{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:49:01Z","timestamp":1787240941230,"version":"build-2736575974"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study aims to assess the performance of the Xpert HPV test for the detection and genotyping of high-risk HPVs (HR-HPV) on FFPE cervical cancer (CC) tissues and to determine the distribution of HR-HPV genotypes in a CC Tunisian series.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The Xpert HPV test was conducted on purified DNA from 134 FFPE CC tissues. A single-tube multiplex polymerase chain reaction (PCR) served as a comparator assay to evaluate Xpert HPV performance in detecting and genotyping HR-HPVs. Discordant cases were tested using uniplex PCR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The Xpert HPV test generated valid results in 131\/134 (97.8%) samples. Sensitivity, specificity, positive and negative predictive values of Xpert HPV for HR-HPV detection among valid samples were 99.16%, 100%, 100%, and 92.31%, respectively. Agreement between Xpert HPV and multiplex PCR for HPV detection was observed in 131\/134 cases (97.8%), with a kappa value of 0.892. Agreement between Xpert HPV and Multiplex PCR for HR-HPV genotyping was 96.6%. Combining assays results and after confirmation with uniplex PCR, HR-HPVs were detected in 119\/134 (88.8%) samples and 11 HR-HPV genotypes were detected with a predominance of HPV 16 (71%), followed by HPV 31 (8%) and HPV 18 (5%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study demonstrated a high accuracy of the Xpert-HPV test for HR-HPVs detection and genotyping in FFPE CC tissues and revealed a distinct distribution of HR-HPVs in Tunisia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0333600","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T17:25:20Z","timestamp":1761326720000},"page":"e0333600","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["HPV testing in cervical cancer formalin-fixed paraffin embedded tissues: Reliability of the Xpert HPV test and high-risk HPV genotypes distribution in Tunisia"],"prefix":"10.1371","volume":"20","author":[{"given":"Yasmine","family":"Ben Taher","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7176-5201","authenticated-orcid":true,"given":"Mariem","family":"Ben Rekaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emna","family":"Romdhane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baligh","family":"Miladi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Bel Hadj Kacem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Med H\u2019mayada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Ben Mansour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farah","family":"Sassi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emna","family":"Chelbi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monia","family":"Tangour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahlem","family":"Blel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0366-4630","authenticated-orcid":true,"given":"Soumaya","family":"Rammeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,10,24]]},"reference":[{"issue":"3","key":"pone.0333600.ref001","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"H Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"issue":"1","key":"pone.0333600.ref002","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F","article-title":"Human papillomavirus is a necessary cause of invasive cervical cancer worldwide","volume":"189","author":"JM Walboomers","year":"1999","journal-title":"J Pathol"},{"key":"pone.0333600.ref003","doi-asserted-by":"crossref","first-page":"710209","DOI":"10.3389\/fpubh.2021.710209","article-title":"HPV Prevalence and Genotype Distribution Among Women From Hengyang District of Hunan Province, China","volume":"9","author":"S Tang","year":"2021","journal-title":"Front Public Health"},{"issue":"4","key":"pone.0333600.ref004","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1002\/jmv.22011","article-title":"HPV Types and Variants Among Cervical Cancer Tumors in Three Regions of Tunisia","volume":"83","author":"K KrennHrubec","year":"2011","journal-title":"J Med Virol"},{"issue":"3","key":"pone.0333600.ref005","first-page":"297","article-title":"Prevalence of HPV infection in precancerous and cancerous lesions of the uterine cervix in Tunisia","volume":"68","author":"N Missaoui","year":"2010","journal-title":"Ann Biol Clin (Paris)"},{"issue":"15","key":"pone.0333600.ref006","doi-asserted-by":"crossref","first-page":"6769","DOI":"10.7314\/APJCP.2015.16.15.6769","article-title":"Type-Specific Human Papillomavirus Distribution in Invasive Squamous Cervical Carcinomas in Tunisia and Vaccine Impact","volume":"16","author":"E Ennaifer","year":"2015","journal-title":"Asian Pac J Cancer Prev"},{"issue":"1","key":"pone.0333600.ref007","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s13027-021-00392-1","article-title":"Distribution of human papillomavirus in precancerous and cancerous cervical neoplasia in Tunisian women","volume":"16","author":"R Bel Haj Rhouma","year":"2021","journal-title":"Infect Agent Cancer"},{"issue":"6","key":"pone.0333600.ref008","doi-asserted-by":"crossref","first-page":"479","DOI":"10.3390\/jpm11060479","article-title":"HPV Status and Individual Characteristics of Human