Compass - Randomised Controlled Trial of Primary HPV Testing for Cervical Screening in Australia

NCT02328872 | Active Not Recruiting DMC

• 1 other identifier: Exec-PP-12
• Study Type: interventional
• Target: 76,181
• Locations: 1 country
• Sites: 1

Brief Summary

Compass is a randomised controlled trial of primary HPV testing for cervical cancer screening in Australia. A pilot study involving 5,000 women was carried out in 2013-2014. The trial will involve recruiting 76,300 women from primary health clinics. Women aged 25-69, attending for cervical screening or for routine follow-up will be invited to participate in the 2-arm trial. A liquid-based cytology (LBC) sample will be taken from consenting women and sent to VCS Pathology. Women will be randomised in a 1:2 parallel group allocation to LBC and HPV arms using randomisation with the minimisation procedure, with stratification by birth cohort according to whether offered HPV vaccination in Australia's national publicly-funded HPV vaccination program (date of birth \>=July 1st 1980 and \<1st July 1980). In the LBC (active control) arm, women will undergo 2.5 yearly image read cytology screening with reflex HPV triage testing for low grade cytology. In the HPV (intervention) arm women will undergo 5 yearly HPV screening with partial genotyping enabling separate identification of HPV16 and HPV18 and referral of this group for diagnostic evaluation, and secondary randomisation of "intermediate risk" women testing positive for oncogenic HPV (but not HPV 16 or 18) to either image read LBC screening or dual-stained (DS) cytology testing with p16/Ki67. The laboratory reports issued to practitioners will specify the recommended management for women, according to study arm and test results.Participating women will be flagged and clinical outcomes will be tracked via the Compass Register. Data linkage between the Compass Register and HPV vaccination records held on the Australian Immunisation Register will be performed in order to integrate vaccination and screening histories for trial participants. Participants will be actively followed for an anticipated 5 years from the time of recruitment and the primary outcome is based on the total cumulative detection of CIN3+ after exit testing at 5 years. The anticipated study completion date of March 2027 takes into consideration the final migration of participants to the National Cancer Screening Register and allows for two years to follow-up any intermediate risk results occurring in the last of the recruited trial participants.

Conditions

Cervical Intraepithelial Neoplasia; Cancer of the Cervix

Keywords

screening; cervical screening; Human Papillomavirus (HPV); cancer prevention

Outcome Measures

Primary Outcomes (1)

• Cumulative CIN3+ (Cervical Intraepithelial Neoplasia Grade 3 or invasive cervical cancer) (ITT)

  The primary outcome will be cumulative CIN3+ at 5 years following a 5 year HPV exit testing round in both arms, in women randomised to the HPV arm vs. women randomised to the LBC arm, adjusted for censoring after CIN2+ treatment. For the primary outcome, intention to treat analysis will be performed with closed loop testing for non-inferiority and superiority if non-inferiority is declared. Assuming a total average CIN3+ rate in the LBC arm (across unvaccinated and vaccinated women) of 0.94%, and an absolute non-inferiority margin of 0.22%, the trial will have 78% power with 97.5% confidence to detect non-inferiority for the HPV arm, allowing for a 15% non-compliance rate.

  Expected 5 year follow-up

Secondary Outcomes (7)

• Cumulative CIN3+ in baseline screen-negative women (ITT)

  Expected 5 year follow-up

• Cumulative CIN3+ in baseline screen-negative women (per protocol)

  Expected 5 year follow-up

• Cumulative CIN2+ in baseline screen-negative women (ITT)

  Expected 5 year follow-up

• Baseline CIN2+ and CIN3+

  Following recruitment

• CIN2+ in women randomised to HPV testing at baseline with other oncogenic HPV

  Expected 12-24 month follow-up

Study Arms (2)

Intervention (HPV Arm)

EXPERIMENTAL

Molecular testing for HPV with partial genotyping for types 16/18, with referral of the HPV16/18-positive group for diagnostic evaluation, and secondary randomisation of women testing positive for other oncogenic HPV infection (not 16/18), to either image-read cytology screening or dual-stained (DS) cytology testing with p16/Ki67 - the "HPV arm". Screening performed 5 yearly.

Device: Molecular testing for HPV

Control (LBC Arm)

ACTIVE COMPARATOR

Image-read liquid based cytology (LBC) screening with reflex HPV triage testing for low grade smears, the "LBC arm." Screening performed 2.5 yearly.

Device: Liquid Based Cytology

Interventions

Molecular testing for HPV DEVICE

Molecular testing for HPV with a test allowing partial genotyping for separate identification of types 16/18 from cervical samples. The technology used in this trial will be approved by the Therapeutic Goods Administration (TGA) Australia. It will identify the major HPV oncogenic genotypes in a pool and separately identify HPV 16 and 18. It will also satisfy performance criteria for relative sensitivity and specificity compared to Hybrid Capture 2 (HC2 ) as articulated by Meijer et al, 2009, Guidelines for human papillomavirus DNA test requirements for primary cervical cancer screening in women 30 years and older.

Intervention (HPV Arm)

Liquid Based Cytology DEVICE

The liquid based cytology (LBC) used in this trial will be will be approved by the Therapeutic Goods Administration (TGA) Australia for LBC and appropriately validated and (TGA approved) to perform human papillomavirus testing from a cytology sample.

