Automatic delineation and detection of the primary tumour (GTVp) and lymph nodes (GTVn) using PET and CT in head and neck cancer and recurrence-free survival prediction can be useful for diagnosis and patient risk stratification. We used data from nine different centres, with 524 and 359 cases used for training and testing, respectively. We utilised posterior sampling of the weight space in the proposed segmentation model to estimate the uncertainty for false positive reduction. We explored the prognostic potential of radiomics features extracted from the predicted GTVp and GTVn in PET and CT for recurrence-free survival prediction and used SHAP analysis for explainability. We evaluated the bias of models with respect to age, gender, chemotherapy, HPV status, and lesion size. We achieved an aggregate Dice score of 0.774 and 0.760 on the test set for GTVp and GTVn, respectively. We observed a per image false positive reduction of 19.5% and 7.14% using the uncertainty threshold for GTVp and GTVn, respectively. Radiomics features extracted from GTVn in PET and from both GTVp and GTVn in CT are the most prognostic, and our model achieves a C-index of 0.672 on the test set. Our framework incorporates uncertainty estimation, fairness, and explainability, demonstrating the potential for accurate detection and risk stratification. Full article

The current study aims to profile sarcopenic condition (both at baseline and developed during treatment) in oropharyngeal carcinoma (OPC) patients treated with curative radiotherapy (RT) +/− chemotherapy and to evaluate its impact on oncological outcomes and toxicity. A total of 116 patients were included in this retrospective single-center study. Sarcopenia assessment at baseline and at 50 Gy re-evaluation CT was obtained from two different methodologies: (i) the L3-skeletal muscle index (SMI) derived from the contouring of the cross-sectional area (CSA) of the masticatory muscles (CSA-MM); and (ii) the paravertebral and sternocleidomastoid muscles at the level of the third cervical vertebra (CSA-C3). Based on L3-SMI from CSA-MM, developing sarcopenic condition during RT (on-RT sarcopenia) was associated with worse progression-free survival (PFS) (p = 0.03) on multivariable analysis and a trend of correlation with overall survival (OS) was also evident (p = 0.05). According to L3-SMI derived from CSA-C3, on-RT sarcopenia was associated with worse PFS (p = 0.0096) and OS (p = 0.013) on univariate analysis; these associations were not confirmed on multivariable analysis. A significant association was reported between becoming on-RT sarcopenia and low baseline haemoglobin (p = 0.03) and the activation of nutritional counselling (p = 0.02). No significant associations were found between sarcopenia and worse RT toxicity. Our data suggest that the implementation of prompt nutritional support to prevent the onset of sarcopenia during RT could improve oncological outcomes in OPC setting. Full article

In this study, through a cohort study of 10 million people, we investigated the association between estimated glomerular filtration rate (eGFR) and head and neck cancer (HNC) incidence. This is an observational cohort study using data from the national health claims database established by the Korean National Health Insurance Service (NHIS). We selected 9,598,085 participants older than 20 years who had undergone health checkups in 2009. A health checkup involves the history of any diseases, current health status, and results of several physical and blood exams including eGFR. We investigated the presence of HNC diagnosis in their national health insurance data from 2010 to 2018. Of the 9,598,085 participants, 10,732 had been newly diagnosed with HNC in the 9-year follow-up. In the multivariate Cox proportional hazard model, participants with elevated eGFR were associated with a risk of HNC incidence (HR = 1.129; 95% CI = 1.075–1.186 for eGFR = 90–104 mL/min/1.73 m² and HR = 1.129; 95% CI = 1.076–1.194 for eGFR ≥ 105 mL/min/1.73 m²) compared with those with eGFR 60–89 mL/min/1.73 m². Among HNC, the incidences of oral cavity, oropharyngeal, hypopharyngeal, and laryngeal cancers were significantly increased in the elevated eGFR group. According to the subgroup analysis, participants with eGFR ≥ 60 mL/min/1.73 m² were correlated with risk of HNC incidence in middle age, non/mild drinker, low BMI, no diabetes, and no hypertension patients compared with those with eGFR < 60 mL/min/1.73 m². Elevated eGFR was associated with the risk of some type of HNC, even in individuals with adjusted hypertension and diabetes without chronic diseases. The results of this study have implications for etiological investigations and preventive strategies. Full article

