Hot Clinical Trials to Watch in 2023!
The Compass trial, which is a large-scale randomised controlled trial of Primary HPV DNA testing for cervical cancer screening in Australia, has recently been featured in Nature Medicine’s article: “11 clinical trials that will shape medicine in 2023”
Compass, which began recruiting in 2013, is the first major trial which is investigating cervical screening methods in a population with high rates of vaccination against HPV. It has recruited 81,000 women in two phases, and has been conducted by the Australian Centre for Prevention of Cervical Cancer (ACPCC) and the Daffodil Centre. The Compass trial is co-led by Prof Karen Canfell at the Daffodil Centre and Prof Marion Saville at the ACPCC.
Prophylactic HPV vaccines, which protect against cervical cancer, were first rolled out in Australia 15 years ago. As time moves on, more women who have previously been vaccinated become eligible for cervical screening. Because Australia was the first country to implement a publicly-funded HPV vaccination program, women aged 25-40 years have been offered vaccination but are also now eligible for cervical screening. This makes Australian women the ideal population to conduct a trial on cervical screening methods in a widely vaccinated cohort.
While cervical screening has traditionally used the Pap smear (cervical cytology) method, a more sensitive method which performs molecular testing to detect the presence of HPV is becoming more widely used, with Australia updating its cervical screening guidelines to HPV testing in 2017. In 2021, and with the support of modelling conducted by the Daffodil Centre, the World Health Organisation recommended HPV testing as the primary method for cervical screening. However, primary HPV screening has not yet been directly assessed in a highly vaccinated population.
The Compass trial aims to ascertain both the effectiveness of 5-yearly primary HPV testing vs 2.5 yearly Liquid Based Cytology screening in both vaccinated and unvaccinated cohorts and to determine the optimal method of managing women who are HPV-positive, investigating triage tests to determine which women require immediate investigation.
Compass is also investigating new next-generation HPV testing platforms and technologies for triage testing. This is expected to improve the overall performance of HPV testing at a program level.
The results from the Compass Trial are informing the national screening guidelines for the Australian program and safety monitoring of the primary HPV-based cervical screening program. Initial results from the Compass Pilot have already demonstrated increased detection of cervical precancerous lesions in a partially vaccinated population.* Later this year, we expect to release results on the five year follow-up from the pilot experience and on first round of HPV screening within the main trial. It is expected that these findings will provide key evidence to many countries around the world who are considering transitioning from cytology-based screening to primary HPV screening.
*Canfell K et al., PLoSMED 2018.