usual courier system.

National Cervical Screening Program policies and standards for smear takers, colposcopists and laboratories will be followed throughout this service evaluation project. This means that women who fail to attend their appointment will be followed up by the clinician responsible for their care. In addition the study co-ordinator will assist clinicians in the follow up of women.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Upon receipt and logging of the sample at the Diagnostic Medlab, individual subject allocation to one of the study arms will be performed using a computer-generated randomisation sequence in a 1:2:2 ratio; stratified by age at recruitment (<30 years; 30+ years).

Neither the participant nor the practitioner will be aware of subject allocation at the time of the cervical screening visit and LBC sampling. Allocation will not be concealed in the laboratory (for reasons of practicality).
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Randomized clinical trial, three - arm.
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Objectives 1, 2 and 3
Focus groups will be used to collect information from trial participants and provider groups about the women’s understanding and acceptance of HPV testing as the primary screening test and the providers’ understanding of this new screening process. It is anticipated that there will be four focus groups (Maori women, Pacific women, women of other ethnicities and provider groups). A sample of 7 – 12 people will be drawn for each group from study participants and providers. The facilitator will brainstorm and discuss questions with participants. Primarily open ended questions related to objectives 1,2 and 3 will be used as well as prompts to explore questions in more depth. The participants’ responses from each group session will be transcribed and content analysis will be performed.

Objective 4
Total laboratory processing start time will be defined as time and date a sample is received and logged at specimen reception to the time when the final report is entered into the laboratory electronic database. Total sample processing time (TPT) will be defined as the time from specimen load to HPV result being available on the manufacturer’s output. For hands-on time (HOT), record the start and stop of the hands-on processing times. The main outcome measure will be the TPT per sample. The mean and 95% confidence interval for TPT and median TPT will be calculated across all samples for HPV processing.

Objective 5
The Dual Stain test positivity results in HPV 16/18 and in other oncogenic HPV positive women will be calculated across all available samples. These positivity rates will be compared with, and potentially pooled with similar data from Compass Australia.

Objective 6
An IT specification will be developed as a secondary outcome (no statistical plan appropriate for this objective)

Objective 7
Test positivity rates will be pooled with Round one screening test results from the Compass Australia pilot study to estimate the test positivity rates by age (overall, <30 and 30+) for the primary screening tests (LBC and HPV).

This is largely a qualitative research process examining for the introduction of primary HPV screening. Data will be pooled with co-investigators in Australia as well as will be analysed for New Zealand.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
1/08/2014
Actual
8/08/2014
Date of last participant enrolment
Anticipated
30/06/2015
Actual
4/05/2015
Date of last data collection
Anticipated
Actual
Sample size
Target
500
Accrual to date
Final
500
Recruitment outside Australia
Country [1] 6166 0
New Zealand
State/province [1] 6166 0
Auckland

Funding & Sponsors
Funding source category [1] 289454 0
Commercial sector/Industry
Name [1] 289454 0
Roche Diagnostics Ltd (Pharmaceutical company)
Country [1] 289454 0
New Zealand
Primary sponsor type
Commercial sector/Industry
Name
Roche Diagnostics Ltd (Pharmaceutical company)
Address
15 Rakino Way, Mt Wellington 1060
Country
New Zealand
Secondary sponsor category [1] 288141 0
Government body
Name [1] 288141 0
National Cervical Screening Unit (Ministry of Health)
Address [1] 288141 0
133 Molesworth St, Wellington 6011
Country [1] 288141 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291212 0
Health and Disability Ethics Committee
Ethics committee address [1] 291212 0
Health and Disability Ethics Committees
Ministry of Health
C/- MEDSAFE, Level 6, Deloitte House
10 Brandon Street
PO Box 5013
Wellington
6011
Ethics committee country [1] 291212 0
New Zealand
Date submitted for ethics approval [1] 291212 0
24/09/2013
Approval date [1] 291212 0
27/11/2013
Ethics approval number [1] 291212 0
13/NTA/170

Summary
Brief summary
Women enrolled in the National Cervical Screening Programme (NCSP) present for regular cervical smears (cytology) to screen for early cervical abnormalities (precancer). Nearly all cervical cancers are now known to be caused by certain types of human papillomavirus (high risk human papillomavirus, hrHPV).

In 2009 New Zealand introduced an HPV immunisation program for young women against the 2 most common HPV types. Cervical screening is currently a cost effective intervention in New Zealand, but this will become progressively less so as HPV immunisation uptake increases. Changes to the NCSP will be required to improve cost effectiveness in the context of HPV immunisation, but any such changes cannot be made without evaluation of new technologies and processes.

Overseas studies have shown that primary HPV screening is more sensitive in detecting precancerous lesions than cytology, can be performed less frequently, is more costeffective in countries with an HPV immunization program, such as NZ and may require fewer colposcopy referrals.

Several developed countries are moving to implement or pilot hrHPV testing,. This project will examine the use of HPV as a primary screening test over a one year period with respect to:

1. Acceptability of the change to women

2. Changes to the NZ Cervical Screening Guidelines

3. Education of colposcopists, GPs and nurses about HPV testing in respect to interpretation of results, referral and management of women with abnormal results

4. Laboratory processing of specimens including time and motion studies

5. Requirements for associated information technology changes including to the NCSP register

The study has some similarities to a larger Australian study, conducted by the University of New South Wales and Victorian Cytology Service, which will test 5000 women. For some analyses, results will be pooled with the Australian study
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 49366 0
Dr Mee Ling Yeong
Address 49366 0
Pathologist – Clinical Leader.
Auckland District Health Board, Anatomic Pathology Service, 37-41 Carbine Rd, Mt Wellington, Auckland 1060
Country 49366 0
New Zealand
Phone 49366 0
+64 021 764622
Fax 49366 0
+64 095716442
Email 49366 0
[email protected]
Contact person for public queries
Name 49367 0
Dr Mee Ling Yeong
Address 49367 0
Pathologist – Clinical Leader.
Auckland District Health Board, Anatomic Pathology Service, 37-41 Carbine Rd, Mt Wellington, Auckland 1060
Country 49367 0
New Zealand
Phone 49367 0
+64 021 764622
Fax 49367 0
+64 095716442
Email 49367 0
[email protected]
Contact person for scientific queries
Name 49368 0
Dr Mee Ling yeong
Address 49368 0
Pathologist – Clinical Leader.
Auckland District Health Board, Anatomic Pathology Service, 37-41 Carbine Rd, Mt Wellington, Auckland 1060
Country 49368 0
New Zealand
Phone 49368 0
+64 021 764622
Fax 49368 0
+64 095716442
Email 49368 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AIWill cervical screening remain cost-effective in women offered the next generation nonavalent HPV vaccine? Results for four developed countries2016https://doi.org/10.1002/ijc.30392
Dimensions AIMenopausal Hormone Therapy use and breast cancer risk by receptor subtypes: Results from the New South Wales Cancer Lifestyle and EvaluAtion of Risk (CLEAR) study2018https://doi.org/10.1371/journal.pone.0205034
N.B. These documents automatically identified may not have been verified by the study sponsor.