{"paper_id":"338b4af2-e567-4f4c-b9fa-566c1c9d9df9","body_text":"The \"Silent\" Upstaging: A Real-World Analysis of Discordance Between Clinical and Pathological Staging in Oral Squamous Cell Carcinoma and Its Implications for Treatment Intensification | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The \"Silent\" Upstaging: A Real-World Analysis of Discordance Between Clinical and Pathological Staging in Oral Squamous Cell Carcinoma and Its Implications for Treatment Intensification Ashmita This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8837067/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Accurate staging is the cornerstone of management in Head and Neck Squamous Cell Carcinoma (HNSCC). The 8th edition of the AJCC/UICC TNM staging system introduced Depth of Invasion (DOI) and Extracapsular Extension (ECE) to refine prognostic stratification. However, significant discrepancies often exist between pre-operative clinical staging (cTNM) and post-operative pathological staging (pTNM). This study evaluates the magnitude and clinical impact of this discordance in a real-world cohort. Methods: We conducted a retrospective analysis of 52 patients with biopsy-proven Squamous Cell Carcinoma (SCC) of the oral cavity and oropharynx treated at a tertiary cancer center. Patients underwent standard clinical staging followed by definitive surgical resection and neck dissection. Clinical (cT) and pathological (pT) stages were compared to calculate concordance rates, sensitivity, and specificity. High-risk pathological features, including DOI, Worst Pattern of Invasion (WPOI), Perineural Invasion (PNI), and Lymphovascular Invasion (LVI), were correlated with staging upgrades. Results: The overall concordance between cT and pT staging was only 23.0%. A profound \"upstaging\" phenomenon was observed, with 45.0% of patients receiving a higher pathological stage than determined clinically (e.g., cT2 to pT3). The primary driver of upstaging was the underestimation of DOI on clinical examination and imaging, which demonstrated a moderate negative correlation with Disease-Free Interval (DFI) (r = -0.35). Despite the high rate of pathological upstaging, adjuvant Chemoradiation (CRT) effectively neutralized the risk, resulting in comparable DFI between high-risk and low-risk cohorts (Mean DFI: 4.2 vs. 4.0 years; p > 0.05). Conclusion: Clinical staging significantly underestimates the extent of disease in nearly half of oral cancer patients, primarily due to the \"invisible\" nature of deep invasion (DOI). This \"silent upstaging\" underscores the critical need for advanced pre-operative imaging protocols (e.g., MRI with specific DOI sequences) and supports the routine use of adjuvant intensification in pathologically upstaged patients. Oncology Oral Squamous Cell Carcinoma TNM Staging Diagnostic Accuracy Depth of Invasion Treatment Escalation Head and Neck Cancer Full Text Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-8837067\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":588753283,\"identity\":\"585fcf99-0fb9-4714-bb76-d78dc5e1427c\",\"order_by\":0,\"name\":\"Ashmita\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA70lEQVRIiWNgGAWjYFACHgaGBAYGO3725oMPQFw+4rQkMCRL9hxLNgBx2YjSArSGccONHDMJEJ+gFv7+s0c3PPxhx8xwI8Gs8muOnQwbA/PDRzfwaJG4kZd2IyEhmY+x50HabdltyUCHsRkb5+Cz5gaPGVALMzMze8Kx25LbmIFaeNik8WmRP38GpKWesY0hsa1Ycls9YS0GB3JAWg4z9nAkszF+3HaYsBbDGyAtaceTJXiOMUszbjvOw8ZMwC9yQIfd/GFTbWd/vP/jx5/bqu2BcfrwMV7vIwNmHjBJrHIQYPxBiupRMApGwSgYMQAAmvFJP5aFIsMAAAAASUVORK5CYII=\",\"orcid\":\"https://orcid.org/0009-0008-5550-2960\",\"institution\":\"Institute Of Post Graduate Medical Education And Research\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"\",\"middleName\":\"\",\"lastName\":\"Ashmita\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2026-02-10 06:20:09\",\"currentVersionCode\":1,\"declarations\":{\"humanSubjects\":true,\"vertebrateSubjects\":false,\"conflictsOfInterestStatement\":false,\"humanSubjectEthicalGuidelines\":true,\"humanSubjectConsent\":true,\"humanSubjectClinicalTrial\":false,\"humanSubjectCaseReport\":false,\"vertebrateSubjectEthicalGuidelines\":false},\"doi\":\"10.21203/rs.3.rs-8837067/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-8837067/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":102398106,\"identity\":\"f5670cca-0969-4a4a-ac8a-40ca71595144\",\"added_by\":\"auto\",\"created_at\":\"2026-02-11 10:21:00\",\"extension\":\"pdf\",\"order_by\":1,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":347731,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"headandneckfinal.