Only clinically validated human papillomavirus (HPV) tests should be used in cervical cancer screening. VALGENT provides a framework to validate new HPV tests. In the VALGENT-3 study, the clinical accuracy of the recently launched Abbott Alinity m HR HPV assay (Alinity m) to detect cervical precancerous lesions was assessed against the standard comparator test (Hybrid Capture 2; HC2) and additionally against two previously validated alternative comparator tests (Abbott RealTime HR HPV and Roche cobas 4800 assays). Validation was conducted using 1,300 consecutive cervical samples from women attending an organized population-based cervical screening program enriched with 300 cytologically abnormal samples. Overall hrHPV test concordance was assessed by kappa values; the concordance for HPV-16 and HPV-18 was assessed for Alinity m, RealTime, and cobas, and the Linear Array (Roche) was used for more detailed genotyping concordance. In the total study population, the relative sensitivity and specificity for CIN2+ and CIN3+ of Alinity m compared to HC2 was 1.02 (95% CI:0.99–1.06) and 1.03 (95% CI:0.99–1.06), respectively. The relative specificity for ≤ CIN1 was 1.01 (95% CI:1.00–1.02) (all pni ≤ 0.001). Alinity m showed non-inferior clinical accuracy among women 30 years or older when cobas or RealTime were used as comparators. HPV genotype-specific concordance between Alinity m and the three comparator tests showed excellent agreement, with kappa values ranging between 0.82 and 1.00. In conclusion, Alinity m fulfils the international accuracy requirements for use in cervical cancer screening and shows excellent HPV genotype-specific concordance with three clinically validated HPV tests.

Nasopharyngeal swabs are considered the preferential collection method for SARS-CoV-2 diagnostics. Alternative sampling procedures that are less invasive and do not require a healthcare professional, such as saliva collection, would be more preferable. We compared saliva specimens and nasopharyngeal (NP) swabs with respect to sensitivity in detecting SARS-CoV-2. We obtained a nasopharyngeal and two saliva specimens (collected by spitting or oral swabbing) from more than 2500 individuals. All samples were tested by RT-qPCR detecting RNA of SARS-CoV-2. We compared the test sensitivity on the two saliva collections with the nasopharyngeal specimen for all subjects and stratified by symptom status and viral load. Of the 2850 patients for which all three samples were available, 105 were positive on NP, whereas 32 and 23 were also positive on saliva spitting and saliva swabbing samples, respectively. The sensitivity of the RT-qPCR to detect SARS-CoV-2 among NP-positive patients was 30.5% (95% CI=1.9%-40.2%) for saliva spitting, and 21.9% (95% CI=14.4%-31.0%) for saliva swabbing. However, when focusing on subjects with medium to high viral load, sensitivity on saliva increased substantially: 93.9% (95% CI=79.8%-99.3%) and 76.9% (95% CI=56.4-91.0) for spitting and swabbing, respectively, regardless of symptomatic status. Our results suggest that saliva cannot readily replace nasopharyngeal sampling for SARS-CoV-2 diagnostics but may enable identification of the most contagious cases with medium to high viral loads.

Background The comparative performance of saliva and nasopharyngeal samples for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by reverse transcriptase polymerase chain reaction (RT-PCR) in children remains unclear. As schools reopen around the world, there is an interest in the use of saliva samples for detection of SARS-CoV-2 in children to circumvent barriers with nasopharyngeal sampling. We systematically reviewed the literature to understand the performance of saliva sampling using RT-PCR on naso- and/or oropharyngeal swabs as the reference standard. Methods Articles from PubMed/MEDLINE and Living Evidence were accessed until 28th April 2021. A search method without restriction to children population was applied and during the review phase, if a study included patients <18 years old, authors were contacted to provide additional information on the subset of children. Studies were eligible if they reported on matched saliva and naso- and/or oropharyngeal samples, taken from the same patient on the same day. Studies using other respiratory samples such as sputum samples were excluded. Each paired patient sample had to be tested on the same RT-PCR platform. Results Ten studies were included, comprising 1486 matched saliva and on naso- and/or oropharyngeal pairs from children aged 0 to 18 years old. The pooled absolute sensitivity and specificity of saliva sampling using RT-PCR on nasopharyngeal samples as the reference standard was 84.5% (95% CI; 78.0%-90.3%) and 99.5% (95% CI; 98.2%-100.0%). Comparable performance of saliva to nasopharyngeal samples was shown in both symptomatic and asymptomatic children. Stratified analyses of various covariates showed no significant differences. Discussion Our pooled accuracy estimates of RT-PCR SARS-CoV-2 testing on saliva in children did not seem to be different from meta-analyses of studies that enrolled mainly adults. Saliva could potentially be considered an alternative sampling method for screening in children and to pick up those with high viral load.

