Evidence suggests that positive screening test performance declines upon subsequent screening in women with a history of negative HPV and Pap co-tests1. We examined the positive predictive value (PPV) of the hybrid capture 2 (HC2) and cobas HPV screen tests, and cobas genotyping at the baseline and 48 mo. exit screens in the HPV FOCAL Trial.
HPV FOCAL is a randomized trial comparing liquid-based cytology (LBC) to high-risk (hr) HPV for cervical cancer screening. Of 9,552 women randomized to the Intervention arm, 9,514 had valid baseline HC2 and cobas results (cobas was blinded at baseline). Round 1 colposcopy referral was based on baseline HC2 positive together with LBC ≥ASCUS or 12 mo. persistent HC2 positivity. At 48 mo. exit, 8,330 women had valid HC2, cobas and LBC results (no blinding at exit), of whom 7,664 were baseline HC2 and cobas negative. Colposcopy referral at 48 mo. was based on HC2 positivity, LBC ≥ASCUS or cobas HPV 16/18 positivity. We calculated PPV for each screen test and for cobas genotyping at both screening rounds.
PPVs for CIN2+ and CIN3+ at Round 1 and 48 mo. exit are shown in the table. At Round 1, cobas HPV 16/18 positive women had significantly higher CIN2+ and CIN3+ PPVs vs. other HPV test results; PPVs for HC2, cobas and cobas non-16/18 hrHPV were similar. At 48 mo. exit, all CIN2+ and CIN3+ PPVs were lower than at Round 1. For cobas HPV 16/18 positive women, CIN2+ and CIN3+ PPVs were higher, but no longer significantly, than other HPV test results.
| Test result | Round 1 | Round 1 | 48 Mo. Exit | 48 Mo. Exit |
| CIN2+ (n=149) | CIN3+ (n=68) | CIN2+ (n=30) | CIN3+ (n=9) | |
| HC2+ | 0.19 (0.17-0.23) | 0.09 (0.07-0.11) | 0.10 (0.07-0.14) | 0.03 (0.01-0.06) |
| cobas+ | 0.17 (0.15-0.20) | 0.08 (0.06-0.10) | 0.08 (0.05-0.12) | 0.03 (0.01-0.05) |
| cobas+ (16/18) | 0.30 (0.24-0.36) | 0.19 (0.14-0.25) | 0.17 (0.09-0.28) | 0.06 (0.02-0.15) |
| cobas+ (non-16/18 hrHPV) | 0.13 (0.10-0.16) | 0.04 (0.03-0.06) | 0.05 (0.03-0.09) | 0.02 (0.01-0.05) |
At the baseline screen, cobas HPV 16/18 positive women had significantly higher PPVs for CIN2+ and CIN3+ than other HPV test results, but at 48 mo. exit the PPVs for cobas HPV 16/18 positives were no longer significantly higher. As expected, due to lower CIN2+ and CIN3+ prevalence at 48 mo., all PPVs were lower than at baseline. Further research will be required to assess the ongoing utility of screening and triage approaches at subsequent screening rounds following HPV implementation.
1Castle, Kinney et al. Impact of a history of negative co-tests on positive screening test performance. HPV 2017 Conference, Capetown, Abstract HPV17-0313.