Randomised trial of HPV self-sampling among non-attenders in the Slovenian cervical screening programme ZORA: comparing three different screening approaches
Article Category: Research Article
Published Online: Sep 14, 2018
Page range: 399 - 412
Received: May 20, 2018
Accepted: Jul 13, 2018
DOI: https://doi.org/10.2478/raon-2018-0036
© 2018 Urska Ivanus, Tine Jerman, Alenka Repse Fokter, Iztok Takac, Veronika Kloboves Prevodnik, Mateja Marcec, Ursula Salobir Gajsek, Maja Pakiz, Jakob Koren, Simona Hutter Celik, Kristina Gornik Kramberger, Ulrika Klopcic, Rajko Kavalar, Simona Sramek Zatler, Biljana Grcar Kuzmanov, Mojca Florjancic, Natasa Nolde, Srdjan Novakovic, Mario Poljak, Maja Primic Zakelj, published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.
Background
To overcome obstacles within the Slovenian organised cervical cancer screening programme, a randomised pilot study of human papillomavirus (HPV) self-sampling among non-attenders was performed, aiming to assess three different screening approaches.
Participants and methods
Non-attenders aged 30–64 years from two Slovenian regions were randomised to two HPV self-sampling groups–the opt-in (I1, n = 14.400) and the opt-out (I2, n = 9.556), with a control group (P, n = 2.600). Self-collected samples were analysed using the Hybrid Capture 2 assay. HPV-positive women were invited to a colposcopy. The overall and type-specific intention-to-screen response rates and histological outcomes with a positive predictive value (PPV) according to the women’s age, the screening approach, the level of protection resulting from previous screening history, and the region of residence were assessed.
Results
Of the 26.556 women enrolled, 8.972 (33.8%) responded with self-sample for HPV testing and/or traditional cytology within one year of enrolment. Response rates were 37.7%, 34.0% and 18.4% (p < 0.050) for opt-out, opt-in and control groups. Cervical intraepithelial neoplasia (CIN)2+ was diagnosed in 3.9/1.000, 3.4/1.000, and 3.1/1.000 women (p > 0.050), respectively. PPV of the HPV self-sampling was 12.0% and 9.6% for CIN2+ and CIN3+. The highest PPV was obtained in non-attenders in screening programme for more than 10-years and concordant results of HPV testing with 40.8% for CIN2+ and 38.8% for CIN3+.
Conclusions
The results of our study show that a high response to HPV self-sampling can be achieved also in an opt-in approach, if women are encouraged to choose between self-sampling at home and screening with gynaecologist. In addition, clinically important risk difference for a high-grade cervical lesion exists in the case of a positive result of HPV testing on self-collected samples, depending on the length of the interval since last screening. Stratified management of these women should be strongly considered. Women who were not screened with cytology for at least 10 years should be referred to immediate colposcopy for histology verification instead to delayed re-testing.