Search Results (240)

Recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) carries a poor prognosis; however, immune checkpoint inhibitors have emerged as critical therapeutic options. Although the KEYNOTE-048 trial established the efficacy of pembrolizumab, the population was restricted to major sites (e.g., oral cavity, oropharynx, hypopharynx, and larynx), excluding subsites such as the paranasal sinuses and nasopharynx. To evaluate outcomes in these populations, we conducted a multicenter retrospective study of 167 patients with R/M SCCHN treated with pembrolizumab between December 2019 and February 2022. The cohort comprised 127 patients with tumors in included sites and 27 in excluded subsites. Primary endpoints included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), and immune-related adverse events (irAEs). In the excluded subsite group, median OS was 15.2 months (1-year rate: 70.6%), and median PFS was 4.9 months (1-year rate: 21.2%). The ORR was 22.2% and the DCR was 59.3%. The incidence of irAEs was 25.9%, with Grade ≥ 3 events in 3.7%. Survival outcomes did not differ significantly from those in included sites. These findings suggest the potential efficacy and safety of pembrolizumab in subsites excluded from KEYNOTE-048, warranting validation in prospective trials. Full article

American tegumentary leishmaniasis (ATL) and other infectious granulomatous diseases (IGDs) may present with oral/oropharyngeal mucosal lesions (OOPML). IGD-OOPML can result from fungal, parasitic, or bacterial infections, and squamous cell carcinoma (SCC) represents the main differential diagnosis. ATL, other IGD, and SCC share overlapping clinical and epidemiological features, making diagnostic suspicion challenging. This study compared sociodemographic and clinical characteristics among ATL, other IGD, and SCC. Descriptive, comparative, and multivariable logistic regression analyses were performed. Among 7551 patients, 213 met inclusion criteria (83-SCC and 130-IGD). Except for smoking, which differed only between ATL and SCC, most IGD parameters were similar. Male patients predominated in all groups. SCC patients were significantly older (p < 0.001) and had a shorter median disease duration (p = 0.007). The presence of pain increased the odds of SCC-OOPML by 3.96 times (95% CI 1.97–12.51). SCC patients were more likely to present lesions in a single subsite, either the oral cavity or oropharynx. Painful, ulcerated, or exophytic lesions favored SCC diagnosis, whereas infiltrative, granular, or mulberry-like lesions, involvement of multiple subsites, or associated nasal and laryngeal lesions suggested IGDs. Although clinical differentiation remains difficult, these findings may support early diagnostic suspicion, prompt treatment, and reduced sequelae. Full article

This retrospective study provides an extensive evaluation of feline squamous cell carcinoma (SCC), comparing oral and cutaneous SCC, as well as different oral/cutaneous sites, with respect to sex, age, breed, and coat length. It was based on 4300 SCCs submitted to LABOKLIN GmbH & Co. KG from 2017 to 2023. No sex predisposition was identified. Affected cats were predominantly older (median age 13 years). SCC risk increased with age, although cats of very young age were also affected. Breed predispositions were not found. However, compared to non-pedigree cats, Persians, Norwegian Forest Cats, British Shorthairs (BSH), Chartreux, and Siamese cats showed a reduced risk, as did longhaired cats. The predominant sites were the oral cavity (41.0%, 1762/4300) and skin (35.8%, 1540/4300). Maine Coons, BSHs, Persians, and Norwegian Forest Cats, as well as longhaired cats, developed oral SCC more frequently. Intraoral, gingival (36.2%, 637/1762) and lingual (19.0%, 334/1762) SCC predominated. Common cutaneous sites included the pinnae (35.0%, 539/1540), unspecified head/neck regions (8.8%, 135/1540), and the nose (8.7%, 134/1540). Maine Coons and BSHs showed less auricular SCC; Sphynx had more on the trunk. These findings emphasise SCC as a crucial differential diagnosis for oral and cutaneous lesions, even in young cats. Full article

