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Trial registered on ANZCTR


Registration number
ACTRN12611000547943
Ethics application status
Approved
Date submitted
20/05/2011
Date registered
30/05/2011
Date last updated
5/09/2019
Date data sharing statement initially provided
5/09/2019
Date results information initially provided
5/09/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
PRINCess: The Prediction of Regression in CIN2 - The Conservative Management of Cervical Intraepithelial Neoplasia (CIN) 2 in Young Women
Scientific title
PRINCess: The Prediction of Regression in CIN2 - A prospective study of young women under the age of 25 with biopsy proven CIN2 undergoing conservative management with assessment of regression, stable disease and progression.
Secondary ID [1] 284794 0
Nil Known
Universal Trial Number (UTN)
U1111-1116-3209
Trial acronym
PRINCess
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cervical Intraepithelial Neoplasia (CIN) 2 257833 0
Condition category
Condition code
Cancer 258002 258002 0 0
Cervical (cervix)

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Conservative Management for Cervical Intraepithelial Neoplasia (CIN) 2 for 24 months i.e. six monthly colposcopy and cervical biopsy for a total of two years
Intervention code [1] 256895 0
Not applicable
Comparator / control treatment
No treatment
Control group
Uncontrolled

Outcomes
Primary outcome [1] 258862 0
Progression rates of CIN 2 in women under the age of 25. Progression will be detected at colposcopy in conjunction with smear and biopsy.
Timepoint [1] 258862 0
24 months
Primary outcome [2] 258863 0
Regression rates of CIN 2 in women under the age of 25.
Regression will be detected at colposcopy in conjunction with smear and biopsy.
Timepoint [2] 258863 0
24 months
Primary outcome [3] 258926 0
To identify the safety of follow-up, as opposed to surgical management, of CIN 2, in young women under the age of 25.
The outcome is either progression, regression or no change after 2 years - all assessed by colposcopy, smear and biopsy.
Timepoint [3] 258926 0
24 months
Secondary outcome [1] 264988 0
The correlation of CIN 2 with immunohistochemical parameters: P16, Proex, Ki67, HPV typing will be assessed.
Timepoint [1] 264988 0
24 months
Secondary outcome [2] 265097 0
Compliance with follow-up will also be assessed as an outcome measure.
Compliance will be assessed by attendance at clinic, routine prompts to clinic will be allowed.
Timepoint [2] 265097 0
24 months

Eligibility
Key inclusion criteria
All women up to the age of 25 attending colposcopy clinics with biopsy proven CIN 2 with the entire lesion accessible at colposcopy. Participants in this study must agree to six monthly colposcopy and cervical biopsy for a total of two years.
Minimum age
15 Years
Maximum age
25 Years
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria include those women with higher grade cervical intraepithelial neoplasia and findings suspicions for invasion on colposcopic assessment. Adenocarcinoma-in-situ is an exclusion category as is incomplete colposcopy.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 8555 0
The Royal Women's Hospital - Parkville
Recruitment hospital [2] 8556 0
The Chris O’Brien Lifehouse - Camperdown
Recruitment postcode(s) [1] 16659 0
3052 - Parkville
Recruitment postcode(s) [2] 16660 0
2050 - Camperdown
Recruitment outside Australia
Country [1] 2791 0
New Zealand
State/province [1] 2791 0
Christchurch

Funding & Sponsors
Funding source category [1] 257352 0
University
Name [1] 257352 0
University of Otago - Christchurch
Address [1] 257352 0
Private Bag 4711
Christchurch 8140
Country [1] 257352 0
New Zealand
Funding source category [2] 257353 0
Hospital
Name [2] 257353 0
Canterbury District Health Board
Address [2] 257353 0
Private Bag 4710
Christchurch 8140
Country [2] 257353 0
New Zealand
Funding source category [3] 267141 0
Charities/Societies/Foundations
Name [3] 267141 0
Cancer Society of New Zealand, Canterbury West Coast Division
Address [3] 267141 0
PO Box 13450
Christchurch
Country [3] 267141 0
New Zealand
Funding source category [4] 289410 0
Government body
Name [4] 289410 0
Health Research Council NZ
Address [4] 289410 0
PO Box 5541
Wellesley Street
Auckland 1141
Country [4] 289410 0
New Zealand
Primary sponsor type
University
Name
University of Otago - Christchurch
Address
Private Bag 4711
Christchurch 8140
Country
New Zealand
Secondary sponsor category [1] 256594 0
Hospital
Name [1] 256594 0
Canterbury District Health Board
Address [1] 256594 0
Private Bag 4710
Christchurch 8140
Country [1] 256594 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 259374 0
Multiregion Ethics Committee - New Zealand
Ethics committee address [1] 259374 0
PO Box 5013
Wellington
Ethics committee country [1] 259374 0
New Zealand
Date submitted for ethics approval [1] 259374 0
Approval date [1] 259374 0
14/04/2010
Ethics approval number [1] 259374 0
MEC/09/07/079
Ethics committee name [2] 291171 0
Ethics Review Committe (RPAH Zone)
Ethics committee address [2] 291171 0
Research Development office
Royal Prince Alfred Hospital
Camperdown NSW 2050
Ethics committee country [2] 291171 0
Australia
Date submitted for ethics approval [2] 291171 0
Approval date [2] 291171 0
14/11/2013
Ethics approval number [2] 291171 0
13/RPAH/352

