Safe thresholds for hybrid capture 2 test in primary cervical screening

Substantial evidence shows that testing for human papillomavirus (HPV) DNA with hybrid capture 2 is more sensitive but less specific than cytology at detecting high grade cervical intraepithelial neoplasia.1 The sensitivity of hybrid capture 2 relative to cytology depends on the quality of the cytology, but its absolute sensitivity is uniformly high (about 96% overall and >90% in most studies).2 Its specificity depends on the level of HPV infection in the population. Typically 6-10% of women aged 30-64 will test positive⇑.

For many years studies have looked at whether increasing the threshold for positivity would make the test more useful by trading a small loss in sensitivity for a large reduction in the clinical false positive rate. In the linked systematic review (doi:10.1136/bmj.d2757), Rebolj and colleagues assess randomised controlled trials that investigated the effect of different cut-off points on the sensitivity and specificity of the hybrid capture 2 test.3 The authors suggest that the standard cut off of 1 relative light units/cut off (rlu/co) should be changed to 10 rlu/co.

Although the data show that the loss of sensitivity associated with increasing the cut-off point is small …