Papillomavirus Infection as Predictors for Clinical Outcome of Locally Advanced Cervical Cancer","volume":"11","author":"L Mkrtchian","year":"2021","journal-title":"J Pers Med"},{"issue":"6","key":"pone.0333600.ref009","doi-asserted-by":"crossref","first-page":"952","DOI":"10.3390\/diagnostics11060952","article-title":"HPV-Negative Cervical Cancer: A Narrative Review","volume":"11","author":"F Arezzo","year":"2021","journal-title":"Diagnostics (Basel)"},{"key":"pone.0333600.ref010","article-title":"Classification of tumours: female genital tumours [Internet","author":"World Health Organization","year":"2020","edition":"5"},{"issue":"9","key":"pone.0333600.ref011","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1016\/j.cmi.2020.03.033","article-title":"Commercially available molecular tests for human papillomaviruses: a global overview","volume":"26","author":"M Poljak","year":"2020","journal-title":"Clin Microbiol Infect"},{"issue":"8","key":"pone.0333600.ref012","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1016\/j.cmi.2021.04.031","article-title":"2020 list of human papillomavirus assays suitable for primary cervical cancer screening","volume":"27","author":"M Arbyn","year":"2021","journal-title":"Clin Microbiol Infect"},{"issue":"1","key":"pone.0333600.ref013","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1186\/s12985-018-1076-6","article-title":"Validation of intra- and inter-laboratory reproducibility of the Xpert HPV assay according to the international guidelines for cervical cancer screening","volume":"15","author":"A Akbari","year":"2018","journal-title":"Virol J"},{"issue":"2","key":"pone.0333600.ref014","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.jiph.2016.04.017","article-title":"Comparison of Xpert\u00ae HPV and Hybrid Capture\u00ae 2 DNA Test\u2122 for detection of high-risk HPV infection in cervical atypical squamous cells of undetermined significance","volume":"10","author":"AA Rabaan","year":"2017","journal-title":"J Infect Public Health"},{"issue":"9","key":"pone.0333600.ref015","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/j.jmoldx.2023.06.004","article-title":"Comparison of the Clinical Accuracy of Xpert HPV Assay on Vaginal Self-Samples and Cervical Clinician-Taken Samples within the VALHUDES Framework","volume":"25","author":"A Latsuzbaia","year":"2023","journal-title":"J Mol Diagn"},{"issue":"10","key":"pone.0333600.ref016","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1111\/apm.12727","article-title":"Testing for high-risk HPV in cervical and tonsillar paraffin-embedded tissue using a cartridge-based assay","volume":"125","author":"E Virtanen","year":"2017","journal-title":"APMIS"},{"key":"pone.0333600.ref017","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.jcv.2016.02.007","article-title":"Formalin fixed paraffin embedded (FFPE) material is amenable to HPV detection by the Xpert(\u00ae) HPV assay","volume":"77","author":"D Guerendiain","year":"2016","journal-title":"J Clin Virol"},{"key":"pone.0333600.ref018","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.oraloncology.2017.07.016","article-title":"Evaluation of the Xpert\u00ae HPV assay in the detection of Human Papillomavirus in formalin-fixed paraffin-embedded oropharyngeal carcinomas","volume":"72","author":"MG Don\u00e0","year":"2017","journal-title":"Oral Oncol"},{"issue":"1","key":"pone.0333600.ref019","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1750-9378-6-1","article-title":"Single-tube multiplex PCR using type-specific E6\/E7 primers and capillary electrophoresis genotypes 21 human papillomaviruses in neoplasia","volume":"6","author":"M Dictor","year":"2011","journal-title":"Infect Agent Cancer"},{"key":"pone.0333600.ref020","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.f2778","article-title":"Diagnostic accuracy studies: how to report and analyse inconclusive test results","volume":"346","author":"B Shinkins","year":"2013","journal-title":"BMJ"},{"issue":"1","key":"pone.0333600.ref021","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1136\/ijgc-2021-003014","article-title":"Human papillomavirus-independent cervical cancer","volume":"32","author":"A Fernandes","year":"2022","journal-title":"Int J Gynecol Cancer"},{"issue":"14","key":"pone.0333600.ref022","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1200\/JCO.21.01930","article-title":"Human Papillomavirus Infection Determines Prognosis in Cervical Cancer","volume":"40","author":"J Lei","year":"2022","journal-title":"J Clin Oncol"},{"issue":"39","key":"pone.0333600.ref023","doi-asserted-by":"crossref","first-page":"66352","DOI":"10.18632\/oncotarget.18558","article-title":"Prognostic value of HPV DNA status in cervical cancer before treatment: a systematic review and meta-analysis","volume":"8","author":"P Li","year":"2017","journal-title":"Oncotarget"},{"issue":"24","key":"pone.0333600.ref024","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.21037\/atm-22-5930","article-title":"HPV and radiosensitivity of cervical cancer: a narrative review","volume":"10","author":"Y Huang","year":"2022","journal-title":"Ann Transl Med"},{"issue":"1","key":"pone.0333600.ref025","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s13027-020-00332-5","article-title":"Prognostic implication of human papillomavirus