Comparison of Hybrid capture 2 testing at different thresholds with cytology as primary cervical screening test

Abstract

Background: We evaluated the performance of primary high-risk human papillomavirus (hrHPV) testing by hybrid capture 2 (HC2) with different thresholds for positivity, in comparison with conventional cytology.

Methods: We used data of 25,871 women (aged 30-60 years) from the intervention group of the VUSA-Screen study (VU University Medical Center and Saltro laboratory population-based cervical screening study), who were screened by cytology and hrHPV. Primary outcome measure was the number of cervical intraepithelial neoplasia grade 3 or higher (CIN3+), detected within 3 years. We compared baseline cytology testing with three possible hrHPV screening strategies at different relative light unit/cutoff (RLU/CO) thresholds.

Results: Compared with baseline cytology testing, hrHPV DNA testing as a sole primary screening instrument did not yield a superior sensitivity, as well as lower colposcopy referral rate and lower false positivity rate at any RLU/CO threshold. The hrHPV screening at 1 RLU/CO threshold with cytology triage at baseline and at 12 months revealed the highest sensitivity for CIN3+ (relative sensitivity of 1.32), although still displaying a lower colposcopy referral rate than cytology testing (relative colposcopy rate of 0.94). Higher thresholds (>1 RLU/CO) yielded lower colposcopy rates, but resulted in substantial loss in sensitivity.

Conclusions: The hrHPV testing at the commonly used threshold of 1 RLU/CO with cytology triage at baseline and at 12 months showed a much higher sensitivity with a lower colposcopy referral rate compared with cytology testing.

Figure 1

Flowchart of the study design. BMD, borderline or mild dyskaryosis; colpo, colposcopy; cyto, cytology; hrHPV, high-risk human papillomavirus; m, months.

Figure 2

Relative sensitivity vs relative false positivity rate for three strategies for hybrid capture 2 (HC2)-positive women at different relative light unit/cutoff (RLU/CO) thresholds compared with baseline cytology (cyto) testing, for detection of cervical intraepithelial neoplasia grade 3 or higher (CIN3+). Relative sensitivity for detection of CIN3+ is plotted on the y-axis, against the relative false positivity rate on the x-axis. The used HC2 RLU/CO thresholds are indicated at the respective positions above each plot. I: quadrant with relative sensitivity and relative false positivity rate greater than cytology; II: panel with relative sensitivity greater than and relative false positivity rate lower than cytology; III: panel with relative sensitivity lower than and relative false positivity rate lower than cytology; IV: panel with relative sensitivity and relative false positivity rate lower than cytology. BMD, borderline or mild dyskaryosis.