**1. Introduction**

Cervical cancer is one of the most important malignancies affecting women and caused about 342,000 deaths in 2020. It is well-known that this type of tumour is caused by persisting infection of high-risk human papillomavirus (hrHPV). Recently, the World Health Organization (WHO) developed a global strategy for cervical cancer elimination to be reached by 2030, and one of the points of this strategy is to reach the 70% of women screened using a high-performance test by the age of 35, and again by the age of 45 [1].

Eighty-five percent of cervical cancer deaths occur in developing countries, where it still represents the first leading cancer death cause. Self-sampling could be an additional strategy to reach unscreened and under-screened women, especially in middle- and lowincome countries.

As of now, the global use of HPV self-sampling is still limited. Only 17 countries with identified screening programs recommend the use of self-sampling in primary screening

or to reach non-responder women. However, the COVID-19 pandemic has accelerated worldwide self-sampling introduction, which is now considered an important strategy to increase screening coverage in the coming years [2].

The importance of self-sampling in improving adherence to cervical cancer screening has been well documented in the last few years, especially for women not participating in prevention programs due to different socio-cultural reasons [3,4]. The main barrier is related to the need for a physician or healthcare worker for cervical specimen collection [5]. The use of alternative and less invasive samples, such as self-collected vaginal and first-void urine samples, represents the best choice to overcome this issue.

Different devices are commercially available and seem to be suitable for this purpose. However, the accuracy of clinically validated PCR-based human papillomavirus detection kits on self-samples needs to be evaluated as compared to clinician-collected samples, as already reported in a recent meta-analysis by Arbyn et al. [6]. Previous studies have already shown that HPV testing conducted on vaginal self-samples has a similar sensitivity compared to testing on physician-collected cervical samples for the detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) [6–8]. Nevertheless, the sample preparation and preanalytical processes used are highly different [9]. Different assays suggest in their manufacturer instructions to start from different specimen volumes for hrHPV detection, and this could influence the result obtained, especially for self-collected samples. Moreover, the results obtained from samples collected using dry vaginal swabs could be conditioned from the solution volume used for swab resuspension.

Urine seems to be a good, non-invasive, and more acceptable material for the detection of HPV and sexually transmitted infections [10–12]. Moreover, because first-void urine contains exfoliated cells from the cervix [13], it could be considered a specimen alternative to a clinician-collected cervical sample for the molecular detection of HPV. Furthermore, several studies have recently been published reporting consistent results from the use of urine samples for HPV detection [14–18]. Also for this kind of sample, the performance of urine-based HPV testing for CIN2+ detection is affected by the various HPV assays and non-standardized urine collection methods [14].

The objective of this pilot study was to evaluate accuracy of the BD Onclarity™ HPV assay on self-collected vaginal and first-void urine samples as compared to cliniciancollected cervical samples.

The BD Onclarity™ assay has been internationally validated for liquid-phase cytology samples for use in primary HPV screening according to both the Mejer guidelines and the VALGENT genotyping protocol [19,20]; in this study we evaluated the performance of this test, already extensively studied in a screening setting, on self-collected samples in order to assess its usefulness to increase adherence to screening programs.

In particular, in this pilot study, we decided to use the same BD Onclarity™ protocol that is used for cervical specimens, without making changes, in order to discover whether the same protocol could also work for different samples compared to a liquid-phase cytology sample.
