Raising the cutoff level for a Hybrid capture 2 result

New findings indicate that the cutoff level for the Hybrid capture 2 test (Qiagen; Gaithersburg, Maryland) for primary screening for high-grade cervical intraepithelial neoplasia (CIN) can be increased to reduce the burden on women while still meeting international sensitivity recommendations. The findings come from a systematic review of randomized controlled trials without meta-analysis, which was not possible because of the heterogeneity of the trials.

Researchers found that the relative sensitivity for CIN grade III or higher at cutoff levels of greater than or equal to 2, 4, 5, and 10 relative light units (rlu)/cutoff (co) compared with a cutoff level of greater than or equal to 1 rlu/co varied by trials. At their lowest, the values were 0.97, 0.92, and 0.91, respectively. The investigators observed a similar pattern for CIN grade II or higher. They also found that specificity increased by at least 1%, 2%, and 3%, respectively, so that women could avoid up to 24%, 39%, and 53% of false-positive Hybrid capture 2 test results (ie, results not associated with high-grade neoplasia). For example, a cutoff greater than or equal to 10 rlu/co reduced the risk for a false-positive result by about one-half among women 30 years of age and older. In younger women, the higher cutoff reduced the risk for a false-positive result by about one-third.

Recently published international recommendations for HPV screening in women 30 years of age and older require that new tests to detect HPV DNA demonstrate 90% or higher sensitivity for CIN grade II or higher compared with the sensitivity of the Hybrid capture 2 test using the cutoff greater than or equal to 1 rlu/co. In addition, experts recommend that sensitivity of HPV screening for CIN grade III or higher be above 90%. The researchers concluded that using a cutoff for the Hybrid capture 2 between greater than or equal to 2 rlu/co and greater than or equal to 10 rlu/co meets these requirements.