Influence of resuspension volume on dry sampling devices taken for human papillomavirus testing: implications for self-sampling
Abstract
Optimization of technical parameters that influence the performance of human papillomavirus (HPV) testing on self-taken samples is important. Here, the authors assessed the impact of resuspension volume on the detection of HPV using four validated HPV assays. Two self-sampling devices, FLOQSwabs® and Evalyn® Brushes, were inoculated with dilutions of HPV-16-positive cell line, then resuspended in various volumes of ThinPrep. The influence of vortexing during resuspension was also assessed. At target concentrations around the assay cutoff, larger volumes led to decreased HPV detection. Interestingly, the effect(s) of vortexing differed by the self-sampling device. Resuspension in 5 ml or less may maximize the detection of HPV sequences. Using a proxy of clinical material, the current observations underline the importance of optimizing preanalytical laboratory processes to support high-quality HPV testing of self-samples.
METHOD SUMMARY
Two commonly used sampling devices, FLOQSwab® and Evalyn® Brush, were used alongside four clinically validated HPV detection assays, Anyplex™ II HPV 28, Aptima HPV, Alinity m HR HPV and cobas® 8800 HPV. The sampling device was submerged into suspensions of an HPV-16-containing cell line (1–2 copies of HPV-16 per cell) at known concentrations, and then resuspended in various volumes of ThinPrep. Cellular concentrations ranged from 105 cells/ml to 103 cells/ml, and resuspension volumes were either 3 ml, 5 ml, 10 ml or 20 ml, to reflect the range of volumes found in the literature. The impact of using a vortex at the time of resuspension was also assessed.
Self-sampling for the detection of human papillomavirus (HPV) is an area of growing importance for the improvement of global cervical screening uptake. A recent meta-analysis demonstrated that the sensitivity of HPV testing using clinically validated PCR-based assays for the detection of cervical intraepithelial neoplasia grade 2 or worse on self-samples is similar to clinician-taken samples [1]. Furthermore, offering self-sampling is already a part of core cervical screening programs in certain settings, including the Netherlands [2]. Given the increasing appetite to implement self-sampling, it is important that technical and operational aspects of sample handling and testing are considered if this approach is to be used at scale. Notably, at the time of the preparation of this manuscript, few HPV test manufacturers have a formal, on-label claim for a self-collection device, including tests that have been validated according to international clinical performance criteria for use in cervical screening programs [3]. The onus is thus on the HPV laboratory community to optimize and validate practical steps that can support self-sampling.
To address this, investigators have looked at the influence of various technical and environmental factors relevant to HPV self-sampling, including the influence of the collection device itself [4,5], resuspension media (if dry) [6] and pretesting storage time and temperature [7,8]. Collection devices themselves can include a buffer or can be dispatched “dry”. If used in a home setting, dry sampling devices are often perceived as attractive as they obviate issues around buffer spillage or misuse. However, there are concerns that the deterioration of HPV nucleic acid in dry self-samples may be more rapid than in devices placed in a stabilization buffer [9].
Self-sampling has already been implemented as part of routine cervical screening programs in certain settings, including the Netherlands [2], the Capital Region of Denmark, Australia, Norway [10] and Sweden [11]. In these programs, dry swabs are distributed with resuspension subsequently taking place in the laboratory. As dry self-samples are increasingly used, technical validation to support their optimal processing in the laboratory is relevant and timely, although some gaps in the literature are evident. For example, there is no clear consensus around the optimal resuspension volume of dry samples at the laboratory. Volumes have varied across studies, ranging from 1 to 20 ml [8,12]. Arguably, these volumes have been applied for understandable, yet pragmatic reasons, for example, 20 ml is the volume in prefilled commercially available liquid-based cytology (LBC) vials, commonly used for cervical screening.
There is a shortage of data on the influence of resuspension volume on dry self-samples and how this may impact HPV detection. The aim of the current research was to address this systematically by challenging two commonly used self-sampling devices, FLOQSwab® (Copan Italia S.p.A, Brescia, Italy) and Evalyn® Brush (Rovers Medical Devices, Oss, The Netherlands) with cultured HPV material over a range of resuspension volumes and concentrations. The application of four validated HPV detection technologies provided insight into any observable differences across platforms. The influence of using a vortex (versus no vortex) on HPV detection was also assessed.
