Redefining Diagnostic Pathways in Oral Squamous Cell Carcinoma: Insights from a Two-Year Cohort Managed Without Biopsy

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Biopsy, the diagnostic gold standard, is often delayed due to systemic, financial, and sociocultural barriers. This study evaluates the role of structured clinical frameworks, imaging, and supportive care in the management of OSCC referrals without biopsy and histopathological examination. Methods: A retrospective cohort study was conducted on 242 patients referred to a tertiary dental outpatient department between January 2023 and December 2024 with suspected OSCC, no prior biopsy, and available contrast-enhanced computed tomography (CECT). Assessments included the Seven S lesion framework, Simplified Oral Hygiene Index (OHI-S), trismus grading, lymph node examination, provisional TNM staging (AJCC 8th edition), and CECT findings. All patients received standardized symptomatic management (analgesics, antimicrobials, antiseptic mouthwash, gastroprotectants, nutritional supplements) and counselling for habit cessation. Descriptive statistics were applied. Results: Of 242 patients (198 males [81.8%], 44 females [18.2%]; median age 39 years), the majority reported gutka (51% males, 70% females) or smokeless tobacco use. Lesions primarily involved the retromolar trigone (46%) and gingivobuccal sulcus (37%). OHI-S was poor in 68% of cases. Trismus occurred in 47%. CECT revealed cortical erosion (27%), muscle infiltration (39%), and level IIb nodal involvement (14%). Provisional TNM staging included cT2N0 (36%), cT3N1 (24%), and cT4N2 (19%). Reported barriers to biopsy were financial constraints (33%), fear (24%), lack of facilities (20%), sociocultural reasons (11%), and anatomical difficulty (12%). Conclusion: In the absence of biopsy, structured clinical assessment, imaging, and supportive care enable effective provisional diagnosis and timely referral. This approach provides a practical diagnostic pathway with implications for policy, education, and early OSCC management. Dentistry Oral squamous cell carcinoma Seven S framework TNM staging Biopsy barriers Contrast-enhanced computed tomography Supportive care. Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Oral squamous cell carcinoma (OSCC) constitutes the vast majority of oral malignancies and remains a major cause of cancer-related morbidity and mortality worldwide, with particularly high incidence and mortality in South and Southeast Asia.[1,2,3,4 ]The regional burden reflects widespread use of tobacco (smoked and smokeless), areca nut (betel quid) products such as gutka and pan masala, heavy alcohol use and persistent socioeconomic disadvantage; these exposures are also associated with distinct lesion distributions (for example, gingivobuccal sulcus and retromolar trigone predilection in users of smokeless products).[5,6,7,8] Contemporary molecular and epidemiologic work emphasises both carcinogen-driven field change and tumour heterogeneity as central to OSCC pathogenesis and prognosis.[9] Histopathological confirmation by incisional biopsy continues to be the diagnostic gold standard and forms the basis of definitive diagnosis, grading and pathological staging.[10] The American Joint Committee on Cancer (AJCC) 8th edition incorporated critical changes — most notably clinical and pathological depth of invasion (DOI) for T-category and extra nodal extension (ENE) in N-categorization — that link histopathology closely to prognostic models and treatment decisions.[11,12] Notwithstanding the centrality of biopsy, multiple studies from a range of settings document frequent and sometimes prolonged delays to tissue diagnosis; these delays are driven by a mix of patient-level (fear, awareness, habits), system-level (access, cost, facility capacity) and logistical barriers and are associated with more advanced stage at presentation and worse outcomes.[13,14,15,16] Where histopathology is delayed or initially unavailable, clinicians commonly combine structured clinical description, functional indices and imaging to form a provisional working diagnosis and triage plan. The Seven S lesion framework (site, size, shape, surface, colour, consistency, symptoms) provides a standardized approach to lesion description that improves communication and triage.[17 ]The Simplified Oral Hygiene Index (OHI-S) is a validated, readily applied index that captures oral hygiene and microbial burden — factors that may influence local disease progression and symptom burden.[18 ]Cross-sectional imaging, particularly contrast-enhanced computed tomography (CECT), plays a practical role in identifying clinically occult features (mandibular cortical erosion, cancellous involvement, muscle infiltration, nodal disease including level IIb, and radiologic signs of ENE) that meaningfully affect provisional staging and urgency of referral.[19,20,21,22,23 ]Non-invasive adjuncts such as autofluorescence and optical coherence tomography (OCT) are increasingly studied as point-of-care tools to highlight suspicious mucosal areas, while salivary biomarker research and artificial-intelligence approaches aim to strengthen non-biopsy diagnostic pathways.[24,25,26,27,28,29,30] Supportive, symptom-directed care (analgesia, infection control, antiseptic mouthwashes, gastroprotection, nutritional support) together with focused counselling for habit cessation are essential components of pragmatic pathways when definitive diagnostic steps are delayed; these measures reduce morbidity, preserve function and may improve the patient’s readiness for definitive treatment. [31,32,33] This study reports a two-year retrospective cohort of 242 patients referred with suspected OSCC who had not undergone prior incisional biopsy and had available CECT imaging. By documenting lesion descriptors (Seven S), OHI-S, clinical staging (AJCC 8thEd criteria applied provisionally), imaging findings and the nature of biopsy-barriers, and by describing a standardized supportive-care bundle, we aim to present a pragmatic diagnostic pathway for settings where histopathology is delayed or initially unavailable and to place those findings in the context of current evidence and health-systems realities. Materials and Methods Study design and setting: This retrospective observational cohort study was conducted in the Dental Outpatient Department of a tertiary teaching medical hospital which is actively involved in screening of oral malignancy and potentially malignant lesions as per state government