high risk HPV detection from urine and self-collected specimens as patient friendly alternative for physician taken smears

Since 2017, the Dutch screeningsprogram for cervical cancer has changed. In the
new screeningsprogram women are tested on the presence of human papillomavirus
(HPV) in physician taken smears. A HPV-test (DNA-based) is more sensitive in
detecting cervical changes. The new test detects more women with cervical
abnormalities as compared to microscopical analysis of cervical cells. Not
every woman feels comfortable to visit a physician for cervical sampling
(physician taken smear). For these women, it is possible to request a
self-sampling device (Evalyn Brush). Evalyn Brush samples are also tested for
HPV presence and in this way early detection of cervical changes is possible.
The Evalyn Brush is already an accepted method and used in the Dutch
screeningsprogram for cervical cancer (P. Ketelaars et al. 2017, M. Leinonen et
al. 2018). Another option for HPV detection is urine. Both urine and/or a
self-collected specimen of the cervix can serve as more patient-friendly ways
of sampling. However, we don*t know how much urine, which DNA/RNA isolation
method, and which HPV detection method will results in the most optimal HPV
detection as compared to the physician taken smear (A. Vosters et al. 2014, A.
Leeman et al. 2017, S. Van Keer et al. 2017).
Therefore, we want to ask non-pregnant HPV-positive patients (18 years or
older) to sample 2 times with the Evalyn Brush and to collect urine by using
the Collipee system. The Collipee system enables collection of first void
urine. In this way, we can investigate with which method HPV is best detected.
Furthermore, we can study HPV stability in time. This is necessary because it's
unclear how fast women send self-collected samples to the screeningslaboratory.
Results are compared with the results from the smears taken by the
gynecologist.

The main goal of this technical feasibility study is to investigate with which
HPV isolation and detection method urine and the Evalyn Brush can be combined.
HPV stability in urine and on the Evalyn Brush will be investigated as it*s
unclear how fast women send self-collected samples to the laboratory. It*s
unknown what the effect is on HPV detection when samples are not tested
immediately.

1) Investigate if HPV DNA and/or RNA can be detected on the Evalyn Brush on
timepoints T=0 and 4 days after sampling (determine if HPV degrades on Evalyn
Brush in time).
2) Investigate which HPV detection method can be combined with the Evalyn Brush
and which method provides most optimal results compared to the physician taken
smear (gold standard).
3) Investigate if urine can be used for HPV DNA and/or RNA detection by
comparing different isolation and detection methods.

Small technical feasibilty study to investigate different parameters: 1) sample
type, 2) isolation methods, and 3) HPV detection methods. Gynecologist includes
women and provides Collipee system and 2 Evalyn Brushes. Patient samples will
be anonimised and labelled 1-10 for the researchers. Gynecologist can trace
back results to patients. Patients will only be informed about diagnostic smear.
Inclusion of women stops when both urine and 2 Evalyn Brushes of 10 women are
collected. When a woman doesn*t provide urine, but she does provide 2 Evalyn
Brushes than the brushes will be used for the study. More than 10 women will
then by included. When a woman does not want to participate in the study after
providing samples, those samples or results will be excluded.

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