Introduction of primary screening using high-risk HPV DNA detection in the Dutch cervical cancer screening programme: a population-based cohort study

Abstract

BackgroundIn January 2017, the Dutch cervical cancer screening programme transitioned from cytomorphological to primary high-risk HPV (hrHPV) DNA screening, including the introduction of self-sampling, for women aged between 30 and 60 years. The Netherlands was the first country to switch to hrHPV screening at the national level. We investigated the health impact of this transition by comparing performance indicators from the new hrHPV-based programme with the previous cytology-based programme.MethodsWe obtained data from the Dutch nationwide network and registry of histo- and cytopathology (PALGA) for 454,573 women eligible for screening in 2017 who participated in the hrHPV-based programme between 1 January 2017 and 30 June 2018 (maximum follow-up of almost 21 months) and for 483,146 women eligible for screening in 2015 who participated in the cytology-based programme between 1 January 2015 and 31 March 2016 (maximum follow-up of 40 months). We compared indicators of participation (participation rate), referral (screen positivity; referral rate) and detection (cervical intraepithelial neoplasia (CIN) detection; number of referrals per detected CIN lesion).ResultsParticipation in the hrHPV-based programme was significantly lower than that in the cytology-based programme (61% vs 64%). Screen positivity and direct referral rates were significantly higher in the hrHPV-based programme (positivity rate: 5% vs 9%; referral rate: 1% vs 3%). CIN2+ detection increased from 11 to 14 per 1000 women screened. Overall, approximately 2.2 times more clinical irrelevant findings (i.e. ≤CIN1) were found in the hrHPV-based programme, compared with approximately 1·3 times more clinically relevant findings (i.e. CIN2+); this difference was mostly due to a national policy change recommending colposcopy, rather than observation, of hrHPV-positive, ASC-US/LSIL results in the hrHPV-based programme.ConclusionsThis is the first time that comprehensive results of nationwide implementation of hrHPV-based screening have been reported using high-quality data with a long follow-up. We have shown that both benefits and potential harms are higher in one screening round of a well-implemented hrHPV-based screening programme than in an established cytology-based programme. Lower participation in the new hrHPV programme may be due to factors such as invitation policy changes and the phased roll-out of the new programme. Our findings add further to evidence from trials and modelling studies on the effectiveness of hrHPV-based screening.

<p>Clinical Performance of Human Papillomavirus (HPV) Testing versus Cytology for Cervical Cancer Screening: Results of a Large Danish Implementation Study</p>

“…This is in line with the findings of randomised trials [2][3][4][5][6][7][8] and supports the higher sensitivity of HPV testing than cytology. Moreover, our finding is in line with previous implementation studies from England, 12 Netherlands, 28 Italy 21,22,25 and Finland. 18 In our study, the CIN3+ detection was 40-50% higher in the HPV than cytology group.…”

“…Our analysis also showed that HPV screening resulted in more colposcopy referrals at baseline than cytology, in line with previous results. 12,18,21,22,25,28 Excessive colposcopy referrals are problematic because they may lead to overtreatment of regressive CIN2, 4 and CIN treatment may increase the risk of pregnancy-related morbidity. 38 In our study, approximately 80% more women were referred to immediate colposcopy in the HPV than cytology group (3.8% versus 2.1%).…”

“…Our referral rate in the HPV group (3.8%) was similar to the baseline referral rate in the English pilot (4.2%), 12 but slightly higher than in the Dutch HPV-based screening program (3.0%). 28 In our study, we used a highly sensitive HPV-based screening strategy, referring all women with HPV16/18 regardless of cytology. This corresponds to algorithms in the USA 39 and Australia, 16 whereas most European countries only refer HPV-positive women with abnormal cytology.…”

“…This corresponds to algorithms in the USA 39 and Australia, 16 whereas most European countries only refer HPV-positive women with abnormal cytology. 12,15,18,19,28 In the cytology group, we employed a conservative strategy, where women with LSIL were only referred to colposcopy if they were HPV mRNA positive. This is consistent with Danish guidelines 29 which recommend HPV mRNA testing for LSIL triage, because it has been shown that HPV mRNA testing of LSIL provides higher specificity and lower referral rates than HPV DNA testing of LSIL, with similar sensitivity.…”

“…[11][12][13][14][15][16][17] On this basis, data on the performance of HPV-based screening in a real-world clinical setting, in contrast to a randomised research setting, are beginning to emerge. 12,15,[18][19][20][21][22][23][24][25][26][27][28] However, only few of these studies compared HPV-based screening with a contemporary control group screened by cytology. 12,18,19 In Denmark, national guidelines recommend screening every 3 years in women aged 23-49 and every 5 years in women aged 50-64.…”