The self-sampling journey: technical considerations and challenges
L Connor et al. (June 2023). The self-sampling journey: technical considerations and challenges. www.HPVWorld.com, 232
An increasing number of countries are adopting self-sampling as a means to offer cervical screening. Furthermore, self-sampling is no longer considered solely as an option for those who are “hard to reach” with a number of countries now providing it for all women of screening age. This direction has been predicated in part on evidence to suggest the performance of HPV testing on self-samples for the detection of high-grade cervical lesions is similar to clinician-taken samples1.
While self-sampling is an important and exciting development to support the achievement of the WHO cervical cancer elimination goals, it is also the case that comparatively, HPV testing on self-sampling is less evolved in relation to technical optimisation and workflow. This is evident in the relatively small number of clinically validated HPV assays that have a formal claim for the use of self-taken samples compared to clinician-taken samples.
In this piece, we attempt to describe the key stages in the “journey” of a self-sample from collection to testing and reflect on some of the challenges for programme-leads and associated laboratories from a technical perspective. The stages are separated into:
- Collection
- Preservation
- Stability
- Recovery
- Resuspension
As depicted in Figure 1, with this general scaffold first being proposed by Vaughan et al. at the International Papillomavirus Conference 2021 meeting in Toronto2.
Considering the first stage, there is undoubtedly an increasing amount of choice of collection devices. In a scoping review nearly 10 years ago, the authors found 43 devices that were either specifically used or had the potential for self-sampling3. At the time, few devices were CE-marked for vaginal collection – Evalyn Brush (Rovers Medical Devices, Netherlands), HerSwab (Eve Medical, Canada), Delphi Screener (Delphi-Bioscience BV, Netherlands), Qvintip (Aprovix, Sweden). Since then, more devices have obtained CE-marking for vaginal collection including the Copan FLOQSwab (Copan Diagnostics Inc, California) and Rovers Viba Brush (Rovers Medical Devices, Netherlands). While the CE-marking of these devices may be for broader microbiological applications, some have been integrated in HPV screening programmes and arguably, to date, the devices most frequently in use are Evalyn Brushes and FLOQSwabs. However, this is a rapidly evolving field so the community should be alert to new evidence in the literature, as well as the detail of emerging claims from HPV assay manufacturers.
Many individual studies have shown that certain self-sampling devices exhibit similar performance to clinician-taken samples although some of these studies have been performed within clinic populations4,5,6.
Having a range of well-validated devices may be beneficial as it would be naïve to conclude that one device will suit all settings – local decision-making taking into account the population to be served, climate, cultural mores and existing lab and logistical infrastructure will be key. While more data on longitudinal stability and tolerance(s) of HPV nucleic acid (NA) on the range of existing self-sampling devices will be welcome, there is evidence to show that HPV NA on certain dry devices appears as analytically stable over for up to 32 weeks7. Dry devices are attractive as they obviate the risk of spillage/leakage. However, samples in the buffer may offer the potential advantage of increased stability of biomaterial.
If devices are to be transported dry, the process of recovering and resuspending sample material requires consideration. For example, resuspension volume has differed across studies, ranging from 1.2ml8 to 20ml9; and more data to support the rationale of resuspension would be welcome. To this end we investigated the influence of resuspension volumes using two of the more commonly used self-sampling devices inoculated with HPV cell line material. We showed that volumes of 5ml or less could mitigate against the loss of analytical sensitivity for HPV (Figure 2A & 2B)10,11. Although we appreciate that cell lines are only a proxy of a clinical sample, their ability to be standardised can help quantify the influence of external variables on HPV recovery.
In addition to volume, the type of buffer warrants attention; while we know that certain cytology media are effective, they may arguably be over-engineered for this application, particularly if low-cost non-toxic, effective alternatives exist with similar sensitivity levels12.
In conclusion, self-sampling represents an impactful and important opportunity to support engagement in cervical screening. However, the steps required to support the end-to-end process (i.e. from sample to result) are not trivial and require proper consideration and optimisation to ensure maximum quality. Quality and validation frameworks that incorporate self-taken samples will be important in the same way that such frameworks have been invaluable for ensuring HPV tests are fit for purpose in clinician-taken samples. Certainly, the international HPV (and screening) community will benefit from working collaboratively to share their knowledge and experience of the practical aspects of self-sampling, and we welcome the opportunity to share our perspective in HPV World.
