Primary hrHPV DNA Testing in Cervical Cancer Screening: How to Manage Screen-Positive Women? A POBASCAM Trial Substudy

M. G. Dijkstra, D. van Niekerk, D. C. Rijkaart, F. J. van Kemenade, D. A. M. Heideman, P. J. F. Snijders, C. J. L. M. Meijer, J. Berkhof
2013 Cancer Epidemiology, Biomarkers and Prevention  
High-risk human papillomavirus (hrHPV) testing has higher sensitivity but lower specificity than cytology for cervical (pre)-cancerous lesions. Therefore, triage of hrHPV-positive women is needed in cervical cancer screening. Methods: A cohort of 1,100 hrHPV-positive women, from a population-based screening trial (POBASCAM: n ¼ 44,938; 29-61 years), was used to evaluate 10 triage strategies, involving testing at baseline and six months with combinations of cytology, HPV16/18 genotyping, and/or
more » ... genotyping, and/or repeat hrHPV testing. Clinical endpoint was cervical intraepithelial neoplasia grade 3 or worse (CIN3 þ ) detected within four years; results were adjusted for women not attending repeat testing. A triage strategy was considered acceptable, when the probability of no CIN3 þ after negative triage (negative predictive value, NPV) was at least 98%, and the CIN3 þ risk after positive triage (positive predictive value, PPV) was at least 20%. Results: Triage at baseline with cytology only yielded an NPV of 94.3% [95% confidence interval (CI), 92.0-96.0] and a PPV of 39.7% (95% CI, 34.0-45.6). An increase in NPV, against a modest decrease in PPV, was obtained by triaging women with negative baseline cytology by repeat cytology (NPV 98.5% and PPV 34.0%) or by baseline HPV16/18 genotyping (NPV 98.8% and PPV 28.5%). The inclusion of both HPV16/18 genotyping at baseline and repeat cytology testing provided a high NPV (99.6%) and a moderately high PPV (25.6%). Conclusions: Triaging hrHPV-positive women by cytology at baseline and after 6 to 12 months, possibly in combination with baseline HPV16/18 genotyping, seems acceptable for cervical cancer screening. Impact: Implementable triage strategies are provided for primary hrHPV screening in an organized setting. Cancer Epidemiol Biomarkers Prev; 23(1); 1-9. Ó2013 AACR. Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis):
doi:10.1158/1055-9965.epi-13-0173 pmid:23733907 fatcat:7l75cbhbqrgo3l25bf2jw5gx2m