Oral oncology最新文献

{"title":"Patient-derived 3D organoid platform for functional assessment of GPC3-targeted CAR T cell cytotoxic activity in head and neck squamous cell carcinoma","authors":"Han-Na Yoon ,&nbsp;Jin-ha Kim ,&nbsp;Doeon Gu ,&nbsp;Jonghyun Lee ,&nbsp;Soo Yoon Kim ,&nbsp;Hye Jin Kim ,&nbsp;Jaehyeon Jeong ,&nbsp;Dongkwan Shin ,&nbsp;Yuh-Seog Jung ,&nbsp;Man Ki Chung ,&nbsp;Sang-Jin Lee ,&nbsp;Sung Yong Choi","doi":"10.1016/j.oraloncology.2025.107814","DOIUrl":"10.1016/j.oraloncology.2025.107814","url":null,"abstract":"<div><h3>Background</h3><div>Head and neck squamous cell carcinoma (HNSCC) remains a therapeutic challenge owing to its marked heterogeneity and limited immunotherapy efficacy, underscoring the need for improved therapeutic strategies and preclinical systems supporting clinical translation.</div></div><div><h3>Method</h3><div>We established a simplified and optimized 3D head and neck cancer organoid (HNCO)–chimeric antigen receptor (CAR) T cell co-culture platform that maintains uniform spheroid architecture (&gt;500 μm) to recapitulate physiological hypoxia while preserving the tumor secretome. CAR T cell cytotoxic activity was assessed through multimodal readouts—structural disruption, ATP-based viability, and granzyme B secretion. Following initial organoid seeding, the workflow proceeded without physical manipulation, enabling concurrent multimodal assessment of CAR T cell activity from a single co-culture.</div></div><div><h3>Results</h3><div>Analysis of The Cancer Genome Atlas (TCGA) data revealed that high glypican-3 (GPC3) expression was associated with poor survival in patients with HNSCC. We generated GPC3-targeted CAR T (GPC3-CAR T) cells. Using our co-culture platform, we evaluated the cytotoxic activity of GPC3-CAR T cells against five HNCOs harboring diverse genetic alterations and variable GPC3 expression. Organoids with high or moderate GPC3 expression consistently exhibited structural disintegration, reduced viability, and increased granzyme B secretion, whereas GPC3-low organoids showed heterogeneous responses.</div></div><div><h3>Conclusions</h3><div>This proof-of-concept study introduces a patient-derived 3D organoid platform for functional assessment of CAR T cell cytotoxic activity in HNSCC. Our findings suggest that GPC3-CAR T therapy may be clinically applicable to subsets of patients with HNSCC, while emphasizing the need for functional validation to account for interpatient heterogeneity in clinical translation.</div></div>","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"172 ","pages":"Article 107814"},"PeriodicalIF":3.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145725145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A pilot study of a digital workflow for navigated tumor bed marking to reduce clinical target volume during adjuvant radiotherapy for oral squamous cell carcinoma","authors":"Frederik Holdorf ,&nbsp;Henning Schliephake ,&nbsp;Kathi Goldstein ,&nbsp;Lennart Johannes Gruber ,&nbsp;Phillipp Brockmeyer ,&nbsp;Martin Leu ,&nbsp;Stefan Rieken ,&nbsp;Boris Schminke","doi":"10.1016/j.oraloncology.2025.107820","DOIUrl":"10.1016/j.oraloncology.2025.107820","url":null,"abstract":"<div><h3>Purpose</h3><div>The treatment of advanced-stage oral squamous cell carcinoma (OSCC) often requires adjuvant radiotherapy to improve the survival rate. Accurately defining the clinical target volume (CTV) is critical for radiation treatment to maximize the radiation dose and minimize negative side effects. However, precise planning remains difficult because of postoperative anatomical changes, which may lead to oversized volumes with increased collateral damage to adjacent tissues. The aim of this study is to suggest a digital planning algorithm to improve the precision of CTV definition.</div></div><div><h3>Methods</h3><div>In this pilot study, intraoperative digital tracings of tumor resection margins were located in the preoperative computed tomography (CT) datasets of ten patients with advanced OSCC using the Brainlab Curve navigation system. OSCCs of the tongue were excluded from this analysis because of their unique anatomical features. The preoperative scans with digital tracings were aligned with the postoperative scans to identify the desired CTV. The digitally navigated CTVs were compared with the CTVs resulting from conventional planning.</div></div><div><h3>Results</h3><div>Our findings demonstrated that the digital workflow can be easily integrated into the surgical procedure and provides a straightforward and reproducible method to achieve a statistically significant average reduction of 25.71% in the CTV.