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Background: Patients with head and neck cancer (HNC) often demonstrate stress, distress, anxiety, depression, and are at risk for suicide. These affect their quality of life (QoL) but less attention has been given to psychological variables that may impact response to treatment., Objectives: This study aims to systematically review publications during 2013-2023 to collate evidence on the effects of psychological variables on HNC treatment outcomes., Methods: We searched Ovid Medline, PubMed, Scopus, and Web of Science for articles that examined psychological factors related to treatment outcomes in patients with HNC., Results: There were 29 studies (5 before treatment, 2 during, 17 after, and 5 covering the whole management trajectory) including 362,766 patients. The psychological factors were either behavioral (adjustment and coping strategy, unrealistic ideas, self-blame), cognitive (elevated risk of psychiatric co-comorbidity), or emotional (distress, depression, anxiety, nervousness, and fear of disfigurement and complications). It was found that there was a relationship between depression and decreased survival in patients with HNC. Pretreatment pain was an independent predictor of decreased survival in a large sample of patients. The distress level was approximately  54%, emotional problems ranged between 10 and 44%, while financial difficulties were identified in 54% of the patients. Sixty-nine percent of patients were reported to have used at least one cost-coping strategy within 6 months after treatment initiation. During post-treatment period, depression increased from 15% at the baseline to 29%, while the fear of recurrence was found among at least 35% of patients., Discussion and Conclusion: Several psychological factors predict QoL and survival among HNC survivors. Distress encompasses depression and anxiety, and physical burden from HNC diagnosis and treatment. Routine screening and early interventions that target distress could improve HNC survivors' QoL. A systematic and standardized measurement approach for QoL is warranted to homogenize these findings and to understand the underlying relationships., (© 2024. The Author(s).)

