{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:50:16Z","timestamp":1790272216954,"version":"4.1.0"},"reference-count":41,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2018,9,11]],"date-time":"2018-09-11T00:00:00Z","timestamp":1536624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Seventh Framework Programme","award":["603019"],"award-info":[{"award-number":["603019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In this diagnostic test validation study, we assessed the clinical accuracy and HPV genotyping performance of the INNO-LiPA HPV Genotyping Extra 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\u201319.2%) in the screening population. HrHPV testing with INNO-LiPA had a sensitivity for CIN2+ of 96.9% (95% CI, 92.1\u201399.1%) which was non-inferior to HC2 (relative sensitivity of 1.01; 95% CI, 0.97\u20131.04; pn.inf = 0.0002) and a specificity for \u2264CIN1 of 85.3% (95% CI, 83.2\u201387.3%) which was inferior to HC2 (relative specificity of 0.95; 95% CI, 0.93\u20130.97; pn.inf = 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.<\/jats:p>","DOI":"10.3390\/ijms19092704","type":"journal-article","created":{"date-parts":[[2018,9,11]],"date-time":"2018-09-11T11:40:02Z","timestamp":1536666002000},"page":"2704","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Clinical Evaluation of INNO-LiPA HPV Genotyping EXTRA II Assay Using the VALGENT Framework"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8654-679X","authenticated-orcid":false,"given":"Lan","family":"Xu","sequence":"first","affiliation":[{"name":"Unit of Cancer Epidemiology, Belgian Cancer Centre, Sciensano (Previously Scientific Institute of Public Health), 1050 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizaveta","family":"Padalko","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Microbiology and Immunology, Ghent University Hospital, 9000 Gent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"O\u0161trbenk","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3216-7564","authenticated-orcid":false,"given":"Mario","family":"Poljak","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Arbyn","sequence":"additional","affiliation":[{"name":"Unit of Cancer Epidemiology, Belgian Cancer Centre, Sciensano (Previously Scientific Institute of Public Health), 1050 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.virol.2014.12.028","article-title":"International standardization and classification of human papillomavirus types","volume":"476","author":"Bzhalava","year":"2015","journal-title":"Virology"},{"key":"ref_2","unstructured":"(2018, September 11). Biological Agents: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Available online: http:\/\/publications.iarc.fr\/Book-And-Report-Series\/Iarc-Monographs-On-The-Evaluation-Of-Carcinogenic-Risks-To-Humans\/Biological-Agents-2012."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1002\/path.4424","article-title":"Are twenty human papillomavirus types causing cervical cancer?","volume":"234","author":"Arbyn","year":"2014","journal-title":"J. Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/S1470-2045(09)70096-8","article-title":"A review of human carcinogens\u2014Part B: Biological agents","volume":"10","author":"Bouvard","year":"2009","journal-title":"Lancet Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"F88","DOI":"10.1016\/j.vaccine.2012.06.095","article-title":"Evidence regarding HPV testing in secondary prevention of cervical cancer","volume":"30","author":"Arbyn","year":"2012","journal-title":"Vaccine"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/S0140-6736(13)62218-7","article-title":"Efficacy of HPV-based screening for prevention of invasive cervical cancer: Follow-up of four European randomised controlled trials","volume":"383","author":"Ronco","year":"2014","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1002\/ijc.30579","article-title":"Eurogin 2016 Roadmap: How HPV knowledge is changing screening practice","volume":"140","author":"Wentzensen","year":"2017","journal-title":"Int. J. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.jcv.2015.10.023","article-title":"Commercially available molecular tests for human papillomaviruses (HPV): 2015 update","volume":"76","author":"Poljak","year":"2016","journal-title":"J. Clin. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1056\/NEJMoa0808516","article-title":"HPV screening for cervical cancer in Rural India","volume":"360","author":"Sankaranarayanan","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1016\/S1470-2045(09)70156-1","article-title":"HPV testing in combination with liquid-based cytology in primary cervical screening (ARTISTIC): A randomised controlled trial","volume":"10","author":"Kitchener","year":"2009","journal-title":"Lancet Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1128\/JCM.00012-11","article-title":"Comparison of Clinical and Analytical Performance of the Abbott RealTime High Risk HPV Test to the Performance of Hybrid Capture 2 in Population-Based Cervical Cancer Screening","volume":"49","author":"Poljak","year":"2011","journal-title":"J. Clin. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3680","DOI":"10.1128\/JCM.02078-05","article-title":"Cross-sectional comparison of an automated hybrid capture 2 assay and the consensus GP5+\/6+ PCR method in a population-based cervical screening program","volume":"44","author":"Hesselink","year":"2006","journal-title":"J. Clin. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1093\/jnci\/djn444","article-title":"Efficacy of HPV DNA testing with cytology triage and\/or repeat HPV DNA testing in primary cervical cancer screening","volume":"101","author":"Naucler","year":"2009","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/S1470-2045(11)70296-0","article-title":"Human papillomavirus testing for the detection of high-grade cervical intraepithelial neoplasia and cancer: Final results of the POBASCAM randomised controlled trial","volume":"13","author":"Rijkaart","year":"2012","journal-title":"Lancet Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1002\/ijc.24010","article-title":"Guidelines for human papillomavirus DNA test requirements for primary cervical cancer screening in women 30 years and older","volume":"124","author":"Meijer","year":"2009","journal-title":"Int. J. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.cmi.2015.04.015","article-title":"Which high-risk HPV assays fulfil criteria for use in primary cervical cancer screening?","volume":"21","author":"Arbyn","year":"2015","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1016\/S1470-2045(11)70188-7","article-title":"Performance of carcinogenic human papillomavirus (HPV) testing and HPV16 or HPV18 genotyping for cervical cancer screening of women aged 25 years and older: A subanalysis of the ATHENA study","volume":"12","author":"Castle","year":"2011","journal-title":"Lancet Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.ygyno.2015.01.551","article-title":"Prevalence of high-risk human papilloma virus genotypes and associated risk of cervical precancerous lesions in a large U.S. screening population: Data from the ATHENA trial","volume":"137","author":"Monsonego","year":"2015","journal-title":"Gynecol. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.pvr.2016.05.004","article-title":"Need for expanded HPV genotyping for cervical screening","volume":"2","author":"Cuzick","year":"2016","journal-title":"Papillomavir. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1016\/S0002-9440(10)65462-4","article-title":"Technical advance. Short fragment polymerase chain reaction reverse hybridization line probe assay to detect and genotype a broad spectrum of human papillomavirus types","volume":"155","author":"Melchers","year":"1999","journal-title":"Am. J. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2508","DOI":"10.1128\/JCM.37.8.2508-2517.1999","article-title":"Development and clinical evaluation of a highly sensitive PCR-reverse hybridization line probe assay for detection and identification of anogenital human papillomavirus","volume":"37","author":"Kleter","year":"1999","journal-title":"J. Clin. Microbiol."},{"key":"ref_22","unstructured":"(2018, August 11). Fujirebio Europe Upgrades its HPV (Human Papillomamvirus) Genotyping Panel with the Launch of the INNO-LiPA HPV Genotyping Extra II Assay. Fujirebio Europe Upgrades its HPV (Human Papillomamvirus). Available online: https:\/\/www.fujirebio-europe.com\/media-and-events\/news\/2015\/fujirebio-europe-upgrades-its-hpv-human-papillomavirus-genotyping-panel."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.jcv.2017.12.001","article-title":"Assessment of the Roche Linear Array HPV genotyping test within the VALGENT framework","volume":"98","author":"Xu","year":"2018","journal-title":"J. Clin. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3544","DOI":"10.1128\/JCM.01282-17","article-title":"Evaluation of the clinical performance of the HPV-Risk assay using the VALGENT-3 panel","volume":"55","author":"Polman","year":"2017","journal-title":"J. Clin. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"159","DOI":"10.2307\/2529310","article-title":"The measurement of observer agreement for categorical data","volume":"33","author":"Landis","year":"1977","journal-title":"Biometrics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1016\/S0002-9440(10)65688-X","article-title":"Novel short-fragment PCR assey for highly sensitive broad-spectrum detection of anogenital human papillomaviruses","volume":"153","author":"Kleter","year":"1998","journal-title":"Am. J. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1093\/oxfordjournals.jncimonographs.a003487","article-title":"Chapter 12: Human papillomavirus technologies","volume":"2003","author":"Iftner","year":"2003","journal-title":"J. Natl. Cancer Inst. Monogr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1007\/978-1-59745-423-0_15","article-title":"Cervical cytology biobanks as a resource for molecular epidemiology","volume":"675","author":"Arbyn","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"S14","DOI":"10.1016\/j.jcv.2015.09.014","article-title":"VALGENT: A protocol for clinical validation of human papillomavirus assays","volume":"76","author":"Arbyn","year":"2016","journal-title":"J. Clin. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1002\/ijc.27891","article-title":"Prevalence and viral load of 51 genital human papillomavirus types and 3 subtypes","volume":"132","author":"Schmitt","year":"2013","journal-title":"Int. J. Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1158\/1055-9965.EPI-12-1067","article-title":"Viral load of high-risk human papillomaviruses as reliable clinical predictor for the presence of cervical lesions. Cancer Epidemiol","volume":"22","author":"Schmitt","year":"2013","journal-title":"Biomarkers Prev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1128\/JCM.00087-13","article-title":"Multiple HPV infections with high viral loads are associated with cervical lesions but do not differentiate grades of cervical abnormalities","volume":"51","author":"Schmitt","year":"2013","journal-title":"J. Clin. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3272","DOI":"10.1128\/JCM.01366-15","article-title":"Clinical and analytical performance of the Onclarity HPV assay using the VALGENT framework","volume":"53","author":"Cuschieri","year":"2015","journal-title":"J. Clin. Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.1128\/JCM.00897-16","article-title":"Performance of a cartridge based assay for the detection of clinically significant HPV infection\u2014Lessons from VALGENT (Validation of HPV Genotyping Tests)","volume":"54","author":"Cuschieri","year":"2016","journal-title":"J. Clin. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3996","DOI":"10.1128\/JCM.01962-14","article-title":"Clinical evaluation of a GP5+\/6+-based Luminex assay having full high-risk HPV genotyping capability and an internal control","volume":"52","author":"Geraets","year":"2014","journal-title":"J. Clin. Microbiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.jcv.2016.05.004","article-title":"Clinical and analytical performance of the PapilloCheck HPV-Screening assay using the VALGENT framework","volume":"81","author":"Heard","year":"2016","journal-title":"J. Clin. Virol."},{"key":"ref_37","unstructured":"(2018, August 11). Smernice za celostno obravnavo \u017eensk s predrakavimi spremembami materni\u010dnega vratu. Available online: https:\/\/zora.onko-i.si\/fileadmin\/user_upload\/dokumenti\/strokovna_priporocila\/2011_Smernice_web.pdf."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1093\/annonc\/mdp471","article-title":"European Guidelines for Quality Assurance in Cervical Cancer Screening. Second Edition\u2014Summary Document","volume":"21","author":"Arbyn","year":"2010","journal-title":"Ann. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1002\/sim.1213","article-title":"On tests of equivalence via non-unity relative risk for matched-pair design","volume":"22","author":"Tang","year":"2003","journal-title":"Stat. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/BF02295996","article-title":"Note on the sampling error of the difference between correlated proportions or percentages","volume":"12","author":"McNemar","year":"1947","journal-title":"Psychometrika"},{"key":"ref_41","unstructured":"Fleiss, J.L, Levin, B., and Paik, M.C. (2013). Statistical Methods for Rates and Proportions, John Wiley & Sons. [2nd ed.]."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/9\/2704\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:19:51Z","timestamp":1760195991000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/9\/2704"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,11]]},"references-count":41,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2018,9]]}},"alternative-id":["ijms19092704"],"URL":"https:\/\/doi.org\/10.3390\/ijms19092704","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,11]]}}}