Oral Cancer: The Latest Advances in Clinical and Basic Research (Second Edition)

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Clinical Research of Cancer".

Deadline for manuscript submissions: 31 January 2026 | Viewed by 2468

Special Issue Editors


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Guest Editor
Department of Oral and Maxillofacial Surgery, Institute of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
Interests: oral cancer; orthognathic surgery; cleft lip and palate; implantology; traumatology
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Oral and Maxillofacial Surgery, Institute of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
Interests: signal transduction; oral diseases; oral surgery; cancer biology apoptosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The number of patients with oral cancer has been growing in recent years. Generally speaking, diagnosis at a low stage is beneficial for a good prognosis, and recently, a new molecular target drug and immune checkpoint inhibitor were found to prolong survival after recurrence and distant metastasis.

Although treatment results can be improved through chemoradiotherapy and surgery with wide resection and reconstruction, some patients suffer from poor prognosis.  We must always consider the appropriateness of new treatments and conduct basic research based on each patient's cancer prognosis.

In this Special Issue, we welcome the submission of original research articles and reviews on the latest advances in clinical and basic research related to oral cancer.

We look forward to receiving your contributions.

Dr. Kenji Yamagata
Dr. Fumihiko Uchida
Guest Editors

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Keywords

  • oral cancer
  • clinical research
  • basic research
  • surgery
  • radiotherapy
  • chemotherapy
  • molecular biology
  • immune checkpoint inhibitor

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Published Papers (4 papers)