</div></div><div><h3>Conclusion</h3><div>This innovative approach to digital tracing of the resection margins in postoperative CT scans significantly increases the precision of CTV planning. Clinical studies will be needed to test the oncological safety compared to conventional planning algorithms and the potential for improved outcomes with respect to side effects and quality of life.</div></div>","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"172 ","pages":"Article 107820"},"PeriodicalIF":3.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145737457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The diagnostic trade-off in post-treatment surveillance for HPV-positive oropharyngeal carcinoma","authors":"Yaling Tang ,&nbsp;Heng Gan ,&nbsp;Xin Gan","doi":"10.1016/j.oraloncology.2025.107798","DOIUrl":"10.1016/j.oraloncology.2025.107798","url":null,"abstract":"","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"172 ","pages":"Article 107798"},"PeriodicalIF":3.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145617264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated geriatric assessment and intervention in the head and neck oncology care pathway reduces adverse events and does not affect survival","authors":"Beniamino Vincenzoni Padovan ,&nbsp;Marleen Beenker ,&nbsp;Johannes A. Langendijk ,&nbsp;Hans Paul van der Laan ,&nbsp;Boukje A.C. van Dijk ,&nbsp;Geertrudia H. de Bock ,&nbsp;Boudewijn E.C. Plaat ,&nbsp;Pauline de Graeff ,&nbsp;Suzanne Festen ,&nbsp;Gyorgy B. Halmos","doi":"10.1016/j.oraloncology.2025.107811","DOIUrl":"10.1016/j.oraloncology.2025.107811","url":null,"abstract":"<div><h3>Objective</h3><div>The number of older/frail patients with head and neck cancer (HNC) is increasing. They are more frail compared to patients with other malignancies. Therefore, geriatric care is increasingly integrated into the HNC care pathway. The aim of this study was to investigate how integrated geriatric care affects treatment outcomes in HNC patients irrespective of treatment intention.</div></div><div><h3>Methods</h3><div>This retrospective study compared treatment-related adverse outcomes (grade ≥ 2 Clavien-Dindo surgical complications and grade ≥ 2 CTCAE (chemo)radiotoxicity), and one-year mortality in two patient cohorts. In the first cohort (2014–2016), geriatric screening was only observational i.e. without intervention. In the second cohort (2019–2020), a complete geriatric pathway was integrated into the oncological care pathway, including an onco-geriatric MDT (multidisciplinary team meeting), referral to the geriatrician with intervention, if needed. Multivariable logistic regression analysis was performed to identify factors associated with adverse events and one-year mortality, including the cohort period.</div></div><div><h3>Results</h3><div>This study included 640 patients; 369 from the first cohort and 271 from the second cohort. The second cohort showed significantly fewer adverse events (34.6 %) compared to the first (65.4 %) (OR 0.41; 95 % CI 0.27–0.63: p &lt; 0.001). Reductions were seen in surgical complications (OR 0.57; 95 % CI 0.32–1.01) as well as (chemo)radiotoxicity (OR 0.39; 95 % CI 0.20–0.76). No significant differences were observed in one-year mortality (OR 0.88; CI 0.59–1.48). Adverse events were significantly linked to malnutrition, advanced tumor stage and concomitant radiotherapy treatment.</div></div><div><h3>Conclusion</h3><div>Integration of geriatric care in the HNC pathway reduces treatment-related adverse events, without altering one-year mortality.</div></div>","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"172 ","pages":"Article 107811"},"PeriodicalIF":3.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145701447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NOTCH1 loss promotes chemo and radio-resistance in head and neck cancer","authors":"Mushfiq H. Shaikh ,&nbsp;Walid Gazala ,&nbsp;Cindy Zeng ,&nbsp;Mahdi Farzad Naimi ,&nbsp;Matthew Cecchini ,&nbsp;Amir Karimi ,&nbsp;Halema Khan ,&nbsp;Krista Joris ,&nbsp;Shengjie Ying ,&nbsp;Harrison Pan ,&nbsp;Mohd Wessam Al Jawhri ,&nbsp;David A. Palma ,&nbsp;Joe S. Mymryk ,&nbsp;Peter YF. Zeng ,&nbsp;John W. Barrett ,&nbsp;Anthony C. Nichols","doi":"10.1016/j.oraloncology.2025.107815","DOIUrl":"10.1016/j.oraloncology.2025.107815","url":null,"abstract":"<div><h3>Introduction</h3><div>Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, with over 700,000 new cases diagnosed annually. HPV-associated HNSCC patients generally respond well to standard therapies; however, about 15–20 % experience recurrence, while the rate is approximately 50 % in non-HPV-associated HNSCC. Identifying biomarkers for treatment failure is crucial for optimizing treatment strategies. Our lab’s whole genome sequencing (WGS) data has identified <em>NOTCH1</em> mutations as enriched in recurrent HPV-positive HNSCC cases. This study investigates whether <em>NOTCH1</em> deletion confers treatment resistance in both HPV-positive and HPV-negative HNSCC models.