Clinical validation of the PapilloCheck assay according to international guidelines for HPV test requirements for cervical screening

Objective To compare the clinical performance of the PapilloCheck assay (Greiner Bio-One, Germany) with that of the clinically validated high-risk HPV GP5+/6+-PCR according to the international guidelines for HPV test requirements for cervical screening (Meijer et al., IJC., 2009). Methods 1,437 cervical scrapings of women without evidence CIN2+ and 192 of women with CIN3+, originating from a population-based screening cohort (POBASCAM) were tested with both PapilloCheck and the GP5+/6+-PCR. In addition, intra-laboratory reproducibility over time and inter-laboratory agreement of the PapilloCheck assay were assessed on another set of 550 cervical samples. Clinical sensitivity and specificity values of the PapilloCheck assay were compared with those of GP5+/6+-PCR by non-inferiority score testing using previously defined thresholds for non-inferiority, i.e., relative sensitivity for CIN2+ >90% and relative specificity for CIN2+ >98%. For intraand inter-laboratory agreement a lower confidence bound not less than 87 % was used as threshold. Conclusions When restricting PapilloCheck analysis to the 14 hrHPV types targeted by GP5+/6+-PCR the clinical sensitivity and specificity were 95.8 % (95 % CI 92.8–98.8) and 96.7 % (95 % CI 95.7–97.7), respectively. By comparison, these figures were 96.4 % (95 % CI : 93.9–98.9) and 97.7 % (95 % CI : 96.9–98.5), respectively, for GP5+6+-PCR. Both the clinical sensitivity and specificity of PapilloCheck were non-inferior to that of GP5+/6+-PCR (non-inferiority score test ; P