Main findings
Our study showed good concordance in HPV detection between paired self-samples and GP-collected samples. Home-based self-sampling using the Evalyn Brush was a well-accepted screening method. Compared with GP-sampling, no cases of underlying CIN2+ were overlooked by self-sampling.
Strengths and limitations
A key strength of our study was that we used a combination of a clinically validated self-sampling device and a clinically validated automated PCR-based HPV DNA test assay on paired samples [
10,
19]. Furthermore, women collected the self-sample at home without supervision by healthcare professionals, which is the most relevant setting for testing self-sampling before its rollout in a routine screening program.
The main limitation is the time span between the GP-collected samples and self-samples, making the results not directly comparable. Still, the questionnaire data helped us to interpret discordant results. Another explanation for the discordant results could be that the self-samples had been subjected to freezing at -80 °C prior to the HPV testing which potentially could have affected the amount of HPV DNA in the self-samples, unlike the GP-collected samples which have not been frozen. However, since DNA is generally considered to be stable at -80 °C, we assume that this has not significantly affected the results and conclusions of this study. Our study population comprised women with ASC-US of whom one fourth was referred for colposcopy due to concurrent HPV infection; thus, histological results were not available for women with HPV-negative GP-collected samples. Ideally, histological results should have been available from all women. This was not possible in our set-up. Still, the available histological results allowed us to make the important conclusion that no cases of underlying CIN2+ had been overlooked by self-sampling which is important when implementing self-sampling in routine screening practice.
Even though our study population can be considered a “low-risk” population compared with the referral populations that have typically been targeted in similar studies [
7], our population is still not representative of a screening population. Consequently, this study cannot be generalized to such populations.
Interpretation and comparison with previous studies
The concordance in our study (k = 0.70) was comparable with the mean k (k = 0.71) reported for brush devices combined with PCR-based HPV DNA tests in the review by Schmeink et al. [
7], but higher than the mean k (k = 0.66) in the review by Petiginat et al. [
8]. This difference might be explained by differences in self-sampling devices, HPV tests, laboratory protocols, and study populations (screening or referral population). In our study, some of the discrepancy in the HPV concordance between self-sampling and GP-sampling could plausibly also be explained by spontaneous clearance or a new HPV exposure due to the time span separating the samples.
In our study, the sensitivity and specificity of HPV detection (of any type) was 80.9% and 91.6% in self-samples, respectively, when using the GP-collected samples as reference standard. These results are comparable to those by Van Baars et al. [
10] who found a sensitivity of 82.7% and a specificity of 89.5% for HPV detection using the Evalyn Brush together with the clinically validated PCR-based GP5+/6+ HPV DNA test in a referral population. Thus, self-sampling using validated HPV DNA analyses seems feasible, but the optimal combination of self-sample device and HPV DNA test remains unknown.
Ketelaars et al. [
9] found no significant differences in HPV16/18 prevalence between samples, whereas the prevalence of HPV of other types was significantly higher in self-samples (8.0%) than in GP-collected samples (6.3%). We observed no significant differences in the HPV prevalence between samples, but the same trend was seen, especially for the prevalence of HPV of other types (21.1% versus 18.3%, respectively). The higher HPV prevalence in self-samples compared with GP-collected samples increases referral rates, especially because reflex cytology triage is not possible on self-sampled material. To avoid excessive referral rates in women with HPV-positive self-samples without underlying CIN2+, a direct triage method like DNA methylation [
20] could be considered to reduce referral rates and prevent overtreatment.
Most importantly, we showed that no underlying CIN2+ cases were overlooked by self-sampling. Some of the women in the GP-collected HPV negative/self-sample HPV-positive group might possibly have had underlying CIN2+, but this cannot be explored further in this study since referral for colposcopy was based on the result of the GP-collected sample.
The self-sampling device and user instructions must be acceptable if we wish to improve screening participation by this method. In our study, more than 85% expressed confidence in having collected the self-sample correctly, and only 5% expressed discomfort with collecting the sample. Hence, home-based self-sampling using the Evalyn Brush appeared to be a well-accepted screening method. Yet, almost 10% reported uncertainty regarding sample collection and some stated the lack of a click when rotating the brush as their reason. Despite small numbers, this finding is higher than reported by Van Baars et al. [
10] (3.0%) and Ketelaars et al. [
9] (0.8%) who used the same device in a referral and screening population, respectively. This difference might be explained by the fact that the women in our study performed home-based self-sampling, whereas in the study by Van Baars et al. [
10] the women performed clinic-based self-sampling allowing them to ask questions and receive guidance. Nevertheless, our results suggest that if home-based self-sampling were to be rolled out in a routine setting, it should be considered giving women the opportunity to contact healthcare professionals for guidance.