Hybribio's 14 High-Risk HPV with 16/18 genotyping real-time PCR (HBRT-H14) is a human papillomavirus (HPV) assay with approval from the China Food and Drug Administration that is widely used in ...China. VALGENT (VALidation of HPV GENotyping Tests) is an established framework for evaluating HPV tests' clinical performance relative to validated comparators. The aim of this study was to assess the clinical accuracy of HBRT-H14 following international validation criteria. Within VALGENT-3, clinical performance of HBRT-H14 was compared with Hybrid Capture 2 (HC2), Linear Array HPV genotyping test (Linear Array), and Cobas 4800 HPV test (Cobas). VALGENT-3 comprised 1,300 consecutive samples and 300 abnormal cytological samples from the Slovenian cervical cancer screening program. Disease was defined as histologically confirmed cervical intraepithelial neoplasia scoring grade 2 or worse (CIN2+) and CIN3+, and two negative cytology results in a row were a proxy for nondisease. In the total study population, relative sensitivity and specificity of HBRT-H14 versus HC2 for detecting CIN2+ were 0.98 (95% confidence interval CI, 0.94 to 1.03;
noninferiority
< 0.01) and 0.97 (95% CI, 0.96 to 0.99;
= 0.78), respectively. Applying an optimized
cutoff, defined using Linear Array and Cobas as bridging tests, yielded relative values of 0.98 (95% CI, 0.94 to 1.03;
< 0.01) and 1.01 (95% CI, 1.00 to 1.03;
< 0.01), respectively. In conclusion, HBRT-H14 was as sensitive but less specific than HC2 for detecting cervical precancer at the predefined cutoff. However, HBRT-H14 fulfilled international accuracy criteria for cervical cancer screening when using an optimized cutoff and might be attractive in low-resource settings given its low cost.
Highlights • At least 193 commercial HPV tests and 127 variants of the original tests are available. • There was a 54% increase in the number of HPV tests in comparison with 2012. • All but two ...commercial HPV tests target alpha-HPV types only. • Only 35% of tests have performance evaluations published in peer-reviewed literature. • Manufacturers should invest greater effort into evaluating their products.
The Alinity m HR HPV assay (Alinity) is a novel human papillomavirus (HPV) assay that individually identifies genotypes HPV16, HPV18, and HPV45 while reporting on 11 other high-risk HPV (hrHPV) ...genotypes in two aggregates: HPV31/33/52/58 and HPV35/39/51/56/59/66/68. The clinical performance of Alinity for screening for cervical cancer was evaluated in population-based settings. For women aged ≥30 years, the clinical sensitivity (
= 68) and specificity (
= 3,077) for the detection of cervical intraepithelial neoplasia grade 2+ (CIN2+) of Alinity were 100.0% and 92.4%, respectively, and were not inferior to those of the Qiagen Digene Hybrid Capture 2 high-risk HPV DNA assay (hc2) (
= 0.0006 and
< 0.0001, respectively). The intralaboratory reproducibility and interlaboratory agreement of Alinity were 96.7% (kappa, 0.92) and 98.7% (kappa, 0.97), respectively. In the group ≥30 years of age, women who were baseline hrHPV negative had a lower risk for CIN2+ at 3 years using Alinity (0.04%) than those with a normal baseline cytology (0.65%) and had a risk comparable to that determined by the Abbott RealTime High Risk HPV assay (0.04%), hc2 (0.08%), or the Roche Cobas 4800 HPV assay (0.04%). High-risk HPV16/18 infection was associated with a significantly higher baseline and 3-year CIN2+ and CIN3+ risk than the absence of HPV16/18 or the presence of hrHPVs at the baseline (all
values were <0.05). The baseline CIN2+ risk was 8.8% for those with HPV31/33/52/58 infection and 2.5% for those with HPV35/39/51/56/59/66/68 infection, while the 3-year CIN2+ risk was 17.0% and 4.9%, respectively (relative risk, 3.4
= 0.03 and 3.5
= 0.003, respectively), suggesting that extended genotyping by Alinity may be valuable in improving patient risk stratification. Alinity fulfills international consensus guideline criteria for primary cervical cancer screening and can be considered clinically validated, demonstrating safety comparable to that of other clinically validated HPV tests.
