Sisse Helle Njor

Objective: We studied how representative cytologically abnormal women ("referral populations") are with respect to uncovering differences between human papillomavirus (HPV) assays in the primary screening where most women are cytologically normal.

Methods: A total of 4997 women were tested with SurePath (R) cytology, and Hybrid Capture 2 (HC2), cobas, CLART and APTIMA HPV assays. Women with positive test results were offered a follow-up. For all detected HPV infections and HPV-positive high-grade cervical intraepithelial neoplasia (>= CIN2), we studied the distributions of assay-specific signal strengths in the baseline samples as documented by the assays' automatically generated reports. We calculated the likelihood of test result discordance as the proportion of HPV-positive samples that were not confirmed by all four assays.

Results: Median signal strengths for HPV infections were weaker in normal than abnormal cytology (P= CIN2. The four HPV assays more frequently returned discordant test results in normal than in abnormal cytology. Relative frequency of discordance in detecting HPV infections was 0.39 (95% confidence interval: 0.33-0.48) for abnormal vs normal cytology.

Conclusions: These data suggest that referral population studies, by not including sufficient numbers of cytology normal women, underestimate the differences between HPV assays that would become apparent in primary screening.