types in cervical cancer patients: a systematic review and meta-analysis","volume":"15","author":"Y Xu","year":"2020","journal-title":"Infect Agent Cancer"},{"key":"pone.0333600.ref026","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.pvr.2018.10.005","article-title":"Human papillomavirus genotype and prognosis of cervical cancer: Favorable survival of patients with HPV16-positive tumors","volume":"6","author":"M Onuki","year":"2018","journal-title":"Papillomavirus Res"},{"key":"pone.0333600.ref027","first-page":"138469","article-title":"Ancillary studies in determining human papillomavirus status of squamous cell carcinoma of the oropharynx: a review","volume":"2011","author":"RL Cantley","year":"2011","journal-title":"Patholog Res Int"},{"issue":"8","key":"pone.0333600.ref028","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1038\/s41379-019-0249-1","article-title":"HPV-negative tumors of the uterine cervix","volume":"32","author":"I Nicol\u00e1s","year":"2019","journal-title":"Mod Pathol"},{"key":"pone.0333600.ref029","doi-asserted-by":"crossref","first-page":"152054","DOI":"10.1016\/j.anndiagpath.2022.152054","article-title":"Diagnostic value of p16 and Ki-67 expression in cervical glandular intraepithelial disease: A review","volume":"62","author":"P Pereira Pinto","year":"2023","journal-title":"Ann Diagn Pathol"},{"issue":"10","key":"pone.0333600.ref030","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0077771","article-title":"Improved PCR performance using template DNA from formalin-fixed and paraffin-embedded tissues by overcoming PCR inhibition","volume":"8","author":"D Dietrich","year":"2013","journal-title":"PLoS One"},{"issue":"1","key":"pone.0333600.ref031","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.4102\/ajlm.v11i1.1587","article-title":"Practical tips to using formalin-fixed paraffin-embedded tissue archives for molecular diagnostics in a South African setting","volume":"11","author":"BS van Deventer","year":"2022","journal-title":"Afr J Lab Med"},{"key":"pone.0333600.ref032","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.pvr.2015.05.002","article-title":"Performance of the Xpert HPV assay in women attending for cervical screening","volume":"1","author":"J Cuzick","year":"2015","journal-title":"Papillomavirus Research"},{"key":"pone.0333600.ref033","doi-asserted-by":"crossref","first-page":"104756","DOI":"10.1016\/j.jcv.2021.104756","article-title":"The challenges of defining sample adequacy in an era of HPV based cervical screening","volume":"137","author":"K Cuschieri","year":"2021","journal-title":"J Clin Virol"},{"issue":"1","key":"pone.0333600.ref034","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.cmi.2017.05.020","article-title":"Concordant testing results between various human papillomavirus assays in primary cervical cancer screening: systematic review","volume":"24","author":"L de Thurah","year":"2018","journal-title":"Clin Microbiol Infect"},{"issue":"1","key":"pone.0333600.ref035","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0147326","article-title":"Human Papillomavirus Assays and Cytology in Primary Cervical Screening of Women Aged 30 Years and Above","volume":"11","author":"M Rebolj","year":"2016","journal-title":"PLoS One"},{"issue":"1","key":"pone.0333600.ref036","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1186\/s12864-017-3612-y","article-title":"Deep sequencing of HPV E6\/E7 genes reveals loss of genotypic diversity and gain of clonal dominance in high-grade intraepithelial lesions of the cervix","volume":"18","author":"J Shen-Gunther","year":"2017","journal-title":"BMC Genomics"},{"issue":"1","key":"pone.0333600.ref037","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/s12985-019-1197-6","article-title":"CIN2+ detection of the HPV DNA Array genotyping assay in comparison with the Cobas 4800 HPV test and cytology","volume":"16","author":"A Pesic","year":"2019","journal-title":"Virol J"},{"issue":"3","key":"pone.0333600.ref038","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1128\/JCM.02115-08","article-title":"Sequence variation of human papillomavirus type 16 and measurement of viral integration by quantitative PCR","volume":"47","author":"M Jiang","year":"2009","journal-title":"J Clin Microbiol"},{"issue":"11","key":"pone.0333600.ref039","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":"S de Sanjose","year":"2010","journal-title":"Lancet Oncol"},{"issue":"10451","key":"pone.0333600.ref040","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/S0140-6736(24)01097-3","article-title":"Causal attribution of human papillomavirus genotypes to invasive cervical cancer worldwide: a systematic analysis of the global literature","volume":"404","author":"F Wei","year":"2024","journal-title":"Lancet"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0333600","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T17:25:27Z","timestamp":1761326727000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0333600"}},"subtitle":[],"editor":[{"given":"Ivan","family":"Sabol,","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,10,24]]},"references-count":40,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10,24]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0333600","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,24]]}}}