health policy and has as Medical Officer In charge dedicated for the same , (Coauthor number 3 under supervision of HOD Coauthor No2 )between January 2023 and December 2024. The study included adult patients (≥18 years) presenting with clinical suspicion of OSCC, such as non-healing oral ulcers of more than four weeks’ duration, trismus, persistent mucosal lesions, spontaneous tooth loss, or unexplained neck swelling. Eligibility criteria required that patients had not undergone prior incisional biopsy and had contrast-enhanced computed tomography (CECT) of the mandible and neck available. Patients with histologically confirmed OSCC prior to referral, recurrent or previously treated cases, or incomplete records were excluded. Clinical assessments: Each patient underwent systematic evaluation using the Seven S lesion framework, which records site, size, shape, surface, colour, consistency, and symptoms. Oral hygiene status was assessed using the Simplified Oral Hygiene Index (OHI-S), categorizing scores as good (≤1.0), moderate (1.1–3.0), or poor (>3.0). Trismus was graded as mild (25–35 mm), moderate (11–24 mm), or severe (≤10 mm). Lymph nodes were examined across levels I–V for size, tenderness, and fixation. [7,8,9,10] Provisional staging was assigned using the American Joint Committee on Cancer (AJCC) 8th edition TNM system.[4] Imaging: All patients underwent CECT of the mandible and neck with a slice thickness of ≤2.5 mm. Images were evaluated for cortical erosion, cancellous extension, muscle infiltration, nodal involvement across cervical levels, extra nodal extension, and perineural spread. Supportive management: Patients received standardized symptomatic care, including tramadol (50 mg as needed), chlorhexidine 0.2% mouthwash (three times daily), amoxicillin–clavulanic acid 625 mg (three times daily), metronidazole 400 mg (three times daily), pantoprazole with domperidone (once daily), and a daily multivitamin supplement. Individualized counselling sessions focused on habit cessation, reinforcement of oral hygiene practices, awareness of symptoms, and timely oncology referral. Biopsy barriers: Barriers to undergoing biopsy were categorized as financial, fear-related, lack of facilities, sociocultural reasons, or anatomical difficulty. Statistical analysis: Data were entered into SPSS version 24 and analysed using descriptive statistics. Frequencies, percentages, medians, and ranges were calculated, as appropriate. Results A total of 242 patients were included, comprising 198 males (81.8%) and 44 females (18.2%), with a median age of 39 years (range: 24–70 years). The peak incidence occurred in the 30–45-year age group. (Table 1). Risk habit analysis showed that among males, gutka use was most common (51%), followed by smokeless tobacco (46%), bidi (38%), and alcohol (32%); 62% reported combined use of two or more habits. Among females, gutka was also most prevalent (70%), followed by smokeless tobacco (55%) and alcohol (9%); combined habit use was noted in 9%. Importantly, 90% of patients reported habit reduction following symptom onset. (Table 2). Clinically, trismus was the most frequent presentation (47%), followed by non-healing ulcer lasting more than four weeks (39%), pain (60%), neck swelling (19%), and tooth exfoliation (21%). Other complaints included burning sensation (15%), bleeding (25%), paraesthesia (15%), and odynophagia (10%). (Table 3). Lesion characteristics based on the Seven S framework revealed that the retromolar trigone (46%) and gingivobuccal sulcus (37%) were the most common sites, with the majority of lesions measuring 2–4 cm (73%). Lesions were predominantly irregular in shape (65%), ulcerated (70%), erythematous (50%), and indurated (79%). (Table 4) Oral hygiene assessment showed that 68% of patients had poor OHI-S scores, 25% had moderate scores, and only 7% had good scores. (Table 5). Lymph node examination revealed palpable nodes in 60% of patients, most commonly at levels Ia/Ib (35%) and IIa (20%). (Table 6). CECT findings demonstrated cortical erosion in 27% of cases, muscle infiltration in 39%, level IIb nodal involvement in 14%, extra nodal extension in 12%, and perineural spread in 5%. (Table 7). Provisional TNM staging classified patients as cT1N0 (11%), cT2N0 (36%), cT3N1 (24%), cT4N2 (19%), and cT4N3 (10%). (Table 8). Biopsy barriers were reported as financial constraints (33%), fear (24%), lack of facilities (20%), sociocultural factors (11%), and anatomical difficulty (12 % ). (Table 9). All patients received the standardized supportive care regimen, with over 90% adherence at follow-up. Discussion In this large, two-year cohort of 242 patients referred with suspected OSCC but without prior biopsy, a structured clinical framework combined with CECT imaging and standardized supportive care allowed consistent provisional tumour characterisation and triage. The Seven S descriptors and OHI-S highlighted site-specific patterns and a high prevalence of poor oral hygiene, while imaging identified occult features (cortical erosion, muscle infiltration, level IIb nodal disease, and radiologic ENE) that influenced provisional cTNM assignment and referral urgency. Barriers to obtaining biopsy were multifactorial (financial, fear, facility limitations, sociocultural constraints and anatomical difficulty) and mirrored previously described determinants of diagnostic delay. The predominance of retromolar trigone and gingivobuccal sulcus lesions in this cohort aligns with epidemiologic data linking smokeless tobacco and areca nut placement to mucosal carcinogenesis at these sites.[5,6,7,8 ]The observed demographic and habit patterns echo national and regional series describing earlier age at presentation and a strong association with gutka/smokeless tobacco in South Asia. [ 6 , 7 ] Diagnostic delays and biopsy avoidance remain a recurrent global problem. Studies across low- and middle-income countries and in some high-income settings document patient-level delays (late presentation, fear, low awareness) and system-level delays (limited access to biopsy facilities, cost, referral bottlenecks) that translate into later stage at diagnosis and worse outcomes.[ 13 , 14 , 15 , 16 , 34 ] Our findings on the composition of barriers (financial and fear-related predominance) are consistent with prior qualitative and registry-based analyses.[ 14 , 35 ] The inclusion of DOI and ENE in AJCC 8th edition staging has sharpened the link between histopathology and prognosis; in the absence of immediate histology, imaging (with careful radiologic criteria) can detect features suggestive of deeper invasion and ENE that help triage but cannot fully substitute for pathology.