Summary
Brief summary
Cervical intraepithelial neoplasia 1, 2 or 3 is the term used to describe a range of cellular changes on the cervix that over time can regress to normal or progress to cervical cancer. Cervical cancers are usually preceded by a long phase of preinvasive disease. Evidence has shown that there is a 43% likelihood of regression of CIN 2, a 35% likelihood of persistence of CIN 2 and a 20% probability of progression to CIN 3. Evidence in adolescents has shown an even higher rate of regression. The current treatment for this abnormality is a LLETZ biopsy of the cervix. This treatment is associated with complications in future pregnancies – premature rupture of membranes and preterm labour. Because of the high regression rate and pregnancy complications, young women, up to age 25, with biopsy proven CIN 2 at Christchurch and Dunedin Hospitals will be offered inclusion in the study. This will involve 6 monthly colposcopy clinic visits where a cervical smear, biopsy and tests for HPV, Proex, P16, Ki67 as opposed to immediate surgical management. If there is progression of this change to CIN 3 throughout follow-up a LLETZ will be offered. Follow-up is for 24 months – if the CIN 2 abnormality persists, LLETZ will be offered.
Trial website
Trial related presentations / publications
Public notes
The trial has recruited women in many New Zealand hospitals.

Contacts
Principal investigator
Name 31445 0
A/Prof Peter H Sykes
Address 31445 0
University of Otago - Christchurch
Department of O & G
Private Bag 4711
Christchurch 8140
Country 31445 0
New Zealand
Phone 31445 0
+64 3 364 4630
Fax 31445 0
+64 3 364 4634
Email 31445 0
peter.sykes@otago.ac.nz
Contact person for public queries
Name 14692 0
Ms Ms Dianne Harker
Address 14692 0
Private Bag 4711
Christchurch
Country 14692 0
New Zealand
Phone 14692 0
+64 3 3644624
Fax 14692 0
+64 3 3644634
Email 14692 0
dianne.harker@otago.ac.nz
Contact person for scientific queries
Name 5620 0
A/Prof Associate Professor Peter Sykes
Address 5620 0
Christchurch Women’s Hospital
Private Bag 4710
Christchurch
Country 5620 0
New Zealand
Phone 5620 0
+64 3 3644630
Fax 5620 0
+64 3 3644634
Email 5620 0
peter.sykes@otago.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
IPD sharing not planned.
What supporting documents are/will be available?
Study protocol
Informed consent form
How or where can supporting documents be obtained?
Type [1] 3202 0
Study protocol
Citation [1] 3202 0
Link [1] 3202 0
Email [1] 3202 0
peter.sykes@otago.ac.nz
Other [1] 3202 0
Attachment [1] 3202 0
Type [2] 3203 0
Informed consent form
Citation [2] 3203 0
Link [2] 3203 0
Email [2] 3203 0
peter.sykes@otago.ac.nz
Other [2] 3203 0
Attachment [2] 3203 0
Summary results
Have study results been published in a peer-reviewed journal?
Yes
Journal publication details
Publication date and citation/details [1] 4529 0
Innes CRH, Sykes PH, Harker D, Williman JA, Van der Griend RA, Whitehead M, Hibma M, Lawton BA, Fitzgerald P, Dudley NM, Petrich S, Faherty J, Bergzoll C, Eva L, Sadler L, Simcock BJ (2018). Changes in human papillomavirus genotypes associated with cervical intraepithelial neoplasia grade 2 lesions in a cohort of young women (2013-2016). Papillomavirus Research. 6, 77-82.
Attachments [1] 4529 0
Publication date and citation/details [2] 4530 0
Sykes P, Innes C, Harker D, Whitehead M, van der Griend R, Lawton B, Hibma M, Fitzgerald P, Dudley N, Petrich S, Faherty J, Bergzoll C, Eva L, Parker C, Sadler L, Simcock B (2016). Observational management of CIN2 in young women: A prospective multicentre trial. Journal of Lower Genital Tract Disease, 20, 343-347.
Attachments [2] 4530 0
Other publications
Have study results been made publicly available in another format?
Yes
Other publication details