One of the most important challenges in laryngological practice is the early diagnosis of laryngeal cancer. Detection of non-vibrating areas affected by neoplastic lesions of the vocal folds can be crucial in the recognition of early cancerogenous infiltration. Glottal pathologies associated with abnormal vibration patterns of the vocal folds can be detected and quantified using High-speed Videolaryngoscopy (HSV), also in subjects with severe voice disorders, and analyzed with the aid of computer image processing procedures. We present a method that enables the assessment of vocal fold pathologies with the use of HSV. The calculated laryngotopographic (LTG) maps of the vocal folds based on HSV allowed for a detailed characterization of vibration patterns and abnormalities in different regions of the vocal folds. We verified our methods with HSV recordings from 31 subjects with a normophonic voice and benign and malignant vocal fold lesions. We proposed the novel Stiffness Asymmetry Index (SAI) to differentiate between early glottis cancer (SAI = 0.65 ± 0.18) and benign vocal fold masses (SAI = 0.16 ± 0.13). Our results showed that these glottal pathologies might be noninvasively distinguished prior to histopathological examination. However, this needs to be confirmed by further research on larger groups of benign and malignant laryngeal lesions. Full article

The polypeptide N-Acetylgalactosaminyltransferase 14 (GALNT14) rs9679162 and mRNA expression were associated with treatment outcome in various cancers. However, the relation of GALNT14 and head and neck cancer were nuclear. A total of 199 patients with head and neck squamous cell carcinoma (HNSCC) were collected in this study, including oral SCC (OSCC), oropharyngeal SCC (OPSCC), laryngeal SCC (LSCC), and others. The DNA and RNA of cancer tissues were extracted using the TRI Reagent method. The rs9679162 was analyzed using polymerase chain reaction (PCR) and sequencing methods in 199 DNA specimens, and the mRNA expression was analyzed using quantitative reverse transcription PCR (RT-qPCR) methods in 68 paired RNA specimens of non-cancerous matched tissues (NCMT) and tumor tissues. The results showed that the genotype of TT, TG, and GG appeared at 30%, 44%, and 26%, respectively. Non-TT genotype or G alleotype were associated with alcohol, betel nut, and cigarette using among patients with OSCC, and it also affected the treatment and survival of patients with OSCC and LSCC. High GALNT14 mRNA expression levels increased lymphatic metastasis of patients with HNSCC, and treatment and survival in patients with OPSCC. Overall, the GALNT14-rs9679162 genotype and mRNA expression level can be used as indicators of HNSCC treatment prognosis. Full article

Background: Postcricoid carcinoma is a rare but aggressive type of hypopharyngeal carcinoma with poor prognosis and high mortality; thus, it is indispensable to investigate the surgical efficacy and multimodal strategies. Methods: This retrospective study included postcricoid carcinoma patients undergoing surgical resection from 2008 to 2022. Treatment methods and clinical characteristics were analyzed to evaluate prognostic factors for oncological outcomes. Results: Of 72 patients, 13 cases were in the I–II stage and 59 in the III–IV stage. The overall survival (OS) was 50.0%; the laryngeal function preservation rate was 69.4%. Univariate analysis found that high mortality was associated with low tumor differentiation, lymph node metastasis, neck recurrence, and smoke history via log-rank test (p < 0.05); postoperative radiotherapy (RT) remained positive in OS (p = 0.04). The multivariable model further revealed that lymph node metastasis was a dominant determinant after accounting for covariates (HR 1.75; 95% CI 0.85–3.59). The data also indicated that neoadjuvant chemotherapy (NAC) and tumor diameter ≤ 2 cm were causing lower rates of pharyngeal fistula and locoregional relapse. Conclusions: Surgeons should emphasize high-risk features and optimize individualized surgical procedures for postcricoid carcinoma patients. Combined with multimodal treatments, it is feasible to reconstruct laryngeal function and lessen postoperative morbidities in advanced patients. Full article

