Referral population studies underestimate differences between human papillomavirus assays in primary cervical...

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.

A total of 4997 women were tested with SurePath® 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.

Median signal strengths for HPV infections were weaker in normal than abnormal cytology (P<.001, adjusted for women's age, multiple infections and the reason for taking the sample). For HC2, they were RLU/CO 11.0 (interquartile range, IQR: 3.3-52.8) vs 124.2 (IQR: 22.8-506.9), respectively; for cobas, Ct 33.5 (IQR: 29.6-37.5) vs 26.9 (IQR: 23.7-31.3), respectively; for APTIMA, S/CO 10.2 (IQR: 5.8-11.3) vs 11.1 (IQR: 9.4-15.5), respectively. Similar patterns were observed for HPV-positive ≥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.

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.