</div></div><div><h3>Methods</h3><div>Four HPV-positive (HPV+) HNSCC cell lines (UWO23, UWO37, UMSCC47, and 93VU147) and two HPV-negative (HPV−) HNSCC cell lines (FaDu and Cal27) were examined. We used siRNA to knock down <em>NOTCH1</em> expression, confirmed by qPCR, and then used CRISPR editing to generate stable <em>NOTCH1</em> knockout (KO) cells. The knockout was validated by real-time qPCR and western blotting. Cell viability, clonogenicity, and invasiveness were then evaluated through viability, colony formation, and invasion assays.</div></div><div><h3>Results</h3><div>The siRNA-mediated <em>NOTCH1</em> knockdown increased cellular proliferation in both HPV+ and HPV− HNSCC lines, with similar effects observed in CRISPR-edited <em>NOTCH1</em>-KO cells. Colony formation and invasion assays demonstrated higher aggression and invasiveness in <em>NOTCH1</em>-KO cells compared to non-targeting controls (NTC). IC50 analysis showed that <em>NOTCH1</em>-KO cells exhibited enhanced cisplatin resistance in both HPV+ and HPV− lines, with increased radiation resistance also observed in <em>NOTCH1</em>-KO cells.</div></div><div><h3>Conclusion</h3><div>Our findings indicate that <em>NOTCH1</em> loss in both HPV+ and HPV− HNSCC cell lines leads to increased aggressiveness, clonogenicity, invasiveness, and resistance to chemotherapy and radiation. This suggests that <em>NOTCH1</em> loss may be a potential biomarker for identifying HNSCC patients at higher risk of treatment failure, supporting a more personalized, intensive therapeutic approach.</div></div>","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"172 ","pages":"Article 107815"},"PeriodicalIF":3.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145714937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methodological considerations in profiling the immune microenvironment and HPV status of oral multiple primary cancers","authors":"Shanshan Yuan,&nbsp;Jingjing Gao","doi":"10.1016/j.oraloncology.2025.107822","DOIUrl":"10.1016/j.oraloncology.2025.107822","url":null,"abstract":"","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"172 ","pages":"Article 107822"},"PeriodicalIF":3.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patterns of metastasis and nodal disease in tongue and buccal carcinomas: Case-based reflections in Delhi NCR Region","authors":"Kripa Bajaj ,&nbsp;Ramya Ramadoss ,&nbsp;Sandhya Sundar ,&nbsp;Suganya Panneer Selvam ,&nbsp;Hema Shree K.","doi":"10.1016/j.oraloncology.2025.107816","DOIUrl":"10.1016/j.oraloncology.2025.107816","url":null,"abstract":"<div><h3>Background</h3><div>Oral squamous cell carcinoma (OSCC) is a large source of cancer-related morbidity in India especially when it involves the tongue and the buccal mucosa. Despite the fact that TNM staging provides a global framework, regional patterns of metastasis, comorbidity interaction and concordance between imaging and pathology are not uniformly represented. This study will investigate nodal disease patterns in a group of people in the Delhi National Capital Region (NCR) and will suggest more specific treatments. The research aims to facilitate early diagnosis and intervention pathways and to reduce inequality in healthcare service provision.</div></div><div><h3>Methods</h3><div>Twenty patients with OSCC who had been diagnosed between 2023 and 2025 were the subjects of a retrospective study conducted on tertiary oncology centres in Delhi NCR. Inclusion criteria were confirmation of primary OSCC of the tongue or buccal mucosa, availability of PET −CT or MRI images, full TNM staging, and comorbidity information. Data visualization included heatmaps, scatter plot, cluster diagram and radar charts. Along with the imaging concordance, tumour site, the size of the lesion, nodal involvement, and the burden of comorbidity were evaluated.