Background: Radiomics is a rapidly growing field used to leverage medical radiological images by extracting quantitative features. These are supposed to characterize a patient's phenotype, and when combined with artificial intelligence techniques, to improve the accuracy of diagnostic models and clinical outcome prediction., Objectives: This review aims at examining the application areas of artificial intelligence-based radiomics (AI-based radiomics) for the management of head and neck cancer (HNC). It further explores the workflow of AI-based radiomics for personalized and precision oncology in HNC. Finally, it examines the current challenges of AI-based radiomics in daily clinical oncology and offers possible solutions to these challenges., Methods: Comprehensive electronic databases (PubMed, Medline via Ovid, Scopus, Web of Science, CINAHL, and Cochrane Library) were searched following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. The quality of included studies and their risk of biases were evaluated using the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD)and Prediction Model Risk of Bias Assessment Tool (PROBAST)., Results: Out of the 659 search hits retrieved, 45 fulfilled the inclusion criteria. Our review revealed that the application of AI-based radiomics model as an ancillary tool for improved decision-making in HNC management includes radiomics-based cancer diagnosis and radiomics-based cancer prognosis. The radiomics-based cancer diagnosis includes tumor staging, tumor grading, and classification of malignant and benign tumors. Similarly, radiomics-based cancer prognosis includes prediction for treatment response, recurrence, metastasis, and survival. In addition, the challenges in the implementation of these models for clinical evaluations include data imbalance, feature engineering (extraction and selection), model generalizability, multi-modal fusion, and model interpretability., Conclusion: Considering the highly subjective and interobserver variability that is peculiar to the interpretation of medical images by expert clinicians, AI-based radiomics seeks to offer potentially useful quantitative information, which is not visible to the human eye or unintentionally often remain ignored during clinical imaging practice. By enabling the extraction of this type of information, AI-based radiomics has the potential to revolutionize HNC oncology, providing a platform for more personalized, higher quality, and cost-effective care for HNC patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The impact of societal factors on the occurrence of head and neck cancers (HNCs) remains understudied, especially in the Nordic countries., Methods: To quantify the association between socio-economic status (SES) and the occurrence of HNCs, this cohort study uses data from the Nordic Occupational Cancer project that combine occupational and cancer registry data from 1961 to 2005 of 14.9 million individuals aged between 30 and 64 years. Occupational categories were combined into seven socio-economic categories. Standardized incidence ratio (SIR) analyses were conducted with the cancer incidence rates for the entire national study populations used as reference rates., Results: Altogether, 83 997 HNCs-72% in men and 28% in women-were recorded. Among men, a gradient of risk associated with SES was observed for cancers of the tongue, other oral cavity subsites, pharynx, oropharynx and larynx in groups with lower SES. Managers showed decreased SIRs of 0.50 to -0.90 also for cancers of the lip, tongue, other oral cavity subsites, oropharynx, nasopharynx, nose and larynx. In contrast, excess risks of tongue, other oral cavity subsites, pharyngeal, oropharyngeal and laryngeal cancers were observed among clerical (SIRs 1.05-1.16), skilled workers (1.04-1.14), unskilled workers (1.16-1.26) and economically inactive men (1.38-1.87). Among women, no risk gradient similar to that in men was revealed., Conclusions: The current study underscores the influence of SES on the incidence of HNCs and highlights the need for targeted interventions, including tobacco and alcohol control policies, and improved access to healthcare services, particularly for socio-economically disadvantaged populations., (© The Author(s) 2024; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Radiotherapy is one of the mainstay treatment modalities for the management of non-metastatic head and neck cancer (HNC). Notable improvements in treatment outcomes have been observed in the recent decades. Modern radiotherapy techniques, such as intensity-modulated radiotherapy and charged particle therapy, have significantly improved tumor target conformity and enabled better preservation of normal structures. However, because of the intricate anatomy of the head and neck region, multiple critical neurological structures such as the brain, brainstem, spinal cord, cranial nerves, nerve plexuses, autonomic pathways, brain vasculature, and neurosensory organs, are variably irradiated during treatment, particularly when tumor targets are in close proximity. Consequently, a diverse spectrum of late neurological sequelae may manifest in HNC survivors. These neurological complications commonly result in irreversible symptoms, impair patients' quality of life, and contribute to a substantial proportion of non-cancer deaths. Although the relationship between radiation dose and toxicity has not been fully elucidated for all complications, appropriate application of dosimetric constraints during radiotherapy planning may reduce their incidence. Vigilant surveillance during the course of survivorship also enables early detection and intervention. This article endeavors to provide a comprehensive review of the various neurological complications of modern radiotherapy for HNC, summarize the current incidence data, discuss methods to minimize their risks during radiotherapy planning, and highlight potential strategies for managing these debilitating toxicities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: In general, survival outcomes for patients with Head and Neck Cancer (HNC) has improved over recent decades. However, mortality within six months after diagnosis for curative patients remains at approximately 5%. The aim of this study was to identify risk factors for early death among patients with curative treatment, and furthermore, to analyze whether the risk of early death changed over recent years., Material and Method: This real-world, population-based, nationwide study from the Swedish Head and Neck Cancer Register (SweHNCR) included all patients ≥18 years diagnosed with HNC with a curative treatment intent at the multidisciplinary tumor board from 2008 to 2020. A total of 16,786 patients were included., Results: During the study period a total of 618 (3.7%) patients with curative-intended treatment died within six months of diagnosis. Patients diagnosed between 2008 and 2012 had a six-month mortality rate of 4.7% compared to 2.5% for patients diagnosed between 2017 and 2020, indicating a risk reduction of 53% (p <0.001) for death within six months. The mean time to radiation therapy from diagnosis in the 2008-2012 cohort was 38 days, compared to 22 days for the 2017-2020 cohort, (p <0.001). The mean time to surgery from diagnosis was 22 days in 2008-2012, compared to 15 days for the 2017-2020 cohort, (p <0.001). Females had a 20% lower risk of dying within six months compared to males (p = 0.013). For every year older the patient was at diagnosis, a 4.8% (p <0.001) higher risk of dying within six months was observed. Patients with a WHO score of 1 had approximately 2.4-times greater risk of early death compared to WHO 0 patients (p <0.001). The risk of early death among WHO 4 patients was almost 28 times higher than for WHO 0 patients (p <0.001). Patients with a hypopharyngeal tumor site had a 2.5-fold higher risk of dying within six months from diagnosis compared to oropharyngeal tumor patients (p <0.001)., Conclusions: We found that the risk of early death decreased significantly from 2008 to 2020. During this period, the mean time to the start of treatment was significantly reduced both for surgery and oncological treatment regimes. Among patients with a curative treatment intention, increased risk of early death was associated with male sex, older age, advanced disease, increased WHO score, and a hypopharyngeal tumor site., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Talani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: A significant proportion of patients with head and neck squamous cell carcinoma (HNSCC) are malnourished at diagnosis. In this study, we investigated how pretreatment body mass index (BMI) and fat-free mass index (FFMI) correlate with early death, and whether these measurements are useful markers of prognosis for risk stratification of head and neck cancer patients., Methods: Patients (n = 404) with newly diagnosed, curable HNSCC and WHO performance status 0-2 were prospectively included and met with a study representative before treatment initiation, as well as up to four follow-up visits. All patients provided an estimate of body weight at 6 months prior to diagnosis. Bioelectrical impedance analysis (BIA) was performed for all patients before treatment initiation., Results: Most patients had oropharyngeal (46%), oral cavity (28%), or laryngeal cancer (12%). Forty-five (11%) patients met the standardized criteria for malnutrition according to the Global Leadership Initiative on Malnutrition (GLIM) at diagnosis. FFMI at diagnosis was lower in patients who died within 6 and 12 months after the start of treatment than in patients who survived these time points (p = 0.035 and p = 0.005, respectively)., Conclusions: In this study, pretreatment FFMI was an independent prognostic factor for death within 6 and 12 months after the start of treatment in patients with HNSCC. Pretreatment BMI was not an independent risk factor for death within 6 and 12 months after treatment termination. Thus, FFMI may be useful for risk stratification of patients with head and neck cancer., (© 2024 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Malignant carotid body tumors (MCBT) are rare and diagnosed after detection of nodal or distant metastases. This systematic review (SR) focuses on MCBT initially approached by surgery. Preferred Reporting Items for SR and Meta-Analysis (MA) guided the articles search from 2000 to 2023 on PubMed, Scopus, and Web of Science. Among 3548 papers, 132 (337 patients) were considered for SR; of these, 20 (158 patients) for MA. Malignancy rate was 7.3%, succinate dehydrogenase (SDH) mutation 17%, age at diagnosis between 4th and 6th decades, with a higher prevalence of females. MCBTs were mostly Shamblin III, with nodal and distant metastasis in 79.7% and 44.7%, respectively. Malignancy should be suspected if CBT >4 cm, Shamblin III, painful or otherwise symptomatic, at the extremes of age, bilateral, with multifocal disease, and SDHx mutations. Levels II-III clearance should be performed to exclude nodal metastases and adjuvant treatments considered on a case-by-case basis., (© 2024 The Authors. Head & Neck published by Wiley Periodicals LLC.)