[11,12,20,21,22,23 ]Clinical-radiologic concordance varies by subsite and imaging quality; therefore, provisional staging is best viewed as a practical triage tool rather than definitive staging. CECT has practical advantages (speed, wide availability, bone detail) for the initial assessment of suspected OSCC, and prior series report good sensitivity and specificity for cortical bone erosion and gross muscle invasion when performed with adequate technique.[ 19 , 21 , 36 ] MRI offers superior soft-tissue contrast and may better evaluate deep muscle invasion and perineural spread; PET-CT and advanced protocols can further characterise nodal disease and distant metastasis when indicated.[22,23,37 ]Radiologic signs of ENE and suspected level IIb involvement are especially important because they change referral urgency and potential operative planning, though final confirmation requires histopathology.[ 20 , 38 ] Adjunct technologies such as autofluorescence and OCT are attractive point-of-care tools to highlight suspicious mucosal regions and to guide targeted biopsy when possible; systematic reviews and comparative studies indicate variable sensitivity and specificity but suggest value as screening/triage adjuncts rather than standalone diagnostics.[24,25,26 ]Salivary biomarkers and liquid-biopsy approaches show promise for non-invasive case-finding and risk stratification but are not yet ready to replace tissue diagnosis in routine clinical practice; ongoing research aims to validate panels of proteins, cytokines, microRNAs and ctDNA in large, prospective cohorts.[ 27 , 28 , 29 , 30 , 31 ] Artificial-intelligence and radiomics methods are being developed to increase the yield of imaging for features such as ENE and depth of invasion; these remain investigational but have accelerated in recent years.[ 22 , 39 ] Standardized symptomatic care — analgesics, antimicrobials for local infection, antiseptic mouthwash, gastroprotectants, nutritional supplementation — reduced morbidity and maintained function while patients completed diagnostic pathways or were routed to tertiary oncology services. This aligns with palliative and supportive-care literature emphasising early symptom management in head and neck cancer to preserve oral intake, reduce pain and maintain quality of life. [ 31 , 32 ] Counselling for habit cessation is an essential, evidence-based public-health and individual measure; observational data show reduced risk with cessation and potential improvement in outcomes when habit cessation interventions are integrated into care pathways. [ 6 , 7 , 40 ] The distribution of biopsy barriers observed (financial constraints, fear and lack of facilities) underscores the need for system-level interventions: decentralised biopsy capacity, subsidised diagnostics, community education, and culturally appropriate counselling.13–16,34,35 Spatial access, socioeconomic deprivation and health-system investment are consistently linked with later stage at presentation and worse outcomes in oral cancer registries; our cohort reinforces the importance of policy measures that reduce out-of-pocket costs and bring diagnostic services closer to affected communities.[ 5 , 12 , 41 ] Strengths This study’s strengths include a large cohort size of biopsy-naïve, consecutively referred patients managed under a consistent protocol; prospective capture of standardized clinical descriptors (Seven S), routine OHI-S scoring, and systematic CECT review; and documentation of pragmatic supportive-care measures and biopsy-barriers — an approach that mirrors real-world practice in many resource-constrained settings. Limitations Key limitations are its retrospective design, the absence of histopathological confirmation in the cohort by definition (so definitive diagnosis, grading and pathological staging are unknown), single-centre conduct that may limit generalisability, lack of longer-term outcome or survival data, and the inherent limitations of radiologic inference for DOI and ENE compared with histology. Imaging-interpretation variability and the lack of uniform access to MRI or PET in all patients may also have affected diagnostic granularity. Implications and future directions When biopsy is delayed or initially unavailable, a pragmatic, structured pathway that combines standardized lesion description (Seven S), OHI-S, high-quality CECT (or MRI where available), and a bundled supportive-care protocol allows safe provisional triage and timely oncology referral. However, these pathways should be coupled with system-level strategies (improving access to low-cost biopsy; telepathology; decentralised minor-operating services; patient education; and habit-cessation programs) and prospective evaluation. Future prospective studies should compare provisional radiologic-clinical staging with final histopathology, measure time-to-definitive treatment, and examine survival and patient-reported outcomes. Research into validated non-invasive diagnostic adjuncts (salivary biomarkers, OCT, validated autofluorescence algorithms and AI-assisted imaging) offers a complementary route to reduce diagnostic delays, but these require robust validation in large, representative cohorts before they can supplant tissue diagnosis. Conclusion In settings where histopathological confirmation is delayed or initially unavailable, a structured diagnostic pathway that combines systematic clinical assessment (Seven S descriptors and OHI-S), high-quality cross-sectional imaging (CECT ± MRI where available), provisional AJCC-based clinical staging, and a standardized supportive-care bundle enables safe, timely provisional diagnosis and prioritised referral for patients with suspected OSCC. This pragmatic approach reduces patient morbidity during diagnostic delays, highlights those with imaging-suggestive aggressive features (depth of invasion, cortical erosion, extra nodal extension, level IIb nodal disease) who require urgent oncologic assessment, and identifies modifiable system-level barriers to definitive diagnosis. Implementation of such pathways should be paired with health-system interventions — decentralised, low-cost biopsy capacity, patient education and counselling, subsidised diagnostics, and validation of non-invasive adjuncts (autofluorescence, OCT, salivary biomarkers, and AI-assisted imaging) — and evaluated in prospective studies to compare provisional