Randomised trial of HPV self-sampling among non-attenders in the Slovenian cervical screening programme ZORA: comparing three different screening approaches

Abstract

BackgroundTo 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 methodsNon-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.ResultsOf 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+.ConclusionsThe 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.

Self-sampling for human papillomavirus (HPV) testing: a systematic review and meta-analysis

“…After two independent reviewers screened in duplicate and gained consensus, 149 articles were pulled for full-text review. Of these, 33 studies (reported in 34 articles) were included in the review 21–54…”

“…Substantial heterogeneity was present in all meta-analyses of screening uptake. Combining all self-sampling kit dissemination methods, meta-analysis of the 29 reported effect sizes from RCTs21–25 27 29–36 38–47 50–54 found that women were twice as likely to use cervical cancer screening services through self-sampling compared with standard-of-care screening practices (RR: 2.13, 95% CI 1.89 to 2.40, I-squared: 99.34) (figure 2).…”

“…In the 23 RCTs comparing opt-out HPV self-sampling (kit directly mailed to home address) with control,22–24 27 29–36 39 42 43 45–47 51–54 meta-analysis found that HPV self-sampling was associated with twice the likelihood of attending screening compared with control (RR: 2.27, 95% CI 1.89 to 2.71, I-squared: 99.27) (figure 3). These RCTs all took place in Europe, except for two in Canada and one in Nigeria.…”

“…Meta-analysis of five RCTs29 30 35 36 47 found a non-significant increase in likelihood of HPV screening participation for opt-in HPV self-sampling where participants requested or picked up self-sampling kits compared with control (RR: 1.28, 95% CI 0.90 to 1.82, I-squared: 98.36) (figure 5). These RCTs all took place in Europe among women aged 30–65 who were hard to reach through conventional cervical cancer screening programmes.…”

“…Of the 29 included RCTs, 26 took place in high-income countries21–25 27 29–36 41–47 50–54 and 3 in LMICs38–40 as classified by the World Bank. In meta-analysis, HPV self-sampling was associated with increased uptake in both economic classifications, with greater impact in high-income countries (RR: 2.24, 95% CI 1.86 to 2.71, I-squared: 99.38) than in LMICs (RR: 1.54, 95% CI 1.01 to 2.34, I-squared: 98.43).…”