Cervical Cancer Screening and Human Papillomavirus (HPV ... - KCE

16 Cervical cancer screening and HPV KCE reports vol.38
defined at HSIL+ for an outcome of CIN2+ was 7% higher than for CP and this
difference was significant (ratio: 1.07; CI: 1.03-1.12). For AutoCyte, the relative PPV
was significantly higher than CP when the threshold was ASCUS+ for both outcomes:
ratio of 1.26 (CI: 1.07-1.56) for CIN2+ and 1.22 (CI: 1.10-1.36) for CIN1+, but there
was only one study that contributed data 52 . Repeating the meta-analysis of the testpositivity
rate ratio, restricted to studies where the PPV for CIN2+ was sufficiently
documented, showed: increased positivity rate for HSIL+ in ThinPrep and
AutoCyte/SurePath compared to CP (for ThinPrep: ratio: 1.52; CI: 1.10-2.12; for
AutoCyte/SurePath: 1.53; 1.03-2.27) and an increased rate of LSIL in ThinPrep (ratio:
1.79; CI: 1.05-3.06).
2.4.2.3 Accuracy for histological confirmed CIN2+
Test
threshold
In Table 5, we summarise the relative sensitivity and specificity for CIN2+ pooled from
six studies, separated by cytological cut-off. In five of the six studies, a concomitant
design was used (3 with split-samples 53, 54, 51 and 2 with separate samples 55, 56 ). The sixth
study was a 2-cohort trial, where LBC and CP were rotated every 6 months 57 . The
evaluated LBC systems were: ThinPrep (n=4), AutoCyte (n=1) and DNA Citoliq System
(n=1). The variation of the accuracy ratios, considered at cut-off HSIL or worse and
ASCUS or worse, is illustrated in Table 5. No statistically significant differences in
pooled diagnostic accuracy could be discerned: the confidence intervals around the
ratios always included unity. Moreover, the confidence intervals were small.
Nevertheless some heterogeneity due to one or two studies could be notified in some
forest plots. At cutoff HSIL+, Confortini found a marginally significantly higher
sensitivity for LBC 56 . At cutoff ASCUS, Longatto Filho, detected significantly more
CIN2+ in LBC but at the expense of significantly more false positive cases 51 . Outlying
higher specificity of LBC was observed in the study of Confortini, which was due to the
very high rate of atypical conventional smears 56 . Omission of this study, decreased the
relative specificity, but the difference between LBC and CP just did not reach the level
of statistical significance (ratio= 0.93; 95% CI: 0.87-1.01).
Table 5. Ratio of sensitivity and specificity for CIN2+ of liquid-based cytology
(LBC) relative to the conventional Pap smear (CP), pooled from 6 studies (5
with concomitant testing designing and 1 2-cohort trial) with complete
verification by colposcopy and/or biopsy.
95% CI 95% CI
Ratio of
sensitivities
(LBC/CP) Lower Upper
Ratio of
specificities
(LBC/CP) Lower upper # studies
HSIL+ 1.00 0.90 1.10 0.99 0.98 1.01 6
LSIL+ 1.03 0.95 1.12 0.97 0.93 1.01 6
ASCUS+ 1.02 0.96 1.09 1.02 0.92 1.41 6
2.4.2.4 Quality judgment
In Table 6, the pooled rate of unsatisfactory smears in LBC and CP, and their ratios are
shown for 2-cohort studies. In general the quality of liquid-based smears is higher than
conventional ones (ratio for unsatisfactory smears < 1). Only in AutoCyte/SurePath
smears this finding was significant: ratio 0.17 (95% CI: 0.10-0.32), whereas it was
marginally insignificant in ThinPrep smears (ratio=0.66; CI: 0.42-1.02) due to substantial
inter-study heterogeneity. Few studies documented the reason why smears were
qualified as unsatisfactory. Inadequate fixation or presence of abundant inflammation
was significantly or almost significantly reduced in LBC: pooled ratio for poor fixation of
0.12 (95% CI: 0.01-1.03) and 0.02 (95% CI: 0.00-0.04); and for inflammation of 0.15 (95%
CI: 0.07-0.29) and 0.13 (95% CI: 0.09-0.18), respectively when LBC smears were
prepared with ThinPrep or AutoCyte/SurePath. The frequency of inadequate smears