Alinity m HR HPV Assay Fulfills Criteria for Human Papillomavirus Test Requirements in Cervical Cancer Screening Settings.

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 (n = 68) and specificity (n = 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) (P = 0.0006 and P < 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 P 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 [P = 0.03] and 3.5 [P = 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.

Oštrbenk Valenčak A ，Šterbenc A ，Seme K ，Poljak M ... -  《-》

Comparison of the clinical and analytical performance of Alinity m HR HPV and cobas 4800 HPV assays in a population-based screening setting.

The recently launched Abbott Alinity m HR HPV (Alinity) assay separately identifies high-risk human papillomavirus (hrHPV) genotypes HPV16, HPV18, and HPV45, and reports 11 other genotypes as two aggregates. Clinical and analytical performance of Alinity was compared with the cobas 4800 HPV assay on 4,334 women aged 20-64 years attending routine, population-based organized cervical cancer screening during 2009/2010. After 36 months, they were invited to participate in the second screening round (2012-2014) and later followed-up through centralized national cervical cancer screening registry. In women 30 and older, the clinical sensitivity for cervical intraepithelial neoplasia grade 2+ (CIN2+) was 100.0% (95% CI, 88.2-100.0%) for Alinity and 100.0% (95% CI, 88.2-100.0%) for cobas, and for CIN3+ 100.0% (95% CI, 78.9-100.0%) for both assays. The clinical specificity for ≤ CIN1 in women 30 and older was 92.4% (95% CI, 91.4-93.3%) and 92.9% (95% CI, 91.9-93.7%), respectively. The assays demonstrated excellent overall agreement for hrHPV detection (97.9%) and genotype-specific agreement for HPV16 (99.6%), HPV18 (99.8%), and other hrHPV (98.1%). Overall positive agreement and positive agreements for HPV16, HPV18, and other hrHPV genotypes were 84.3%, 89.1%, 73.2%, and 82.3%. Based on a 5-year CIN3+ risk, slightly more HPV-positive women would require referral to immediate colposcopy after testing with Alinity vs. cobas (4.1% vs. 3.8%; p = 0.470), but significantly fewer Alinity-tested women would need a 6- to 12-month follow-up visit compared with those tested with cobas (5.0% vs. 8.6%; p < 0.0001). Alinity and cobas have comparable clinical performance and showed excellent overall and genotype-specific agreement. The Alinity's extended genotyping ability could help predict the 5-year CIN3+ risk and cost-saving management of HPV-screen-positive women.

Oštrbenk Valenčak A ，Bertram A ，Gröning A ，Poljak M ... -  《-》

Three-year longitudinal data on the clinical performance of the Abbott RealTime High Risk HPV test in a cervical cancer screening setting.

Testing cervical smears for the presence of high-risk human papillomaviruses (hrHPV) increases the sensitivity for detecting women with underlying high-grade cervical intraepithelial neoplasia (CIN) and provides better and longer protection against invasive cervical cancer compared to cytology testing alone. The Abbott RealTime High Risk HPV test (RealTime) is a hrHPV DNA test with concurrent partial genotyping for HPV16 and HPV18 and aggregate detection of 12 other hrHPV types that have been extensively analytically and clinically evaluated over the last 6 years. To provide the first 3-year longitudinal data regarding the clinical performance of RealTime, the risk of CIN2+ according to various negative baseline characteristics, and baseline and future risk for CIN2+ at 3 years for women with baseline infection with various hrHPV types were assessed in a cohort of 3,920 Slovenian women that had hrHPV DNA and/or cytology in 36- to 48-month follow-up results after a baseline screening round in 2009/2010. A total of 36 CIN2+ cases were identified in the second screening round. Of these, 17 CIN2+ cases were identified passively through questionnaires/data registries and 19 cases actively as the result of actions triggered by second-round cytology and/or HPV test results. Accumulation of CIN2+ cases during follow-up occurred predominantly in woman with normal cytology at baseline. Among women >30 years old, significantly better protection against CIN2+ at 3 years was associated with a negative hrHPV DNA result at baseline (risk for CIN2+ 0.04% [95 CI, 0.00-0.22%]) than by normal cytology at baseline (risk for CIN2+ 0.68% [95 CI, 0.40-1.08%]). Women with baseline HPV16 infection had a significantly higher risk of CIN2+ at baseline (21.9% [95 CI, 15.2-30.4%]) and baseline plus future risk at 3 years for CIN2+ (33.3% [95 CI, 24.7-44.0%]) in comparison to women with baseline non-HPV16/18 hrHPV infection (7.0% [95 CI, 4.6-10.2%]) or those that were hrHPV-positive (11.7% [95 CI, 9.1-14.9%]). 3-year longitudinal data reinforce evidence from previous studies that RealTime can be safely used in primary HPV-based cervical cancer screening. Concurrent partial genotyping for HPV16/18 should be strongly considered as a triage method for HPV screen-positive women.

Poljak M ，Oštrbenk A ，Seme K ，Šterbenc A ，Jančar N ，Vrtačnik Bokal E ... -  《-》

The clinical effectiveness and cost-effectiveness of primary human papillomavirus cervical screening in England: extended follow-up of the ARTISTIC randomised trial cohort through three screening rounds.

C Kitchener H ，Canfell K ，Gilham C ，Sargent A ，Roberts C ，Desai M ，Peto J ... -  《-》

Assessment of the Roche Linear Array HPV Genotyping Test within the VALGENT framework.

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.

Xu L ，Oštrbenk A ，Poljak M ，Arbyn M ... -  《-》