•Cervical cancer screening with HPV tests should use only clinically validated assays.•This VALGENT study is the first to demonstrate that Linear Array HPV assay fulfils the international validation ...criteria for screening.•Linear Array HPV assay could become the standard comparator for HPV assays with genotyping capacity in the future.
Cervical cancer screening programs are switching from cytology-based screening to high-risk (hr) HPV testing. Only clinically validated tests should be used in clinical practice.
To assess the clinical performance of the Roche Linear Array HPV genotyping test (Linear Array) within the VALGENT-3 framework.
The VALGENT framework is designed for comprehensive comparison and clinical validation of HPV tests that have limited to extended genotyping capacity. The Linear Array enables type-specific detection of 37 HPV types. For the purpose of this study, Linear Array results were designated as positive only if one of the 13 hrHPV types also included in the Hybrid Capture 2 (HC2) was detected. The VALGENT-3 framework comprised 1600 samples obtained from Slovenian women (1300 sequential cases from routine cervical cancer screening enriched with 300 cytological abnormal samples). Sensitivity for cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) (n=127) and specificity for <CIN2 (n=1216) were assessed for Linear Array and for HC2 and non-inferiority of Linear Array relative to HC2 was checked. In addition, the prevalence of separate hrHPV types in the screening population, as well as the concordance for presence of HPV16, HPV18 and other hrHPV types between Linear Array and the Abbott RealTime High Risk HPV test (RealTime) were assessed.
The clinical sensitivity and specificity for CIN2+ of the Linear Array in the total study population was 97.6% (95% CI, 93.3–99.5%) and 91.7% (95% CI, 90.0–93.2%), respectively. The relative sensitivity and specificity of Linear Array vs HC2 was 1.02 95% CI, 0.98–1.05, (p<0.001) and 1.02 95% CI, 1.01–1.03, (p<0.001), respectively The overall prevalence of hrHPV using the Linear Array in the screening population was 10.5% (95% CI, 8.9–12.3%) with HPV16 and HPV18 detected in 2.3% and 0.9% of the samples, respectively. Excellent agreement for presence or absence of HPV16, HPV18 and other hrHPV between Linear Array and RealTime was observed.
Linear Array showed similar sensitivity with higher specificity to detect CIN2+ compared to HC2. Detection of 13 hrHPV types with Linear Array fulfils the clinical accuracy requirements for primary cervical cancer screening.
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 against two previously validated alternative comparator tests (Abbott RealTi
e 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 high-risk HPV test concordance was assessed by kappa values; the concordance for HPV-16 and HPV-18 was assessed for Alinity m, RealTi
e, 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 cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and CIN3+ of Alinity m compared to HC2 was 1.02 (95% confidence interval CI, 0.99 to 1.06) and 1.03 (95% CI, 0.99 to 1.06), respectively. The relative specificity for nondiseased subjects (≤CIN1) was 1.01 (95% CI, 1.00 to 1.02) (all
≤ 0.001). Alinity m showed noninferior clinical accuracy among women 30 years or older when cobas or RealTi
e was used as a comparator. HPV genotype-specific concordance between Alinity m and the three comparator tests showed excellent agreement, with kappa values ranging from 0.82 to 1.00. In conclusion, Alinity m fulfills the international accuracy requirements for use in cervical cancer screening and shows excellent HPV genotype-specific concordance with three clinically validated HPV tests.