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Research

11 pages, 578 KB  
Article
Sentinel Lymph Node Biopsy Versus Elective Neck Dissection in Carcinoma of the Tongue and Floor of the Mouth
by Carolin Naegeli-Pullankavumkal, Tamara Manser, Tarun Mehra, Niels Jan Rupp, Thomas Gander, Martin W. Huellner and Martin Lanzer
Cancers 2025, 17(19), 3098; https://doi.org/10.3390/cancers17193098 - 23 Sep 2025
Viewed by 66
Abstract
Background/Objectives: Lymph node metastases represent the most important prognostic factor for survival in patients with localized squamous cell carcinoma (SCC) of the oral cavity. In patients with carcinoma of the tongue or floor of the mouth, elective neck dissection (END) has been the [...] Read more.
Background/Objectives: Lymph node metastases represent the most important prognostic factor for survival in patients with localized squamous cell carcinoma (SCC) of the oral cavity. In patients with carcinoma of the tongue or floor of the mouth, elective neck dissection (END) has been the standard of care, but it has been replaced at many centers by sentinel lymph node biopsy (SLNB). This study’s purpose was to measure and compare recurrence rates between END and SLNB in patients with early SCC of the oral cavity. Methods: Patients were included in this retrospective monocenter cohort study, performed at the University Hospital of Zürich, if they underwent either END or SLNB for oral squamous cell carcinoma (OSCC) of the tongue or floor of the mouth between January 2008 and December 2018. Only patients with early-stage tumors and a clinically negative neck (T1 or T2; cN0) who had a follow-up period of at least 5 years were included. Patients with a T3 or T4 tumor or a clinically positive neck were excluded, as were those who previously underwent therapy for another head and neck carcinoma. The predictor variable was the surgical treatment used, with subjects divided into two groups: END and SLNB. The main outcome variable was the time to recurrent disease, defined as the time between the primary surgical treatment and the diagnosis of recurrence. The covariates were primary tumor location, pT status, pN status, histopathological grade and postoperative radiotherapy. We used descriptive analysis, univariate analysis and the logrank test, with a p-value < 0.05 considered statistically significant. We deliberately refrained from multivariate analysis due to insignificant statistical results in the univariate analysis. Results: In total, 82 patients (46 male, 36 female; median age at the time of surgery: 58.9 years) were included, with a median observation period of 4.3 years. The main primary tumor location was the floor of the mouth (62.2%). The SLNB cohort had smaller primary tumors in comparison to the END cohort (20% vs. 37% pT2, respectively). Furthermore, pN+ disease was more prevalent in the END group in comparison to the SLNB group (81.8% vs. 74.1% pN0, respectively). Recurrence-free survival was not significantly different between the two groups. Subgroup analysis demonstrated a higher risk of recurrent disease in pN+ groups undergoing SLNB compared to those undergoing END. Conclusions: We demonstrate that SLNB is a useful tool for assessing lymph nodes of the neck. In cases of pN+ necks after SLNB and subsequent neck dissection, patients need to be closely followed up with due to the risk of recurrent disease. Full article
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22 pages, 2763 KB  
Article
PIAS1 Shapes a Tumor-Suppressive Microenvironment by Suppressing Immune Evasion in Oral Squamous Cell Carcinoma
by Parisa Ghahremanifard, Jinsu An, Ayan Chanda, Angela M. Y. Chan, Steven C. Nakoneshny, T. Wayne Matthews, Shamir P. Chandarana, Robert D. Hart, Martin D. Hyrcza, Joseph C. Dort, Shirin Bonni and Pinaki Bose
Cancers 2025, 17(17), 2905; https://doi.org/10.3390/cancers17172905 - 4 Sep 2025
Viewed by 656
Abstract
Background: The SUMO E3 ligase PIAS1 (Protein Inhibitor of Activated STAT1) regulates pathways such as TGFβ signaling and has been implicated in multiple cancers. However, its role in the tumor microenvironment (TME), particularly in non-malignant stromal and immune cells, remains poorly understood. This [...] Read more.
Background: The SUMO E3 ligase PIAS1 (Protein Inhibitor of Activated STAT1) regulates pathways such as TGFβ signaling and has been implicated in multiple cancers. However, its role in the tumor microenvironment (TME), particularly in non-malignant stromal and immune cells, remains poorly understood. This study aimed to characterize the expression and functional relevance of PIAS1 within the TME of oral squamous cell carcinoma (OSCC). Methods: PIAS1 protein expression was assessed via immunohistochemistry (IHC) on OSCC tissue microarrays. Single-cell RNA-sequencing (scRNA-seq) datasets from OSCC tumors and normal tissues were analyzed to map cell-type-specific PIAS1 expression. Downstream effects were evaluated using differential gene expression, Ingenuity Pathway Analysis (IPA), gene set enrichment analysis (GSEA), and cell–cell communication inference. Results: IHC analysis revealed that higher stromal PIAS1 levels correlated with improved survival. scRNA-seq analysis showed an increase in the proportion of PIAS1-expressing cells across most stromal and immune cell populations within OSCC-derived tumors compared to their counterparts in adjacent normal tissue. However, when comparing PIAS1-positive cells, expression levels were significantly reduced in cancer cells, CAFs, TAMs, T cells, and endothelial cells within the TME. PIAS1-positive CAFs, TAMs, and T cells exhibited activation of apoptotic and tumor-suppressive pathways, while PIAS1-negative counterparts showed enrichment of immunosuppressive signaling and immune checkpoint expression. Cell–cell communication analyses indicated that PIAS1 fosters an immune-activated TME by promoting pro-inflammatory signaling, M1-like TAM polarization, and T cell activation. Conclusions: PIAS1 expression in stromal and immune cells is associated with tumor-suppressive reprogramming of the OSCC microenvironment. These findings position PIAS1 as a potential modulator of anti-tumor immunity and candidate target for therapeutic intervention. Full article