PTPRF interacting protein alpha 1 (PPFIA1) encodes for liprin-α1, a member of the leukocyte common antigen-related protein tyrosine phosphatase (LAR-RPTPs)-interacting protein family. Liprin-α1 localizes to adhesive and invasive structures in the periphery of cancer cells, where it modulates migration and invasion in head and neck squamous cell carcinoma (HNSCC) and breast cancer. To study the possible role of liprin-α1 in anticancer drug responses, we screened a library of oncology compounds in cell lines with high endogenous PPFIA1 expression. The compounds with the highest differential responses between high PPFIA1-expressing and silenced cells across cell lines were inhibitors targeting mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinases (ERK) signaling. KRAS proto-oncogene, GTPase (KRAS)-mutated MDA-MB-231 cells were more resistant to trametinib upon PPFIA1 knockdown compared with control cells. In contrast, liprin-α1-depleted HNSCC cells with low RAS activity showed a context-dependent response to MEK/ERK inhibitors. Importantly, we showed that liprin-α1 depletion leads to increased p-ERK1/2 levels in all our studied cell lines independent of KRAS mutational status, suggesting a role of liprin-α1 in the regulation of MAPK oncogenic signaling. Furthermore, liprin-α1 depletion led to more pronounced redistribution of RAS proteins to the cell membrane. Our data suggest that liprin-α1 is an important contributor to oncogenic RAS/MAPK signaling, and the status of liprin-α1 may assist in predicting drug responses in cancer cells in a context-dependent manner., (© 2024 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Background: The clinical significance of single cell invasion and large nuclear diameter is not well documented in early-stage oral tongue squamous cell carcinoma (OTSCC)., Methods: We used hematoxylin and eosin-stained sections to evaluate the presence of single cell invasion and large nuclei in a multicenter cohort of 311 cases treated for early-stage OTSCC., Results: Single cell invasion was associated in multivariable analysis with poor disease-specific survival (DSS) with a hazard ratio (HR) of 2.089 (95% CI 1.224-3.566, P = 0.007), as well as with disease-free survival (DFS) with a HR of 1.666 (95% CI 1.080-2.571, P = 0.021). Furthermore, large nuclei were associated with worse DSS (HR 2.070, 95% CI 1.216-3.523, P = 0.007) and with DFS in multivariable analysis (HR 1.645, 95% CI 1.067-2.538, P = 0.024)., Conclusion: Single cell invasion and large nuclei can be utilized for classifying early OTSCC into risk groups., (© 2024. The Author(s).)

