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

Abstract

Background

Human papillomavirus (HPV) testing is increasingly used as the primary cervical cancer screening test. In a large pilot implementation, we compared participation, referrals and detection of high-grade cervical intraepithelial neoplasia (CIN) in HPV- versus cytology-based cervical cancer screening.

Methods

The implementation was embedded into the routine screening program at Lillebaelt Hospital, Department of Pathology, Vejle, Denmark. Based on the area of residence, women aged 30–59 years were screened by either HPV testing (with HPV16/18 genotyping and cytology triage) or cytology (with HPV triage for minor abnormalities). Our analysis includes women invited or screened during May 2017–May 2018 (invited: n=35,081; screened: n=28,352) with 6 months of follow-up. Information on screening results and sociodemographic characteristics were obtained from registers. Using logistic regression, we estimated odds ratios (ORs) with 95% confidence intervals (CIs) of participation, referral and CIN3+-detection in HPV- versus cytology-based screening, adjusting for sociodemographic characteristics.

Results

Participation was virtually identical in the HPV- and cytology group (58.4% vs 58.8%; OR_adjusted=0.97, 95% CI, 0.93–1.01). Referral to colposcopy was more common in the HPV- than cytology group (3.8% vs 2.1%; OR_adjusted=1.88, 95% CI, 1.63–2.17). More cases of CIN3+ were detected in the HPV- than cytology group (1.0% vs 0.7%, OR_adjusted=1.47; 95% CI, 1.13–1.91).

Conclusion

Participation did not differ between HPV- and cytology-based screening. HPV-based screening detected more cases of CIN3+, but in this initial screening round also led to more colposcopies than cytology-based screening.

Keywords:

• human papillomavirus
• cervical cancer
• cervical intraepithelial neoplasia
• screening
• HPV testing
• cytology
• secondary prevention

Acknowledgments

Interim findings of this paper were presented in part as oral presentations at the 32nd International Papillomavirus Conference (Sydney, Australia, October 2018); the 2018 EUROGIN conference (Lisbon, Portugal, December 2018); and the 2019 EUROGIN conference (Monaco, December 2019).

Author Contributions

MW, SKK, LTT, DOE and CM initiated, planned and designed the study. MW, SKK and LTT obtained funding. MW organized the implementation of HPV-based screening. DOE was responsible for HPV testing and other laboratory procedures. LTT performed registry linkages, data management and statistical analyses. KF assisted with the statistical analyses. LTT wrote the first draft of the manuscript. All authors contributed to analysis and interpretation of results, drafting and revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

HPV tests for this study were provided at reduced cost by Roche. Louise T. Thomsen reports grants from Lundbeck Foundation during the conduct of the study. Susanne K. Kjær has previously received speakers’ fees, advisory board fees and a research grant from Merck, who is the manufacturer of a vaccine against HPV. All other authors declare no potential competing interests.

Additional information

Funding

This study was funded by the Lundbeck Foundation (grant no. R287-2018-1454), the Mermaid project (Mermaid 2), and by Lillebaelt Hospital, Region of Southern Denmark.