16/18 genotyping in triage of persistent human papillomavirus infections with negative cytology in the English cervical screening pilot

Matejka Rebolj,Miles Holbrook,Adam R Brentnall,Xenia Tyler,Henry Kitchener,Tanya Levine,John Smith,Karin Denton,Alexandra Sargent,Christopher Mathews,John Tidy

doi:10.1038/s41416-019-0547-x

Abstract

BackgroundIn the English pilot of primary cervical screening with high-risk human papillomavirus (HR-HPV), we exploited natural viral clearance over 24 months to minimise unnecessary referral of HR-HPV+ women with negative cytology. Three laboratories were permitted to use 16/18 genotyping to select women for referral at 12-month recall. We estimated the clinical impact of this early genotyping referral.MethodsThe observed numbers of women referred to colposcopy and with detected high-grade cervical intraepithelial neoplasia (CIN2+), and of women who did not attend early recall in the three laboratories were compared with those estimated to represent a situation without an early genotyping referral. The 95% confidence intervals (CI) for the differences between the protocols were calculated by using a parametric bootstrap.ResultsAmongst 127,238 screened women, 16,097 (13%) had HR-HPV infections. The genotyping protocol required 5.9% (95% CI: 4.4–7.7) additional colposcopies and led to a detection of 1.2% additional CIN2+ (95% CI: 0.6–2.0), while 2.3% (95% CI: 2.1–2.5) fewer HR-HPV+/cytology− women did not attend the early recall compared with the non-genotyping protocol.ConclusionsIn a screening programme with high quality of triage cytology and high adherence to early recall,16/18 genotyping of persistent HPV infections does not substantially increase CIN2+ detection.

Highlights

In the English pilot of primary cervical screening with high-risk human papillomavirus (HR-HPV), we exploited natural viral clearance over 24 months to minimise unnecessary referral of HR-HPV+ women with negative cytology
In several countries including the USA and Australia, HPV 16/18 genotyping is being used at baseline to identify women with negative cytology at increased risk of underlying cervical intraepithelial neoplasia (CIN), for immediate referral.[2,3]
Using data from the English HPV pilot we estimated there would be a small increase in CIN2+ detection for HPV 16/18 genotyping compared with non-genotyping triage protocols for women with persistent HR-HPV infections and negative cytology

Summary

Introduction

In the English pilot of primary cervical screening with high-risk human papillomavirus (HR-HPV), we exploited natural viral clearance over 24 months to minimise unnecessary referral of HR-HPV+ women with negative cytology. METHODS: The observed numbers of women referred to colposcopy and with detected high-grade cervical intraepithelial neoplasia (CIN2+), and of women who did not attend early recall in the three laboratories were compared with those estimated to represent a situation without an early genotyping referral. CONCLUSIONS: In a screening programme with high quality of triage cytology and high adherence to early recall,16/18 genotyping of persistent HPV infections does not substantially increase CIN2+ detection. In several countries including the USA and Australia, HPV 16/18 genotyping is being used at baseline to identify women with negative cytology at increased risk of underlying cervical intraepithelial neoplasia (CIN), for immediate referral.[2,3] In these cases, the decision to refer HPV 16/18 positive women is made on a single screening sample

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Results

Conclusion