{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:38:37Z","timestamp":1787027917101,"version":"build-2736575974"},"reference-count":54,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T00:00:00Z","timestamp":1617062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"USL Umbria 1 of Perugia, Umbria Region","award":["as extension of finalized research project \u201cHPV as primary screening test in cervical cancer prevention: from DNA to mRNA? A randomised controlled trial test in a double testing study with long term follow-up\u201d presented by Lazio Region and approved by the"],"award-info":[{"award-number":["as extension of finalized research project \u201cHPV as primary screening test in cervical cancer prevention: from DNA to mRNA? A randomised controlled trial test in a double testing study with long term follow-up\u201d presented by Lazio Region and approved by the"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Objective: To evaluate the clinical accuracy of Hepika test to identify cancer\/precancerous lesions of the uterine cervix. Materials and Methods: A multicentre retrospective study was carried out in 2018 and included 330 liquid-based cytology samples from three Italian centres of women aged 25\u201364 who had been tested for the human papillomavirus (HPV) and whose histology or follow-up outcome was known. Hepika is an enzyme-linked immunosorbent assay (ELISA) targeting the protein complexes E6#p53 and E7#pRb. After excluding samples without sufficient residual material, the clinical accuracy of Hepika test was evaluated in 274 samples: adenocarcinoma (ADC) (4), squamous cell carcinoma (SCC) (7), adenocarcinoma in situ (AIS) (1), cervical intraepithelial neoplasia (CIN) grade 3 (60), CIN2 (51), CIN1 (34), and negative histology (117). Association, sensitivity, and specificity for carcinoma, CIN3+ and CIN2+ are reported. Results: Positive Hepika test was associated with a high probability of carcinoma (odds ratio (DOR) = 33.68, 95% confidence interval (CI) 7.0\u2013163.1); sensitivity was 81.8%, specificity, 88.2%. A positive Hepika test showed a weaker association with CIN3+ lesions (DOR = 3.5; 95% CI 1.75\u20136.99) and lower sensitivity (27.8%). Conclusion: The Hepika test was found to be an accurate biomarker for HPV-induced cervical carcinoma. Population-based prospective studies are needed to confirm the clinical usefulness of the Hepika test in the differential diagnosis of HPV-induced invasive lesions.<\/jats:p>","DOI":"10.3390\/diagnostics11040619","type":"journal-article","created":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T09:57:04Z","timestamp":1617098224000},"page":"619","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Multicentre Evaluation of Hepika Test Clinical Accuracy in Diagnosing HPV-Induced Cancer and Precancerous Lesions of the Uterine Cervix"],"prefix":"10.3390","volume":"11","author":[{"given":"Daniela","family":"Gustinucci","sequence":"first","affiliation":[{"name":"Laboratorio Unico di Screening USL Umbria 1, 06124 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Ciccocioppo","sequence":"additional","affiliation":[{"name":"Cytopathology Unit, Renzetti Hospital, 66034 Lanciano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Coppola","sequence":"additional","affiliation":[{"name":"Pathology Unit, San Filippo Neri Hospital, 00135 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Negri","sequence":"additional","affiliation":[{"name":"Pathology Unit, Central Hospital Bolzano, 39100 Bolzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4473-7560","authenticated-orcid":false,"given":"Gianfranco","family":"Zannoni","sequence":"additional","affiliation":[{"name":"Department of Woman, Child and Public Health Sciences, Gynecopathology and Breast Pathology Unit, Catholic University of Sacred Hearth, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basilio","family":"Passamonti","sequence":"additional","affiliation":[{"name":"Laboratorio Unico di Screening USL Umbria 1, 06124 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Cesarini","sequence":"additional","affiliation":[{"name":"Laboratorio Unico di Screening USL Umbria 1, 06124 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciro","family":"Ianzano","sequence":"additional","affiliation":[{"name":"Cytopathology Unit, Renzetti Hospital, 66034 Lanciano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Andreano","sequence":"additional","affiliation":[{"name":"Pathology Unit, Renzetti Hospital, 66034 Lanciano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjuta","family":"Pireddu","sequence":"additional","affiliation":[{"name":"Pathology Unit, USL Umbria 1, 06012 Citt\u00e0 di Castello, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Giorgi-Rossi","sequence":"additional","affiliation":[{"name":"Epidemiology Unit, Azienda Unit\u00e0 Sanitaria Locale\u2014Istituto di Ricovero e Cura a Carattere Scientifico di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,30]]},"reference":[{"key":"ref_1","unstructured":"WHO (2019, January 30). Human Papillomavirus (HPV) and Cervical Cancer. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/human-papillomavirus-(hpv)-and-cervical-cancer."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of inci-dence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1002\/(SICI)1097-0215(19980209)75:4<536::AID-IJC8>3.0.CO;2-U","article-title":"International trends in the incidence of cervical cancer: I. Adenocarcinoma and adenosquamous cell carcinomas","volume":"75","author":"Vizcaino","year":"1998","journal-title":"Int. J. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1023\/A:1018435522475","article-title":"International incidence rates of invasive cervical cancer after introduction of cytological screening","volume":"8","author":"Gustafsson","year":"1997","journal-title":"Cancer Causes Control."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1002\/(SICI)1097-0215(19970410)71:2<159::AID-IJC6>3.0.CO;2-#","article-title":"International incidence rates of invasive cervical cancer before cytological screening","volume":"71","author":"Gustafsson","year":"1997","journal-title":"Int. J. Cancer"},{"key":"ref_6","unstructured":"IARC (1986). Working Group on Cervical Cancer Screening and the UICC Project Group on the Evaluation of Screening Programmes for Cancer. Screening for cancer of the uterine cervix. IARC Sci. Publ., 76, 1\u2013315."},{"key":"ref_7","first-page":"443","article-title":"New Strategies for Papillomavirus-Based Cervical Screening","volume":"9","author":"Lorincz","year":"2013","journal-title":"Women\u2019s Health"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1136\/jcp.55.4.244","article-title":"The causal relation between human papillomavirus and cervical cancer","volume":"55","author":"Bosch","year":"2002","journal-title":"J. Clin. Pathol."},{"key":"ref_9","first-page":"337","article-title":"Long term predictive values of cytology and human papillomavirus testing in cervical cancer screening: Joint European cohort study","volume":"13","author":"Dillner","year":"2008","journal-title":"BMJ"},{"key":"ref_10","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_11","doi-asserted-by":"crossref","unstructured":"US Preventive Services Task Force (2018). Screening for cervical cancer: US Preventive Services Task Force Recommendation Statement. JAMA, 320, 674\u2013686.","DOI":"10.1001\/jama.2018.10897"},{"key":"ref_12","unstructured":"Anttila, A., Arbyn, M., Bergeron, C., Cuzick, J., De Vuyst, H., Dillner, J., Dillner, L., Ducarroz, S., Franceschi, S., and Giorgi Rossi, P. (2018, April 20). European Guidelines for Quality Assurance in Cervical Cancer Screening\u2014Second Edition. Available online: https:\/\/op.europa.eu\/en\/publication-detail\/-\/publication\/a41a4c40-0626-4556-af5b-2619dd1d5ddc\/language-en."},{"key":"ref_13","unstructured":"Ministero Della Salute (2020, March 24). Piano Nazionale Della Prevenzione 2014\u20132018, Available online: http:\/\/www.salute.gov.it\/imgs\/C_17_pubblicazioni_2285_allegato.pdf."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1093\/jnci\/djn065","article-title":"Results at Recruitment From a Randomized Controlled Trial Comparing Human Papillomavirus Testing Alone With Conventional Cytology as the Primary Cervical Cancer Screening Test","volume":"100","author":"Ronco","year":"2008","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S1470-2045(09)70360-2","article-title":"Efficacy of human papillomavirus testing for the detection of invasive cervical cancers and cervical intraepithelial neoplasia: A randomised controlled trial","volume":"11","author":"Ronco","year":"2010","journal-title":"Lancet Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1006\/scbi.1999.0144","article-title":"Immortalization of human cells and their malignant conversion by high risk human papillomavirus genotypes","volume":"9","year":"1999","journal-title":"Semin. Cancer Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1093\/jnci\/92.9.690","article-title":"Papillomaviruses Causing Cancer: Evasion From Host-Cell Control in Early Events in Carcinogenesis","volume":"92","author":"Hausen","year":"2000","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/S1470-2045(08)70103-7","article-title":"Natural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: A retrospective cohort study","volume":"9","author":"McCredie","year":"2008","journal-title":"Lancet Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"van den Heuvel, S. (2005). Cell-cycle regulation. WormBook, 1\u201316.","DOI":"10.1895\/wormbook.1.28.1"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5201","DOI":"10.1038\/sj.onc.1206554","article-title":"Human papillomaviruses: Targeting differentiating epithelial cells for malignant transformation","volume":"22","author":"Fehrmann","year":"2003","journal-title":"Oncogene"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"F55","DOI":"10.1016\/j.vaccine.2012.06.083","article-title":"The Biology and Life-Cycle of Human Papillomaviruses","volume":"30","author":"Doorbar","year":"2012","journal-title":"Vaccine"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"26","DOI":"10.2174\/138920209787581235","article-title":"Molecular Signature of HPV-Induced Carcinogenesis: pRb, p53 and Gene Expression Profiling","volume":"10","author":"Garaulet","year":"2009","journal-title":"Curr. Genom."