clinical-radiologic staging against final histopathology, time-to-treatment, and patient-centred outcomes. Key recommendations • Adopt a standardised clinic imaging + supportive-care pathway for biopsy-naïve referrals to ensure prompt triage. • Prioritise patients with radiologic signs of deep invasion or ENE for expedited oncology evaluation. • Address financial and access barriers to biopsy through decentralisation and subsidised services. • Prospectively validate non-invasive diagnostic adjuncts and compare provisional staging with histopathologic outcomes in future studies. Declarations Ethics and ethical clearance The study was given waiver from ethical clearance as per STROBE guidelines. As a retrospective study, the requirement for written informed consent was waived. To minimize psychological distress in the absence of histopathological confirmation, patients were informed only of a “provisional diagnosis.” Acknowledgements Department of ENT, Department of Radiodiagnosis, Nursing staff of Oral Cancer Screening OPD -Department of Dental Surgery Ethical Considerations The STROBE guidelines for studies were followed, This retrospective study utilized de-identified data from medical records, since patient data was taken from records and anonymized no ethical clearance is required for the study and prior to surgical intervention and interview of patient written informed consent was taken from all patients for use of their data for research & publication thus, ethical clearance from an Institutional Review Board was not required. Artificial intelligence and computer tools were used to assist in data extraction, statistical calculations, and drafting sections of the manuscript to enhance accuracy and efficiency. All intellectual contributions, including study design, data interpretation, and conclusions, were made by the authors. The study adhered to the Declaration of Helsinki and was approved by the institutional research committee. All authors contributed significantly, reviewed, and approved the final manuscript. No conflicts of interest are declared. References Warnakulasuriya S (2009) Global epidemiology of oral and oropharyngeal cancer. Oral Oncol 45(4–5):309–316 Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90 Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55(2):74–108 Sankaranarayanan R, Ramadas K, Amarasinghe H et al (2015) Oral cancer: prevention, early detection, and treatment. 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Int J Oral Sci 15:135–142 D’Cruz AK et al (2015) Neck management and implications for staging and timing (NEJM 2015 elective ND trial). N Engl J Med 373:521–529 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-7660260","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":517764676,"identity":"ccfa9acb-3297-4558-930f-22de49bea151","order_by":0,"name":"Chandrashekhar 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08:00:32","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":29584,"visible":true,"origin":"","legend":"","description":"","filename":"BlindedText.docx","url":"https://assets-eu.researchsquare.com/files/rs-7660260/v1/a8f9b471d4e17eb5d9ccb01b.docx"},{"id":91963656,"identity":"660a692c-0a14-4506-91e9-fd136f821563","added_by":"auto","created_at":"2025-09-23 08:08:33","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":342,"visible":true,"origin":"","legend":"","description":"","filename":"rs7660260.json","url":"https://assets-eu.researchsquare.com/files/rs-7660260/v1/18a3f5ba2a4487053db3c9d4.json"},{"id":91963657,"identity":"4be7eaf7-a4ad-493a-89e5-206a9e2a0e58","added_by":"auto","created_at":"2025-09-23 08:08:33","extension":"xml","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":74992,"visible":true,"origin":"","legend":"","description":"","filename":"rs76602600enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-7660260/v1/26fedf9bb49e27e07ab8b038.xml"},{"id":91963654,"identity":"ec405020-4648-4591-8957-1a00e8a32ec0","added_by":"auto","created_at":"2025-09-23 08:08:32","extension":"xml","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":69751,"visible":true,"origin":"","legend":"","description":"","filename":"rs76602600structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7660260/v1/ca3f8a78696b054196f1ad16.xml"},{"id":91963073,"identity":"fb6ca84c-f5c5-4b4c-94d4-316ab49490f4","added_by":"auto","created_at":"2025-09-23 08:00:32","extension":"html","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":82609,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7660260/v1/df86495bd3b4d45c917d13df.html"},{"id":91963067,"identity":"ca9e56c8-f1a5-4e77-8004-8f6efa97c844","added_by":"auto","created_at":"2025-09-23 08:00:32","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":94967,"visible":true,"origin":"","legend":"\u003cp\u003eDiagnostic pathway flowchart for suspected OSCC without prior biopsy\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe demographic, habit, clinical, and staging data for suspected OSCC patients can be visualized in multiple comparative tables and charts as shown below, summarizing key findings.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7660260/v1/992d108bf5ee9b863fe000e1.png"},{"id":91963655,"identity":"e300e02b-7ae7-40e7-a202-f19f9297db4b","added_by":"auto","created_at":"2025-09-23 08:08:32","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":28536,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eGender Distribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBar chart showing the gender split among 242 suspected OSCC patients: 81.8% males and 18.2% females.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7660260/v1/bd8e587387d79ef18e14172d.png"},{"id":91963070,"identity":"ae660c40-4429-4398-a48a-4861aee9ac98","added_by":"auto","created_at":"2025-09-23 08:00:32","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":47083,"visible":true,"origin":"","legend":"\u003cp\u003eRisk habit prevalence among males and females with suspected OSCC\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7660260/v1/b860ce751e6c0aec9cc05826.png"},{"id":91963068,"identity":"80204412-be16-447a-8ea7-94506b9a601c","added_by":"auto","created_at":"2025-09-23 08:00:32","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":55862,"visible":true,"origin":"","legend":"\u003cp\u003eClinical Symptoms Prevalence\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-7660260/v1/5fba7728d3b3c738b7e0447e.png"},{"id":91964458,"identity":"0b8b6bb0-e57d-41d0-aa97-87125a347ed0","added_by":"auto","created_at":"2025-09-23 08:11:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":826385,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7660260/v1/4b19905d-38cf-477b-bdea-d2c50ca3dc4c.