Purpose: The Nordic countries (27 M) all have comparable, publicly funded healthcare systems, and the management of sinonasal tumours is centralised to the 21 university hospitals. We sought to assess and compare the treatment practice of sinonasal tumours across the Nordic countries., Methods: A web-based questionnaire was sent to all university hospital departments of otorhinolaryngology-head and neck surgery in the Nordic countries., Results: Answers were obtained from all 21 Nordic university hospitals. The endoscopic approach was widely utilised by all, with most (62%) centres reporting 3-4 surgeons performing endoscopic sinonasal tumour surgery. Finland reported the lowest rates of centralisation among university hospitals despite having the highest number of 0.1-1 M catchment population hospitals. Most centres (88%) opted for the endoscopic approach in a patient case warranting medial maxillectomy. In a case of a Kadish C esthesioneuroblastoma, most (52%) of the centres preferred an endoscopic approach. Most centres (62%) reported favouring the endoscopic approach in a case describing a juvenile angiofibroma. Regarding a case describing a sinonasal undifferentiated carcinoma, consensus was tied (38% vs. 38%) between endoscopic resection followed by postoperative (chemo)radiotherapy (RT/CRT) and induction chemotherapy followed by RT/CRT or surgery followed by RT/CRT., Conclusion: Endoscopic approach was widely utilised in the Nordic countries. The case-based replies showed differences in treatment practice, both internationally and nationally. The rate of centralisation among university hospitals remains relatively low, despite the rarity of these tumours., (© 2023. The Author(s).)

Background: In recent years, enhanced recovery after surgery (ERAS) guidelines have been developed to optimize pre-, intra-, and postoperative care of surgical oncology patients. The aim of this study was to compare management outcome of patients undergoing head and neck cancer (HNC) surgery with free flap reconstruction at our institution before and after the implementation of the ERAS guidelines., Methods: This retrospective study comprised 283 patients undergoing HNC surgery with free flap reconstruction between 2013 and 2020. Patients operated before and after the implementation of the ERAS protocol in October 2017 formed the pre-ERAS group (n = 169), and ERAS group (n = 114), respectively., Results: In the pre-ERAS group the mean length of stay (LOS) and intensive care unit length of the stay (ICU-LOS) were 20 days (range 7-79) and 6 days (range 1-32), and in the ERAS group 13 days (range 3-70) and 5 days (range 1-24), respectively. Both LOS (p < 0.001) and ICU-LOS (p = 0.042) were significantly reduced in the ERAS group compared to the pre-ERAS group. There were significantly fewer medical complications in the ERAS group (p < 0.003). No difference was found between the study groups in the surgical complication rate or in the 30-day or 6-month mortality rate after surgery., Conclusions: We found reduced LOS, ICU-LOS, and medical complication rate, but no effect on the surgical complication rate after implementation of the ERAS guidelines, which supports their use in major HNC surgery., (© 2023. The Author(s).)

Background: Oropharyngeal squamous cell carcinoma (OPSCC) can be treated with definitive (chemo)radiotherapy ((C)RT) or primary surgical treatment (PST) with or without postoperative oncologic treatment. The prognosis of OPSCC does not essentially depend on the treatment modality, which allows to consider secondary decision-making aspects such as treatment costs when recommending an individual treatment modality. We attempted to analyze the costs associated with definitive (C)RT and PST in the treatment of OPSCC in Finland., Materials and Methods: We included 73 patients diagnosed with OPSCC at the Helsinki University Hospital (HUS) (Helsinki, Finland) in 2019 and 2020. Treatment costs were defined as the costs incurred in the specialized medical care during the first 12 months after the diagnosis was established., Results: Definitive RT and definitive CRT were on a 1-year horizon associated with median costs of approximately 10 700€ and 13 300€, respectively; while, the median costs of PST equaled about 40 600€. The costs of definitive (C)RT mostly consisted of the costs of (chemo)radiotherapy sessions; while, the operating room costs and the costs of intensive care and stay on a ward drove the costs of PST., Conclusions: PST is associated with 2-3 times higher median costs than definitive (C)RT in Finland. The finding differs from the results previously reported in North America, which is related, e.g., to differences in the treatment practices as well as in the regulation of the health care systems., (© 2023. The Author(s).)

