TY - JOUR
T1 - False-positive Human Papillomavirus DNA tests in cervical screening
T2 - it is all in a definition
AU - Rebolj, Matejka
AU - Pribac, Igor
AU - Lynge, Elsebeth
N1 - Copyright © 2010 Elsevier Ltd. All rights reserved.
PY - 2011/1
Y1 - 2011/1
N2 - Aim: Based on data from randomised controlled trials (RCT) on primary cervical screening, it has been reported that the problem of more frequent false-positive tests in Human Papillomavirus (HPV) DNA screening compared to cytology could be overcome. However, these reports predominantly operated with a narrow definition of a (false-)positive test. The aim of this paper was to illustrate how the narrow definition affected the measured adverse effects of HPV DNA screening compared with cytology screening. Methods: In the European RCT data, we measured the impact of the narrow definition of a positive screening test on the published relative positive predictive values (PPV), an indicator of the relative frequency of false-positive screening tests. Results: Using the trialists' definitions of positive screening tests, HPV screening combined with cytology triage had relative PPVs of 0.87 (95% confidence interval (CI): 0.60-1.26) for ≥CIN3 based on Swedish RCT data, and 0.78 (0.52-1.16) for ≥CIN2 in the Italian Phase 1 RCT (25-34 years). These PPVs changed to 0.44 (0.30-0.64) and 0.51 (0.33-0.79), respectively, when all positive HPV or cytology screening tests were accounted for. In the Finnish RCT data, HPV screening using the cut-off point of ≥10 pg/ml had a relative PPV of 0.27 (0.15-0.50) for ≥CIN3, which changed to 1.84 (0.99-3.41). Conclusion: The relative PPV was incorrectly estimated in six out of seven studies. In three of those six studies, the relative PPV changed significantly after inclusion of the previously erroneously excluded false-positive HPV or cytology tests.
AB - Aim: Based on data from randomised controlled trials (RCT) on primary cervical screening, it has been reported that the problem of more frequent false-positive tests in Human Papillomavirus (HPV) DNA screening compared to cytology could be overcome. However, these reports predominantly operated with a narrow definition of a (false-)positive test. The aim of this paper was to illustrate how the narrow definition affected the measured adverse effects of HPV DNA screening compared with cytology screening. Methods: In the European RCT data, we measured the impact of the narrow definition of a positive screening test on the published relative positive predictive values (PPV), an indicator of the relative frequency of false-positive screening tests. Results: Using the trialists' definitions of positive screening tests, HPV screening combined with cytology triage had relative PPVs of 0.87 (95% confidence interval (CI): 0.60-1.26) for ≥CIN3 based on Swedish RCT data, and 0.78 (0.52-1.16) for ≥CIN2 in the Italian Phase 1 RCT (25-34 years). These PPVs changed to 0.44 (0.30-0.64) and 0.51 (0.33-0.79), respectively, when all positive HPV or cytology screening tests were accounted for. In the Finnish RCT data, HPV screening using the cut-off point of ≥10 pg/ml had a relative PPV of 0.27 (0.15-0.50) for ≥CIN3, which changed to 1.84 (0.99-3.41). Conclusion: The relative PPV was incorrectly estimated in six out of seven studies. In three of those six studies, the relative PPV changed significantly after inclusion of the previously erroneously excluded false-positive HPV or cytology tests.
KW - Adult
KW - Cervical Intraepithelial Neoplasia
KW - DNA, Viral
KW - Early Detection of Cancer
KW - False Positive Reactions
KW - Female
KW - Humans
KW - Middle Aged
KW - Papillomaviridae
KW - Papillomavirus Infections
KW - Randomized Controlled Trials as Topic
KW - Sensitivity and Specificity
KW - Uterine Cervical Neoplasms
KW - Vaginal Smears
U2 - 10.1016/j.ejca.2010.08.010
DO - 10.1016/j.ejca.2010.08.010
M3 - Journal article
C2 - 20833033
SN - 0959-8049
VL - 47
SP - 255
EP - 261
JO - European Journal of Cancer, Supplement
JF - European Journal of Cancer, Supplement
IS - 2
ER -