Materials & methods
HPV materials & determination of assay limit of detection
SiHa cells, an immortalized cell line from uterine tissue that contains 1–2 copies of HPV-16 per cell, were used as a proxy of a clinical specimen in this study. Cells were obtained from American Type Culture Collection (catalogue number HTB-35). Cells were grown in Eagle's minimum essential medium (LGC Standards, Middlesex, UK) supplemented with 10% fetal calf serum (Life Technologies, CA, USA). Cells were harvested using 0.25% trypsin/EDTA (Life Technologies, CA, USA) and immediately resuspended in ThinPrep (Hologic, MA, USA). ThinPrep Solution is a methanol-based reagent that serves as a transport, preservative and antibacterial medium for gynecologic samples and is a validated medium for HPV testing.
Serial dilutions of the cellular material were prepared in ThinPrep ranging from 106 cells/ml to 1 cell/ml. Dilutions were tested using four commercially available validated HPV assays, Anyplex™ II HPV 28 (Seegene, Seoul, South Korea), Alinity m HR HPV (Abbott Molecular, IL, USA), cobas® 8800 HPV Test (Roche Diagnostics, Basel, Switzerland) and Aptima HPV assay (Hologic, MA, USA), to identify the limiting dilution. All assays target DNA other than the Aptima assay, which targets mRNA. The limiting dilution of the four assays was defined as the lowest concentration where detection was observed across all assays and was 103 cells/ml. SiHa cell suspensions at three concentrations, the limiting dilution and two logs higher (103 cells/ml, 104 cells/ml and 105 cells/ml) were thus selected for inoculation of the sampling devices.
Introduction of HPV material to self-sampling devices & resuspension in various volumes
Two self-sampling devices were used: FLOQSwab® and Evalyn® Brush. A FLOQSwab® is a sampling swab utilizing flocking and consists of a plastic shaft with an orientation and break point and a soft tip consisting of Nylon® fibers. The Evalyn® Brush has flexible plastic bristles and is contained within a retractable casing with wings to control insertion depth into the vagina. Example(s) of the application of these respective devices for HPV testing can be found in various studies [13–16]. Each device was inoculated with 1 ml SiHa cell suspension (103, 104 or 105 cells/ml), then subsequently resuspended into either 3, 5, 10 or 20 ml of ThinPrep solution to reflect the range of volumes used in previously published studies [4,5,7]. During this process, one set of device heads was manually swirled ten times, then removed and discarded. A duplicate set was prepared but, rather than manual manipulation, the device head was vortexed in the media for 10 s at 2700 r.p.m. then removed and discarded. Each volume and concentration were tested in triplicate. All testing was performed according to the manufacturers' instructions.
HPV detection assays
Four HPV assays were used: Anyplex™ II HPV 28, Aptima HPV, Alinity m HR HPV and cobas® 8800 HPV. The Anyplex™ II HPV 28 is generally applied for HPV genotyping with the remaining three generally applied for cervical screening. All screening assays fulfill Meijer 2009 criteria for adequate performance in a primary screening setting [17]: Anyplex™ II HPV 28 is a semiquantitative assay that can detect 28 HPV types including all established high-risk types; Aptima HPV is a qualitative assay capable of detecting HPV E6/E7 viral mRNA from 14 high-risk types; Alinity m HR HPV is a quantitative assay able to detect HPV DNA sequences from the L1 region of 14 high-risk types and individually differentiate HPV-16, HPV-18 and HPV-45; cobas® 8800 HPV is a qualitative real-time assay that can detect the L1 region of 14 high-risk HPV types, including being able to differentiate HPV-16 and HPV-18. Testing by Anyplex™ II HPV 28 and Alinity m HR HPV was performed at the Scottish HPV Reference Laboratory at the Royal Infirmary of Edinburgh. Aptima HPV testing was done by the HPV Research Group at the University of Edinburgh. Testing by cobas® 8800 HPV was carried out at the Virology Department, Manchester University NHS Foundation Trust.
