Clinical validation of a type-specific real-time quantitative human papillomavirus PCR against the performance of hybrid capture 2 for the purpose of cervical cancer screening.
To be acceptable for use in cervical cancer screening, a new assay that detects DNA of high-risk human papillomavirus (hrHPV) types must demonstrate high reproducibility and performance not inferior to that of a clinically validated HPV test. In the present study, a real-time quantitative PCR (qPCR) assay targeting the E6 and E7 genes of hrHPV was compared with Hybrid Capture 2 (hc2) in a Belgian cervical cancer screening setting. In women >30 years old, the sensitivity and specificity for intraepithelial neoplasias of grade 2 or worse (93 cases of cervical intraepithelial neoplasias of grade 2 or worse (CIN2+) and 1,207 cases of no CIN or CIN1) were 93.6% and 95.6%, respectively, and those of hc2 were 83.9% and 94.5%, respectively {relative sensitivity of qPCR/hc2 = 1.12 [95% confidence interval (CI), 1.01 to 1.23]; relative specificity = 1.01 [95% CI, 0.99 to 1.03]}. A score test showed that the sensitivity (P < 0.0001) and specificity (P < 0.0001) of the qPCR assay were not inferior to those of hc2 at the required thresholds of 90% and 98%, respectively. The overall agreement of hrHPV positivity between the two runs of the qPCR tests was 98.7% (95% CI, 97.5 to 99.4%), with a kappa value of 0.96 (95% CI, 0.83 to 1.00). The qPCR assay used in this study can be considered a reliable HPV assay that fulfills the clinical validation criteria defined for use in cervical cancer screening.
RIATOL, Department of Molecular Diagnostics, Sonic Healthcare Benelux, Antwerp, Belgium. christophe.depuydt@riatol.be
C E
CE
Depuydt
I H
IH
Benoy
J F A
JF
Beert
A M
AM
Criel
J J
JJ
Bogers
M
M
Arbyn
D000328:Adult; D000368:Aged; D001530:Belgium; D002273:Carcinogens; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D006801:Humans; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000821:virology*; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods*; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control* / Q000821:virology*; D014764:Viral Proteins / Q000235:genetics; D014773:Virology / Q000379:methods
D002273:Carcinogens; D014764:Viral Proteins