The selective uptake of screening by healthy participants and its impact on the evaluation of screening effectiveness in non-randomized studies have been discussed, but hardly studied. We quantified excess mortality among cervical screening non-participants compared to participants. Based on Danish healthcare registers, we determined women's participation in cervical screening in 1990–1993 (one screening round) and 1990–1997 (two screening rounds). Women were followed until end of 2010. We computed hazard ratios (HR) comparing non-participants' and participants' risk of death, and analyzed the impact of age, calendar period of screening evaluation, screening intensity, length of follow-up and cause of death. After one screening round, the 17-year HR of death in non-participants was 1.61 (95% CI: 1.59–1.63), with an increasing trend over calendar time. After two rounds, regular non-participants had a HR of 2.09 (95% CI: 2.05–2.14) compared to regular participants. The HR for human papillomavirus (HPV)-related cancers other than cervical cancer was 3.80 (95% CI: 2.67–5.41). Younger women, whose coverage rates were higher, had higher all-cause mortality HRs. Women screened more frequently than recommended had the same mortality as those screened as recommended. Acute illness did not seem to be a major reason for non-participation, as the excess risk of death was not higher in the first years following screening evaluation. Non-participants in cervical screening had substantially higher all-cause mortality than participants, and a particularly increased risk of HPV-related causes of death. These results indicate that improper control for the selective uptake of cervical screening may result in overestimating its effectiveness.What's new?
In countries with routine cancer screening, certain factors are associated with choosing not to participate. These factors are also associated with poorer overall health; however, their impact on all-cause mortality is not clear. In this study, the authors quantified excess mortality among non-participants in cervical-cancer screening in Denmark. Long-term, all-cause mortality was substantially higher in non-participants, as was their risk of dying from HPV-related cancers. These results indicate that improper control for the selective uptake of cervical screening may result in overestimating its effectiveness.