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-8837067/v1_covered_997e0faf-2088-4539-b780-6037a1c4e129.pdf\"}],\"financialInterests\":\"The authors declare no competing interests.\",\"formattedTitle\":\"\\u003cp\\u003e\\u003cstrong\\u003eThe \\\"Silent\\\" Upstaging: A Real-World Analysis of Discordance Between Clinical and Pathological Staging in Oral Squamous Cell Carcinoma and Its Implications for Treatment Intensification\\u003c/strong\\u003e\\u003c/p\\u003e\",\"fulltext\":[],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":false,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":true,\"hideJournal\":true,\"highlight\":\"\",\"institution\":\"Institute of Post Graduate Medical Education and Research\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":true,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":true,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Oral Squamous Cell Carcinoma, TNM Staging, Diagnostic Accuracy, Depth of Invasion, Treatment Escalation, Head and Neck Cancer\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-8837067/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-8837067/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003eBackground:\\u003c/strong\\u003e Accurate staging is the cornerstone of management in Head and Neck Squamous Cell Carcinoma (HNSCC). The 8th edition of the AJCC/UICC TNM staging system introduced Depth of Invasion (DOI) and Extracapsular Extension (ECE) to refine prognostic stratification. However, significant discrepancies often exist between pre-operative clinical staging (cTNM) and post-operative pathological staging (pTNM). This study evaluates the magnitude and clinical impact of this discordance in a real-world cohort.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eMethods:\\u003c/strong\\u003e We conducted a retrospective analysis of 52 patients with biopsy-proven Squamous Cell Carcinoma (SCC) of the oral cavity and oropharynx treated at a tertiary cancer center. Patients underwent standard clinical staging followed by definitive surgical resection and neck dissection. Clinical (cT) and pathological (pT) stages were compared to calculate concordance rates, sensitivity, and specificity. High-risk pathological features, including DOI, Worst Pattern of Invasion (WPOI), Perineural Invasion (PNI), and Lymphovascular Invasion (LVI), were correlated with staging upgrades.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eResults:\\u003c/strong\\u003e The overall concordance between cT and pT staging was only 23.0%. A profound \\\"upstaging\\\" phenomenon was observed, with 45.0% of patients receiving a higher pathological stage than determined clinically (e.g., cT2 to pT3). The primary driver of upstaging was the underestimation of DOI on clinical examination and imaging, which demonstrated a moderate negative correlation with Disease-Free Interval (DFI) (r = -0.35). Despite the high rate of pathological upstaging, adjuvant Chemoradiation (CRT) effectively neutralized the risk, resulting in comparable DFI between high-risk and low-risk cohorts (Mean DFI: 4.2 vs. 4.0 years; p \\u0026gt; 0.05).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConclusion:\\u003c/strong\\u003e Clinical staging significantly underestimates the extent of disease in nearly half of oral cancer patients, primarily due to the \\\"invisible\\\" nature of deep invasion (DOI). This \\\"silent upstaging\\\" underscores the critical need for advanced pre-operative imaging protocols (e.g., MRI with specific DOI sequences) and supports the routine use of adjuvant intensification in pathologically upstaged patients.\\u003c/p\\u003e\",\"manuscriptTitle\":\"The \\\"Silent\\\" Upstaging: A Real-World Analysis of Discordance Between Clinical and Pathological Staging in Oral Squamous Cell Carcinoma and Its Implications for Treatment Intensification\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2026-02-11 03:42:34\",\"doi\":\"10.21203/rs.3.rs-8837067/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"5dd1dfb2-6e6b-4934-87e9-6bf506e83ba1\",\"owner\":[],\"postedDate\":\"February 11th, 2026\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[{\"id\":62635662,\"name\":\"Oncology\"}],\"tags\":[],\"updatedAt\":\"2026-02-11T03:42:34+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2026-02-11 03:42:34\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-8837067\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-8837067\",\"identity\":\"rs-8837067\",\"version\":[\"v1\"]},\"buildId\":\"XKTyCvWXoU3ODBz1xrDgd\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}