Oral squamous cell carcinoma (OSCC) is one of the most prevalent types of cancer in the oral cavity and head and neck region. Due to its location and psychological and social implications, early detection and treatment are very important. A liquid biopsy can be used to diagnose cancer by analyzing samples of bodily fluids, such as saliva, blood, or urine, for specific molecules released by tumor cells. The objective of this study was to evaluate the use of liquid biopsy in the diagnosis of oral squamous cell carcinoma. A systematic review was carried out, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO: CRD420251238037). Articles taken into consideration for the review were published before 30 September 2025. The search for manuscripts for the review was conducted using PubMed, Scopus, Google Scholar, and Cochrane databases. Forty-three articles were deemed eligible for inclusion in the systematic review. Key data extracted from the studies included authorship, publication date, study location, methodology, number of participants, and reported complications. Most of the analyzed biomarkers showed promising potential for future use in liquid biopsy for OSCC diagnosis. Tumor DNA and miRNA demonstrated the highest diagnostic accuracy. The standard approach to diagnosis and planning treatment relies on tumor biopsy and diagnostic imaging. Liquid biopsy may complement this process by enabling early detection in high-risk populations and monitoring response to therapy. As such, it serves as a prognostic factor or therapeutic target, successfully identifying disease recurrence. Full article

Background/Objectives: Oral squamous cell carcinoma (OSCC) remains a major therapeutic challenge due to treatment-related toxicity and impaired oral tissue regeneration. This study aimed to develop and characterize a novel biocomposite based on bioactive compounds from Ganoderma lucidum incorporated into marine collagen derived from Rhizostoma pulmo and to evaluate its physicochemical properties, antioxidant and antimicrobial activities, and in vitro antitumor potential in the oral cavity. Methods: Hydroalcoholic extracts of G. lucidum and pepsin-soluble collagen peptides from R. pulmo jellyfish were prepared and combined to obtain two hydrogel biocomposites with different component ratios. Chemical and structural characterization was performed using HPLC-DAD, SDS-PAGE, FT-IR, circular dichroism, and spectrophotometric assays. Antioxidant activity was assessed by DPPH radical scavenging and reducing power assays, while antimicrobial activity was evaluated against oral pathogens using diffusion and MIC methods. In vitro biological activity was investigated using MTT viability and scratch migration assays on human OSCC cell lines (SCC-9 and HSC-3). Results: The biocomposites preserved the structural integrity of type I collagen and incorporated polysaccharides and polyphenols from G. lucidum. The combined formulations showed enhanced antioxidant and antimicrobial activities compared with collagen alone. In vitro assays demonstrated dose- and time-dependent reductions in OSCC cell viability and delayed cell migration, with effects comparable to those of G. lucidum extract. Conclusions: The G. lucidum–R. pulmo biocomposite exhibits favorable physicochemical properties and demonstrates antioxidant, antimicrobial, and in vitro antitumor activity. These findings support its potential as a multifunctional biomaterial for further investigation as an adjunct approach in oral cancer-related applications. Full article

Background: A wide percentage (25–40%) of patients affected by head and neck squamous cell carcinoma (HNSCC) are over 70 years old, and they present with different characteristics if compared to younger patients. Elderly patients often receive less intensive, non-surgical, and non-multimodal treatments. Although age does not mean frailty, the elderly are at a higher risk of developing toxicity. In fact, several studies enrolling patients treated with cisplatin + radiotherapy (CISPLATIN + RT) or cetuximab + radiotherapy (Cet + RT) showed reduced efficacy over 65 years. Methods: We conducted a multicenter retrospective analysis in patients with Locally Advanced HNSCC aged over 65 years, who underwent Cet-RT, diagnosed in the period between 2017 and 2024. The primary endpoint was to describe Overall Survival (OS), the secondary endpoints were Progression Free Survival (PFS) and the percentage and type of Adverse Events (AEs). Patients received a geriatric assessment using the G8 questionnaire. Results: Data regarding Eighty-Two (82) patients were analyzed, median age was 74 years (range 65–84), most patients had oral cavity (26.8%) and laryngeal cancer (37.8%). Fifty-six point one (56.1%) of patients were smokers, and 17.1% reported alcohol consumption. All patients completed radiotherapy, and 80.5% of them developed AEs, which in 25.6% of cases were G3–4 toxicities. No relationship was found between G3–4 AEs and age (p = 0.596), G8score < 14 (p = 0.804), and smoking (p = 0.245)/drinking habits (p = 0.341). Median OS was 58 months, with a slightly non-significant positive trend in OS for patients who were non-smokers and those who did not develop G3–4 AEs (p = 0.786 and 0.799, respectively). Association between folliculitis and OS was statistically significant (p = 0.001). Conclusions: In elderly patients, Cet-RT represents a feasible, well-tolerated option, although further prospective studies are needed. Full article

