Participation and relative cost of attendance by direct-mail compared to opt-in invitation strategy for HPV self-sampling targeting cervical screening non-attenders: A large-scale, randomized, pragmatic study.

Broad accessibility to cervical cancer screening and high participation rate is essential to reduce cervical cancer incidence. HPV self-sampling is an alternative to clinician collected cervical samples to increase accessibility and screening coverage. To inform on deployment strategies of HPV self-sampling, this large-scale, randomized, pragmatic study compared two invitation modalities; direct-mail and opt-in. The study included screening non-attenders from the Capital Region of Denmark randomly allocated (1:4) to a direct-mail or opt-in invitation for cervical screening by HPV self-sampling. Primary endpoint was screening participation; secondary endpoints were HPV prevalence and histology outcome. Adherence to follow-up and cost were also evaluated. After exclusion of hysterectomized/non-accessible women, 49,393 women were invited: 9639 by direct-mail, and 39,754 by the opt-in offer. A direct-mail invitation for HPV self-sampling yielded a significant higher participation than an opt-in invitation. HPV self-sample participation for direct-mail was 25.2% (n = 2426), opt-in participation was 20.2% (n = 8047), adjusted OR = 1.27, 95% CI 1.20-1.34. Participation increased with age (p < .0001) for both strategies and decreased with screening history of non-attendance (p < .0001). Interaction between invitation strategy and age/screening history was found; more women below 50 years of age participated by direct-mail compared to opt-in (p < .0001) and higher participation by direct-mail group was found in women with a short history of non-attendance (p < .0001). Participation of long-term unscreened women was similar between arms. The relative cost was ≈14 HPV self-sample kits distributed per additional participant by direct-mail over opt-in. HPV prevalence, adherence to follow-up, and detection of high-grade cervical intraepithelial neoplasia was similar between invitation strategies.