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

• Published in: BMJ open 2014-01, Vol.4 (1), p.e003460-e003460
• Main Authors: Nygård, Mari, Røysland, Kjetil, Campbell, Suzanne, Dillner, Joakim
• Format: Article
• Language: English
• Subjects: Adult; Cervical cancer; Early Detection of Cancer; Female; Follow-Up Studies; Health Services Research; Humans; Medicin och hälsovetenskap; Middle Aged; Norway; Papillomaviridae - isolation & purification; Prospective Studies; Time Factors; Uterine Cervical Neoplasms - epidemiology; Uterine Cervical Neoplasms - virology
• ISSN: 2044-6055; 2044-6055
• DOI: 10.1136/bmjopen-2013-003460

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 Proofer-negatives; 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.