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eRedefining Diagnostic Pathways in Oral Squamous Cell Carcinoma: Insights from a Two-Year Cohort Managed Without Biopsy\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eOral squamous cell carcinoma (OSCC) constitutes the vast majority of oral malignancies and remains a major cause of cancer-related morbidity and mortality worldwide, with particularly high incidence and mortality in South and Southeast Asia.[1,2,3,4 ]The regional burden reflects widespread use of tobacco (smoked and smokeless), areca nut (betel quid) products such as gutka and pan masala, heavy alcohol use and persistent socioeconomic disadvantage; these exposures are also associated with distinct lesion distributions (for example, gingivobuccal sulcus and retromolar trigone predilection in users of smokeless products).[5,6,7,8] Contemporary molecular and epidemiologic work emphasises both carcinogen-driven field change and tumour heterogeneity as central to OSCC pathogenesis and prognosis.[9]\u003c/p\u003e\n\u003cp\u003eHistopathological confirmation by incisional biopsy continues to be the diagnostic gold standard and forms the basis of definitive diagnosis, grading and pathological staging.[10] The American Joint Committee on Cancer (AJCC) 8th edition incorporated critical changes — most notably clinical and pathological depth of invasion (DOI) for T-category and extra nodal extension (ENE) in N-categorization — that link histopathology closely to prognostic models and treatment decisions.[11,12] Notwithstanding the centrality of biopsy, multiple studies from a range of settings document frequent and sometimes prolonged delays to tissue diagnosis; these delays are driven by a mix of patient-level (fear, awareness, habits), system-level (access, cost, facility capacity) and logistical barriers and are associated with more advanced stage at presentation and worse outcomes.[13,14,15,16]\u003c/p\u003e\n\u003cp\u003eWhere histopathology is delayed or initially unavailable, clinicians commonly combine structured clinical description, functional indices and imaging to form a provisional working diagnosis and triage plan. The Seven S lesion framework (site, size, shape, surface, colour, consistency, symptoms) provides a standardized approach to lesion description that improves communication and triage.[17 ]The Simplified Oral Hygiene Index (OHI-S) is a validated, readily applied index that captures oral hygiene and microbial burden — factors that may influence local disease progression and symptom burden.[18 ]Cross-sectional imaging, particularly \u003cstrong\u003econtrast-enhanced computed tomography\u003c/strong\u003e (CECT), plays a practical role in identifying clinically occult features (mandibular cortical erosion, cancellous involvement, muscle infiltration, nodal disease including level IIb, and radiologic signs of ENE) that meaningfully affect provisional staging and urgency of referral.[19,20,21,22,23 ]Non-invasive adjuncts such as autofluorescence and optical coherence tomography (OCT) are increasingly studied as point-of-care tools to highlight suspicious mucosal areas, while salivary biomarker research and artificial-intelligence approaches aim to strengthen non-biopsy diagnostic pathways.[24,25,26,27,28,29,30]\u003c/p\u003e\n\u003cp\u003eSupportive, symptom-directed care (analgesia, infection control, antiseptic mouthwashes, gastroprotection, nutritional support) together with focused counselling for habit cessation are essential components of pragmatic pathways when definitive diagnostic steps are delayed; these measures reduce morbidity, preserve function and may improve the patient’s readiness for definitive treatment. [31,32,33]\u003c/p\u003e\n\u003cp\u003eThis study reports a two-year retrospective cohort of 242 patients referred with suspected OSCC who had not undergone prior incisional biopsy and had available CECT imaging. By documenting lesion descriptors (Seven S), OHI-S, clinical staging \u003cstrong\u003e(AJCC\u0026nbsp;\u003c/strong\u003e8thEd criteria applied provisionally), imaging findings and the nature of biopsy-barriers, and by describing a standardized supportive-care bundle, we aim to present a pragmatic diagnostic pathway for settings where histopathology is delayed or initially unavailable and to place those findings in the context of current evidence and health-systems realities.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy design and setting:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective observational cohort study was conducted in the Dental Outpatient Department of a tertiary teaching medical hospital which is actively involved in screening of oral malignancy and potentially malignant lesions as per state government health policy and has as Medical Officer In charge dedicated for the same , (Coauthor number 3 under supervision of HOD Coauthor No2 )between January 2023 and December 2024.\u003c/p\u003e\n\u003cp\u003eThe study included adult patients (≥18 years) presenting with clinical suspicion of OSCC, such as non-healing oral ulcers of more than four weeks’ duration, trismus, persistent mucosal lesions, spontaneous tooth loss, or unexplained neck swelling. Eligibility criteria required that patients had not undergone prior incisional biopsy and had contrast-enhanced computed tomography (CECT) of the mandible and neck available. Patients with histologically confirmed OSCC prior to referral, recurrent or previously treated cases, or incomplete records were excluded.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical assessments:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEach patient underwent systematic evaluation using the Seven S lesion framework, which records site, size, shape, surface, colour, consistency, and symptoms. Oral hygiene status was assessed using the Simplified Oral Hygiene Index (OHI-S), categorizing scores as good (≤1.0), moderate (1.1–3.0), or poor (\u0026gt;3.0). Trismus was graded as mild (25–35 mm), moderate (11–24 mm), or severe (≤10 mm). Lymph nodes were examined across levels I–V for size, tenderness, and fixation. [7,8,9,10] Provisional staging was assigned using the American Joint Committee on Cancer (AJCC) 8th edition TNM system.