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1111\/j.1346-8138.2000.tb02126.x","article-title":"Molecular Mechanism of Carcinogenesis by Human Papillomavirus-16","volume":"27","author":"Ishiji","year":"2000","journal-title":"J. Dermatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"607","DOI":"10.6026\/97320630008607","article-title":"Molecular screening of compounds to the predicted Protein-Protein Interaction site of Rb1-E7 with p53-E6 in HPV","volume":"8","author":"Shaikh","year":"2012","journal-title":"Bioinformation"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1016\/S1470-2045(10)70230-8","article-title":"Human papillomavirus genotype attribution in invasive cervical cancer: A retrospective cross-sectional worldwide study","volume":"11","author":"Quint","year":"2010","journal-title":"Lancet Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7690","DOI":"10.1038\/sj.onc.1202953","article-title":"The role of the E6-p53 interaction in the molecular pathogenesis of HPV","volume":"18","author":"Thomas","year":"1999","journal-title":"Oncogene"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/nature16481","article-title":"Structure of the E6\/E6AP\/p53 complex required for HPV-mediated degradation of p53","volume":"529","author":"Ruiz","year":"2016","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1111\/j.1600-0463.2010.02618.x","article-title":"Interaction of viral oncoproteins with cellular target molecules: Infection with high-risk vs low-risk human papillomaviruses","volume":"118","author":"Pim","year":"2010","journal-title":"APMIS"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/s12253-008-9056-6","article-title":"Human Papilloma Virus (HPV) and Host Cellular Interactions","volume":"14","author":"Mammas","year":"2008","journal-title":"Pathol. Oncol. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1128\/JVI.77.2.1551-1563.2003","article-title":"Endogenous Human Papillomavirus E6 and E7 Proteins Differentially Regulate Proliferation, Senescence, and Apoptosis in HeLa Cervical Carcinoma Cells","volume":"77","author":"DeFilippis","year":"2003","journal-title":"J. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.mad.2003.10.001","article-title":"Transition to an irreversible state of senescence in HeLa cells arrested by repression of HPV E6 and E7 genes","volume":"125","author":"Kang","year":"2004","journal-title":"Mech. Ageing Dev."},{"key":"ref_32","first-page":"S4","article-title":"The Detection of Complexed Proteins E6\/P53 and E7\/Prb In Relation to the Carcinogenesis of the Uterine Cervix","volume":"2","author":"Maccallini","year":"2014","journal-title":"J. Cytol. Histol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1002\/ijc.25474","article-title":"Immortalization of oral keratinocytes by functional inactivation of the p53 and pRb pathways","volume":"128","author":"Smeets","year":"2011","journal-title":"Int. J. Cancer"},{"key":"ref_34","unstructured":"GISCi. Gruppo Italiano Screening Cervicale (2021, March 24). Raccomandazioni sul Test HR-HPV Come Test di Screening Primario e Rivisitazione del Ruolo del Pap Test. Available online: https:\/\/www.gisci.it\/documenti\/documenti_gisci\/documento_hpv.pdf."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Nayar, R., and Solomon, D. (2004). The Bethesda System for Reporting Cervical Cytology, Springer.","DOI":"10.1007\/978-1-4612-2042-8"},{"key":"ref_36","unstructured":"Kurman, R.J., Carcangiu, M.L., Herrington, C.S., and Young, R.H. (2014). WHO Classification of Tumours of Female Reproductive Organs, IARC."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1159\/000320912","article-title":"Repeat Processing of Residual ThinPrep Pap Tests: Sampling of the Vial May Not Be Invariably Homogeneous","volume":"55","author":"Grapsa","year":"2011","journal-title":"Acta Cytol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1309\/AJCPZ5JY6FCVNMOT","article-title":"High-risk human papillomavirus testing in women with ASC-US cytology: Results from the ATHENA HPV study","volume":"135","author":"Stoler","year":"2011","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1097\/00019606-200009000-00004","article-title":"Human Papillomavirus Detection by the Hybrid Capture II Assay: A Reliable Test to Select Women With Normal Cervical Smears at Risk for Developing Cervical Lesions","volume":"9","author":"Clavel","year":"2000","journal-title":"Diagn. Mol. Pathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2741","DOI":"10.1002\/ijc.28900","article-title":"The clinical impact of using p16INK4a immunochemistry in cervical histopathology and cytology: An update of recent developments","volume":"136","author":"Bergeron","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1001\/jamainternmed.2019.0306","article-title":"Clinical Evaluation of Human Papillomavirus Screening with p16\/Ki-67 Dual Stain Triage in a Large Organized Cervical Cancer Screening Program","volume":"179","author":"Wentzensen","year":"2019","journal-title":"JAMA Intern. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1016\/j.ejca.2011.10.010","article-title":"Concurrent infections with multiple human papillomavirus (HPV) types in the New Technologies for Cervical Cancer (NTCC) screening study","volume":"48","author":"Carozzi","year":"2012","journal-title":"Eur. J. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1093\/ajcp\/aqv019","article-title":"Use of Cytology, E6\/E7 mRNA, and p16INK4a\u2013Ki-67 to Define the Management of Human Papillomavirus (HPV)\u2013Positive Women in Cervical Cancer Screening","volume":"145","author":"Gustinucci","year":"2016","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1016\/S1470-2045(08)70208-0","article-title":"Use of p16-INK4A overexpression to increase the specificity of human papillomavirus testing: A nested substudy of the NTCC randomised controlled trial","volume":"9","author":"Carozzi","year":"2008","journal-title":"Lancet Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1309\/BEPQXTCQD61RGFMJ","article-title":"Clinical role of p16INK4a expression in liquid-based cervical cytology: Correlation with HPV testing and histologic diagnosis","volume":"129","author":"Benevolo","year":"2008","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/S1470-2045(12)70529-6","article-title":"Risk of high-grade cervical intraepithelial neoplasia during follow-up in HPV-positive women according to baseline p16-INK4A results: A prospective analysis of a nested substudy of the NTCC randomised controlled trial","volume":"14","author":"Carozzi","year":"2013","journal-title":"Lancet Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1002\/ijc.28407","article-title":"Prognostic value of p16-INK4A protein in women with negative or CIN1 histology result: A follow-up study","volume":"134","author":"Pacchiarotti","year":"2013","journal-title":"Int. J. Cancer"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1128\/CVI.00388-12","article-title":"Direct Human Papillomavirus E6 Whole-Cell Enzyme-Linked Immunosorbent Assay for Objective Measurement of E6 Oncoproteins in Cytology Samples","volume":"19","author":"Yang","year":"2012","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2989","DOI":"10.1128\/jvi.69.5.2989-2997.1995","article-title":"Integration of human papillomavirus type 16 into the human genome correlates with a selective growth advantage of cells","volume":"69","author":"Jeon","year":"1995","journal-title":"J. Virol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1126\/science.2157286","article-title":"Association of human papillomavirus types 16 and 18 E6 proteins with p53","volume":"248","author":"Werness","year":"1990","journal-title":"Science"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11262-009-0412-8","article-title":"The biological properties of E6 and E7 oncoproteins from human papillomaviruses","volume":"40","author":"Ghittoni","year":"2010","journal-title":"Virus Genes"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1002\/rmv.1822","article-title":"Human papillomavirus molecular biology and disease association","volume":"25","author":"Doorbar","year":"2016","journal-title":"Rev. Med. Virol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3878","DOI":"10.1158\/0008-5472.CAN-04-0009","article-title":"Systematic Review of Genomic Integration Sites of Human Papillomavirus Genomes in Epithelial Dysplasia and Invasive Cancer of the Female Lower Genital Tract","volume":"64","author":"Wentzensen","year":"2004","journal-title":"Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1002\/ijc.29872","article-title":"Dysregulation of host cellular genes targeted by human papillomavirus (HPV) integration contributes to HPV-related cervical carcinogenesis","volume":"138","author":"Zhang","year":"2016","journal-title":"Int. J. Cancer"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/4\/619\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:10:28Z","timestamp":1760364628000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/4\/619"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,30]]},"references-count":54,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["diagnostics11040619"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics11040619","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,30]]}}}