DISCLOSURE
LC and KC institution/employer have previously received research funding and associated consumables from the following in the last 3 years for HPV-related projects: Cepheid, EUROIMMUN, GeneFirst, SelfScreen, Hiantis, Seegene, Roche, Abbott, and Hologic.
AS is a member of various expert groups providing advice to the English Cervical Screening Programme including on HPV self-sampling; holds an honorary contract with the University of Manchester to support research into HPV testing in urine samples and Professional Clinical Advisor to the English Cervical Screening Programme. AS laboratory has been provided with Roche HPV kits free of charge for a urine study.
References
1. Arbyn M, Smith S, Temin S, Sultana F, Castle P. Detecting cervical precancer and reaching underscreened women by using HPV testing on self samples: updated meta-analyses. BMJ. k4823 (2018) . Available from: https://www.bmj.com/content/363/bmj.k4823
2. Vaughan L, Galbraith D, Gary E et al. Optimizing HPV self-collection – A laboratory perspective. International Papillomavirus Conference (IPVC). #600 (2021).
3. Trevitt S, Simpson S and Wood A. New and Emerging Self-Sampling Technologies for Human Papillomavirus (HPV) Testing. United Kingdom: The NIHR Horizon Scanning Centre. University of Birmingham (2014). Available from: http://dx.doi.org/10.13140/RG.2.2.12612.63366
4. Jentschke M, Chen K, Arbyn M et al. Direct comparison of two vaginal self-sampling devices for the detection of human papillomavirus infections. Journal of Clinical Virology. 82, 46-50 (2016). Available from: https://doi.org/10.1016/j.jcv.2016.06.016
5. Ertik FC, Kampers J, Hülse F et al. CoCoss-Trial: Concurrent Comparison of Self-Sampling Devices for HPV-Detection. International Journal of Environmental Research and Public Health. 18, 10388 (2021). Available from: https://doi.org/10.3390/ijerph181910388
6. Cadman L, Reuter C, Jitlal M et al. A Randomized Comparison of Different Vaginal Self-sampling Devices and Urine for Human Papillomavirus Testing—Predictors 5.1. Cancer Epidemiology, Biomarkers & Prevention. 30(4), 661-668 (2021). Available from: https://doi.org/10.1158/1055-9965.epi-20-1226
7. Ejegod D, Pedersen H, Alzua G, Pedersen C, Bonde J. Time and temperature dependent analytical stability of dry-collected Evalyn HPV self-sampling brush for cervical cancer screening. Papillomavirus Research. 5, 192-200 (2018). Available from: https://doi.org/10.1016/j.pvr.2018.04.005
8. Lin C, Zeng X, Cui J et al. Stability Study of Cervical Specimens Collected by Swab and Stored Dry Followed by Human Papillomavirus DNA Detection Using the cobas 4800 Test. Journal of Clinical Microbiology. 55(2), 568-573 (2017). Available from: https://doi.org/10.1128/jcm.02025-16
9. Wolfrum S, Koutsky L, Hughes J et al. Evaluation of dry and wet transport of at-home self-collected vaginal swabs for human papillomavirus testing. Journal of Medical Microbiology. 61(11), 1538-1545 (2012). Available from: https://doi.org/10.1099/jmm.0.046110-0
10. Connor L, Sargent A, Bhatia R, et al. Influence of resuspension volume on dry sampling devices taken for HPV testing; implications for self-sampling. International Papillomavirus Conference (IPVC). #132 (2021).
11. Connor L, Elasifer H, Sargent A, et al. Influence of resuspension volume on dry sampling devices taken for HPV testing: implications for self-sampling. Biotechniques. 74(2), 77-84 (2023). Available from: https://doi.org/10.2144/btn-2022-0084
12. Badman S, Vallely A, Pardo C et al. A comparison of ThinPrep against four non-volatile transport media for HPV testing at or near the point of care. Pathology. 53(2), 264-266 (2021). Available from: https://doi.org/10.1016/j.pathol.2020.10.006