In 2012, VALidation of human papillomavirus (HPV) GENotyping Tests (VALGENT) was initiated to provide a formalized and uniform study framework for comparison and validation of HPV assays with ...genotyping capability. In VALGENT-3, the clinical and analytical performance of Anyplex II HPV HR detection (Anyplex) was compared to that of the Hybrid Capture 2 HPV DNA test (hc2) and the cobas 4800 HPV test (cobas). The panel comprises 1,300 stored samples that were obtained from women 25 to 64 years old who participated in the Slovenian cancer screening program, enriched with 300 samples from women with abnormal cervical cytology. The sensitivity and specificity of Anyplex were noninferior to those of hc2, with a relative sensitivity of 1.01 (95% confidence interval CI, 0.97 to 1.04) for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and 1.01 (95% CI, 0.97 to 1.06) for CIN3+ and relative specificity of 1.02 (95% CI, 1.00 to 1.03) for a CIN grade of ≤1. The clinical sensitivity of Anyplex for CIN2+ and CIN3+ was comparable to that of hc2 (
values for McNemar test
of 0.655 and 0.564, respectively), but its specificity was significantly higher (
= 0.008). The sensitivity and specificity of Anyplex were also noninferior to those of cobas, with relative sensitivity of 1.01 (95% CI, 0.98 to 1.04) for CIN2+ and 1.01 (95% CI, 0.99 to 1.04) for CIN3+ and relative specificity of 1.00 (95% CI, 0.99 to 1.01) (
value of >0.05 in all cases). Regardless of the clinical outcome (CIN2+ or CIN3+), age restriction (women ≥30 years old), or comparator test used, Anyplex consistently showed excellent clinical performance and can be considered validated for primary cervical cancer screening.
In this diagnostic test validation study, we assessed the clinical accuracy and HPV genotyping performance of the INNO-LiPA HPV Genotyping
II (INNO-LiPA) within the VALGENT-3 framework. VALGENT is ...designed to assess the analytical and clinical performance of HPV tests with genotyping capacity. The VALGENT-3 panel comprised 1300 consecutive cervical cell specimens enriched with 300 samples with abnormal cytology obtained from women attending the Slovenian cervical cancer screening programme. The INNO-LiPA allows type-specific detection of 32 HPV types; however, for the clinical accuracy assessment, we considered it as high-risk (hr)HPV positive when at least one of the following HPV types was present: HPV16, HPV18, HPV31, HPV33, HPV35, HPV39, HPV45, HPV51, HPV52, HPV56, HPV58, HPV59, and HPV68. Clinical accuracy for detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was compared between INNO-LiPA and Hybrid Capture 2 (HC2), which is a standard comparator test for HPV tests used in cervical cancer screening. In addition, hrHPV and type-specific detection HPV types were compared between INNO-LiPA and Linear Array HPV Genotyping Test (Linear Array). The prevalence of hrHPV determined by INNO-LiPA was 17.1% (95% CI, 15.0⁻19.2%) in the screening population. HrHPV testing with INNO-LiPA had a sensitivity for CIN2+ of 96.9% (95% CI, 92.1⁻99.1%) which was non-inferior to HC2 (relative sensitivity of 1.01; 95% CI, 0.97⁻1.04;
= 0.0002) and a specificity for ≤CIN1 of 85.3% (95% CI, 83.2⁻87.3%) which was inferior to HC2 (relative specificity of 0.95; 95% CI, 0.93⁻0.97;
= 0.9998). Genotyping agreement between INNO-LiPA and Linear Array was excellent for hrHPV, HPV16, HPV18, HPV35, HPV45, HPV58 and HPV59, but good or fair for other HPV types. To conclude, INNO-LiPA demonstrated non-inferior clinical sensitivity but lower specificity compared to HC2 in addition to excellent concordance compared to Linear Array for hrHPV and some genotypes.
Blood culture systems are a potential alternative to classical cultivation of fungi on mycological media, but there are limited data on the suitability of these systems for culturing other sample ...types (e.g., sterile body fluids). We conducted a prospective study to evaluate different types of blood culture (BC) bottles for the detection of different fungal species in non-blood samples. A total of 43 fungal isolates were tested for their ability to grow in BD BACTEC Mycosis-IC/F (Mycosis bottles), BD BACTEC Plus Aerobic/F (Aerobic bottles) and BD BACTEC Plus Anaerobic/F (Anaerobic bottles) (Becton Dickinson, East Rutherford, NJ, USA) BC bottles inoculated with spiked samples without the addition of blood or fastidious organism supplement. Time to detection (TTD) was determined for all BC types tested and compared between groups. In general, Mycosis and Aerobic bottles were similar (
> 0.05). The Anaerobic bottles failed to support growth in >86% of cases. The Mycosis bottles were superior in detecting
,
spp. and
spp. (
< 0.05). The performance of Mycosis and Aerobic bottles was similar, but if cryptococcosis or aspergillosis is suspected, the use of Mycosis bottles is recommended. Anaerobic bottles are not recommended for fungal detection.
