Cytology versus HPV testing for cervical cancer screening in the general population.

BACKGROUND: Cervical cancer screening has traditionally been based on cervical cytology. Given the aetiological relationship between human papillomavirus (HPV) infection and cervical carcinogenesis, HPV testing has been proposed as an alternative screening test. OBJECTIVES: To determine the diagnostic accuracy of HPV testing for detecting histologically confirmed cervical intraepithelial neoplasias (CIN) of grade 2 or worse (CIN 2+), including adenocarcinoma in situ, in women participating in primary cervical cancer screening; and how it compares to the accuracy of cytological testing (liquid-based and conventional) at various thresholds. SEARCH METHODS: We performed a systematic literature search of articles in MEDLINE and Embase (1992 to November 2015) containing quantitative data and handsearched the reference lists of retrieved articles. SELECTION CRITERIA: We included comparative test accuracy studies if all women received both HPV testing and cervical cytology followed by verification of the disease status with the reference standard, if positive for at least one screening test. The studies had to include women participating in a cervical cancer screening programme who were not being followed up for previous cytological abnormalities. DATA COLLECTION AND ANALYSIS: We completed a 2 x 2 table with the number of true positives (TP), false positives (FP), true negatives (TN), and false negatives for each screening test (HPV test and cytology) used in each study. We calculated the absolute and relative sensitivities and the specificities of the tests for the detection of CIN 2+ and CIN 3+ at various thresholds and computed sensitivity (TP/(TP + TN) and specificity (TN/ (TN + FP) for each test separately. Relative sensitivity and specificity of one test compared to another test were defined as sensitivity of test-1 over sensitivity of test-2 and specificity of test-1 over specificity of test-2, respectively. To assess bias in the studies, we used the Quality Assessment of Diagnostic test Accuracy Studies (QUADAS) tool. We used a bivariate random-effects model for computing pooled accuracy estimates. This model takes into account the within- and between-study variability and the intrinsic correlation between sensitivity and specificity. MAIN RESULTS: We included a total of 40 studies in the review, with more than 140,000 women aged between 20 and 70 years old. Many studies were at low risk of bias. There were a sufficient number of included studies with adequate methodology to perform the following test comparisons: hybrid capture 2 (HC2) (1 pg/mL threshold) versus conventional cytology (CC) (atypical squamous cells of undetermined significance (ASCUS)+ and low-grade squamous intraepithelial lesions (LSIL)+ thresholds) or liquid-based cytology (LBC) (ASCUS+ and LSIL+ thresholds), other high-risk HPV tests versus conventional cytology (ASCUS+ and LSIL+ thresholds) or LBC (ASCUS+ and LSIL+ thresholds). For CIN 2+, pooled sensitivity estimates for HC2, CC and LBC (ASCUS+) were 89.9%, 62.5% and 72.9%, respectively, and pooled specificity estimates were 89.9%, 96.6%, and 90.3%, respectively. The results did not differ by age of women (less than or greater than 30 years old), or in studies with verification bias. Accuracy of HC2 was, however, greater in European countries compared to other countries. The results for the sensitivity of the tests were heterogeneous ranging from 52% to 94% for LBC, and 61% to 100% for HC2. Overall, the quality of the evidence for the sensitivity of the tests was moderate, and high for the specificity.The relative sensitivity of HC2 versus CC for CIN 2+ was 1.52 (95% CI: 1.24 to 1.86) and the relative specificity 0.94 (95% CI: 0.92 to 0.96), and versus LBC for CIN 2+ was 1.18 (95% CI: 1.10 to 1.26) and the relative specificity 0.96 (95% CI: 0.95 to 0.97). The relative sensitivity of HC2 versus CC for CIN 3+ was 1.46 (95% CI: 1.12 to 1.91) and the relative specificity 0.95 (95% CI: 0.93 to 0.97). The relative sensitivity of HC2 versus LBC for CIN 3+ was 1.17 (95% CI: 1.07 to 1.28) and the relative specificity 0.96 (95% CI: 0.95 to 0.97). AUTHORS' CONCLUSIONS: Whilst HPV tests are less likely to miss cases of CIN 2+ and CIN 3+, these tests do lead to more unnecessary referrals. However, a negative HPV test is more reassuring than a negative cytological test, as the cytological test has a greater chance of being falsely negative, which could lead to delays in receiving the appropriate treatment. Evidence from prospective longitudinal studies is needed to establish the relative clinical implications of these tests.

Comparison and validation of metadta for meta-analysis of diagnostic test accuracy studies.