Background: Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity, often necessitating extensive surgical resection. Such interventions may result in complex intraoral defects requiring immediate reconstruction to restore function and aesthetics. Objective: This case report highlights the surgical management of a patient with OSCC involving the tongue, floor of the mouth and mandibular ridge, reconstructed using a radial forearm free flap (RFFF). Case report: A 51-year-old male with a history of heavy smoking presented with a necrotic lesion affecting the left mandibular alveolar ridge, floor of the mouth, and tongue. Methods: Histopathological examination confirmed a diagnosis of moderately differentiated keratinizing OSCC (G2). After oncologic resection and selective neck dissection, the defect was reconstructed using an RFFF harvested from the left forearm. The facial artery and anterior jugular vein served as recipient vessels for microvascular anastomosis. A split-thickness skin graft (STSG) was used to close the donor site. Results: The postoperative course was generally favorable. Minor complications, including a localized hematoma and neck wound dehiscence, were conservatively managed. Functional outcomes such as oral intake and wrist mobility were successfully restored with rehabilitation. The RFFF provided durable, well-vascularized coverage over exposed mandibular bone, critical for minimizing the risk of osteoradionecrosis in the context of planned adjuvant radiotherapy. Conclusions: The radial forearm free flap remains a reliable reconstructive option for complex oral defects post-OSCC resection. Multidisciplinary collaboration and meticulous surgical technique are essential to achieve optimal oncologic, functional, and aesthetic outcomes. Full article

Mucins are a family of heavily glycosylated proteins that form the main organic component of the oral mucosal barrier complex. Transmembrane mucin 1 (tMUC1) is anchored at the superficial epithelial surface to provide a protective function. The interaction of tMUC1 with oral microbes provides nutrients and physicochemical protection, promotes adhesion, and increases the microbe residence time in the oral cavity. Mucin-degrading microorganisms in the consortia also offer some advantages to oral microbes. The high molecular weight of mucin glycoproteins is hard to study because of their size, complexity, and heterogeneity. This review discusses how mucin facilitates oral microbiome colonization and how mucin–microbial interactions influence the development of oral cancer, mainly oral squamous cell carcinoma. Full article

Head and neck cancers account for approximately 3.0% of all new cancer diagnoses. 18F-FDG PET/CT plays an important role in the initial staging of these cancers, especially in the detection of nodal and distant metastatic disease, outperforming conventional imaging techniques. It helps identify occult primary tumors and synchronous second primary malignancies. PET/CT findings can lead to treatment plan alterations both in surgical and primary or adjuvant chemoradiation plans. High negative predictive value at treatment response assessment provides valuable prognostic implications. PET/CT can predict outcomes at baseline and during or after treatment. Full article