Statistical analysis
Positivity for HPV-16, given the nature of the material used, is presented as either full (all three replicates), partial (detected in one or two replicates only) or no detection. The cumulative detection rate was calculated by adding the total number of instances where HPV was detected across all assays for each device at each volume. The influence of resuspension volume on HPV positivity was assessed for each variable, cell concentration, assay and sampling device, allowing for interassay and interdevice comparisons. The influence of vortexing on the qualitative detection of HPV was also performed according to the device. Agreement was determined using 2 × 2 contingency tables with manual manipulation and vortexing as the variables. Overall agreement was calculated as percentages, including 95% CIs, separately for each device and stratified by assay. McNemar's test was used to evaluate the distribution of discrepant results. p-values < 0.05 were considered statistically significant.
Results & discussion
Influence of resuspension volume on HPV detection at varying concentrations of HPV-16 target
At 105 cells/ml concentrations using FLOQSwabs®, the resuspension volume did not affect the qualitative detection of HPV-16 in any assays with 100% detection observed across replicates (Table 1). At 104 cells/ml, resuspension volumes of 3 ml, 5 ml and 10 ml were associated with a minimum cumulative detection rate of 83.3% (95% CI: 61.8–94.5), whereas, at 20 ml, the cumulative detection rate decreased to 66.6% (95% CI: 44.6–83.5). At limiting dilutions (103 cells/ml), volumes greater than 5 ml led to cumulative detection rates of 33.3% (95% CI: 16.4–55.3) and 25% (95% CI: 10.6–47.0) for 10 ml and 20 ml, respectively. This is compared with cumulative detection rates of 70.8% (95% CI: 48.7–86.5) and 54.1% (95% CI: 33.2–73.8) at 3 ml and 5 ml, respectively. Interassay variation was modest and CIs overlapped with respect to cumulative detection per assay indicating statistical significance between them was not demonstrated.
| Concentration (cells/ml) | Resuspension volume | Anyplex™ II HPV 28 | Aptima HPV | Alinity m HR HPV | cobas® 8800 HPV | Cumulative total, all assays (%, 95% CI) | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| Manual | Vortex | Manual | Vortex | Manual | Vortex | Manual | Vortex | |||
| 105 | 3 ml | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 24/24 (100%, 82.8–100) |
| 5 ml | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 24/24 (100%, 82.8–100) | |
| 10 ml | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 24/24 (100%, 82.8–100) | |
| 20 ml | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 24/24 (100%, 82.8–100) | |
| 104 | 3 ml | 3 | 3 | 2 | 2 | 3 | 3 | 3 | 3 | 22/24 (91.6%, 71.5–98.5) |
| 5 ml | 3 | 3 | 2 | 3 | 3 | 3 | 3 | 3 | 23/24 (95.8%, 76.8–99.7) | |
| 10 ml | 2 | 2 | 2 | 2 | 3 | 3 | 3 | 3 | 20/24 (83.3%, 61.8–94.5) | |
| 20 ml | 1 | 3 | 2 | 1 | 3 | 2 | 1 | 3 | 16/24 (66.6%, 44.6–83.5) | |
| 103 | 3 ml | 1 | 2 | 3 | 2 | 3 | 3 | 0 | 3 | 17/24 (70.8%, 48.7–86.5) |
| 5 ml | 1 | 1 | 1 | 2 | 1 | 3 | 2 | 2 | 13/24 (54.1%, 33.2–73.8) | |
| 10 ml | 0 | 1 | 0 | 2 | 0 | 3 | 1 | 1 | 8/24 (33.3%, 16.4–55.3) | |
| 20 ml | 0 | 1 | 1 | 1 | 2 | 0 | 0 | 1 | 6/24 (25.0%, 10.6–47.0) | |
| Total | 23 | 28 | 25 | 27 | 30 | 32 | 25 | 31 | ||
| Total per assay (%, 95% CI) | 51/72 (70.8%, 58.8–80.6) | 52/72 (72.2%, 60.2–81.8) | 62/72 (86.1%, 75.5–92.8) | 56/72 (77.8%, 66.2–86.4) | ||||||
At 105 cells/ml, Evalyn® Brushes produced similar results to FLOQSwabs® in that varying the resuspension volume did not affect detection rates (Table 2). Concentrations of 104 cells/ml produced cumulative detection rates of 95.8% (95% CI: 76.8–99.7) for 3 ml and 91.6% (95% CI: 71.5–98.5) for both 5-ml and 10-ml volumes. The cumulative detection was reduced to 58.3% (95% CI: 36.9–77.2) when 20 ml was used.
