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Comparative Study
. 2018 Jan;118(1):138-144.
doi: 10.1038/bjc.2017.371. Epub 2017 Nov 14.

High-grade cervical intraepithelial neoplasia in human papillomavirus self-sampling of screening non-attenders

J U H Lam  1 , K M Elfström  2 , D M Ejegod  1 , H Pedersen  1 , C Rygaard  1 , M Rebolj  3 , E Lynge  4 , K E Juul  5 , S K Kjær  5   6 , J Dillner  2   7 , J Bonde  1   3
Affiliations
Comparative Study

High-grade cervical intraepithelial neoplasia in human papillomavirus self-sampling of screening non-attenders

J U H Lam et al. Br J Cancer. 2018 Jan.

Abstract

Background: Self-sampling for human papillomavirus (HPV) offered to women who do not participate in cervical cancer screening is an increasingly popular method to increase screening coverage. The rationale behind self-sampling is that unscreened women harbour a high proportion of undetected precancer lesions. Here, we compare the cervical intraepithelial neoplasia grade 2 or worse (⩾CIN2) detection rate between non-attenders who participated in self-sampling and women attending routine screening.

Methods: A total of 23 632 women who were qualified as non-attenders in the Copenhagen Region were invited for HPV-based self-sampling. Of these, 4824 women returned a self-sample, and HPV-positive women were referred for cytology and HPV co-testing as follow-up. The entire cohort and a reference cohort (3347 routinely screened women) were followed for histopathology confirmed ⩾CIN2. Odds ratio (OR) and the relative positive predictive value of ⩾CIN2 detection between the two populations were estimated.

Results: Women participating in self-sampling had a higher ⩾CIN2 detection than women undergoing routine cytology-based screening (OR=1.83, 95% CI: 1.21-2.77) and a similar detection as routinely screened women tested with cytology and HPV testing (OR=1.03, 95% CI: 0.75-1.40). The positive predictive value for ⩾CIN2 was higher in screening non-attenders than in routinely HPV- and cytology-screened screened women (36.5% vs 25.6%, respectively).

Conclusions: Self-sampling offered to non-attenders showed higher detection rates for ⩾CIN2 than routine cytology-based screening, and similar detection rates as HPV and cytology co-testing. This reinforces the importance of self-sampling for screening non-attenders in organised cervical cancer screening.

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Conflict of interest statement

JUHL attended meetings with various HPV device manufacturers. MR attended meetings with various HPV device manufacturers. She and her former employer received fees for lectures on her behalf from Qiagen. DME attended meetings with various HPV device manufacturers. She received honoraria from BD and Qiagen for lectures. HP attended meetings with various HPV device manufacturers. CR participated in meetings with Roche with fee paid to the University of Copenhagen. EL participated in meetings with Roche and Astra-Zeneca with fees paid to the University of Copenhagen, and was unpaid advisor to GenProbe and NorChip. Roche has provided test kits to Trial23. SKK has received lecture fees, scientific advisory board fees from Merck, Sanofi Pasteur MSD, BD, and unrestricted research grants through the affiliating institute from Merck. JD has received grants to his institution for studies on HPV vaccination from Merck/SPMSD. JB attended meetings with various HPV device manufacturers. He used to serve as a paid advisor to Roche and Genomica, and has received honoraria from Hologic/Gen-Probe, Roche, Qiagen, Genomica, and BD Diagnostics for lectures. He is principal investigator on studies funded by BD diagnostics. Hvidovre Hospital holds a recompense agreement with Genomica on a KRAS/BRAF diagnostic system. KME and KEJ declare no conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of the CSi study design, follow-up triage, and ⩾CIN2 detection rate. *Of all tested samples, 4 were invalid on all HPV assays, 773 samples had a positive test result on any of the three assays, and 246 of these had biopsies taken. Of the 4124 HPV-negative women, 36 had a biopsy taken (for an unknown reason). Because of a hardware failure on the Onclarity assay, some women received their result based on CLART and HC2 only. The samples were later re-tested on Onclarity, with 36 women having a positive test result. Owing to hospital practice, these women did not receive a supplement result. The flowchart illustrates the follow-up process based on the result the women received, that is, the result that influenced their clinical management. **Non-responders remained unscreened during the whole study period; the CIN2 or worse cases detected might be symptom-related indications rather than screening. CIN=cervical intraepithelial neoplasia.
Figure 2
Figure 2
Flowchart of the Horizon study design, follow-up triage, and ⩾CIN2 detection. *Of the 3347 screened women, 16 (0.48%) were inadequate for cytology reading. One of the women had a histology sample registered with normal findings. This contributed to a total of 336 biopsies taken. **Women were followed-up according to routine practice based on the cytology result only. An active follow-up was performed on women with cytology normal HPV-positive findings according to the study protocol that was repeat testing after 18 months. Women with normal cytology and negative HPV test results were referred back to the routine screening programme; some of these had a histology sample taken despite the recommendations. Women who were cytology negative and HPV positive were invited for repeated testing after 18 months. All HPV test results reported here took into account the testing results on any of the four assays. CIN=cervical intraepithelial neoplasia.
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References

    1. Bais AG, van Kemenade FJ, Berkhof J, Verheijen RH, Snijders PJ, Voorhorst F, Babovic M, van Ballegooijen M, Helmerhorst TJ, Meijer CJ (2007) Human papillomavirus testing on self-sampled cervicovaginal brushes: an effective alternative to protect nonresponders in cervical screening programs. Int J Cancer 120(7): 1505–1510. - PubMed
    1. Bjerregaard B, Larsen OB (2011) The Danish Pathology Register. Scand J Public Health 39(7 Suppl): 72–74. - PubMed
    1. Bonde J, Rebolj M, Ejegod DM, Preisler S, Lynge E, Rygaard C (2014) HPV prevalence and genotype distribution in a population-based split-sample study of well-screened women using CLART HPV2 human papillomavirus genotype microarray system. BMC Infect Dis 14: 413. - PMC - PubMed
    1. (2014) Danish Quality Assurance Database for the Cervical Cancer Screening Program Annual report 2014 Vol. 2015.
    1. Dugue PA, Lynge E, Bjerregaard B, Rebolj M (2012) Non-participation in screening: the case of cervical cancer in Denmark. Prev Med 54(3-4): 266–269. - PubMed

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