Background: This study was carried out to observe the upregulation of the free β-subunit of human chorionic gonadotropin (hCGβ) and its prognostic significance in human papillomavirus (HPV)-positive and HPV-negative oropharyngeal squamous cell carcinoma (OPSCC). Materials and methods: A total of 90 patients with OPSCC treated with curative intent at the Helsinki University Hospital (HUS), Helsinki, Finland, during 2012–2016 were included. Serum samples were collected prospectively, and their hCGβ concentrations (S-hCGβ) were determined by an immunofluorometric assay. The expression of hCGβ in tumor tissues was defined by immunohistochemistry (IHC). HPV determination was performed by combining p16-INK4 IHC and HPV DNA PCR genotyping. Overall survival (OS) and disease-specific survival (DSS) were used as survival endpoints. Results: S-hCGβ positivity correlated with poor OS in the whole patient cohort (p < 0.001) and in patients with HPV-negative OPSCC (p < 0.001). A significant correlation was seen between S-hCGβ and poor DSS in the whole cohort (p < 0.001) and in patients with HPV-negative OPSCC (p = 0.007). In a multivariable analysis, S-hCGβ was associated with poor DSS. Of the clinical characteristics, higher cancer stage and grade were associated with S-hCGβ positivity. No statistically significant correlation with tissue positivity of hCGβ was seen in these analyses. Conclusion: S-hCGβ may be a potential independent factor indicating poor prognosis, notably in HPV-negative OPSCC. Full article

Background: Radiotherapy plays an essential role in the treatment of oropharyngeal carcinoma (OPC). The aim of this study was to assess and compare the nutritional status (NS) of patients with HPV-related (HPV+) and non-HPV-related (HPV-) OPC before and after radiotherapy (RT) or chemoradiotherapy (CRT). Methods: The analysis included 127 patients with OPC who underwent radiotherapy (RT) alone, or in combination with chemotherapy (CRT), in the I Radiation and Clinical Oncology Department of Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, Poland. Patients were divided according to HPV status. Confirmation of HPV etiology was obtained from FFPE (formalin-fixed, paraffin-embedded) tissue material and/or extracellular circulating HPV DNA. Basic anthropometric and biochemical parameters before and after RT/CRT were compared between the HPV- and HPV+ groups. The effect of NS on survival was also analyzed. Results: In both groups, a significant decrease in all analyzed nutritional parameters was noted after RT/CRT (p < 0.01). CRT caused significant weight loss and decreases in BMI, albumin, total lymphocyte count (TLC), and hemoglobin concentration, as well as an increase in the Nutritional Risk Score (NRS) 2002, in HPV- and HPV+ patients. A significant decrease in prealbumin levels after CRT was noted only in HPV+ patients. RT caused a significant decrease in hemoglobin concentration and TLC in HPV- patients. There were no significant differences regarding other nutritional parameters after RT in either group. RT did not have negative impact on body mass index (BMI), weight, NRS, CRP, Alb, Prealb, or PNI. Overall survival (OS) and disease-free survival (DFS) were significantly better in patients with a higher BMI in the HPV- group (OS, p = 0.011; DFS, p = 0.028); DFS was significantly better in patients with C-reactive protein (CRP) < 3.5 g/dL in the HPV- (p = 0.021) and HPV+ (p = 0.018) groups, and with total lymphocyte count (TLC) >1.28/mm³ in the HPV+ group (p = 0.014). Higher NRS 2002 was an independent adverse prognostic factor for OS and DFS in HPV-, but not in the HPV+ group. Kaplan–Meier analysis showed that both OS and DFS were significantly better in HPV- patients with lower NRS 2002 scores. However, this relationship was not observed in the HPV+ group. Conclusions: Regardless of HPV status, patients with OPC can develop malnutrition during RT/CRT. Therefore, nutritional support during RT/CRT is required in patients with HPV- and HPV+ OPC. Full article