Control (LBC Arm)

Eligibility Criteria

• Age: 25 Years - 69 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Australian residents with a cervix, aged 25-69 years who are attending for routine cervical screening. (Note: since April 2016 recruitment has been confined to the younger strata, i.e. women age-eligible for HPV vaccination aged at least 25 and born on or after 1st July 1980, as the recruitment target of the older cohort was met).
• Participants may have been previously enrolled in the Compass Pilot but must have been discharged to routine screening. Women may also be in follow-up management for a previous abnormality or unsatisfactory cytology.

You may not qualify if:

• Previous total hysterectomy (uterus and cervix).
• The presence of symptoms or signs for which cervical cancer must be excluded.
• Currently undergoing treatment for cervical cancer.
• Currently enrolled in the Compass Pilot Study.

Sponsors & Collaborators

• VCS Foundation: lead
• University of Sydney: collaborator

Study Sites (1)

VCS Foundation

Carlton, Victoria, 3053, Australia

Location

Related Publications (7)

• Canfell K, Caruana M, Gebski V, Darlington-Brown J, Heley S, Brotherton J, Gertig D, Jennett CJ, Farnsworth A, Tan J, Wrede CD, Castle PE, Saville M. Cervical screening with primary HPV testing or cytology in a population of women in which those aged 33 years or younger had previously been offered HPV vaccination: Results of the Compass pilot randomised trial. PLoS Med. 2017 Sep 19;14(9):e1002388. doi: 10.1371/journal.pmed.1002388. eCollection 2017 Sep.

  PMID: 28926579 BACKGROUND

• Velentzis LS, Egger S, Waller J, Jennett CJ, Brotherton JML, Smith MA, Bateson D, Rogers C, Pagotto A, Skinner R, Taylor N, Edge R, Saville M, Canfell K. Correlates of intention-to-attend and confirmed cervical screening attendance during the COVID-19 pandemic in Australia: Findings from Compass-PLUS, a prospective cohort study. Prev Med Rep. 2024 Aug 5;45:102849. doi: 10.1016/j.pmedr.2024.102849. eCollection 2024 Sep.

  PMID: 39220611 BACKGROUND

• Canfell K, Saville M, Caruana M, Gebski V, Darlington-Brown J, Brotherton J, Heley S, Castle PE. Protocol for Compass: a randomised controlled trial of primary HPV testing versus cytology screening for cervical cancer in HPV-unvaccinated and vaccinated women aged 25-69 years living in Australia. BMJ Open. 2018 Jan 26;8(1):e016700. doi: 10.1136/bmjopen-2017-016700.

  PMID: 29374658 BACKGROUND

• Yuill S, Hall MT, Caruana M, Lui G, Velentzis LS, Smith MA, Wrede CD, Bateson D, Canfell K. Predicted impact of HPV vaccination and primary HPV screening on precancer treatment rates and adverse pregnancy outcomes in Australia 2010-2070: Modelling in a high income, high vaccination coverage country with HPV-based cervical screening. Vaccine. 2025 Apr 30;54:126986. doi: 10.1016/j.vaccine.2025.126986. Epub 2025 Mar 15.

  PMID: 40090212 DERIVED

• Joshy G, Thandrayen J, Koczwara B, Butow P, Laidsaar-Powell R, Rankin N, Canfell K, Stubbs J, Grogan P, Bailey L, Yazidjoglou A, Banks E. Disability, psychological distress and quality of life in relation to cancer diagnosis and cancer type: population-based Australian study of 22,505 cancer survivors and 244,000 people without cancer. BMC Med. 2020 Dec 1;18(1):372. doi: 10.1186/s12916-020-01830-4.

  PMID: 33256726 DERIVED

• Sarich P, Canfell K, Egger S, Banks E, Joshy G, Grogan P, Weber MF. Alcohol consumption, drinking patterns and cancer incidence in an Australian cohort of 226,162 participants aged 45 years and over. Br J Cancer. 2021 Jan;124(2):513-523. doi: 10.1038/s41416-020-01101-2. Epub 2020 Oct 11.

  PMID: 33041337 DERIVED

• Smith MA, Gertig D, Hall M, Simms K, Lew JB, Malloy M, Saville M, Canfell K. Transitioning from cytology-based screening to HPV-based screening at longer intervals: implications for resource use. BMC Health Serv Res. 2016 Apr 26;16:147. doi: 10.1186/s12913-016-1375-9.

  PMID: 27112193 DERIVED

Related Links

• Guidelines for human papillomavirus DNA test requirements for primary cervical cancer screening in women 30 years and older
• Compass Trial Website

MeSH Terms

Conditions

Uterine Cervical Neoplasms; Uterine Cervical Dysplasia

Interventions

Molecular Diagnostic Techniques

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Precancerous Conditions

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques

Study Officials

• Karen Canfell, BE, D.Phil.

  University of Sydney

  PRINCIPAL INVESTIGATOR

• Marion Saville, M.B., Ch.B

  Australian Centre for the Prevention of Cervical Cancer

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 18, 2014
• First Posted: December 31, 2014
• Study Start: January 1, 2015
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): March 1, 2037
• Last Updated: April 17, 2026

Record last verified: 2025-02

Locations

AU (1)