{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T02:14:57Z","timestamp":1783736097508,"version":"3.55.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Department of Science and Technology of Henan Province","award":["231111521100"],"award-info":[{"award-number":["231111521100"]}]},{"name":"Department of Science and Technology of Henan Province","award":["252102521051"],"award-info":[{"award-number":["252102521051"]}]},{"DOI":"10.13039\/100004856","name":"Department of Health","doi-asserted-by":"publisher","award":["SBGJ202102019"],"award-info":[{"award-number":["SBGJ202102019"]}],"id":[{"id":"10.13039\/100004856","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Mark and Jane Gibson Endowment Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Multiple high-risk human papillomavirus (hrHPV) infections are frequently detected in cervical screening, but their biological interactions and clinical significance remain unclear. Because HPV DNA detection indicates viral presence but not transcriptional activity, this exploratory study evaluated viral load, genotype-specific E6\/E7 mRNA expression, localization, and follow-up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Among 12 000 cervical specimens tested for hrHPV, 598 were positive and 72 showed multiple genotypes. Viral load was assessed using the BioPerfectus Multiplex Real-Time assay. A tissue-available subset of 36 dual HPV16 + 52 or HPV16 + 58 cases was analyzed by duplex RNAscope for genotype-specific E6\/E7 mRNA expression and localization. Diagnoses were categorized as benign, low-grade squamous intraepithelial lesion (LSIL), or high-grade squamous intraepithelial lesion (HSIL). Viral load and RNAscope analyses used incompletely matched subsets and were interpreted as complementary, not paired.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Elevated viral load (\u22654.00 log10 copies\/10 000 cells) was associated with HSIL. In cohort-level analyses, diffuse (+++) E6\/E7 mRNA expression was more frequent in HSIL than elevated viral load (95.2% vs 55.5%, P = .01). RNAscope-negative cases were mostly benign or LSIL and showed no progression. Genotype-specific signals were spatially distinct, with rare overlap. Dual-positive cells showed fewer RNA signals than adjacent single-positive cells (P &amp;lt; .001). Higher E6\/E7 mRNA expression showed possible association with LSIL progression, but events were limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In multiplex hrHPV infection, transcriptional activity may better reflect cervical lesion biology than viral DNA burden alone. Genotype-specific E6\/E7 mRNA expression may complement HPV DNA load. Spatially distinct signals and reduced signal intensity in rare dual-positive cells suggest possible interactions between coinfecting hrHPV genotypes, but require prospective validation in fully matched cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiag335","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T11:56:48Z","timestamp":1782302208000},"source":"Crossref","is-referenced-by-count":0,"title":["Comparative Evaluation of E6\/E7 mRNA Expression and Viral DNA Load in Cervical Lesions With Multiple High-Risk Human Papillomavirus Infection"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-8810-3643","authenticated-orcid":false,"given":"Yan","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital , Zhengzhou 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University People's Hospital , Zhengzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6550-5179","authenticated-orcid":false,"given":"Zeng","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University , Jinan ,","place":["China"]},{"name":"Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center , Dallas, Texas ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruijiao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pathology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital , Zhengzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital , Zhengzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Departments of Pathology, International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai ,","place":["China"]},{"name":"Shanghai Key Laboratory of Embryo Original Diseases , Shanghai Jiao Tong University School of Medicine, Shanghai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rujia","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital , Zhengzhou 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