Bioelectrical Impedance Analysis (BIA) is a reliable, non-invasive, objective, and cost-effective body composition assessment method, with high reproducibility. This scoping review aims to evaluate the current scientific and clinical evidence on BIA for body composition assessment in oncology patients, under active treatment. Literature search was conducted through MEDLINE, CINAHL, Scopus and Web of Science databases, following PRISMA-ScR Guidelines. Inclusion criteria comprised studies reporting the use of BIA for body composition evaluation in adults with cancer diagnosis. Studies including non-cancer pathology or only assessing nutritional status were excluded. This scoping review comprised a total of 36 studies: 25 were original studies including 18 prospective studies, six cross-sectional studies and one retrospective study and 11 were systematic reviews. Population size for the included original articles ranged from 18 to 1217 participants, comprising a total of 3015 patients with cancer with a mean baseline Body Mass Index (BMI) ranging from 20.3 to 30.0 kg/m 2 and mean age ranging between 47 and 70 years. Review articles included a total of 273 studies, with a total of 78,350 participants. The current review considered studies reporting patients with head and neck cancer (HNC) ( n = 8), breast cancer (BC) ( n = 4), esophageal cancer (EC) ( n = 2), liver cancer ( n = 2), pancreatic cancer (PC) ( n = 3), gastric cancer (GC) ( n = 3), colorectal cancer (CRC) ( n = 8), lung cancer (LC) ( n = 1), skin cancer (SK) ( n = 1) and multiple cancer types ( n = 6). BIA is a suitable and valid method for the assessment of body composition in oncology. BIA-derived measures have shown good potential and relevant clinical value in preoperative risk evaluation, in the reduction of postoperative complications and hospital stay and as an important prognostic indicator in persons with cancer. Future research on the diagnostic value and clinical applications of BIA and BIA-derived phase angle (PhA) should be conducted in order to predict its impact on patient survival and other clinical outcomes.

Purpose: Second primary cancers (SPCs) after nasopharyngeal cancer (NPC) are rare, but have an impact on the follow-up of this patient population. The aim of this study is to systematically review the literature to determine the prevalence and most typical sites of SPCs after NPC., Methods: We searched the databases of PubMed, Web of Science, and Scopus for articles on SPCs after NPC. The Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines were followed., Results: This review includes data on 89 168 patients with NPC from 21 articles. The mean occurrence for SPCs was 6.6% and varied from 4.9% in endemic areas to 8.7% in non-endemic areas. The most frequent locations of SPCs were oral cavity, pharynx, nose and paranasal sinuses, esophagus and lung., Conclusion: There is an increased risk for a SPC after NPC management, especially in non-endemic areas. However, their mean rate is lower than after other head and neck carcinomas., (© 2023. The Author(s).)

Ferroptosis is an iron-dependent regulatory form of cell death characterized by the accumulation of intracellular reactive oxygen species and lipid peroxidation. It plays a critical role not only in promoting drug resistance in tumors, but also in shaping therapeutic approaches for various malignancies. This review aims to elucidate the relationship between ferroptosis and head and neck cancer treatment by discussing its conceptual framework, mechanism of action, functional aspects, and implications for tumor therapy. In addition, this review consolidates strategies aimed at improving the efficacy of head and neck cancer treatment through modulation of ferroptosis, herein serving as a valuable reference for advancing the treatment landscape for this patient population.

Background: Evidence on the risk of second primary cancer (SPC) following primary laryngeal squamous cell carcinoma (LSCC) is limited, especially in Europe., Methods: Patients diagnosed with primary LSCC from 1953-2018 were retrieved from the Finnish Cancer Registry. A total of 6241 LSCC patients were identified adding to 49,393 person-years (PY) of follow-up until the end of 2019. Only one patient emigrated and was lost to follow-up. Both standardized incidence ratios (SIR) and excess absolute risk (EAR) per 1000 person-years at risk (PYR) of second primary cancer (SPC) were calculated relative to the general population. Only non-laryngeal SPCs diagnosed six months after diagnosis of primary LSCC were included., Results: A SPC was diagnosed in 1244 LSCC patients (20% of all LSCC patients) over the 65-year period, predominantly in men (92%, n  = 1170). Out of all SPCs, 34% were diagnosed within 0.5 to 5 years and 66% after 5 years from primary LSCC. Among male patients, the overall SIR for SPC at any location was 1.61 (95% CI: 1.52-1.71), corresponding to 9.49 excess SPCs per 1000 PYR (95% CI: 8.19-11). The corresponding SIR for women was 1.47 (95% CI: 1.15-1.84), yielding 4.82 excess SPCs per 1000 PYR (95% CI: 2.36-9.84). The risk remained significant even after 20 years of follow-up (SIR for all 1.73, 95% CI: 1.49-2.01 and EAR 16.8 per 1000 PY, 11.88-23.75). The risk for SPC was also significantly elevated in all age groups, except <40. The highest SIRs were for SPCs arising in the mouth/pharynx (SIR for all 3.08, 95% CI: 2.36-3.95 and EAR 0.80 per 1000 PY, 0.55-1.15) and lungs (3.02, 2.75-3.30 and 5.90 per 1000, 5.13-6.78)., Conclusion: Patients with LSCC as primary cancer have a 60% excess risk for an SPC, especially for tobacco-associated cancers, remaining significantly elevated even decades after treatment.

