Comparative effectiveness study on human papillomavirus detection methods used in the cervical cancer screening programme

Abstract

Objectives: To compare the short-term and long-term effectiveness of human papillomavirus (HPV) tests in Norwegian Cervical Cancer Screening Programme (NCCSP). Design: Nationwide register-based prospective follow-up study. Setting: In 2005, the NCCSP implemented HPV testing in follow-up of unsatisfactory, atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) cytology. Participants: 19 065 women with repeat cytology and HPV test after unsatisfactory ASC-US or LSIL screening result in 2005-2009. Interventions: Through individual registry linkages we observed how women were treated in the regular medical care. Main outcome measures: We estimated cumulative incidence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in 6 months and 3 years after repeat cytology and HPV test. Patients diagnosed with CIN2+ in 6 months and 3 years were assessed for initial HPV positivity. Results: 5392 had ASC-US/LSIL and 13 673 had normal/unsatisfactory repeat cytology; for HPV detection 4715 used AMPLICOR HPV Test (Roche Diagnostics, Basel, Switzerland), 9162 Hybrid Capture 2 (HC2) High-Risk HPV DNA Test (QIAGEN, Gaithersburg, Maryland, USA) and 5188 PreTect HPV-Proofer (NorChip, Klokkarstua, Norway). Among those with ASC-US/LSIL repeat cytology, 3-year risk of CIN2+ was 15-fold in Amplicor/HC2- positives compared with Amplicor/HC2-negatives and sevenfold in Proofer-positives compared with Proofernegatives; a 3-year risk of CIN2+ was 2.1% (95% CI 0.7% to 3.4%) in Amplicor-negatives and 7.2% (95% CI 5.4% to 8.9%) in Proofer-negatives. Close to 100% of patients with CIN2+ diagnosed within 6 months tested positive to HPV (all methods). Considering all patients diagnosed with CIN2+ in 3-year follow-up, 97% were initially positive in the Amplicor group and more than 94% in the HC2 group, compared with less than 80% in the Proofer group. Conclusions: While the long-term evaluation of new screening routines showed a good overall performance of triage-HPV DNA testing, the management of HPV-negative women with persistent ASC-US/LSIL was suboptimal.