Background/Objectives: Oral cavity squamous cell carcinoma (OCSCC) is an aggressive malignancy, often diagnosed at an advanced stage and with stagnant survival outcomes despite advances in surgical and oncologic management. Tumor-infiltrating lymphocytes (TILs) have been explored as potential prognostic markers in many solid tumors; however, their role in OCSCC remains under researched. This study aimed to assess the prognostic value of TILs in a cohort of patients with regionally advanced, p16-negative squamous cell carcinoma of all oral cavity subsites and to evaluate for any correlation of TILs and extranodal extension (ENE). Methods: A retrospective study was conducted on 103 consecutive patients treated with comprehensive surgical resection. TILs were quantified using the standardized method proposed by the International Immuno-Oncology Biomarkers Working Group. Statistical analyses evaluated associations with a comprehensive set of independent variables and survival endpoints. Results: High stromal infiltration at the invasive margin (>25%) was independently associated with significantly improved overall survival (HR 4.53, p = 0.005), disease-specific survival (HR 4.49, p = 0.008), and disease-free survival (HR 3.42, p = 0.025). Patients with ENE demonstrated lower TILs compared with ENE-negative patients (median 40% vs. 57.5%), a difference that reached statistical significance in both parametric and nonparametric testing (Welch’s t-test p = 0.032; Mann–Whitney U p = 0.030). Conclusions: TILs quantified by this standardized method are a reliable, independent prognostic biomarker in regionally advanced OCSCC of all subsites and are also associated with extranodal extension of regional metases. This study gives rationale for consideration of inclusion of TILS into future immunotherapeutic decision-making and further investigations of TIL-ENE association. Full article

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

Autoimmune polyendocrine syndrome type 1 (APS-1, APECED) is a rare monogenic disorder caused by biallelic AIRE mutations and is classically associated with chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and adrenal insufficiency. Apart from the autoimmune manifestations, APS-1 is associated with an increased risk of squamous cell carcinoma (SCC), particularly in the oral cavity and esophagus. However, the evidence is patchy and has not yet been systematically reviewed. We conducted a scoping review according to the PRISMA-ScR guidelines. Pub-Med, Scopus, and Web of Science were searched using the terms APS-1/APECED and malignancy until July 2025. Eligible studies reported on APS-1 patients with histologically confirmed head, neck or esophageal cancer. Clinical, pathological, genetic and outcome data were summarized narratively. Nine publications described 19 APS-1 patients with 26 tumors. The mean age at cancer diagnosis was 35 years, with a latency period of ~24 years from the onset of APS-1. Tumors occurred most frequently in the oral cavity (65%), followed by the lip (19%) and esophagus (15%). In 96% of cases, the tumors were SCC. The grade of the tumor varied, and almost half of the cases were diagnosed at an advanced stage. As far as reported, the usual risk factors were not particularly pronounced; many patients did not smoke or drink alcohol. The main treatment consisted of surgery, often in combination with radiotherapy or chemoradiotherapy, alongside long-term antifungal therapy. Despite the multimodal treatment, outcomes were poor: the overall survival rate was ~50%, with recurrence occurring in 38% of cases and a second primary tumor in 26%. A further 14 cases were reported from another Italian cohort, which together with the national cohort dana suggest a risk of approximately ~10% with APS-1; however, the true lifetime risk remains uncertain. Head and neck malignancies in APS-1 occur early, often without classic risk factors, and have a high recurrence and mortality rate. Lifelong surveillance, antifungal stewardship and increased clinical awareness, ideally as part of multidisciplinary treatment pathways, are critical to improving outcomes in this rare but high-risk population. Full article

Background/Objectives: The deep circumflex iliac artery (DCIA) free flap with internal abdominal oblique muscle (IAOM) is a well-known method of reconstruction used in cases of oral cavity neoplasms. Because the IAOM can be insufficient for extensive defects after removal of advanced carcinomas of the tongue, floor of the mouth, or gingiva, the additional preparation of a perforator-supported external abdominal oblique (EAOM) muscle flap can be useful. The aim of this study was to introduce the use of a DCIA flap with an IAOM and EAOM island in the reconstruction of oral cavity compound defects. Methods: A retrospective analysis was performed involving eight patients who underwent reconstruction using a DCIA free flap with IAOM and perforator-supported EAOM island. Patients underwent the operation between June 2021 and February 2025 in the Department of Maxillofacial Surgery of the Rydygier Hospital in Kraków, Poland. Results: A group of eight patients underwent an operation due to squamous cell carcinoma of the oral cavity. The most common primary subsite of disease was the floor of the mouth (n = 4, 50%), followed by the lower gingiva (n = 2, 25%) and retromolar area (n = 2, 25%). All patients required resection involving part of the mandible, the floor of the mouth, and part of the tongue simultaneously with reconstruction using a DCIA free flap with IAOM and perforator-supported EAOM island. Osteotomies were performed in two flaps (one single osteotomy, one double osteotomy). Reconstruction was successfully performed in seven out of eight patients (overall success rate 88%). Conclusions: The DCIA free flap with IAOM and perforator-supported EAOM flap is a reliable method for compound soft tissue and bone defects in maxillofacial reconstruction. The use of IAOM and EAOM can be helpful in cases of three-dimensional soft tissue defects of the lower gingiva, the floor of the mouth, and the tongue. The lower gingiva and floor of the mouth can be reconstructed with IAOM, while the more mobile part of the tongue can be reconstructed with a perforator-supported EAOM island. Full article