Head and neck squamous cell carcinoma forms an anatomically and functionally complex group of malignancies. The significant local aggressiveness and frequent regional relapses motivate ongoing research to identify more reliable and sensitive prognostic and predictive biomarkers. One emerging area of cancer biology is the evaluation of tumor budding at the advancing invasive front of various types of epithelial cancers. Recent studies suggest that tumor budding is a relatively common phenomenon in cancer progression and that it may have important prognostic implications for patients due to its potential to provide valuable insights into the biology and clinical behavior of head and neck cancer. In this review, we aim to provide information about tumor budding in head and neck squamous cell carcinoma. Thus, we hope to shed light on the complex biology of these malignancies, as well as aiding diagnostic, classification, and better characterization and thereby, looking for new avenues for improving patient outcomes., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Liprin-α1 is a scaffold protein involved in cell adhesion, motility, and invasion in malignancies. Liprin-α1 inhibits the expression of metastatic suppressor CD82 in cancers such as oral carcinoma, and the expression of these proteins has been known to correlate negatively. The role of these proteins has not been previously studied in human papillomavirus (HPV)-related head and neck cancers. Our aim was to assess the clinical and prognostic role of liprin-α1 and CD82 in HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) in comparison to HPV-negative OPSCC., Methods: The data included 139 OPSCC patients treated at the Helsinki University Hospital (HUS) during 2012-2016. Immunohistochemistry was utilized in HPV determination and in biomarker assays. Overall survival (OS) was used in the survival analysis., Results: Stronger expression of liprin-α1 in tumor-infiltrating lymphocytes (TILs) was linked to lower cancer stage (p < 0.001) and HPV positivity (p < 0.001). Additionally, we found an association between elevated expression of liprin-α1 and weak expression of CD82 in tumor cells (p = 0.029). In survival analysis, we found significant correlation between favorable OS and stronger expression of liprin-α1 in TILs among the whole patient cohort (p < 0.001) and among HPV-positive patients (p = 0.042)., Conclusions: Increased liprin-α1 expression in the TILs is associated with favorable prognosis in OPSCC, especially among HPV-positive patients., (© 2023. The Author(s).)

Importance: Sarcopenia is an established prognostic factor in patients with head and neck squamous cell carcinoma (HNSCC); the quantification of sarcopenia assessed by imaging is typically achieved through the skeletal muscle index (SMI), which can be derived from cervical skeletal muscle segmentation and cross-sectional area. However, manual muscle segmentation is labor intensive, prone to interobserver variability, and impractical for large-scale clinical use., Objective: To develop and externally validate a fully automated image-based deep learning platform for cervical vertebral muscle segmentation and SMI calculation and evaluate associations with survival and treatment toxicity outcomes., Design, Setting, and Participants: For this prognostic study, a model development data set was curated from publicly available and deidentified data from patients with HNSCC treated at MD Anderson Cancer Center between January 1, 2003, and December 31, 2013. A total of 899 patients undergoing primary radiation for HNSCC with abdominal computed tomography scans and complete clinical information were selected. An external validation data set was retrospectively collected from patients undergoing primary radiation therapy between January 1, 1996, and December 31, 2013, at Brigham and Women's Hospital. The data analysis was performed between May 1, 2022, and March 31, 2023., Exposure: C3 vertebral skeletal muscle segmentation during radiation therapy for HNSCC., Main Outcomes and Measures: Overall survival and treatment toxicity outcomes of HNSCC., Results: The total patient cohort comprised 899 patients with HNSCC (median [range] age, 58 [24-90] years; 140 female [15.6%] and 755 male [84.0%]). Dice similarity coefficients for the validation set (n = 96) and internal test set (n = 48) were 0.90 (95% CI, 0.90-0.91) and 0.90 (95% CI, 0.89-0.91), respectively, with a mean 96.2% acceptable rate between 2 reviewers on external clinical testing (n = 377). Estimated cross-sectional area and SMI values were associated with manually annotated values (Pearson r = 0.99; P < .001) across data sets. On multivariable Cox proportional hazards regression, SMI-derived sarcopenia was associated with worse overall survival (hazard ratio, 2.05; 95% CI, 1.04-4.04; P = .04) and longer feeding tube duration (median [range], 162 [6-1477] vs 134 [15-1255] days; hazard ratio, 0.66; 95% CI, 0.48-0.89; P = .006) than no sarcopenia., Conclusions and Relevance: This prognostic study's findings show external validation of a fully automated deep learning pipeline to accurately measure sarcopenia in HNSCC and an association with important disease outcomes. The pipeline could enable the integration of sarcopenia assessment into clinical decision making for individuals with HNSCC.