Citation type [1] 3208 0
Conference abstract
Citation/DOI/link/details [1] 3208 0
Simcock B, Sykes P, Innes C, Harker D, Williman J, Whitehead M, van der Griend R, Lawton B, Hibma M, Fitzgerald P, Parker C, Sadler L, Dudley N, Petrich S, Eva L, Kathuria J, Abed Ali A, Bergzoll C, Faherty J, Hardie D, Robertson A, Robertson V, Pather S, Fentiman G, Gastrell F, Wrede D, John M, Wright E (2019) Observational management of CIN in young women is safe and appropriate. Proceedings of the Australian Society for Colposcopy and Cervical Pathology Scientific Meeting (March 2019), Auckland, New Zealand.
Attachments [1] 3208 0
Citation type [2] 3209 0
Conference abstract
Citation/DOI/link/details [2] 3209 0
Sykes P, Innes C, Harker D, Whitehead M, Van der Griend R, Lawton B, Hibma M, Fitzgerald P, Williman J, Dudley N, Petrich S, Faherty J, Bergzoll C, Eva L, Parker C, Sadler L, Simcock B (2018). Predictors of regression of CIN2 in women under 25 years: Results of a multi-centre prospective observational study, 32nd International Papillomavirus Conference (October 2018), Sydney, Australia.
Attachments [2] 3209 0
Citation type [3] 3210 0
Conference abstract
Citation/DOI/link/details [3] 3210 0
Simcock B, Innes C, van der Griend R, Williman J, Sadler L, Eva L, Dudley N, Bergzoll C, Lawton B, Sykes P (2017). Changing Face of HPV in CIN2 in Young New Zealand Women. Australian & New Zealand Journal of Obstetrics & Gynaecology, 57(Suppl. 1), 62.
Attachments [3] 3210 0
Citation type [4] 3211 0
Conference abstract
Citation/DOI/link/details [4] 3211 0
Dempster-Rivett K, Innes CRH, Simcock B, Sykes PH (2017). The reliability of colposcopy and cervical cytology in observational management of CIN 2 in women under 25. Proceedings of the Australian Society for Colposcopy and Cervical Pathology Scientific Meeting (March 2017), Sydney, Australia.
Attachments [4] 3211 0
Citation type [5] 3212 0
Conference abstract
Citation/DOI/link/details [5] 3212 0
Sykes PH, Innes CRH, van der Griend RA, Fitzgerald P, Simcock B (2017). Decreasing prevalence of HPV16 & 18 genotypes in young New Zealand women with biopsy-diagnosed CIN2. Proceedings of the Australian Society for Colposcopy and Cervical Pathology Scientific Meeting (March 2017), Sydney, Australia.

Attachments [5] 3212 0
Results – plain English summary
Background: Women with cervical intraepithelial neoplasia grade 2 (CIN2) and grade 3 (CIN3) have a risk of developing cervical cancer and treatment by removing the affected tissue is usually recommended. However, treatment may increase the risk of early labour and delivery in future pregnancies. Studies indicate that CIN2 changes can spontaneously resolve without treatment in some young women. Thus, rather than treatment, close examination of the cervix every 6 months for up to 2 years is often recommended for young women with CIN2. Aims: Document for women <25 years with CIN2, safety of observational management, proportion of cell changes resolving without treatment, and factors which predict whether cell changes will resolve. Results: For the 508 women who completed the study, abnormalities resolved to low grade or normal for 351 (69%) and treatment was avoided, while 157 (31%) had a persistent high grade abnormality which was treated. No women progressed to cancer. Factors which increased the chance that the CIN2 would resolve were (1) not being infected with HPV types 16 or 18, (2) having a small area of abnormal cells (<0.5 cm), (3) abnormal cells appearing ‘low grade’ to a clinician, (4) being a non-smoker, and (5) a low grade smear. Conclusion: CIN2 abnormalities resolved without treatment in the majority of young women. Observational management of CIN2 in young women is safe and avoids the risks of over-treatment.