{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:24:40Z","timestamp":1790688280843,"version":"4.1.0"},"reference-count":27,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Background: Effective triage of HPV DNA-positive women is needed to reduce unnecessary colposcopies while maintaining cervical cancer prevention. We evaluated genotype-specific 7-type HPV E6\/E7 mRNA triage in a real-world screening cohort. Methods: In this population-based single-centre study at the University Hospital of North Norway, 42,791 women underwent primary screening with the cobas HPV DNA assay during the period 2019\u20132024. Among 2370 HPV DNA-positive women, reflex cytology, 7-type HPV mRNA testing, and an ATHENA-derived triage strategy were compared using histologically confirmed CIN3+ through 31 December 2025 as the endpoint. Results: CIN3+ was detected in 60\/2370 women (2.5%). Test positivity was 47.0% for cytology, 54.7% for ATHENA-derived triage, and 33.4% for HPV mRNA. Sensitivity was 78.3%, 86.7%, and 73.3%; specificity was 53.8%, 46.1%, and 67.7%; and PPV was 4.2%, 4.0%, and 5.6%, respectively. Colposcopies per CIN3+ detected were 23.7, 24.9, and 18.0. Conclusions: HPV mRNA triage improved referral precision and colposcopy efficiency, but with lower sensitivity than ATHENA-derived triage. These findings support 7-type HPV mRNA testing as a potentially useful molecular triage option where structured follow-up is feasible.<\/jats:p>","DOI":"10.3390\/pathogens15060584","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T02:37:26Z","timestamp":1780454246000},"page":"584","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genotype-Specific HPV mRNA Triage Improves Colposcopy Efficiency Compared with Cytology and ATHENA-Derived Triage: A Population-Based Study of HPV DNA-Positive Women"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8250-3992","authenticated-orcid":false,"given":"Sveinung Wergeland","family":"S\u00f8rbye","sequence":"first","affiliation":[{"name":"Department of Clinical Pathology, University Hospital of North Norway, 9006 Troms\u00f8, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bente Marie","family":"Falang","sequence":"additional","affiliation":[{"name":"PreTect AS, 3490 Klokkarstua, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Antonsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology, University Hospital of North Norway, 9006 Troms\u00f8, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3559-7153","authenticated-orcid":false,"given":"Elin","family":"Richardsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology, University Hospital of North Norway, 9006 Troms\u00f8, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1097\/LGT.0000000000000525","article-title":"2019 ASCCP Risk-Based Management Consensus Guidelines for Abnormal Cervical Cancer Screening Tests and Cancer Precursors","volume":"24","author":"Perkins","year":"2020","journal-title":"J. Low. Genit. Tract Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1097\/LGT.0000000000000529","article-title":"Risk Estimates Supporting the 2019 ASCCP Risk-Based Management Consensus Guidelines","volume":"24","author":"Egemen","year":"2020","journal-title":"J. Low. Genit. Tract Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1093\/jnci\/djy192","article-title":"Role of Screening History in Clinical Meaning and Optimal Management of Positive Cervical Screening Results","volume":"111","author":"Castle","year":"2019","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1002\/ijc.32950","article-title":"A Study of the Risks of CIN3+ Detection after Multiple Rounds of HPV Testing: Results of the 15-Year Cervical Cancer Screening Experience at Kaiser Permanente Northern California","volume":"147","author":"Hammer","year":"2020","journal-title":"Int. J. Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"S\u00f8rbye, S.W., Falang, B.M., Antonsen, M., and Richardsen, E. (2026). Cervical Cytology and HPV16\/18\/45 mRNA Co-Testing Improve Risk Stratification in Routine Clinical Practice. Cancers, 18.","DOI":"10.3390\/cancers18050834"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1038\/modpathol.2016.80","article-title":"p16\/Ki-67 dual-stained cytology for detecting cervical (pre)cancer in high-risk HPV-positive women","volume":"29","author":"Luttmer","year":"2016","journal-title":"Mod. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1097\/LGT.0000000000000530","article-title":"A Study of Partial Human Papillomavirus Genotyping in Support of the 2019 ASCCP Risk-Based Management Consensus Guidelines","volume":"24","author":"Demarco","year":"2020","journal-title":"J. Low. Genit. Tract Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1097\/LGT.0000000000000865","article-title":"Applying Results of Extended Genotyping to Management of Positive Cervicovaginal Human Papillomavirus Test Results: Enduring Guidelines","volume":"29","author":"Massad","year":"2025","journal-title":"J. Low. Genit. Tract Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1002\/jmv.1890370204","article-title":"Detection of the human papilloma virus type 16 mRNA-transcripts in cytological abnormal scrapings","volume":"37","author":"Falcinelli","year":"1992","journal-title":"J. Med. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"533","DOI":"10.3332\/ecancer.2015.533","article-title":"E6\/E7 mRNA Testing for Human Papilloma Virus-Induced High-Grade Cervical Intraepithelial Disease (CIN2\/CIN3): A Promising Perspective","volume":"9","author":"Origoni","year":"2015","journal-title":"Ecancermedicalscience"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"S\u00f8rbye, S., Falang, B.M., Antonsen, M., and Mortensen, E. (2025). Genotype-Specific HPV mRNA Triage Improves CIN2+ Detection Efficiency Compared to Cytology: A Population-Based Study of HPV DNA-Positive Women. Pathogens, 14.","DOI":"10.20944\/preprints202506.2527.v1"},{"key":"ref_13","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":"Wei","year":"2024","journal-title":"Lancet"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.1002\/ijc.27485","article-title":"Human papillomavirus types in 115,789 HPV-positive women: A meta-analysis from cervical infection to cancer","volume":"131","author":"Guan","year":"2012","journal-title":"Int. J. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Chan, P.K.S., Ho, W.C.S., Chan, M.C.W., Wong, M.C.S., Yeung, A.C.M., Chor, J.S.Y., and Hui, M. (2014). Meta-analysis on prevalence and attribution of human papillomavirus types 52 and 58 in cervical neoplasia worldwide. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0107573"},{"key":"ref_16","first-page":"1705","article-title":"Human papillomavirus type-distribution in cervical cancer in China: The importance of HPV 16 and 18","volume":"20","author":"Chen","year":"2009","journal-title":"Cancer Causes Control"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.3346\/jkms.2012.27.9.1091","article-title":"Prevalence and distribution of human papillomavirus infection in Korean women as determined by restriction fragment mass polymorphism assay","volume":"27","author":"Lee","year":"2012","journal-title":"J. Korean Med. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e52","DOI":"10.3802\/jgo.2019.30.e52","article-title":"Human papillomavirus genotype-specific risk in cervical carcinogenesis","volume":"30","author":"So","year":"2019","journal-title":"J. Gynecol. Oncol."},{"key":"ref_19","first-page":"pky045","article-title":"Burden of Human Papillomavirus (HPV)-Related Cancers Attributable to HPVs 6\/11\/16\/18\/31\/33\/45\/52 and 58","volume":"2","author":"Serrano","year":"2019","journal-title":"JNCI Cancer Spectr."},{"key":"ref_20","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_21","doi-asserted-by":"crossref","first-page":"69","DOI":"10.3390\/jmp4020008","article-title":"Performance of a 7-Type HPV mRNA Test in Triage of HPV DNA Primary Screen Positive Women Compared to Liquid-Based Cytology","volume":"4","author":"Falang","year":"2023","journal-title":"J. Mol. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1159\/000477556","article-title":"The Bethesda System for Reporting Cervical Cytology: A Historical Perspective","volume":"61","author":"Nayar","year":"2017","journal-title":"Acta Cytol."},{"key":"ref_23","first-page":"993","article-title":"Type-specific human papillomavirus distribution in invasive cervical cancer in Korea, 1958\u20132004","volume":"11","author":"Oh","year":"2010","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1097\/LGT.0000000000000802","article-title":"Recommendations for Use of p16\/Ki-67 Dual Stain for Management of Individuals Testing Positive for Human Papillomavirus","volume":"28","author":"Clarke","year":"2024","journal-title":"J. Low. Genit. Tract Dis."},{"key":"ref_25","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_26","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1002\/ijc.33320","article-title":"Methylation Markers FAM19A4 and miR124-2 as Triage Strategy for Human Papillomavirus-Positive Women: A Large European Multicenter Study","volume":"148","author":"Bonde","year":"2021","journal-title":"Int. J. Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1038\/s41591-024-03014-6","article-title":"Cervical Cancer Screening Using DNA Methylation Triage in a Real-World Population","volume":"30","author":"Schreiberhuber","year":"2024","journal-title":"Nat. Med."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/6\/584\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T04:21:20Z","timestamp":1780546880000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/6\/584"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,28]]},"references-count":27,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["pathogens15060584"],"URL":"https:\/\/doi.org\/10.3390\/pathogens15060584","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,28]]}}}