Background Testing for SARS-CoV-2, together with vaccination, is one of the most vital strategies in curbing the current COVID-19 pandemic. The pandemic has led to an unprecedented need for diagnostic testing and the rapid emergence of an abundance of commercial assays on the market. Due to the nature of the pandemic and in the interest of health protection, many of these assays received provisional authorisation for emergency use without thorough validation. To limit false negative and false positive results, it is key to define common criteria that SARS-CoV-2 assays need to fulfil. VALCOR or “VALidation of SARS-CORona Virus-2 assays” is a protocol designed to set up a framework for test validation of SARS-CoV-2 virus assays. Objectives VALCOR is a study protocol for the validation of assays used for confirmation of the presence of SARS-CoV-2 in patients with COVID-19 disease or the screening of carriers of SARS-CoV-2 virus by the identification of viral RNA in oropharyngeal and/or nasopharyngeal specimens or other specimens from the human respiratory tract. Methods The VALCOR panel of samples will contain clinical human specimens and standardised artificial specimens. The collection of clinical specimens will include nasopharyngeal or oropharyngeal specimens or other specimens from the respiratory tract obtained from COVID-19 patients and healthy carriers of SARS-CoV-2 as well as specimens from subjects not carrying SARS-CoV-2. Artificial specimens include calibrated amounts of viral RNA of SARS-CoV-2 sequences provided by established competent agencies that produce reference materials for the assessment of the limit of detection of each assay. The panel of samples are sent from a central reference laboratory (having access to biobanks of clinical specimens tested already for SARS-CoV-2 with a reference comparator assay) to participating laboratories for testing with a SARS-CoV-2 index assay that requires evaluation. Discussion VALCOR provides a harmonised and standard framework to benchmark the testing performance of SARS-CoV-2 assays that are rapidly evolving. As the pandemic incited an urgent need for testing capacity, there is a gap in the comprehensive validation of SARS-CoV-2 assays. This study will generate comprehensive validation data for assays used for the diagnosis of SARS-CoV-2 and may serve as a basis for other validation protocols.

Background The COVID-19 pandemic highlighted the importance of diagnostic testing against curbing the spread of SARS-CoV-2. The urgent need and scale for diagnostic tools resulted in manufacturers of SARS-CoV-2 assays receiving emergency authorization that lacked robust analytical or clinical evaluation. As it is highly likely that testing for SARS-CoV-2 will continue to play a central role in public health, the performance characteristics of assays should be evaluated to ensure reliable diagnostic outcomes are achieved. Methods VALCOR or “VALidation of SARS-CORona Virus-2 assays” is a study protocol designed to set up a framework for test validation of SARS-CoV-2 virus assays. Using clinical samples collated from VALCOR, the performance of Aptima SARS-CoV-2 assay was assessed against a standard comparator assay. Diagnostic test parameters such as sensitivity, specificity and overall per cent agreement were calculated for the clinical performance of Aptima SARS-CoV-2 assay. Results A total of 180 clinical samples were tested with an addition of 40 diluted clinical specimens to determine the limit of detection. When compared to the standard comparator assay Aptima had a sensitivity of 100.0% [95% CI 95.9–100.0] and specificity of 96.7% [95% CI 90.8–99.3]. The overall percent agreement was 98.3% with an excellent Cohen’s coefficient of κ = 0.967 [95% CI 0.929–1.000]. For the limit of detection, Aptima was able to detect all of the diluted clinical samples. Conclusion In conclusion. validation of Aptima SARS-CoV-2 assay using clinical samples collated through the VALCOR protocol showed excellent test performance. Additionally, Aptima demonstrated high analytical sensitivity by detecting all diluted clinical samples corresponding to a low limit of detection.

Human papillomavirus (HPV) assays used in cervical cancer screening should be clinically validated according to international criteria. OncoPredict HPV® Screening (SCR) is a partial genotyping multiplex real‐time PCR assay targeting E6/E7 genes of 13 high‐risk (hr) HPVs. OncoPredict HPV® SCR (index assay) identifies HPV‐16 and HPV‐18 separately, 11 other hrHPV in aggregate and includes quality controls for sample adequacy, DNA extraction efficiency and PCR inhibition. 1300 VALGENT‐2 study samples (from women aged 20–60 attending the Scottish cervical cancer screening program) were tested with the index assay and the GP5+/6+ PCR enzyme immunoassay (standard comparator assay). Non‐inferior accuracy detecting cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) of the index versus comparator was verified. Intra‐ and interlaboratory reproducibility of the index was evaluated by overall concordance and Cohen's kappa, using a sub‐population (n = 526). Relative sensitivity and specificity for CIN2+ of the index versus comparator were 1.01 (95% confidence interval [CI]: 0.99–1.03) and 1.02 (95% CI: 1.0–1.04), respectively. Noninferiority p values were all ≤0.05, except for CIN3+ in patients ≥30 years. Excellent intra‐ and interlaboratory reproducibility was shown with concordance >98% and kappas >0.95. OncoPredict HPV® SCR fulfills the three international validation criteria for hrHPV DNA tests in cervical cancer screening.