HPV immunization programs are mainly focused on girls and boys, but adult women and men could also benefit from vaccination. A multinational CoheaHr-WP4 study investigated the acceptability of HPV ...vaccination among 25-45 years old women. A total of 607 women from Slovenia participated in the study, and 49.6% (301/607) agreed with HPV vaccination, with a significant difference (
< 0.0001) between the two centers. Non-vaccinated women had a higher education (
= 0.0068) and were more frequently in a committed relationship or married (
= 0.01). The most trusted source of medical and vaccination information was healthcare providers (55.2%). The main reasons for vaccine acceptance were protection against HPV-related disease (93.4%), severity of preventable diseases (82.7%), HPV vaccine safety (66.8%), free HPV vaccine availability (62.8%), and the existence of vaccination recommendations (55.5%). The main reasons for refusing vaccination were the need for additional vaccine-related information (31.4%) and vaccine safety concerns (29.4%). To increase vaccine coverage, information about the benefits and safety of HPV vaccination must be widely disseminated to all health professionals and the general public. We are convinced that the knowledge obtained in this study can be reliably applied to other countries in the region that lack such information and have a very high cervical cancer burden.
•First manufacturer-independent head-to-head comparison of Elecsys-N and Elecsys-S.•Evaluated during the exponential growth phase of the epidemic’s second wave.•100 % specificity of both assays on ...572 pre−COVID-19 samples.•High overall (98.68 %) and positive agreement (95.16 %) with kappa value of 0.996.•Concomitant over sequential Elecsys-N/Elecsys-S use recommended.
Accurate anti-SARS-CoV-2 assays are needed to inform diagnostic, therapeutic, and public health decisions. The first manufacturer-independent head-to-head comparison of two rapid high-throughput automated electrochemiluminescence double-antigen sandwich immunoassays targeting total anti-SARS-CoV-2 antibodies against two different viral proteins, Elecsys Anti-SARS-CoV-2 (Elecsys-N) and Elecsys Anti-SARS-CoV-2 S (Elecsys-S) (Roche Diagnostics), was performed in a routine setting during the exponential growth phase of the epidemic’s second wave.
The diagnostic specificity of Elecsys-N and Elecsys-S was initially evaluated on a panel of 572 pre−COVID-19 samples, showing 100 % specificity of both assays. Elecsys-N/Elecsys-S head-to-head comparison used 3,416 consecutive blood samples from individuals that were tested for the presence of anti-SARS-CoV-2 within commercial out-of-pocket serologic testing.
Elecsys-N/Elecsys-S head-to-head comparison showed overall agreement of 98.68 % (3,371/3,416; 95 % CI, 98.23–99.03 %), positive agreement of 95.16 % (884/929; 95 % CI, 93.52–96.41 %), and a high kappa value of 0.996 (95 % CI, 0.956–0.976). Previous SARS-CoV-2 PCR positivity was identified in 14/24 (58.3 %) Elecsys-N negative/Elecsys-S positive individuals and in 4/21 (19.0 %) Elecsys-N positive/Elecsys-S negative individuals.
The first Elecsys-N/Elecsys-S head-to-head comparison showed excellent agreement of two highly specific and rapid high-throughput automated anti-SARS-CoV-2 assays. An important question is whether laboratories offering two different antibody assays could benefit from combining the assays; if so, should use be concomitant or sequential—and, in the latter case, in which order? Based on our results, we favor concomitant over sequential Elecsys-N/Elecsys-S use when testing individuals for anti-SARS-CoV-2 antibodies in high-incidence settings; for example, during the exponential or stationary growth phase of the COVID-19 epidemic.
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