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

Karen Canfell, Marion Saville, Michael Caruana, Val Gebski, Jessica Darlington-Brown, Julia Brotherton, Stella Heley, Philip E. Castle

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

INTRODUCTION: Australia's National Cervical Screening Program (NCSP) currently recommends 2-year cytology in women aged 18-69 years. Following a review of the NCSP prompted by the implementation of human papillomavirus (HPV) vaccination, the programme will transition in 2017 to 5-year primary HPV screening with partial genotyping for HPV16/18 in women aged 25-74 years. Compass is a sentinel experience for the renewed NCSP and the first prospectively randomised trial of primary HPV screening compared with cytology to be conducted in a population with high uptake of HPV vaccination. This protocol describes the main Compass trial, which commenced after a pilot study of ~5000 women completed recruitment.

METHODS AND ANALYSIS: Women aged 25-69 years will be randomised at a 1:2 allocation to (1) 2.5-year image-read, liquid-based cytology (LBC) screening with HPV triage of low-grade smears (active control Arm A) or (2) 5-year HPV screening with partial genotyping and referral of HPV16/18-positive women to colposcopy (intervention Arm B). Women in Arm B positive for other oncogenic HPV (not 16/18) will undergo secondary randomisation at a 1:1 allocation to either LBC or dual-stained (p16INK4a and Ki-67) cytology testing (dual-stained cytology). The primary outcome is cumulative CIN3+ (CIN3, adenocarcinoma in situ and invasive cervical cancer) following a 5-year HPV exit testing round in both arms, in women randomised to the HPV arm versus women randomised to the LBC arm, based on an intention-to-treat analysis. The primary outcome will first be tested for non-inferiority and if declared, the primary outcome will be tested for superiority. A total of 36 300 women in birth cohorts not offered vaccination and 84 700 women in cohorts offered vaccination will be recruited, bringing the final sample size to 121 000. The trial is powered for the secondary outcome of cumulative CIN3+ in screen-negative women, adjusted for censoring after CIN2+ treatment and hysterectomy.

ETHICS AND DISSEMINATION: Approved by the Bellberry Ethics Committee (2014-11-592). Findings will be reported in peer-reviewed journals and presented at scientific meetings.

TRIAL REGISTRATION NUMBER: NCT02328872; Pre-results.

Original languageEnglish (US)
Pages (from-to)e016700
JournalBMJ Open
Volume8
Issue number1
DOIs
StatePublished - Jan 26 2018

Fingerprint

Uterine Cervical Neoplasms
Cell Biology
Randomized Controlled Trials
Vaccination
Ethics Committees
Colposcopy
Intention to Treat Analysis
Human papillomavirus 16
Triage
Random Allocation
Hysterectomy
Sample Size
Referral and Consultation
Parturition

Keywords

  • cervical cancer screening
  • cervical intraepithelial neoplasia.
  • HPV DNA testing
  • human papillomavirus

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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. / Canfell, Karen; Saville, Marion; Caruana, Michael; Gebski, Val; Darlington-Brown, Jessica; Brotherton, Julia; Heley, Stella; Castle, Philip E.

In: BMJ Open, Vol. 8, No. 1, 26.01.2018, p. e016700.

Research output: Contribution to journalArticle

Canfell, Karen ; Saville, Marion ; Caruana, Michael ; Gebski, Val ; Darlington-Brown, Jessica ; Brotherton, Julia ; Heley, Stella ; Castle, Philip E. / 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. In: BMJ Open. 2018 ; Vol. 8, No. 1. pp. e016700.
@article{fe917309a0cf473c9a5c39d32e48439c,
title = "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",
abstract = "INTRODUCTION: Australia's National Cervical Screening Program (NCSP) currently recommends 2-year cytology in women aged 18-69 years. Following a review of the NCSP prompted by the implementation of human papillomavirus (HPV) vaccination, the programme will transition in 2017 to 5-year primary HPV screening with partial genotyping for HPV16/18 in women aged 25-74 years. Compass is a sentinel experience for the renewed NCSP and the first prospectively randomised trial of primary HPV screening compared with cytology to be conducted in a population with high uptake of HPV vaccination. This protocol describes the main Compass trial, which commenced after a pilot study of ~5000 women completed recruitment.METHODS AND ANALYSIS: Women aged 25-69 years will be randomised at a 1:2 allocation to (1) 2.5-year image-read, liquid-based cytology (LBC) screening with HPV triage of low-grade smears (active control Arm A) or (2) 5-year HPV screening with partial genotyping and referral of HPV16/18-positive women to colposcopy (intervention Arm B). Women in Arm B positive for other oncogenic HPV (not 16/18) will undergo secondary randomisation at a 1:1 allocation to either LBC or dual-stained (p16INK4a and Ki-67) cytology testing (dual-stained cytology). The primary outcome is cumulative CIN3+ (CIN3, adenocarcinoma in situ and invasive cervical cancer) following a 5-year HPV exit testing round in both arms, in women randomised to the HPV arm versus women randomised to the LBC arm, based on an intention-to-treat analysis. The primary outcome will first be tested for non-inferiority and if declared, the primary outcome will be tested for superiority. A total of 36 300 women in birth cohorts not offered vaccination and 84 700 women in cohorts offered vaccination will be recruited, bringing the final sample size to 121 000. The trial is powered for the secondary outcome of cumulative CIN3+ in screen-negative women, adjusted for censoring after CIN2+ treatment and hysterectomy.ETHICS AND DISSEMINATION: Approved by the Bellberry Ethics Committee (2014-11-592). Findings will be reported in peer-reviewed journals and presented at scientific meetings.TRIAL REGISTRATION NUMBER: NCT02328872; Pre-results.",
keywords = "cervical cancer screening, cervical intraepithelial neoplasia., HPV DNA testing, human papillomavirus",
author = "Karen Canfell and Marion Saville and Michael Caruana and Val Gebski and Jessica Darlington-Brown and Julia Brotherton and Stella Heley and Castle, {Philip E.}",
year = "2018",
month = "1",
day = "26",
doi = "10.1136/bmjopen-2017-016700",
language = "English (US)",
volume = "8",
pages = "e016700",
journal = "BMJ Open",
issn = "2044-6055",
publisher = "BMJ Publishing Group",
number = "1",

