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Showing content from https://pubmed.ncbi.nlm.nih.gov/28926579/ below:

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

Randomized Controlled Trial

. 2017 Sep 19;14(9):e1002388. doi: 10.1371/journal.pmed.1002388. eCollection 2017 Sep. 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 Karen Canfell^{1 2 3}, Val Gebski⁴, Jessica Darlington-Brown¹, Stella Heley⁵, Julia Brotherton^{5 6}, Dorota Gertig⁶, Chloe J Jennett¹, Annabelle Farnsworth^{2 7}, Jeffrey Tan^{8 9}, C David Wrede^{8 9}, Philip E Castle¹⁰, Marion Saville^{5 8}

Affiliations

¹ Cancer Research Division, Cancer Council New South Wales, Sydney, New South Wales, Australia.
² School of Public Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
³ Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales, Australia.
⁴ NHMRC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia.
⁵ Victorian Cytology Service, Melbourne, Victoria, Australia.
⁶ School of Public Health, University of Melbourne, Melbourne, Victoria, Australia.
⁷ Douglass Hanly Moir Pathology, Sydney, New South Wales, Australia.
⁸ Department of Obstetrics and Gynaecology, Melbourne Medical School, University of Melbourne, Melbourne, Victoria, Australia.
⁹ Department of Oncology & Dysplasia, Royal Women's Hospital, Melbourne, Victoria, Australia.
¹⁰ Albert Einstein College of Medicine, New York, New York, United States of America.

PMID: 28926579
PMCID: PMC5604935
DOI: 10.1371/journal.pmed.1002388

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Randomized Controlled Trial

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

Karen Canfell et al. PLoS Med. 2017.

. 2017 Sep 19;14(9):e1002388. doi: 10.1371/journal.pmed.1002388. eCollection 2017 Sep. Authors Karen Canfell^{1 2 3}, Michael Caruana¹, Val Gebski⁴, Jessica Darlington-Brown¹, Stella Heley⁵, Julia Brotherton^{5 6}, Dorota Gertig⁶, Chloe J Jennett¹, Annabelle Farnsworth^{2 7}, Jeffrey Tan^{8 9}, C David Wrede^{8 9}, Philip E Castle¹⁰, Marion Saville^{5 8} Affiliations

¹ Cancer Research Division, Cancer Council New South Wales, Sydney, New South Wales, Australia.
² School of Public Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
³ Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales, Australia.
⁴ NHMRC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia.
⁵ Victorian Cytology Service, Melbourne, Victoria, Australia.
⁶ School of Public Health, University of Melbourne, Melbourne, Victoria, Australia.
⁷ Douglass Hanly Moir Pathology, Sydney, New South Wales, Australia.
⁸ Department of Obstetrics and Gynaecology, Melbourne Medical School, University of Melbourne, Melbourne, Victoria, Australia.
⁹ Department of Oncology & Dysplasia, Royal Women's Hospital, Melbourne, Victoria, Australia.
¹⁰ Albert Einstein College of Medicine, New York, New York, United States of America.

PMID: 28926579
PMCID: PMC5604935
DOI: 10.1371/journal.pmed.1002388

Item in Clipboard

Abstract

Background: Using primary human papillomavirus (HPV) testing for cervical screening increases detection of high-grade cervical intraepithelial neoplastic lesions and invasive cancer (cervical intraepithelial neoplasia grade 2+ [CIN2+]) compared to cytology, but no evaluation has been conducted in a population previously offered HPV vaccination. We aimed to assess colposcopy referral and CIN2+ detection rates for HPV-screened versus cytology-screened women in Australia's HPV-vaccinated population (by 2014, resident women ≤33 years had been age-eligible for HPV vaccination, with 3-dose uptake across age cohorts being about 50%-77%).

Methods and findings: Compass is an open-label randomised trial of 5-yearly HPV screening versus 2.5-yearly liquid-based cytology (LBC) screening. In the first phase, consenting women aged 25-64 years presenting for routine screening at 47 primary practices in Victoria, Australia, provided a cervical sample and were randomised at a central laboratory at a 1:2:2 allocation to (i) image-read LBC screening with HPV triage of low-grade cytology ('LBC screening'), (ii) HPV screening with those HPV16/18 positive referred to colposcopy and with LBC triage for other oncogenic (OHR) types ('HPV+LBC triage'), or (iii) HPV screening with those HPV16/18 positive referred to colposcopy and with dual-stained cytology triage for OHR types ('HPV+DS triage'). A total of 5,006 eligible women were recruited from 29 October 2013 to 7 November 2014 (recruitment rate 58%); of these, 22% were in the group age-eligible for vaccination. Data on 4,995 participants were analysed after 11 withdrawals; 998 were assigned to, and 995 analysed (99.7%) in, the LBC-screened group; 1,996 assigned to and 1,992 analysed (99.8%) in the HPV+LBC triage group; and 2,012 assigned to and 2,008 analysed (99.8%) in the HPV+DS triage group. No serious trial-related adverse events were reported. The main outcomes were colposcopy referral and detected CIN2+ rates at baseline screening, assessed on an intention-to-treat basis after follow-up of the subgroup of triage-negative women in each arm referred to 12 months of surveillance, and after a further 6 months of follow-up for histological outcomes (dataset closed 31 August 2016). Analysis was adjusted for whether women had been age-eligible for HPV vaccination or not. For the LBC-screened group, the overall referral and detected CIN2+ rates were 27/995 (2.7% [95% CI 1.8%-3.9%]) and 1/995 (0.1% [95% CI 0.0%-0.6%]), respectively; for HPV+LBC triage, these were 75/1,992 (3.8% [95% CI 3.0%-4.7%]) and 20/1,992 (1.0% [95% CI 0.6%-1.5%]); and for HPV+DS triage, these were 79/2,008 (3.9% [95% CI 3.1%-4.9%]) and 24/2,008 (1.2% [95% CI 0.8%-1.6%]) (p = 0.09 for difference in referral rate in LBC versus all HPV-screened women; p = 0.003 for difference in CIN2+ detection rate in LBC versus all HPV-screened women, with p = 0.62 between HPV screening groups). Limitations include that the study population involved a relatively low risk group in a previously well-screened and treated population, that individual women's vaccination status was unknown, and that long-term follow-up data on disease detection in screen-negative women are not yet available.