| Concentration (cells/ml) | Resuspension volume | Anyplex™ II HPV 28 | Aptima HPV | Alinity m HR HPV | cobas® 8800 HPV | Cumulative total, all assays (%, 95% CI) | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| Manual | Vortex | Manual | Vortex | Manual | Vortex | Manual | Vortex | |||
| 105 | 3 ml | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 24/24 (100%, 82.8–100) |
| 5 ml | 3 | 3 | 3 | 2 | 3 | 3 | 3 | 3 | 23/24 (95.8%, 76.8–99.7) | |
| 10 ml | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 24/24 (100%, 82.83–100) | |
| 20 ml | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 24/24 (100%, 82.83–100) | |
| 104 | 3 ml | 3 | 3 | 3 | 2 | 3 | 3 | 3 | 3 | 23/24 (95.8%, 76.8–99.7) |
| 5 ml | 2 | 3 | 3 | 2 | 3 | 3 | 3 | 3 | 22/24 (91.6%, 71.5–98.5) | |
| 10 ml | 3 | 3 | 3 | 2 | 3 | 3 | 3 | 2 | 22/24 (91.6%, 71.5–98.5) | |
| 20 ml | 2 | 1 | 3 | 1 | 3 | 3 | 0 | 1 | 14/24 (58.3%, 36.9–77.2) | |
| 103 | 3 ml | 3 | 1 | 3 | 0 | 2 | 2 | 1 | 3 | 15/24 (62.5%, 40.7–80.4) |
| 5 ml | 3 | 0 | 2 | 3 | 2 | 1 | 0 | 1 | 12/24 (50.0%, 29.6–70.3) | |
| 10 ml | 1 | 0 | 1 | 1 | 0 | 2 | 0 | 1 | 6/24 (25.0%, 10.6–47.0) | |
| 20 ml | 1 | 0 | 2 | 0 | 1 | 0 | 0 | 0 | 4/24 (16.6%, 5.4–38.1) | |
| Total | 30 | 23 | 32 | 22 | 29 | 29 | 22 | 26 | ||
| Total per assay (%, 95% CI) | 53/72 (73.6%, 61.7–83.0) | 54/72 (75.0%, 63.2–84.1) | 58/72 (80.6%, 70.0–88.6) | 48/72 (66.7%, 54.5–77.1) | ||||||
At the limiting dilution with resuspension volumes of 3 ml and 5 ml, the cumulative detection rates were 62.5% (95% CI: 40.7–80.4) and 50% (95% CI: 29.6–70.3), respectively. Resuspending in volumes of 10 ml or greater resulted in cumulative rates of 25% (95% CI: 10.6–47.0) and 16.6% (95% CI: 5.4–38.1), respectively. Again, relatively modest interassay variations were observed, although the magnitude of this variation was larger compared with FLOQSwabs®. The general trend across all assays was that, as resuspension volume increased, HPV detection decreased, particularly at the limiting dilution. All assays, with the exception of cobas®, detected at least one replicate at volumes of 20 ml.
Existing studies have looked at the performance of different self-collection devices [4,5,13], resuspension media [6] and preanalytical storage conditions [7–9,12]. Wolfrum et al. assessed whether self-samples taken using a Dacron swab and transported either wet (in specimen transport medium) or dry had any impact on HPV detection using the Roche Linear Array HPV genotyping test [18]. The study reported high levels of agreement for detecting HPV as well as type-specific HPV between wet and dry samples; however, discordance was discovered to be more common when dry samples were processed more than one week after sample collection. In a similar study by Lin et al., the stability of HPV DNA was investigated and it was reported that HPV was detectable in polyethylene swabs stored dry for up to one month with no loss of test performance using the cobas® 8800 HPV Test [8]. Moreover, other investigators have indicated that HPV is stable for up to 32 weeks on a dry device [7]. Such studies lend credibility to the dissemination of dry self-sampling devices for molecular HPV testing, but to our knowledge, there are no studies that have assessed the influence of resuspension volume in a systematic way.