[4] \u003cstrong\u003eImaging:\u003c/strong\u003e All patients underwent CECT of the mandible and neck with a slice thickness of ≤2.5 mm. Images were evaluated for cortical erosion, cancellous extension, muscle infiltration, nodal involvement across cervical levels, extra nodal extension, and perineural spread.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupportive management:\u003c/strong\u003e Patients received standardized symptomatic care, including tramadol (50 mg as needed), chlorhexidine 0.2% mouthwash (three times daily), amoxicillin–clavulanic acid 625 mg (three times daily), metronidazole 400 mg (three times daily), pantoprazole with domperidone (once daily), and a daily multivitamin supplement. Individualized counselling sessions focused on habit cessation, reinforcement of oral hygiene practices, awareness of symptoms, and timely oncology referral.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBiopsy barriers:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBarriers to undergoing biopsy were categorized as financial, fear-related, lack of facilities, sociocultural reasons, or anatomical difficulty.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData were entered into SPSS version 24 and analysed using descriptive statistics. Frequencies, percentages, medians, and ranges were calculated, as appropriate.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 242 patients were included, comprising 198 males (81.8%) and 44 females (18.2%), with a median age of 39 years (range: 24\u0026ndash;70 years). The peak incidence occurred in the 30\u0026ndash;45-year age group. \u003cb\u003e(Table\u0026nbsp;1).\u003c/b\u003e\u003c/p\u003e\u003cp\u003eRisk habit analysis showed that among males, gutka use was most common (51%), followed by smokeless tobacco (46%), bidi (38%), and alcohol (32%); 62% reported combined use of two or more habits. Among females, gutka was also most prevalent (70%), followed by smokeless tobacco (55%) and alcohol (9%); combined habit use was noted in 9%. Importantly, 90% of patients reported habit reduction following symptom onset. \u003cb\u003e(Table\u0026nbsp;2).\u003c/b\u003e\u003c/p\u003e\u003cp\u003eClinically, trismus was the most frequent presentation (47%), followed by non-healing ulcer lasting more than four weeks (39%), pain (60%), neck swelling (19%), and tooth exfoliation (21%). Other complaints included burning sensation (15%), bleeding (25%), paraesthesia (15%), and odynophagia (10%). \u003cb\u003e(Table\u0026nbsp;3).\u003c/b\u003e\u003c/p\u003e\u003cp\u003eLesion characteristics based on the Seven S framework revealed that the retromolar trigone (46%) and gingivobuccal sulcus (37%) were the most common sites, with the majority of lesions measuring 2\u0026ndash;4 cm (73%). Lesions were predominantly irregular in shape (65%), ulcerated (70%), erythematous (50%), and indurated (79%). \u003cb\u003e(Table\u0026nbsp;4)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e Oral hygiene assessment showed that 68% of patients had poor OHI-S scores, 25% had moderate scores, and only 7% had good scores. \u003cb\u003e(Table\u0026nbsp;5).\u003c/b\u003e Lymph node examination revealed palpable nodes in 60% of patients, most commonly at levels Ia/Ib (35%) and IIa (20%).\u003cb\u003e(Table\u0026nbsp;6).\u003c/b\u003e\u003c/p\u003e\u003cp\u003eCECT findings demonstrated cortical erosion in 27% of cases, muscle infiltration in 39%, level IIb nodal involvement in 14%, extra nodal extension in 12%, and perineural spread in 5%. \u003cb\u003e(Table\u0026nbsp;7).\u003c/b\u003e Provisional TNM staging classified patients as cT1N0 (11%), cT2N0 (36%), cT3N1 (24%), cT4N2 (19%), and cT4N3 (10%). \u003cb\u003e(Table\u0026nbsp;8).\u003c/b\u003e\u003c/p\u003e\u003cp\u003eBiopsy barriers were reported as financial constraints (33%), fear (24%), lack of facilities (20%), sociocultural factors (11%), and anatomical difficulty (12\u003cb\u003e%\u003c/b\u003e). \u003cb\u003e(Table\u0026nbsp;9).\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAll patients received the standardized supportive care regimen, with over 90% adherence at follow-up.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this large, two-year cohort of 242 patients referred with suspected OSCC but without prior biopsy, a structured clinical framework combined with CECT imaging and standardized supportive care allowed consistent provisional tumour characterisation and triage. The Seven S descriptors and OHI-S highlighted site-specific patterns and a high prevalence of poor oral hygiene, while imaging identified occult features (cortical erosion, muscle infiltration, level IIb nodal disease, and radiologic ENE) that influenced provisional cTNM assignment and referral urgency. Barriers to obtaining biopsy were multifactorial (financial, fear, facility limitations, sociocultural constraints and anatomical difficulty) and mirrored previously described determinants of diagnostic delay.\u003c/p\u003e\u003cp\u003eThe predominance of retromolar trigone and gingivobuccal sulcus lesions in this cohort aligns with epidemiologic data linking smokeless tobacco and areca nut placement to mucosal carcinogenesis at these sites.[5,6,7,8 ]The observed demographic and habit patterns echo national and regional series describing earlier age at presentation and a strong association with gutka/smokeless tobacco in South Asia. [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eDiagnostic delays and biopsy avoidance remain a recurrent global problem. Studies across low- and middle-income countries and in some high-income settings document patient-level delays (late presentation, fear, low awareness) and system-level delays (limited access to biopsy facilities, cost, referral bottlenecks) that translate into later stage at diagnosis and worse outcomes.[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e] Our findings on the composition of barriers (financial and fear-related predominance) are consistent with prior qualitative and registry-based analyses.[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eThe inclusion of DOI and ENE in AJCC 8th edition staging has sharpened the link between histopathology and prognosis; in the absence of immediate histology, imaging (with careful radiologic criteria) can detect features suggestive of deeper invasion and ENE that help triage but cannot fully substitute for pathology.[11,12,20,21,22,23 ]Clinical-radiologic concordance varies by subsite and imaging quality; therefore, provisional staging is best viewed as a practical triage tool rather than definitive staging.