(1) Background: NPC patients with de novo distant metastasis appears to be a heterogeneous group who demonstrate a wide range of survival, as suggested by growing evidence. Nevertheless, the current 8th edition of TNM staging (TNM-8) grouping all these patients into the M1 category is not able to identify their survival differences. We sought to identify any anatomic and non-anatomic subgroups in this study. (2) Methods: Sixty-nine patients with treatment-naive de novo M1 NPC (training cohort) were prospectively recruited from 2007 to 2018. We performed univariable and multivariable analyses (UVA and MVA) to explore anatomic distant metastasis factors, which were significantly prognostic of overall survival (OS). Recursive partitioning analysis (RPA) with the incorporation of significant factors from MVA was then performed to derive a new set of RPA stage groups with OS segregation (Set 1 Anatomic-RPA stage groups); another run of MVA was performed with the addition of pre-treatment plasma EBV DNA. A second-round RPA with significant prognostic factors of OS identified in this round of MVA was performed again to derive another set of stage groups (Set 2 Prognostic-RPA stage groups). Both sets were then validated externally with an independent validation cohort of 67 patients with distant relapses of their initially non-metastatic NPC (rM1) after radical treatment. The performance of models in survival segregation was evaluated by the Akaike information criterion (AIC) and concordance index (C-index) under 1000 bootstrapping samples for the validation cohort; (3) Results: The 3-year OS and median follow-up in the training cohort were 36.0% and 17.8 months, respectively. Co-existence of liver-bone metastases was the only significant prognostic factor of OS in the first round UVA and MVA. Set 1 RPA based on anatomic factors that subdivide the M1 category into two groups: M1a (absence of co-existing liver-bone metastases; median OS 28.1 months) and M1b (co-existing liver-bone metastases; median OS 19.2 months, p = 0.023). When pre-treatment plasma EBV DNA was also added, it became the only significant prognostic factor in UVA (p = 0.001) and MVA (p = 0.015), while co-existing liver-bone metastases was only significant in UVA. Set 2 RPA with the incorporation of pre-treatment plasma EBV DNA yielded good segregation (M1a: EBV DNA ≤ 2500 copies/mL and M1b: EBV DNA > 2500 copies/mL; median OS 44.2 and 19.7 months, respectively, p < 0.001). Set 2 Prognostic-RPA groups (AIC: 228.1 [95% CI: 194.8–251.8] is superior to Set 1 Anatomic-RPA groups (AIC: 278.5 [254.6–301.2]) in the OS prediction (p < 0.001). Set 2 RPA groups (C-index 0.59 [95% CI: 0.54–0.67]) also performed better prediction agreement in the validation cohort (vs. Set 1: C-index 0.47 [95% CI: 0.41–0.53]) (p < 0.001); (4) Conclusions: Our Anatomic-RPA stage groups yielded good segregation for de novo M1 NPC, and prognostication was further improved by incorporating plasma EBV DNA. These new RPA stage groups for M1 NPC can be applied to countries/regions regardless of whether reliable and sensitive plasma EBV DNA assays are available or not. Full article

Background: This study aimed to assess the association of 18F-Fluorodeoxyglucose positron-emission-tomography (18F-FDG/PET) and DWI imaging parameters from a primary tumor and their correlations with clinicopathological factors. Methods: We retrospectively analyzed primary tumors in 71 patients with proven HNC. Primary tumor radiological parameters: DWI and FDG, as well as pathological characteristics were analyzed. Spearman correlation coefficient was used to assess the correlation between DWI and FDG parameters, ANOVA or Kruskal–Wallis, independent sample t-test, Mann–Whitney test, and multiple regression were performed on the clinicopathological features that may affect the 18F- FDG and apparent-diffusion coefficient (ADC) of the tumor. Results: No significant correlations were observed between DWI and any of the 18F-FDG parameters (p > 0.05). SUVmax correlated with N-stages (p = 0.023), TLG and MTV correlated with T-stages (p = 0.006 and p = 0.001), and ADC correlated with tumor grades (p = 0.05). SUVmax was able to differentiate between N+ and N− groups (p = 0.004). Conclusions: Our results revealed a non-significant correlation between the FDG-PET and ADC-MR parameters. FDG-PET-based glucose metabolic and DWI-MR-derived cellularity data may represent different biological aspects of HNC. Full article