While it is reasonable to assume that a larger volume of resuspension may have implications for analytical sensitivity, 20 ml resuspension volumes have been used in the past, as this is the standard prefilled volume associated with ThinPrep LBC vials, which are validated biospecimens for HPV testing when samples are taken by a clinician [13,19]. The present results, although based on proxies of a clinical sample, show that, for both sampling devices, FLOQSwabs® and Evalyn® Brushes, larger resuspension volumes reduced qualitative detection of HPV at limiting cellular concentrations and a resuspension volume of 5 ml or less may help mitigate against the loss of sensitivity.
Influence of vortexing on positivity
A duplicate panel was prepared and the effect of using a vortex at the time of resuspension was assessed compared with manual swirling. The impact of vortexing on the qualitative detection of HPV-16 varied according to sampling device and assay. Table 3 presents this data showing agreement between vortexing and no vortexing stratified by each assay and each device.
| Manual manipulation | Vortex manipulation | Overall agreement, % (95% CI) | McNemar's p-value | ||
|---|---|---|---|---|---|
| + | - | Total | |||
| FLOQSwab® | |||||
| Anyplex™: | |||||
| + | 22 | 1 | 23 | ||
| - | 6 | 7 | 13 | ||
| Total | 28 | 8 | 36 | 80.5% (64.9–90.2) | 0.13 |
| Aptima: | |||||
| + | 20 | 5 | 25 | ||
| - | 7 | 4 | 11 | ||
| Total | 27 | 9 | 36 | 66.6% (50.3–79.7) | 0.77 |
| Alinity: | |||||
| + | 27 | 3 | 30 | ||
| - | 5 | 1 | 6 | ||
| Total | 32 | 4 | 36 | 77.7% (61.9–88.2) | 0.72 |
| cobas®: | |||||
| + | 23 | 2 | 25 | ||
| - | 8 | 3 | 11 | ||
| Total | 31 | 5 | 36 | 72.2% (56.0–84.1) | 0.11 |
| Evalyn® Brush | |||||
| Anyplex™ Brush: | |||||
| + | 21 | 9 | 30 | ||
| - | 2 | 4 | 6 | ||
| Total | 23 | 13 | 36 | 69.4% (53.1–81.9) | 0.07 |
| Aptima: | |||||
| + | 20 | 12 | 32 | ||
| - | 2 | 2 | 4 | ||
| Total | 22 | 14 | 36 | 61.1% (44.8–75.2) | <0.05 |
| Alinity: | |||||
| + | 26 | 3 | 29 | ||
| - | 4 | 3 | 7 | ||
| Total | 30 | 6 | 36 | 80.5% (64.9–90.2) | 1.00 |
| cobas®: | |||||
| + | 21 | 1 | 22 | ||
| - | 5 | 9 | 14 | ||
| Total | 26 | 10 | 36 | 83.3% (68.1–92.1) | 0.22 |
In FLOQSwabs®, overall agreement rates for the detection of HPV-16 between manual and vortex methods were 80.5% (95% CI: 64.9–90.2), 66.6% (95% CI: 50.3–79.7), 77.7% (95% CI: 61.9–88.2) and 72.2% (95% CI: 56.0–84.1) for Anyplex[™], Aptima, Alinity and cobas®, respectively. McNemar's analysis showed no statistical significance of the distribution of discordant results indicating that manipulation method at the time of resuspension did not significantly impact detection rates.
For Evalyn® Brushes, overall agreement rates between methods were 69.4% (95% CI: 53.1–81.9), 61.1% (95% CI: 44.8–75.2), 80.5% (95% CI: 64.9–90.2) and 83.3% (95% CI: 68.1–92.1) for Anyplex™, Aptima, Alinity and cobas®, respectively. Manual manipulation was associated with higher qualitative positivity for the Aptima assay (p < 0.05) and nearly reached significance for Anyplex™ (p = 0.07). For the remaining assays, vortexing versus manual manipulation was not significantly associated with qualitative detection.
