Human papillomavirus (HPV) testing detects a higher number of precancerous cervical lesions than cytology-based Pap smears in a female population including a proportion offered HPV vaccination, according to a new study published in PLOS Medicine by Karen Canfell of Cancer Council New South Wales, Australia, researchers at the Victorian Cytology Service, Melbourne, Australia, and colleagues.
Many countries are currently considering switching from classic Pap tests to primary HPV tests for cervical cancer screening, based on the strong evidence linking cervical abnormalities and infection with certain HPV types, and data suggesting that HPV tests detect more high-grade precancerous lesions. However, no study has yet compared the different methods in a population in which younger women had been offered prior HPV vaccination.
In the new Compass pilot study, researchers randomized cervical samples from 4,995 women aged 25-64 in Australia, in a 1:2:2 ratio, to be analyzed by either cytology (with HPV testing of low-grade abnormalities), HPV testing with partial genotyping of the virus for the highest risk types HPV16 and 18, and cytology (for participants with other high-risk HPV genotypes), or HPV testing with partial genotyping and dual-stained cytology. In the first screening round of the trial, the authors assessed the rates of women being referred for further testing and of detection of CIN2+ (high-grade cervical intraepithelial neoplasia) precancerous lesions.
For the cytology 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 the HPV testing and cytology group these were 75/1992 (3.8% [95%CI 3.0-4.7]) and 20/1992 (1.0% [95%CI 0.6-1.5]); and for the HPV and dual-stained cytology group these were 79/2008 (3.9% [95%CI 3.1-4.9]) and 24/2008 (1.2% [95%CI 0.8-1.6]). The researchers found that, in the first round of screening, detection of CIN2+ was significantly increased with HPV testing as compared with cytology, while referral was non-significantly increased. Adverse events were rare, and the one case of early-stage cervical cancer (in the HPV testing plus cytology group) was detected as appropriate by screening.
"These findings provide initial confirmation of an improved performance of primary HPV screening compared to cytology screening in settings with HPV-vaccinated populations," said Dr. Canfell. These findings support the planned imminent introduction of cervical screening by HPV testing in Australia which will occur at the end of 2017.
Compass is an investigator-initiated trial which is conducted and funded by the Victorian Cytology Service (VCS) Ltd., a government-funded health promotion charity. The VCS Ltd. have received equipment and a funding contribution for the Compass trial from Roche Molecular Systems and Roche Tissue Diagnostics, AZ USA. KC/MS are also investigators on Compass in New Zealand, ('Compass NZ') (ACTRN12614000714684) which is conducted and funded by Diagnostic Medlab, now Auckland District Health Board. DML received an equipment and a funding contribution for the Compass trial from Roche Molecular Systems. MC, PC, JB, DG, SH, JDB, DH, JT, CDW are also investigators for Compass Australia. KC receives salary support (Career Development Fellowship) from the National Health and Medical Research Council Australia and non-commercial funding from this agency and a number of other sources including the Department of Health Australia and Cancer Council NSW, Australia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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 I nor my institution on my 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.
Canfell K, Caruana M, Gebski V, Darlington-Brown J, Heley S, Brotherton J, et al. (2017) 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 14(9): e1002388. https://doi.org/10.1371/journal.pmed.1002388
Cancer Research Division, Cancer Council New South Wales, Sydney, New South Wales, Australia
School of Public Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales, Australia
NHMRC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia
Victorian Cytology Service, Melbourne, Victoria, Australia
School of Public Health, University of Melbourne, Melbourne, Victoria, Australia
Douglass Hanly Moir Pathology, Sydney, New South Wales, Australia
Department of Obstetrics and Gynaecology, Melbourne Medical School, University of Melbourne, Melbourne, Victoria, Australia
Department of Oncology & Dysplasia, Royal Women's Hospital, Melbourne, Victoria, Australia
Albert Einstein College of Medicine, New York, New York, United States of America
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