{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:09:29Z","timestamp":1789016969830,"version":"build-2803163510"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Persistent infection with high-risk human papillomavirus (HPV), particularly HPV16 and HPV18, contributes to cervical carcinogenesis through sustained expression of the viral E7 oncoprotein. Although HPV DNA polymerase chain reaction (PCR) is widely used for viral detection, it does not directly reflect biologically active oncogenic transformation within tissue. This study evaluated the diagnostic utility, clinicopathological significance, tissue localization, and concordance of HPV16 and HPV18 E7 immunohistochemistry (IHC) across the spectrum of cervical lesion progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A retrospective study was conducted on 109 formalin-fixed paraffin-embedded cervical tissue specimens representing non-neoplastic, premalignant, and malignant lesions. HPV16 and HPV18 E7 protein expression was assessed by immunohistochemistry and compared with HPV DNA PCR findings. Concordance analysis, receiver operating characteristic (ROC) analysis, and multivariable logistic regression were performed to evaluate diagnostic performance and independent predictive value.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>HPV16 and HPV18 E7 expression increased progressively with lesion severity, with the highest immunoreactivity observed in high-grade squamous intraepithelial lesions and invasive carcinoma. Substantial concordance was observed between IHC and PCR findings for both HPV types. HPV16 demonstrated superior diagnostic performance, with sensitivity, specificity, accuracy, and area under the curve (AUC) values of 92.3%, 83.9%, 89.9%, and 0.925, respectively, compared with HPV18 (90.0%, 79.3%, 83.7%, and 0.894). Multivariable logistic regression identified HPV16 and HPV18 E7 expression as significant independent predictors of disease status. Histopathological evaluation demonstrated progressive localization patterns, transitioning from focal basal\/parabasal staining in low-grade lesions to diffuse full-thickness epithelial and tumor-associated expression in high-grade lesions and invasive carcinoma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>HPV16 and HPV18 E7 immunohistochemistry demonstrated strong association with cervical lesion severity and substantial concordance with PCR findings, supporting its potential utility as a complementary tissue-based biomarker in cervical pathology. The findings further suggest that E7 immunohistochemistry may provide clinically relevant information regarding biologically active HPV-driven transformation and improve lesion characterization in diagnostically challenging cases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1942646","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:28:45Z","timestamp":1789014525000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Diagnostic utility and tissue localization of HPV16 and HPV18 E7 immunohistochemistry in cervical lesion progression: a comparative study with PCR"],"prefix":"10.3389","volume":"16","author":[{"given":"Fatimah Suliman","family":"Mohammad Aljebaly","sequence":"first","affiliation":[{"name":"Department of Pathology, College of Medicine, Qassim University","place":["Buraydah, Qassim, Saudi 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