Background/Objectives: Human papillomavirus (HPV) is a known etiologic agent in oropharyngeal cancers, but its role in oral cavity squamous cell carcinoma (OCSCC) remains unclear. This systematic review and meta-analysis aimed to estimate the global prevalence of HPV in OCSCC and explore variation by clinicodemographic and tumor characteristics. Methods: We systematically searched multiple databases for studies reporting HPV prevalence in OCSCC. Pooled prevalence estimates were calculated, and subgroup analyses examined differences by age, gender, cancer stage, anatomical site, histologic subtype, region, and HPV type (HPV-16 and HPV-18). Heterogeneity and publication bias were assessed using standard meta-analytic techniques. Results: A total of 122 studies involving 16,311 patients were included. The pooled HPV prevalence in OCSCC was 25.8% (95% CI: 20.4–31.2), with HPV-16 and HPV-18 detected in 52.4% and 30.3% of positive cases, respectively. Prevalence varied geographically, from 73% in Singapore to 7.7% in South Korea. Younger patients (<40 years) had higher HPV positivity (29.7%) than older patients (>70 years, 23.8%). Early-stage cancers (stage I) showed higher HPV prevalence (41.8%) than advanced-stage cancers (stage IV, 10.4%). Verrucous carcinoma had the highest HPV positivity (34.1%), and moderately differentiated tumors the lowest (23.4%). HPV prevalence was highest in the lower alveolus (29.5%) and lips (25%), and lowest in the upper gingiva (3.9%). Conclusions: HPV prevalence in OCSCC demonstrates significant heterogeneity across regions and clinical subgroups. These findings emphasize the need for standardized diagnostic approaches and further research into the role of HPV in OCSCC pathogenesis and treatment. Full article

Histopathological grading of oral squamous cell carcinoma is currently based on differentiation of cells, while additional histological parameters, such as the tumor–stroma ratio (TSR), tumor budding (TB), or the combined TSR/tumor budding model could better assess tumor biological behavior and monitoring of patients. Background/Objectives: To integrate risk factors associated with tumor progression: the TSR, TB and TSR/tumor budding model, whose prognostic significance in oral cancer has not yet been evaluated. Methods: An observational cohort retrospective study assembled according to STROBE guidelines on histological materials from 196 patients with invasive squamous cell carcinoma of the oral cavity. The goal of the analysis was to evaluate the association between the tumor stroma ratio, tumor budding, and the combined model of TSR/TB with the clinical and pathologic features of patients with squamous cell carcinoma of the oral cavity and to determine the prognostic value of this model in relation to disease-free survival (DFS) Results: The analysis did not show that the tumor stroma ratio (TSR), tumor budding, and the combined model of TSR/tumor budding were statistically significantly associated with the occurrence of metastatic disease at the start of treatment or during postoperative follow-up, but confirmed the value of depth-of-invasion (DOI) as a negative prognostic factor (HR 15.3, p < 0.001). Conclusions: The TSR, TB, and the combined TSR/TB model were not found to be statistically significant predictors for the disease progression in the Cox regression survival analysis but were found to have a significant correlation with known negative prognostic factors: DOI, neural invasion, and T category. Full article