(1) Background: SMARCB1 (INI-1)-deficient sinonasal carcinoma is a rare sinonasal malignancy; since its discovery and description in 2014, less than 200 cases have been identified. It is almost impossible to perform randomized-controlled trials on novel therapy to improve treatment outcomes in view of its rarity. We performed a systematic review of all the published case reports/series and included our patients for survival analysis. (2) Methods: In this systematic review, we searched from PubMed-MEDLINE, EMBASE, Scopus, Cochrane Library, CINAHL, and Google Scholar for individual patient data to identify and retrieve all reported SMARCB1-deficient sinonasal carcinoma. Clarification on treatment details and the most updated survival outcomes from all authors of the published case reports/series were attempted. Survival analysis for overall survival (OS) and identification of OS prognostic factors were performed. This systematic review was registered with PROSPERO (CRD42022306671). (3) Results: A total of 67 publications were identified from the systematic review and literature search. After excluding other ineligible and duplicated publications, 192 patients reported were considered appropriate for further review. After excluding duplicates and patients with incomplete pretreatment details and survival outcomes, 120 patients were identified to have a complete set of data including baseline demographics, treatment details, and survival outcomes. Together with 8 patients treated in our institution, 128 patients were included into survival analysis. After a median follow up of 17.5 months (range 0.3–149.0), 50 (46.3%) patients died. The 1-year, 2-year and 3-year OS rates were 84.3% (95% CI % 77.6–91.0), 62.9% (95% CI 53.1–72.7), and 51.8% (95% CI 40.8–62.8), respectively, and the median OS was 39.0 months (95% CI 28.5–49.5). Males (p = 0.029) and T4b disease (p = 0.013) were significant OS prognostic factors in univariable analysis, while only T4b disease (p = 0.017) remained significant in multivariable analysis. (4) Conclusions: SMARCB1-deficient sinonasal carcinoma is an extremely aggressive sinonasal malignancy with a dismal prognosis. Early diagnosis and a multimodality treatment strategy are essential for a better treatment and survival outcome. Full article

(1) Purpose: In this article, the authors decided to systematically review the available literature to identify potential correlations regarding secondary oral carcinoma occurring after hematological systemic treatment and oral chronic graft-versus-host disease. (2) Methods: Medline (PubMed) and Scopus (Elsevier) databases were searched, including articles from the years 2002–2022. The 33 unique results were assessed by a PRISMA flowchart, and we rejected 24 papers and included 9 articles in the review. (3) Results: The majority of patients suffered from the oral form of chronic graft-versus-host disease before the diagnosis of oral malignancy. Two common cancer sites were the tongue and buccal mucosa. The exact percentage of secondary oral carcinoma after hematopoietic stem cell transplantation could not be estimated due to a lack of data. (4) Conclusions: Every physician taking part in the follow-up of patients after hematological treatment should be aware of the possibility of secondary neoplastic disease in the oral cavity, especially in patients with oral graft-versus-host disease. Proper follow-up protocols and monitoring are needed in this patient group as the cause of these cancers appears to be multifactorial. Full article

The receptor tyrosine kinase MET has gained attention as a therapeutic target. Although MET immunoreactivity is associated with progressive disease, use of targeted therapies has not yet led to major survival benefits. A possible explanation is the lack of companion diagnostics (CDx) that account for proteolytic processing. During presenilin-regulated intramembrane proteolysis, MET’s ectodomain is shed into the extracellular space, which is followed by γ-secretase-mediated cleavage of the residual membranous C-terminal fragment. The resulting intracellular fragment is degraded by the proteasome, leading to downregulation of MET signaling. Conversely, a membrane-bound MET fragment lacking the ectodomain (MET-EC^-) can confer malignant potential. Use of C- and N-terminal MET monoclonal antibodies (moAbs) has illustrated that MET-EC^- occurs in transmembranous C-terminal MET-positive oral squamous cell carcinoma (OSCC). Here, we propose that ectodomain shedding, resulting from G-protein-coupled receptor transactivation of epidermal growth factor receptor signaling, and/or overexpression of ADAM10/17 and/or MET, stabilizes and possibly activates MET-EC^- in OSCC. As MET-EC^- is associated with poor prognosis in OSCC, it potentially has impact on the use of targeted therapies. Therefore, MET-EC^- should be incorporated in the design of CDx to improve patient stratification and ultimately prolong survival. Hence, MET-EC^- requires further investigation seen its oncogenic and predictive properties. Full article