Conclusions: In this study, primary HPV screening was associated with significantly increased detection of high-grade precancerous cervical lesions compared to cytology, in a population where high vaccine uptake was reported in women aged 33 years or younger who were offered vaccination. It had been predicted that increased disease detection might be associated with a transient increase in colposcopy referral rates in the first round of HPV screening, possibly dampened by HPV vaccine effect; in this study, although the point estimates for referral rates in women in each HPV-screened group were 41%-44% higher than in cytology-screened women, the difference in referral rate between cytology- and HPV-screened women was not significant. These findings provide initial support for the implementation of primary HPV screening in vaccinated populations.

Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12613001207707.

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Conflict of interest statement

I have read the journal's policy and the authors of this manuscript have the following competing interests: KC is Co-PI of an investigator-initiated trial of cytology and primary HPV screening in Australia (‘Compass’), which is conducted and funded by the VCS Ltd, a government-funded health promotion charity. The VCS have received equipment and a funding contribution for the Compass trial from Roche Molecular Systems and Roche Tissue Diagnostics, AZ USA. However neither she nor her institution on her behalf (Cancer Council NSW) receives direct funding from industry for this trial or any other project. MS (Co-PI), JB, DG, SH, report that their institution, VCS Ltd, received equipment and funding from Roche Molecular Systems and Roche Tissue Diagnostics, AZ USA, during the conduct of the study. JDB, MC and CJJ (project coordinator, project statistician and senior research assistant) are on the Compass study team. Compass is conducted and funded by VCS Ltd, a government-funded health promotion charity. The VCS have received equipment and a funding contribution for the Compass trial from Roche Molecular Systems and Roche Tissue Diagnostics, AZ USA. However, neither JDB, MC and CJ nor their institution- CCNSW, receive direct funding from industry for this trial or any other project. PEC reports personal fees and non-financial support from Roche Molecular Systems, outside the submitted work. VG has no COIs to disclose. JT and CDW report that VCS Ltd has provided The Department of Oncology & Dysplasia at The Royal Women’s Hospital (RWH) monetary support to perform verification colposcopies. JT and CDW were paid to perform colposcopies on Compass participants at the standard public sessional rate, as specified by the RWH and the Victorian Senior Doctors EBA.

Figures
Fig 1. Trial profile: CONSORT 2010 flow…

Fig 1. Trial profile: CONSORT 2010 flow diagram.

*The number of eligible women was estimated…

Fig 1. Trial profile: CONSORT 2010 flow diagram.

*The number of eligible women was estimated using the total number of samples sent to the Victorian Cytology Service for cervical screening from the participating clinics. Two recruiting clinics were excluded from this estimate as their non-Compass cervical cytology samples were processed through a different laboratory and thus their precise recruitment rate cannot be obtained. **A total of 5,303 women were initially recruited. ***A total of 297 women were subsequently found to be ineligible because of their age, or because they were currently in follow-up for a previously diagnosed low-grade or high-grade abnormality, or the consent form was not received at the laboratory. ****A further 11 women subsequently withdrew from the trial; these were excluded (1 expressed concerns about the longer interval for screening, 1 did not wish to participate in verification colposcopy, 1 was anxious, 1 moved overseas and requested to be withdrawn, and 7 did not provide specific reasons). This left a total of 4,995 eligible participants for the primary outcome analysis. HPV, human papillomavirus; LBC, liquid-based cytology.

Fig 2. Schematic showing screening and management…

Fig 2. Schematic showing screening and management for each group in the trial.

(i) LBC…

Fig 2. Schematic showing screening and management for each group in the trial.

(i) LBC screening, (ii) HPV+LBC triage screening, and (iii) HPV+DS triage screening. *For more detailed management flowcharts, refer to S1 Text. −ve, negative; +ve, positive; ASC-H, atypical squamous cells–cannot exclude high-grade squamous intraepithelial lesion; ASCUS, atypical squamous cells of undetermined significance; cyto, cytology; HPV, human papillomavirus; HSIL, high-grade squamous intraepithelial lesion; LBC, liquid-based cytology; LSIL, low-grade squamous intraepithelial lesion.

Fig 3. Participant age distribution, compared to…

Fig 3. Participant age distribution, compared to those routinely attending cervical screening in Victoria.

Data…

Fig 3. Participant age distribution, compared to those routinely attending cervical screening in Victoria.

Data on women attending in Victoria for cervical screening in Australia 2012–2013 are from the Australian Institute of Health and Welfare [21].

Fig 4. Estimated colposcopy referral rates by…

Fig 4. Estimated colposcopy referral rates by study group.

(i) Women age-eligible for vaccination (≤33…

Fig 4. Estimated colposcopy referral rates by study group.

(i) Women age-eligible for vaccination (≤33 years in 2014) (N = 1,078). (ii) Women not age-eligible for vaccination (34+ years in 2014) (N = 3,917). (iii) All study participants (N = 4,995). Bars represent 95% confidence intervals. Arm 1: LBC screening; arm 2: HPV+LBC triage screening; arm 3: HPV+DS triage screening. DS, dual-stained; HPV, human papillomavirus; LBC, liquid-based cytology.