Introduction: Several studies have emphasized the potential of artificial intelligence (AI) and its subfields, such as machine learning (ML), as emerging and feasible approaches to optimize patient care in oncology. As a result, clinicians and decision-makers are faced with a plethora of reviews regarding the state of the art of applications of AI for head and neck cancer (HNC) management. This article provides an analysis of systematic reviews on the current status, and of the limitations of the application of AI/ML as adjunctive decision-making tools in HNC management., Methods: Electronic databases (PubMed, Medline via Ovid, Scopus, and Web of Science) were searched from inception until November 30, 2022. The study selection, searching and screening processes, inclusion, and exclusion criteria followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. A risk of bias assessment was conducted using a tailored and modified version of the Assessment of Systematic Review (AMSTAR-2) tool and quality assessment using the Risk of Bias in Systematic Reviews (ROBIS) guidelines., Results: Of the 137 search hits retrieved, 17 fulfilled the inclusion criteria. This analysis of systematic reviews revealed that the application of AI/ML as a decision aid in HNC management can be thematized as follows: (1) detection of precancerous and cancerous lesions within histopathologic slides; (2) prediction of the histopathologic nature of a given lesion from various sources of medical imaging; (3) prognostication; (4) extraction of pathological findings from imaging; and (5) different applications in radiation oncology. In addition, the challenges in implementation of AI/ML models for clinical evaluations include the lack of standardized methodological guidelines for the collection of clinical images, development of these models, reporting of their performance, external validation procedures, and regulatory frameworks., Conclusion: At present, there is a paucity of evidence to suggest the adoption of these models in clinical practice due to the aforementioned limitations. Therefore, this manuscript highlights the need for development of standardized guidelines to facilitate the adoption and implementation of these models in the daily clinical practice. In addition, adequately powered, prospective, randomized controlled trials are urgently needed to further assess the potential of AI/ML models in real-world clinical settings for the management of HNC., (© 2023. The Author(s).)

Tumor-stroma ratio (TSR) has been analyzed in many tumor types. To date, the clinical significance of TSR has not been investigated in oropharyngeal squamous cell carcinoma (OPSCC). We used a recently introduced recommendation for the assessment of TSR in a large cohort of 182 patients with OPSCC treated at the Helsinki University Hospital. The percentage of tumor-associated stroma was estimated in hematoxylin and eosin (HE)-stained sections and categorized into 2 groups: "stroma-high" (>50%) and "stroma-low" (≤50%). In multivariable analysis, TSR had a significant association with patient survival as stroma-high tumors showed worse disease-free survival (hazard ratio [HR] = 3.22, 95% confidence interval [CI] = 1.43-7.26, P = .005), disease-specific survival (HR = 2.48, 95% CI = 1.29-4.74, P = .006), and overall survival (HR = 2.23, 95% CI = 1.29-3.85, P = .004). The prognostic value of TSR was superior to the Tumor-Node-Metastasis classification. In addition, the significant prognostic value of TSR was demonstrated when analyzing human papillomavirus (HPV)-positive and HPV-negative cases separately (P < .05). In conclusion, TSR is a powerful prognostic indicator in OPSCC. It can be assessed quickly without additional costs using standard HE slides. Owing to its simplicity and reproducibility, TSR can be implemented in routine pathology diagnostics and reporting. Patients with stroma-rich tumors have an increased risk of recurrence and cancer-related mortality and may benefit from appropriate intensive treatment strategies with close follow-up., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Head and neck cancers (HNCs) are often diagnosed at an advanced stage. We investigated the lengths and factors associated with patient, primary health care (PHC), and specialist care (SC) delays in T3-T4 oral, oropharyngeal, and laryngeal cancer., Methods: A nationwide prospective questionnaire-based study (n = 203) with the 3-year long data collection period., Results: The median patient, PHC and SC delays were 58, 13, and 43 days, respectively. Lower level of education, heavy alcohol use, hoarseness, difficulties breathing, and eventual palliative treatment associated with a longer patient delay. A lump on the neck or facial swelling associated with a shorter PHC delay. Conversely, if symptoms were treated as an infection, PHC delay was longer. The treatment modality and tumor site affected SC delay., Conclusions: Patient delay stands as the most notable factor contributing to delays before treatment. HNC symptom awareness thus remains especially important among HNC risk groups., (© 2023 Wiley Periodicals LLC.)