</div></div><div><h3>Results</h3><div>Bilateral nodal involvement was higher in the Tongue OSCC, mostly at Level II and III, but the tumours of the buccal mucosa were mostly limited to Level Ib unilateral. Nodal burden was much higher in lesions of around 3.5 cm. Comorbidities (diabetes and chronic kidney disease) were also related to higher FDG uptake and necrosis, but the relationships were not statistically significant. PET-CT had 85 percent agreement with the pathology of the surgery. The decision of treatment was based on the staging with surgery being the preferred treatment option in early disease and chemoradiation in advanced ones.</div></div><div><h3>Conclusion</h3><div>The site and size of tumour have a significant impact on nodal dissemination in OSCC. Bilateral neck dissection can be a wise option in case of early tongue lesions involving the midline but selective unilateral dissection is adequate in selecting cases involving the buccal lesions. It is necessary to couple comorbidity profiling with imaging results when planning pre-treatment. In this study, health systems, health equity, and collaborative oncology care are strengthened.</div></div>","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"172 ","pages":"Article 107816"},"PeriodicalIF":3.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influencing factors on occurrence and prognosis of oral squamous cell carcinoma after organ transplantation","authors":"Yiheng Feng ,&nbsp;Maged Ali Al-Aroomi ,&nbsp;Jie Chen ,&nbsp;Saiwen Song ,&nbsp;Canhua Jiang ,&nbsp;Jie Wang","doi":"10.1016/j.oraloncology.2025.107824","DOIUrl":"10.1016/j.oraloncology.2025.107824","url":null,"abstract":"<div><h3>Objectives</h3><div>Patients who undergo solid organ or hematopoietic stem cell transplantation are at an increased risk of developing oral squamous cell carcinoma (OSCC) due to prolonged immunosuppression. The specific characteristics and prognostic outcomes of OSCC in these post-transplant patients are not well understood. This study aims to investigate the risk, characteristics, and prognostic outcomes of OSCC in post-transplant patients.</div></div><div><h3>Methods</h3><div>This study analyzed the clinical baseline characteristics of OSCC patients with pathological confirmation who had undergone organ transplantation (study group) and non-transplant OSCC patients (control group), all of whom were monitored with comprehensive follow-up. Survival outcomes, including overall survival (OS) and disease-free survival (DFS), were assessed using the Kaplan-Meier method. The Cox proportional hazards model was used to evaluate whether organ transplantation status was an independent risk factor affecting survival.</div></div><div><h3>Results</h3><div>A total of 103 patients were enrolled (study group, n = 17; control group, n = 86). The median age at OSCC diagnosis for study group was 53 years, with tumors primarily located on the tongue (35.3 %), buccal (17.6 %), and gingiva (11.8 %). Control group had a similar median age, with tumors mostly located on the tongue (64.0 %), buccal (16.3 %), and gingiva (8.1 %). Except for one transplant recipient who received conservative management, all patients underwent surgical resection. Cox multivariate analysis identified tumor recurrence (p = 0.002), tumor size (p = 0.016), and vascular invasion (p = 0.006) as significant adverse factors affecting survival.</div></div><div><h3>Conclusion</h3><div>This study emphasizes the importance of organ transplantation history in managing OSCC. Regular screening is essential for early detection and improved survival, particularly under immunosuppressive conditions, in this high-risk group.</div></div>","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"172 ","pages":"Article 107824"},"PeriodicalIF":3.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145787203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence of HPV-independent second primary malignancies following treatment of HPV-associated malignancy","authors":"Sarah C. Nyirjesy ,&nbsp;Yana Al-Inaya ,&nbsp;Selena Zhang ,&nbsp;Omar A. Karadaghy ,&nbsp;Derrick T. Lin ,&nbsp;Daniel G. Deschler ,&nbsp;Allen L. Feng ,&nbsp;Mark A. Varvares ,&nbsp;Adam S. Fisch ,&nbsp;Daniel L. Faden ,&nbsp;Jeremy D. Richmon","doi":"10.1016/j.oraloncology.2025.107790","DOIUrl":"10.1016/j.oraloncology.2025.107790","url":null,"abstract":"<div><div>Second primary tumors after HPV-associated oropharyngeal squamous cell carcinoma (HPV + OPSCCa) are generally assumed to share the same HPV status as the index lesion, and current pathology guidelines discourage repeat HPV testing in recurrent disease. We retrospectively reviewed records from a tertiary academic center (2010–2024) to identify patients with a history of HPV + OPSCCa who subsequently developed an HPV-independent second primary head and neck squamous cell carcinoma. HPV status was determined by p16 immunohistochemistry, high-risk