\u003c/p\u003e\u003cp\u003eCECT has practical advantages (speed, wide availability, bone detail) for the initial assessment of suspected OSCC, and prior series report good sensitivity and specificity for cortical bone erosion and gross muscle invasion when performed with adequate technique.[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e] MRI offers superior soft-tissue contrast and may better evaluate deep muscle invasion and perineural spread; PET-CT and advanced protocols can further characterise nodal disease and distant metastasis when indicated.[22,23,37 ]Radiologic signs of ENE and suspected level IIb involvement are especially important because they change referral urgency and potential operative planning, though final confirmation requires histopathology.[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eAdjunct technologies such as autofluorescence and OCT are attractive point-of-care tools to highlight suspicious mucosal regions and to guide targeted biopsy when possible; systematic reviews and comparative studies indicate variable sensitivity and specificity but suggest value as screening/triage adjuncts rather than standalone diagnostics.[24,25,26 ]Salivary biomarkers and liquid-biopsy approaches show promise for non-invasive case-finding and risk stratification but are not yet ready to replace tissue diagnosis in routine clinical practice; ongoing research aims to validate panels of proteins, cytokines, microRNAs and ctDNA in large, prospective cohorts.[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] Artificial-intelligence and radiomics methods are being developed to increase the yield of imaging for features such as ENE and depth of invasion; these remain investigational but have accelerated in recent years.[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eStandardized symptomatic care \u0026mdash; analgesics, antimicrobials for local infection, antiseptic mouthwash, gastroprotectants, nutritional supplementation \u0026mdash; reduced morbidity and maintained function while patients completed diagnostic pathways or were routed to tertiary oncology services. This aligns with palliative and supportive-care literature emphasising early symptom management in head and neck cancer to preserve oral intake, reduce pain and maintain quality of life. [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] Counselling for habit cessation is an essential, evidence-based public-health and individual measure; observational data show reduced risk with cessation and potential improvement in outcomes when habit cessation interventions are integrated into care pathways. [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eThe distribution of biopsy barriers observed (financial constraints, fear and lack of facilities) underscores the need for system-level interventions: decentralised biopsy capacity, subsidised diagnostics, community education, and culturally appropriate counselling.13\u0026ndash;16,34,35 Spatial access, socioeconomic deprivation and health-system investment are consistently linked with later stage at presentation and worse outcomes in oral cancer registries; our cohort reinforces the importance of policy measures that reduce out-of-pocket costs and bring diagnostic services closer to affected communities.[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]\u003c/p\u003e\n\u003ch3\u003eStrengths\u003c/h3\u003e\n\u003cp\u003eThis study\u0026rsquo;s strengths include a large cohort size of biopsy-na\u0026iuml;ve, consecutively referred patients managed under a consistent protocol; prospective capture of standardized clinical descriptors (Seven S), routine OHI-S scoring, and systematic CECT review; and documentation of pragmatic supportive-care measures and biopsy-barriers \u0026mdash; an approach that mirrors real-world practice in many resource-constrained settings.\u003c/p\u003e\n\u003ch3\u003eLimitations\u003c/h3\u003e\n\u003cp\u003eKey limitations are its retrospective design, the absence of histopathological confirmation in the cohort by definition (so definitive diagnosis, grading and pathological staging are unknown), single-centre conduct that may limit generalisability, lack of longer-term outcome or survival data, and the inherent limitations of radiologic inference for DOI and ENE compared with histology. Imaging-interpretation variability and the lack of uniform access to MRI or PET in all patients may also have affected diagnostic granularity.\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eImplications and future directions\u003c/h2\u003e\u003cp\u003eWhen biopsy is delayed or initially unavailable, a pragmatic, structured pathway that combines standardized lesion description (Seven S), OHI-S, high-quality CECT (or MRI where available), and a bundled supportive-care protocol allows safe provisional triage and timely oncology referral. However, these pathways should be coupled with system-level strategies (improving access to low-cost biopsy; telepathology; decentralised minor-operating services; patient education; and habit-cessation programs) and prospective evaluation. Future prospective studies should compare provisional radiologic-clinical staging with final histopathology, measure time-to-definitive treatment, and examine survival and patient-reported outcomes. Research into validated non-invasive diagnostic adjuncts (salivary biomarkers, OCT, validated autofluorescence algorithms and AI-assisted imaging) offers a complementary route to reduce diagnostic delays, but these require robust validation in large, representative cohorts before they can supplant tissue diagnosis.\u003c/p\u003e\u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn settings where histopathological confirmation is delayed or initially unavailable, a structured diagnostic pathway that combines systematic clinical assessment (Seven S descriptors and OHI-S), high-quality cross-sectional imaging (CECT ± MRI where available), provisional AJCC-based clinical staging, and a standardized supportive-care bundle enables safe, timely provisional diagnosis and prioritised referral for patients with suspected OSCC. This pragmatic approach reduces patient morbidity during diagnostic delays, highlights those with imaging-suggestive aggressive features (depth of invasion, cortical erosion, extra nodal extension, level IIb nodal disease) who require urgent oncologic assessment, and identifies modifiable system-level barriers to definitive diagnosis.