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

26 Cervical cancer screening and HPV KCE reports vol.38
2.7.2 Performance in triage of minor cytological abnormalities
A first meta-analysis 112, 113 concerned the cross-sectional accuracy of HPV DNA testing
to triage women with an index smear showing ASCUS (atypical squamous cells of
undetermined significance) or AGUS (atypical squamous cells of undetermined
significance) for detecting histologically confirmed cervical intraepithelial neoplasia of
grade II or worse disease (CIN2+).
Studies were included if the high-risk probe cocktail of the Hybrid Capture II assay was
applied to women with a prior ASCUS result and if presence or absence of cervical
intra-epithelial was verified by colposcopy and subsequent biopsy and/or endocervical
curettage when colposcopy indicated. Data from two of the three trial arms of the
ASCUS-LSIL triage study (ALTS) were included as well: those referred to colposcopy
and those triaged by Hybrid Capture II 114 . We computed sensitivity and specificity for
two outcome thresholds, CIN 2 or worse and CIN3 or worse (CIN3+), based on the
histological result of the biopsy and assuming that a negative colposcopic impression
corresponds with absence of high-grade CIN. For studies, where also the result of a
repeat Pap smear was documented, we assessed the ratio of the sensitivity and
specificity of HPV testing relative to repeat cytology, using 3 different cytological cutoffs:
ASCUS+, LSIL+ (low-grade squamous intra-epithelial lesion or worse) and HSIL+
(high-grade squamous intra-epithelial lesion or worse). Random effect models were
used for meta-analytical pooling 115 .
A similar second meta-analysis included studies fulfilling the same criteria but where
women with cytological findings of LSIL were enrolled 116 .
2.7.2.1 Triage of atypical cells of undetermined significance
Absolute accuracy
We retrieved 20 studies, where the accuracy of HC2 for triage of women with findings
of ASCUS could be assessed 117-123, 114, 124-131, 77, 132-134 . On average, in 9.7% (95% CI: 7.7-
11.71%) and 4.3% (95% CI: 2.7-5.9%) of cases, underlying CIN2+ or CIN3+ was found
Table 7. The variation of the accuracy of HC2 triage in detecting these high-grade CIN
is displayed in the forest plots in Figure 3. Overall, HC2 had a sensitivity of 92.5% (95%
CI: 90.1-94.9%) and 95.6% (95% CI: 92.8-98.4%) for detecting respectively CIN2+ or
CIN3+. The pooled specificity was 62.5% (95% CI: 57.8-67.3%) when the outcome was
CIN2+ and 59.3% (51.2-67.4%) for CIN3+. Inter-study heterogeneity was not
statistically significant for sensitivity but very significant for specificity. Between 23 and
57% of women tested positive (pooled rate of 42.2; 95% CI: 38.1-46.3%).