Human papillomavirus detection in urine: Effect of a first-void urine collection device and timing of collection.

Great interest has been directed towards the use of first-void (FV) urine as a liquid biopsy for high-risk HPV DNA testing. The aim of this study was to investigate the potential effect of a first generation FV urine collection device on the detection of HPV DNA and to assess if the concentration of HPV DNA varies between FV urine collected in the morning and those collected later during the day. In this prospective cohort study, 33 self-reported HPV-positive women participated. An FV urine sample was collected by these women in the morning (first urine of the day) and another sample was collected later that day for four consecutive days using two different collection methods; i.e., the Colli-Pee® and a standard urine cup. Samples were collected at home and returned at ambient temperature to the laboratory by postal mail. HPV DNA testing was conducted with the Riatol qPCR HPV genotyping assay. Based on the combined generalized linear mixed model used, there was no significant impact of the timing of collection (morning versus later during the day) on copies of HPV DNA, whereas Colli-Pee® collected samples show higher HPV concentrations than cup collected samples. However, at high concentrations of hDNA, the benefit of the Colli-Pee® disappeared.

Human papillomavirus genotype and viral load agreement between paired first-void urine and clinician-collected cervical samples.

The performance and acceptability of first-void urine as specimen for the detection of HPV DNA in a Belgian referral population was evaluated using an optimized sample collection and processing protocol. One hundred ten first-void urine and cervical samples were collected from 25- to 64-year-old women who were referred for colposcopy (January-November 2016). Paired samples were analyzed by the Riatol qPCR HPV genotyping assay. Acceptability data were gathered through questionnaires (NCT02714127). A higher high-risk HPV DNA prevalence was observed in first-void urine (n = 76/110) compared to cervical samples (n = 73/110), with HPV31 and HPV16/31 being most prevalent correspondingly. For both any and high-risk HPV DNA, good agreement was observed between paired samples (Cohen's Kappa of 0.660 (95% CI: 0.486-0.833) and 0.688 (95% CI: 0.542-0.835), respectively). In addition, significant positive correlations in HPV copies (per microliter of DNA extract) between paired samples were observed for HPV16 (rs = 0.670; FDR (false discovery rate)-adjusted p = 0.006), HPV18 (rs = 0.893; FDR-adjusted p = 0.031), HPV31 (rs = 0.527; FDR-adjusted p = 0.031), HPV53 (rs = 0.691; FDR-adjusted p = 0.017), and HPV68 (rs = 0.569; FDR-adjusted p = 0.031). First-void urine sampling using a first-void urine collection device was preferred over a clinician-collected cervical sample. And mostly, first-void urine sampling at home was favored over collection at the clinic or the general practitioner's office. First-void urine sampling is a highly preferred, non-invasive method that ensures good agreement in HPV DNA (copies) with reference cervical samples. It is particularly interesting as a screening technique to reach non-participants, and its clinical performance should be further evaluated.

Long-Term Follow-up of HPV Infection Using Urine and Cervical Quantitative HPV DNA Testing.

The link between infection with high-risk human papillomavirus (hrHPV) and cervical cancer has been clearly demonstrated. Virological end-points showing the absence of persistent HPV infection are now accepted as a way of monitoring the impact of prophylactic vaccination programs and therapeutic vaccine trials. This study investigated the use of urine samples, which can be collected by self-sampling at home, instead of cervical samples for follow-up of an HPV intervention trial. Eighteen initially HPV DNA-positive women participating in an HPV therapeutic vaccine trial were monitored during a three-year follow-up period. A total of 172 urine samples and 85 cervical samples were collected. We obtained a paired urine sample for each of the 85 cervical samples by recovering urine samples from six monthly gynaecological examinations. We performed a small pilot study in which the participating women used a urine collection device at home and returned their urine sample to the laboratory by mail. All samples were analyzed using quantitative real-time HPV DNA PCR. A good association (κ value of 0.65) was found between the presence of HPV DNA in urine and a subsequent cervical sample. Comparisons of the number of HPV DNA copies in urine and paired cervical samples revealed a significant Spearman rho of 0.676. This correlation was superior in women with severe lesions. The HPV DNA results of the small pilot study based on self-collected urine samples at home are consistent with previous and subsequent urine and/or cervical results. We demonstrated that urine sampling may be a valid alternative to cervical samples for the follow-up of HPV intervention trials or programs. The potential clinical value of urine viral load monitoring should be further investigated.