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. 2019 Dec 11;17(1):228.
doi: 10.1186/s12916-019-1460-0.

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

Clare A Aitken  1 , Heleen M E van Agt  2 , Albert G Siebers  3   4 , Folkert J van Kemenade  5 , Hubert G M Niesters  6 , Willem J G Melchers  7 , Judith E M Vedder  4 , Rob Schuurman  8   9 , Adriaan J C van den Brule  10 , Hans C van der Linden  10 , John W J Hinrichs  11   12 , Anco Molijn  13 , Klaas J Hoogduin  13 , Bettien M van Hemel  14 , Inge M C M de Kok  2
Affiliations

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

Clare A Aitken et al. BMC Med. .

Abstract

Background: In 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.

Methods: We 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).

Results: Participation 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.

Conclusions: This 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.

Keywords: Cancer screening programmes; Cervical cancer screening; Population-based screening; hrHPV screening.

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Conflict of interest statement

CA, HvA and IdK report receiving funding from the Dutch National Institute for Public Health and the Environment (Rijksinstituut voor Volksgezondheid en Milieu) for the conduct of this study. AM reports receiving funding from the Facilitaire Samenwerking Bevolkingsonderzoeken for work related to this study and funding from DDL Laboratories outside of the study. All other authors have no conflicts of interest to declare.

Figures

Fig. 1
Fig. 1
a Screening protocol of the cytology-based screening programme. b Screening protocol of the HPV-based screening programme. NILM negative for intraepithelial lesion or malignancy, ASC-US atypical squamous cells of undetermined significance, LSIL low-grade squamous intraepithelial lesion, HSIL high-grade squamous intraepithelial lesion
Fig. 2
Fig. 2
Participation rate in hrHPV-based screening (2017) and in cytology-based screening (2015) by age. 454,573 women participated in the hrHPV-based screening programme, and 483,146 women participated in the cytology-based screening programme. N.B. Please refer to Additional file 1 for a comprehensive explanation of age group criteria. *Pearson’s chi-square test significantly different between test types (p < 0.001)
Fig. 3
Fig. 3
Flowchart of participation, referral and detection within the new hrHPV-based screening programme, 2017 cohort. Pearson’s chi-square test significantly different for hrHPV positivity, direct referral rates and follow-up smear (p < 0.001) and CIN2+ detection rates from direct referral (p = 0.002) between clinician-collected and self-sampling. Pearson’s chi-square test not significantly different for proportions of histology or cytology tests (from direct referral, p = 0.805; from indirect referral, p = 0.042), indirect referral rate (p = 0.974), proportions with recommendation to await next screening invitation (p = 0.884), CIN2+ detection rates from indirect referral (p = 0.319) between clinician-collected and self-sampling. N.B. Sum of advice after screening will not be 100% due to a proportion of screens with repeat cytology due to inadequate cytology quality or loss to follow-up (self-sampling arm only). Cytology was assessed in 90.1% of hrHPV-positive cases in the self-sampling arm. Repeat cytology because of inadequate cytology quality after a positive screen result was recommended in 1.3% of clinician-collected cases and 1.6% of self-sampling cases with cytology (1.3% of self-sampling cases had other recommendations). Repeat cytology because of inadequate cytology quality in a follow-up smear at 6 months was recommended in 1.5% of clinician-collected cases and 1.8% of self-sampling cases
Fig. 4
Fig. 4
Screen positivity and direct referral rates by screening programme and age. Cytology-based screening results are based on the 2015 screening cohort, and hrHPV-based screening results are based on the 2017 screening cohort. Screen positivity in the hrHPV-based screening programme is hrHPV-positive, irrespective of reflex cytology results. 454,573 women participated in the hrHPV-based screening programme, and 483,146 women participated in the cytology-based screening programme. N.B. Please refer to Additional file 1 for a comprehensive explanation of age group criteria. *Pearson’s chi-square test significantly different for screen positivity rates between test types (p < 0.001). †Pearson’s chi-square test significantly different for referral rates between test types (p < 0.001)
Fig. 5
Fig. 5
Total referral and CIN2+ detection rates in all screened women by screening programme and age. Cytology-based screening results are based on the 2015 screening cohort, and hrHPV-based screening results are based on the 2017 screening cohort. 454,573 women participated in the hrHPV-based screening programme, and 483,146 women participated in the cytology-based screening programme. Referral rates include direct and indirect referrals. N.B. Please refer to Additional file 1 for a comprehensive explanation of age group criteria. *Pearson’s chi-square test significantly different for referral rates between test types (p < 0.001). †Pearson’s chi-square test significantly different for CIN2+ detection rates between test types (p < 0.001)
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