The role of self-collection in the WHO Elimination Strategy for cervical cancer

The role of self-collection in the WHO Elimination Strategy for cervical cancer

In November 2020 the WHO launched the Global Strategy to Accelerate the Elimination of Cervical Cancer. The strategy has three pillars covering vaccination, screening and treatment. The target for screening is that 70% of women are screened using a high-performance test by the age of 35, and then again by the age of 45. Human papillomavirus (HPV) nucleic acid amplification tests (NAAT), such as PCR-based assays, meet this criterion of a high-performance test.

Since 2017 when the first country, the Netherlands, moved from a cytology-based national cervical screening program to a HPV-based program, there has been a trend for more and more countries to move away from traditional cytology (Pap)-based screening. According to data from 2022 there are 25 countries which include HPV NAAT as part of their national cervical screening program.

In Australia, a National Cervical Screening Program (NCSP) based on cytology began in 1991 and had seen a reduction in cervical cancer by about 50% within ten years. This reduction has seen cervical cancer cases drop to 800 – 900 cancers per year. The following decade had not seen further reductions in cervical cancer cases and it was clear that the cytology-based NCSP was unlikely to yield further reductions. As a result of a comprehensive review, Australia transitioned to a HPV-based NCSP in December 2017. Australia adopted an unusual approach compared to most other countries embarking on HPV-based screening in that there was no national tender for procurement of HPV NAAT technology. This resulted in a heterogenous approach to which HPV NAAT being used based on the individual requirements of the laboratory undertaking the testing. All HPV NAAT had to be clinically validated and meet some other criteria but at least six different HPV NAAT have been used to report screening tests within the Australian NCSP.

As part of the HPV-based NCSP, self-collection was offered as an alternative screening pathway. In 2017 the data available for the performance of self-collection was best captured by a meta-analysis by Marc Arbyn and colleagues from 2014 which found that there was a statistically significant reduction in sensitivity when (vaginal) self-collection was used, compared with the reference clinician-collected cervical sample. Based on this evidence the availability of self-collection within the Australian NCSP was restricted to individuals who were more than two years overdue for screening (under-screened), who were over 30 years of age, and who refused a clinician-collected sample. This group was less likely to screen but were also at a higher risk of developing cervical cancer with > 70% of cervical cancers diagnosed in under-screened individuals.

To further complicate this, in 2017, there were no commercial HPV NAAT that has self-collection as a manufacturer validated specimen type. In order to be able to offer self-collection, our laboratory undertook a clinical trial comparing the performance for HPV detection of a cheap device, Copan FLOQSwab, with the standard of care cervical collection into liquid-based cytology media. The study was published in 2020 in the Journal of Clinical Virology but the data had already be used to gain accreditation for the use of this method within the Australian NCSP in early 2018. Two other laboratories were able to validated the Copan FLOQSwab and gain accreditation by mid-2022.

Arbyn and colleagues updated their meta-analysis in 2018 and demonstrated that if a PCR-based HPV NAAT assay is used the relative sensitivity and specificity of self-collected vaginal specimens was non-inferior to the clinician-collected specimen. The previous meta-analysis had been dominated by signal amplification HPV NAAT and the reduction in sensitivity for these assay types was also observed in the 2018 study. This shift in the evidence for self-collection provided more confidence in this type of collection as a viable method for cervical screening.

In May 2021 the BD Onclarity HPV assay was CE marked for self-collection and this became the first clinically validated assay to have this option available. Two collection devices, a Copan FLOQSwab and the Rovers Evalyn brush (and the simplified version call the Viba-brush) are listed as part of the manufacturer’s claim. In 2022 Roche also added self-collection to their CE marked assays (cobas and cobas 4800) using a Copan FLOQSwab resuspended in a ThinPrep vial at the point of collection, instead of transporting the device dry as is the case with the BD Onclarity assay.

In 2016 a protocol (VALHUDES) for clinically validating self-collection was published by Arbyn and colleagues. VALHUDES gives a specific criteria with which to assess a self-collection method in terms of sensitivity and specificity, and several different devices and HPV NAAT have been validated using this protocol.

By late 2022 there were eight countries which had a recommendation for self-collection as a part of their national cervical screening program. In Australia the recommendation for restriction of self-collection to only under-screened individuals were removed and universal self-collection became an option in July 2022. This change has seen a large increase in the number of self-collection screening tests with over 40,000 in the first seven months compared to ~30,000 in the 4 years and 7 months when it was restricted to under-screened individuals.

Most countries are not meeting the WHO target of 70% coverage for screening. This is partly due to the inability to collect specimens from the cervix within many of the routine healthcare settings, especially in lower and middle-income countries. Self-collection provides an option which allows women and people with cervices to collect their own sample. The stability of dry swab samples has been demonstrated for extended periods (~30 days) at temperatures at the extremity of the normal range in most environments.

In the past five years, HPV-based cervical screening, and self-collection, has moved from the cutting edge, to a routine and established part of cervical screening approaches. Validations of new devices and HPV NAAT are continuing and the more testing options that are available, the more likely a fit -for-purpose solution (including price) will be available.