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16 pages, 555 KB  
Article
Surgery for T1/2N0 Oropharyngeal Carcinoma Is a Better Treatment Option than Radiotherapy—A Long-Term Follow-Up Study from a Single Japanese High-Volume Cancer Center
by Masahiro Rokugo, Takeshi Shinozaki, Ryo Ishii, Yusuke Ito, Shingo Sakashita, Genichiro Ishii, Takenori Ogawa, Yukio Katori, Kazuto Matsuura and Ryuichi Hayashi
Cancers 2025, 17(11), 1862; https://doi.org/10.3390/cancers17111862 - 31 May 2025
Cited by 1 | Viewed by 779
Abstract
Background: The proportion of oropharyngeal cancers, especially those that are HPV-associated, is increasing, and both surgery and RT are considered effective initial treatments for early-stage oropharyngeal cancer, regardless of p16 status. However, there are still many unknowns regarding the long-term prognosis after initial [...] Read more.
Background: The proportion of oropharyngeal cancers, especially those that are HPV-associated, is increasing, and both surgery and RT are considered effective initial treatments for early-stage oropharyngeal cancer, regardless of p16 status. However, there are still many unknowns regarding the long-term prognosis after initial treatment, the incidence rate of multiple cancers, and the relationship with p16 status. Methods: We retrospectively analyzed 94 cases of T1/2N0 oropharyngeal squamous cell carcinomas (OPSCCs) treated with surgery or radiotherapy between January 2000 and December 2012 at the Japan National Cancer Center Hospital East. The study items include long-term prognosis, p16 status, and the proportion of patients with multiple cancers after receiving treatment for oropharyngeal cancer. Results: The patients included 80 men and 14 women, whose median age was 68 (35–92). The median follow-up time was 2131 days. T1N0 cancer was observed in 34 patients and T2N0 in 60 patients. Surgery was performed for 74 patients, and radiotherapy for 20 patients. Of the patients who underwent surgery, 57 underwent transoral surgery, and 17 underwent pharyngectomy via transcervical approach. Nine of the 17 patients underwent partial pharyngectomy with free-flap reconstruction. The 5-year overall survival rates were 74.9 and 51.0% (p = 0.035); the 5-year disease-specific survival rates were 86.0 and 64.5% (p = 0.116); and the 5-year local control rates, 76.5 and 59.1% (p = 0.106) for the surgery and radiotherapy groups, respectively. Furthermore, 54 (57.4%) of the 94 cases suffered from multiple primary cancers, of which 29 (30.9%) were in the head and neck region and all were metachronous. Conclusions: Initial surgery for T1/2N0 OPSCCs is a proper therapeutic strategy considering the better overall survival and high incidence of multiple primary cancers. Full article
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15 pages, 1351 KB  
Article
The Association Between Skeletal Muscle Mass and Surgical Site Infection and Prognosis in Patients Undergoing Free Flap Reconstructive Surgery for Oral Squamous Cell Carcinoma: A Single-Center, Retrospective Study
by Atsuro Noguchi, Kenji Yamagata, Satoshi Fukuzawa, Kaoru Sasaki, Shohei Takaoka, Fumihiko Uchida, Naomi Ishibashi-Kanno, Mitsuru Sekido and Hiroki Bukawa
Cancers 2025, 17(10), 1729; https://doi.org/10.3390/cancers17101729 - 21 May 2025
Viewed by 529
Abstract
Background/Objectives: Local and systemic factors, including nutritional status, influence the prognosis of oral squamous cell carcinoma (OSCC). Skeletal muscle mass (SMM) loss is a poor prognostic factor in older patients and those with cancer. Herein, we examined the SMM index (SMI), rates of [...] Read more.
Background/Objectives: Local and systemic factors, including nutritional status, influence the prognosis of oral squamous cell carcinoma (OSCC). Skeletal muscle mass (SMM) loss is a poor prognostic factor in older patients and those with cancer. Herein, we examined the SMM index (SMI), rates of surgical site infection (SSI), and prognosis of 92 patients (59 males and 33 females) who underwent resection and free flap reconstructive surgery (FFRS) between 2013 and 2021. Methods: Preoperative computed tomography was performed to measure SMM at L3. The median SMI was 45.94 and 38.03 cm2/m2 in males and females, respectively. Patients were classified into low and high SMI groups based on median SMI, and overall survival (OS) was analyzed. Results: Overall, 47 (51.1%) and 45 (48.9%) patients had low and high SMIs, respectively. SSI occurred in 11 (12.0%) patients; wound dehiscence and delayed wound healing were observed in 22 (23.9%). SSI rates were not significantly different between the low and high SMI groups. Conversely, OS was significantly associated with age, pathological N (pN), extranodal extension (ENE), and SMI (high, 81.1%; low, 60.2%). Univariate analyses revealed significant associations between OS and age (≥65 vs. <65 years), SMI (low vs. high), pN (present vs. none), ENE (present vs. none), and albumin (<4.0 vs. ≥4.0 mg/dL). Cox multivariate analysis included SMI (low vs. high; hazard ratio [HR]: 2.339, 95% confidence interval [CI]: 1.008–5.429; p = 0.015) and ENE (present vs. none; HR: 7.727, 95% CI: 3.083–19.368; p < 0.001). Conclusions: SMI and ENE were identified as independent predictive factors of OS in patients with OSCC undergoing FFRS. Full article
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