We developed metadta, a flexible, robust, and user-friendly statistical procedure that fuses established and innovative statistical methods for meta-analysis, meta-regression, and network meta-analysis of diagnostic test accuracy studies in Stata. Using data from published meta-analyses, we validate metadta by comparing and contrasting its features and output to popular procedures dedicated to the meta-analysis of diagnostic test accuracy studies; (midas [Stata], metandi [Stata], metaDTA [web application], mada [R], and MetaDAS [SAS]). We also demonstrate how to perform network meta-analysis with metadta, for which no alternative procedure is dedicated to network meta-analysis of diagnostic test accuracy data in the frequentist framework. metadta generated consistent estimates in simple and complex diagnostic test accuracy data sets. We expect its availability to stimulate better statistical practice in the evidence synthesis of diagnostic test accuracy studies.

Group B Streptococcus in surgical site and non-invasive bacterial infections worldwide: A systematic review and meta-analysis.

OBJECTIVES: The epidemiology of disease caused by group B Streptococcus (GBS; Streptococcus agalactiae) outside pregnancy and the neonatal period is poorly characterized. The aim of this study was to quantify the role of GBS as a cause of surgical site and non-invasive infections at all ages. METHODS: A systematic review (PROSPERO CRD42017068914) and meta-analysis of GBS as a proportion (%) of bacterial isolates from surgical site infection (SSI), skin/soft tissue infection (SSTI), urinary tract infection (UTI), and respiratory tract infection (RTI) was conducted. RESULTS: Seventy-four studies and data sources were included, covering 67 countries. In orthopaedic surgery, GBS accounted for 0.37% (95% confidence interval (CI) 0.08-1.68%), 0.87% (95% CI 0.33-2.28%), and 1.46% (95% CI 0.49-4.29%) of superficial, deep, and organ/space SSI, respectively. GBS played a more significant role as a cause of post-caesarean section SSI, detected in 2.92% (95% CI 1.51-5.55%), 1.93% (95% CI 0.97-3.81%), and 9.69% (95% CI 6.72-13.8%) of superficial, deep, and organ/space SSI. Of the SSTI isolates, 1.89% (95% CI 1.16-3.05%) were GBS. The prevalence of GBS in community and hospital UTI isolates was 1.61% (1.13-2.30%) and 0.73% (0.43-1.23%), respectively. GBS was uncommonly associated with RTI, accounting for 0.35% (95% CI 0.19-0.63%) of community and 0.27% (95% CI 0.15-0.48%) of hospital RTI isolates. CONCLUSIONS: GBS is implicated in a small proportion of surgical site and non-invasive infections, but a substantial proportion of invasive SSI post-caesarean section.

ANOVA model for network meta-analysis of diagnostic test accuracy data.

Procedures combining and summarising direct and indirect evidence from independent studies assessing the diagnostic accuracy of different tests for the same disease are referred to network meta-analysis. Network meta-analysis provides a unified inference framework and uses the data more efficiently. Nonetheless, handling the inherent correlation between sensitivity and specificity continues to be a statistical challenge. We developed an arm-based hierarchical model which expresses the logit transformed sensitivity and specificity as the sum of fixed effects for test, correlated study-effects to model the inherent correlation between sensitivity and specificity and a random error associated with various tests evaluated in a given study. We present the accuracy of 11 tests used to triage women with minor cervical lesions to detect cervical precancer. Finally, we compare the results with those from a contrast-based model which expresses the linear predictor as a contrast to a comparator test. The proposed arm-based model is more appealing than the contrast-based model since the former permits more straightforward interpretation of the parameters, makes use of all available data yielding shorter credible intervals, and models more natural variance-covariance matrix structures.

Metaprop: a Stata command to perform meta-analysis of binomial data.

BACKGROUND: Meta-analyses have become an essential tool in synthesizing evidence on clinical and epidemiological questions derived from a multitude of similar studies assessing the particular issue. Appropriate and accessible statistical software is needed to produce the summary statistic of interest. METHODS: Metaprop is a statistical program implemented to perform meta-analyses of proportions in Stata. It builds further on the existing Stata procedure metan which is typically used to pool effects (risk ratios, odds ratios, differences of risks or means) but which is also used to pool proportions. Metaprop implements procedures which are specific to binomial data and allows computation of exact binomial and score test-based confidence intervals. It provides appropriate methods for dealing with proportions close to or at the margins where the normal approximation procedures often break down, by use of the binomial distribution to model the within-study variability or by allowing Freeman-Tukey double arcsine transformation to stabilize the variances. Metaprop was applied on two published meta-analyses: 1) prevalence of HPV-infection in women with a Pap smear showing ASC-US; 2) cure rate after treatment for cervical precancer using cold coagulation. RESULTS: The first meta-analysis showed a pooled HPV-prevalence of 43% (95% CI: 38%-48%). In the second meta-analysis, the pooled percentage of cured women was 94% (95% CI: 86%-97%). CONCLUSION: By using metaprop, no studies with 0% or 100% proportions were excluded from the meta-analysis. Furthermore, study specific and pooled confidence intervals always were within admissible values, contrary to the original publication, where metan was used.