}

TY - JOUR

T1 - Protocol for Compass

T2 - 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

AU - Canfell, Karen

AU - Saville, Marion

AU - Caruana, Michael

AU - Gebski, Val

AU - Darlington-Brown, Jessica

AU - Brotherton, Julia

AU - Heley, Stella

AU - Castle, Philip E.

PY - 2018/1/26

Y1 - 2018/1/26

N2 - INTRODUCTION: Australia's National Cervical Screening Program (NCSP) currently recommends 2-year cytology in women aged 18-69 years. Following a review of the NCSP prompted by the implementation of human papillomavirus (HPV) vaccination, the programme will transition in 2017 to 5-year primary HPV screening with partial genotyping for HPV16/18 in women aged 25-74 years. Compass is a sentinel experience for the renewed NCSP and the first prospectively randomised trial of primary HPV screening compared with cytology to be conducted in a population with high uptake of HPV vaccination. This protocol describes the main Compass trial, which commenced after a pilot study of ~5000 women completed recruitment.METHODS AND ANALYSIS: Women aged 25-69 years will be randomised at a 1:2 allocation to (1) 2.5-year image-read, liquid-based cytology (LBC) screening with HPV triage of low-grade smears (active control Arm A) or (2) 5-year HPV screening with partial genotyping and referral of HPV16/18-positive women to colposcopy (intervention Arm B). Women in Arm B positive for other oncogenic HPV (not 16/18) will undergo secondary randomisation at a 1:1 allocation to either LBC or dual-stained (p16INK4a and Ki-67) cytology testing (dual-stained cytology). The primary outcome is cumulative CIN3+ (CIN3, adenocarcinoma in situ and invasive cervical cancer) following a 5-year HPV exit testing round in both arms, in women randomised to the HPV arm versus women randomised to the LBC arm, based on an intention-to-treat analysis. The primary outcome will first be tested for non-inferiority and if declared, the primary outcome will be tested for superiority. A total of 36 300 women in birth cohorts not offered vaccination and 84 700 women in cohorts offered vaccination will be recruited, bringing the final sample size to 121 000. The trial is powered for the secondary outcome of cumulative CIN3+ in screen-negative women, adjusted for censoring after CIN2+ treatment and hysterectomy.ETHICS AND DISSEMINATION: Approved by the Bellberry Ethics Committee (2014-11-592). Findings will be reported in peer-reviewed journals and presented at scientific meetings.TRIAL REGISTRATION NUMBER: NCT02328872; Pre-results.

AB - INTRODUCTION: Australia's National Cervical Screening Program (NCSP) currently recommends 2-year cytology in women aged 18-69 years. Following a review of the NCSP prompted by the implementation of human papillomavirus (HPV) vaccination, the programme will transition in 2017 to 5-year primary HPV screening with partial genotyping for HPV16/18 in women aged 25-74 years. Compass is a sentinel experience for the renewed NCSP and the first prospectively randomised trial of primary HPV screening compared with cytology to be conducted in a population with high uptake of HPV vaccination. This protocol describes the main Compass trial, which commenced after a pilot study of ~5000 women completed recruitment.METHODS AND ANALYSIS: Women aged 25-69 years will be randomised at a 1:2 allocation to (1) 2.5-year image-read, liquid-based cytology (LBC) screening with HPV triage of low-grade smears (active control Arm A) or (2) 5-year HPV screening with partial genotyping and referral of HPV16/18-positive women to colposcopy (intervention Arm B). Women in Arm B positive for other oncogenic HPV (not 16/18) will undergo secondary randomisation at a 1:1 allocation to either LBC or dual-stained (p16INK4a and Ki-67) cytology testing (dual-stained cytology). The primary outcome is cumulative CIN3+ (CIN3, adenocarcinoma in situ and invasive cervical cancer) following a 5-year HPV exit testing round in both arms, in women randomised to the HPV arm versus women randomised to the LBC arm, based on an intention-to-treat analysis. The primary outcome will first be tested for non-inferiority and if declared, the primary outcome will be tested for superiority. A total of 36 300 women in birth cohorts not offered vaccination and 84 700 women in cohorts offered vaccination will be recruited, bringing the final sample size to 121 000. The trial is powered for the secondary outcome of cumulative CIN3+ in screen-negative women, adjusted for censoring after CIN2+ treatment and hysterectomy.ETHICS AND DISSEMINATION: Approved by the Bellberry Ethics Committee (2014-11-592). Findings will be reported in peer-reviewed journals and presented at scientific meetings.TRIAL REGISTRATION NUMBER: NCT02328872; Pre-results.

KW - cervical cancer screening

KW - cervical intraepithelial neoplasia.

KW - HPV DNA testing

KW - human papillomavirus

UR - http://www.scopus.com/inward/record.url?scp=85051811700&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85051811700&partnerID=8YFLogxK

U2 - 10.1136/bmjopen-2017-016700

DO - 10.1136/bmjopen-2017-016700

M3 - Article

C2 - 29374658

AN - SCOPUS:85051811700

VL - 8

SP - e016700

JO - BMJ Open

JF - BMJ Open

SN - 2044-6055

IS - 1

ER -