HPV DNA PCR, or RNA in situ hybridization. Eleven patients developed metachronous HPV-independent malignancies, representing an incidence of 2.5 %. The median interval between tumors was 8.8 years (range, 3.2–16.0 years). Second primaries most often arose in the contralateral base of tongue (55 %) or oral cavity (27 %). All patients had received definitive or adjuvant radiation for the initial tumor, and 73 % received concurrent chemotherapy. Four patients (36 %) reported a smoking history &gt;10 pack-years. Most tumors at both time points were T1 or T2, but node-positive disease was more frequent in first primaries (82 % vs 18 %). Two patients developed a third HPV-independent primary tumor. These findings demonstrate that biologically discordant second primary head and neck cancers can emerge years after HPV + OPSCCa, challenging the assumption of HPV concordance and underscoring the need for long-term surveillance and reconsideration of repeat HPV testing in this population.</div></div>","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"172 ","pages":"Article 107790"},"PeriodicalIF":3.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145669487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hpv-driven rewiring of the tumor immune microenvironment through single-cell profiling informs prognosis and therapy in HNSCC","authors":"Ying Li ,&nbsp;Qianzi Kou ,&nbsp;Chongyang Zheng ,&nbsp;Pengkhun Nov,&nbsp;Changqian Wang,&nbsp;Peizan Ni,&nbsp;Lilin Li,&nbsp;Yangfeng Zhang,&nbsp;Duanyu Wang,&nbsp;Arzoo Prasai,&nbsp;Wen Fu,&nbsp;Jiqiang Li ,&nbsp;Kunpeng Du","doi":"10.1016/j.oraloncology.2025.107789","DOIUrl":"10.1016/j.oraloncology.2025.107789","url":null,"abstract":"<div><h3>Purpose</h3><div>Human papillomavirus (HPV) status is a key prognostic factor in head and neck squamous cell carcinoma (HNSCC), yet the precise immunological mechanisms and robust biomarkers for guiding personalized therapy remain elusive. This study aims to comprehensively delineate how HPV infection reprograms the tumor immune microenvironment (TIME) and to develop a novel prognostic model for stratifying patient outcomes and therapeutic responses.</div></div><div><h3>Methods</h3><div>Multi-omics data from TCGA and GEO databases were integrated. The immune landscape was compared between HPV⁺ and HPV^- HNSCC using bulk transcriptomic deconvolution and single-cell RNA sequencing (scRNA-seq) profiling. A prognostic risk signature was constructed from HPV-associated genes via LASSO-COX regression and validated in independent cohorts. The model was evaluated for its association with immune infiltration, tumor mutational burden, and drug sensitivity. Cellular communication networks were deciphered using CellChat. Hub genes expression was confirmed by immunohistochemistry (IHC).</div></div><div><h3>Results</h3><div>Single-cell profiling revealed that HPV⁺ tumors were characterized by an immunologically active microenvironment with increased infiltration and enhanced crosstalk of cytotoxic CD8⁺ T cells, helper CD4⁺ T cells, and B cells. In contrast, HPV^- tumors exhibited a stromal-rich, immunosuppressive niche. We developed and validated a prognostic model based on seven HPV-related genes (IER3, FHL2, MBOAT2, DSC3, IRAK3, RGMA, BARD1). This risk score robustly stratified patients into high- and low-risk groups with distinct overall survival (low-risk vs. high-risk, P &lt; 0.0001) and was an independent prognostic factor. The low-risk group, mirroring the HPV⁺ phenotype, demonstrated an activated immune milieu, higher expression of immune checkpoints (e.g., PD-1, CTLA-4), and was predicted to be more responsive to both chemotherapy and immunotherapy. Conversely, the high-risk group displayed a barren immune landscape, enriched in stromal and pro-tumorigenic pathways (e.g., MIF, COLLAGEN), and heightened sensitivity to specific targeted agents (e.g., Dasatinib). IHC validation confirmed the tumor-promotive role of hub genes (IER3, FHL2).</div></div><div><h3>Conclusion</h3><div>Our study leverages single-cell profiling to elucidate HPV-driven immunological remodeling in HNSCC. The derived prognostic signature effectively captures the essence of the TIME, serving as a reliable biomarker for predicting patient survival and informing precision therapy, potentially bridging the gap between HPV status and clinical decision-making.</div></div>","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"172 ","pages":"Article 107789"},"PeriodicalIF":3.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145600471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}