The extent of biomaterial capture can be affected by the specific collection device used, as described by Warnke et al. [20] However, most collection devices do not have a clear recommended resuspension procedure for dry samples once received at laboratories. Some studies report using a vortex to resuspend material in media [5,7,8,18], while others did not or were not clear on their resuspension process [4,9,12,13,21,22]. In the current research, using a vortex at the time of resuspension had a different impact on qualitative HPV detection depending on the device. In FLOQSwabs®, using a vortex did not significantly affect qualitative HPV detection. Comparatively, vortexing led to reduced detection (versus manual processing) for Evalyn® Brushes, which was significant for the Aptima assay.
Conclusion
This study has some disadvantages, such as using a small panel of simulated material that only included HPV-16. Additionally, cellular material was prepared and suspended in ThinPrep, a methanol-based fixative, which would not accurately reflect a self-taken sample. Importantly, we cannot say that the reduction in analytical sensitivity observed here translates into a clinically relevant issue given that HPV assays should be calibrated and applied to detect HPV levels associated with clinical disease. This said, we hope that this study provides important analytical data to inform the optimal volume of resuspension. Increasing resuspension volume generally resulted in the reduced qualitative detection of HPV, even with target amplification assays, and a resuspension volume of 5 ml or less may mitigate against false negatives. Future studies that look in detail at other parameters, such as time and environmental tolerances of self-samples in transit, would be welcome, particularly for specific combinations of devices and assays. It should also be stressed that publications that include data on self-sampling include this information on preanalytical steps to support study comparison and inform best practices.
Future perspective
Cervical cancer screening has been instrumental in reducing the burden of cervical cancer. WHO has set targets that if countries are able to meet and be on the path by 2030 to eliminate cervical cancer, then it would be possible within the next century. This is now a possibility due to the availability of excellent vaccines targeting HPV types causing a majority of cancers and screening based on HPV detection. To reach the target of 70% of the global female population being screened at least twice in their lifetime by an HPV test requires thinking beyond traditional clinician-based cervical screening. Self-sampling offers an option to reduce the barriers of screening, is being used in some countries and settings already and has been shown to have similar clinical performance to the detection of cervical precancer. However, preanalytical issues relating to storage, transportation and manipulation of dry and wet self-sampling devices is crucial to ensuring that it remains a suitable alternative approach to clinician-based screening.
Background
HPV self-sampling is gaining importance as an alternative to clinician-based cervical screening.
Preanalytical factors relating to the storage, transportation and manipulation of self-sampling devices are crucial to ensuring good clinical performance for the detection of cervical abnormalities.
Methods
Two commonly used sampling devices were used: FLOQSwab® and Evalyn® Brush.
Devices were dipped into different concentrations of a suspension of HPV-16-containing cell line and then resuspended in various volumes of ThinPrep.
Testing was performed using four clinically recognized assays: Anyplex™ II HPV 28, Aptima HPV, Alinity m HR HPV, and cobas® 8800 HPV.
Results & discussion
Varying resuspension volumes influence HPV-16 detection in dry self-samples resuspended in the laboratory.
A 5-ml or lesser resuspension volume may mitigate sensitivity loss in low cellularity samples or those with HPV levels close to analytical sensitivity thresholds.
The samples assessed were proxies of a clinical sample representing HPV-16 only.
Conclusion
Device- and assay-specific validation of downstream HPV laboratory testing is important and recommended.
Author contributions
L Connor: investigation, formal analysis, methodology and writing: original draft, review and editing. H Elasifer: investigation and resources. A Sargent: investigation, resources and writing: review and editing R Bhatia: conceptualization, project administration and writing: review and editing. C Graham: statistical analysis and writing: review and editing. K Cuschieri: project administration and writing: review and editing.
Financial & competing interests disclosure
L Connor's, H Elasifer's, R Bhatia's and K Cuschieri's institution/employer has received research funding and associated consumables from the following in the last 3 years: Cepheid, Euroimmun, GeneFirst, SelfScreen, Hiantis, Seegene, Roche, Abbott and Hologic. Reagents were provided gratis from Abbott and Aptima for the study. A Sargent has received an honorarium from Roche for speaking at the European Roche Virtual User Group Meeting in 2021. A Sargent has received travel and accommodation funding from BD and Abbott to observe the BS Cor system for HPV testing in 2020 and the prototype Alinity m HPV system for HPV testing in 2019.
The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Open access
This work is licensed under the Creative Commons Attribution 4.0 License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Papers of special note have been highlighted as: • of interest
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