\u003c/p\u003e\n\u003cp\u003eImplementation of such pathways should be paired with health-system interventions — decentralised, low-cost biopsy capacity, patient education and counselling, subsidised diagnostics, and validation of non-invasive adjuncts (autofluorescence, OCT, salivary biomarkers, and AI-assisted imaging) — and evaluated in prospective studies to compare provisional clinical-radiologic staging against final histopathology, time-to-treatment, and patient-centred outcomes.\u003c/p\u003e\n\u003cp\u003eKey recommendations\u003c/p\u003e\n\u003cp\u003e• Adopt a standardised clinic imaging + supportive-care pathway for biopsy-naïve referrals to ensure prompt triage.\u003c/p\u003e\n\u003cp\u003e• Prioritise patients with radiologic signs of deep invasion or ENE for expedited oncology evaluation.\u003c/p\u003e\n\u003cp\u003e• Address financial and access barriers to biopsy through decentralisation and subsidised services.\u003c/p\u003e\n\u003cp\u003e• Prospectively validate non-invasive diagnostic adjuncts and compare provisional staging with histopathologic outcomes in future studies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics and ethical clearance\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;The study was given waiver from ethical clearance as per STROBE guidelines. As a retrospective study, the requirement for written informed consent was waived. To minimize psychological distress in the absence of histopathological confirmation, patients were informed only of a \u0026ldquo;provisional diagnosis.\u0026rdquo;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDepartment of ENT, Department of Radiodiagnosis, Nursing staff of Oral Cancer Screening OPD -Department of Dental Surgery\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Considerations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe STROBE guidelines for studies were followed,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis retrospective study utilized de-identified data from medical records, since patient data was taken from records and anonymized no ethical clearance is required for the study and prior to surgical intervention and interview of patient written informed consent was taken from all patients for use of their data for research \u0026amp; publication thus, ethical clearance from an Institutional Review Board was not required. Artificial intelligence and computer tools were used to assist in data extraction, statistical calculations, and drafting sections of the manuscript to enhance accuracy and efficiency. All intellectual contributions, including study design, data interpretation, and conclusions, were made by the authors. The study adhered to the Declaration of Helsinki and was approved by the institutional research committee. All authors contributed significantly, reviewed, and approved the final manuscript. No conflicts of interest are declared.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWarnakulasuriya S (2009) Global epidemiology of oral and oropharyngeal cancer. Oral Oncol 45(4\u0026ndash;5):309\u0026ndash;316\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. 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N Engl J Med 373:521\u0026ndash;529\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","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; Seven S framework; TNM staging; Biopsy barriers; Contrast-enhanced computed tomography; Supportive care.","lastPublishedDoi":"10.21203/rs.3.rs-7660260/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7660260/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003cbr\u003e\n \u003c/strong\u003eOral squamous cell carcinoma (OSCC) accounts for the majority of oral malignancies in South Asia. Biopsy, the diagnostic gold standard, is often delayed due to systemic, financial, and sociocultural barriers. This study evaluates the role of structured clinical frameworks, imaging, and supportive care in the management of OSCC referrals without biopsy and histopathological examination.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003cbr\u003e\n \u003c/strong\u003eA retrospective cohort study was conducted on 242 patients referred to a tertiary dental outpatient department between January 2023 and December 2024 with suspected OSCC, no prior biopsy, and available contrast-enhanced computed tomography (CECT). Assessments included the Seven S lesion framework, Simplified Oral Hygiene Index (OHI-S), trismus grading, lymph node examination, provisional TNM staging (AJCC 8th edition), and CECT findings. All patients received standardized symptomatic management (analgesics, antimicrobials, antiseptic mouthwash, gastroprotectants, nutritional supplements) and counselling for habit cessation. Descriptive statistics were applied.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003cbr\u003e\n \u003c/strong\u003eOf 242 patients (198 males [81.8%], 44 females [18.2%]; median age 39 years), the majority reported gutka (51% males, 70% females) or smokeless tobacco use. Lesions primarily involved the retromolar trigone (46%) and gingivobuccal sulcus (37%). OHI-S was poor in 68% of cases. Trismus occurred in 47%. CECT revealed cortical erosion (27%), muscle infiltration (39%), and level IIb nodal involvement (14%). Provisional TNM staging included cT2N0 (36%), cT3N1 (24%), and cT4N2 (19%). Reported barriers to biopsy were financial constraints (33%), fear (24%), lack of facilities (20%), sociocultural reasons (11%), and anatomical difficulty (12%).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003cbr\u003e\n \u003c/strong\u003eIn the absence of biopsy, structured clinical assessment, imaging, and supportive care enable effective provisional diagnosis and timely referral. This approach provides a practical diagnostic pathway with implications for policy, education, and early OSCC management.\u003c/p\u003e","manuscriptTitle":"Redefining Diagnostic Pathways in Oral Squamous Cell Carcinoma: Insights from a Two-Year Cohort Managed Without Biopsy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-23 08:00:27","doi":"10.21203/rs.3.rs-7660260/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","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":"ac1a45a0-d21e-4d82-8b5a-9c3b5fdc72f4","owner":[],"postedDate":"September 23rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":55027433,"name":"Dentistry"}],"tags":[],"updatedAt":"2025-09-23T08:00:27+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-23 08:00:27","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7660260","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7660260","identity":"rs-7660260","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}