The projected increase in life expectancy over the next few decades is expected to result in a rise in age-related diseases, including cancer. Head and neck cancer (HNC) is a worldwide health problem with high rates of morbidity and mortality. In this report, we have critically reviewed the literature reporting the management of older patients with HNC. Older adults are more prone to complications and toxicities secondary to HNC treatment, especially those patients who are frail or have comorbidities. Thus, this population should be screened prior to treatment for such predispositions to maximize medical management of comorbidities. Chronologic age itself is not a reason for choosing less intensive treatment for older HNC patients. Whenever possible, also older patients should be treated according to the best standard of care, as nonstandard approaches may result in increased treatment failure rates and mortality. The treatment plan is best established by a multidisciplinary tumor board with shared decision-making with patients and family. Treatment modifications should be considered for those patients who have severe comorbidities, evidence of frailty (low performance status), or low performance status or those who refuse the recommendations of the tumor board., (© 2023. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

Background: The increasing number of patients under surveillance after treatment of human papillomavirus-related oropharyngeal squamous cell carcinoma (OPSCC) places a great burden on healthcare providers., Aims/objectives: The aim of this study was to explore OPSCC recurrences in a long follow-up period: their site, frequency and timepoint after primary treatment, treatment and outcome. The secondary aim was to investigate if the recurrences are diagnosed on routine follow-up visits, and if the p16 status will have an effect on the pattern of recurrences., Material and Methods: We analyzed recurrences within a 10-year follow-up period after completed curatively intended treatment among OPSCC patients in Finland treated between 2000 and 2009. Patient-, tumor-, treatment- and follow-up -related parameters were investigated., Results: Out of 495 patients with no residual tumor during the first six months, 71 (14%) were diagnosed with a recurrence, of which 47 were locoregional and 28 were treated with curative intent. Of the recurrences, 86% were diagnosed during the first 36 months after primary treatment. Only ten recurrences appeared after 36 months. The median OS after recurrence was 10.9 months., Conclusions and Significance: Routine follow-up longer than three years after treatment seems not to be effective in terms of detecting OPSCC recurrences.

Treatment of oral tongue squamous cell carcinoma (OTSCC) frequently includes surgery with postoperative radiotherapy (RT) or chemoradiotherapy (CRT). Resistance to RT or CRT remains a major clinical challenge and highlights the need to identify predictive markers for it. We included 71 OTSCC patients treated with surgery combined with RT or CRT. We evaluated the association between tumor budding, tumor-stroma ratio (TSR), depth of invasion (DOI), tumor-infiltrating lymphocytes (TILs), hypoxia-inducible factor-1alpha (HIF-1alpha) expression, octamer-binding transcription factor 4 (OCT4) expression, high-endothelial venules (HEVs), and disease-free survival (DFS) using uni- and multivariate analyses. No significant association was observed between the different histological and molecular markers (TSR, DOI, TILs, HEV, HIF-1alph, OCT4) and DFS. However, an associative trend between DOI, budding, and DFS was noted. Further studies with larger cohorts are needed to explore the prognostic value of DOI and budding for OTSCC patients treated with postoperative RT or CRT., (© 2023 Scandinavian Societies for Pathology, Medical Microbiology and Immunology.)

Introduction: Limited data exist regarding head and neck cancer (HNC) burden among immigrants who may have distinct characteristics, and hence different incidence rates from the general population. Variations in behavioral habits, cultural lifestyle, or diet may cause variations across different subgroups., Methods: The whole immigrant population of Finnish residents born abroad, and their children were retrieved for the years 1970-2017. First-generation immigrants are defined as individuals born abroad, excluding their children (even if born abroad). The study comprised 0.5 million first-generation immigrants and 0.3 million children, contributing to 6 million and 5 million person-years of follow-up, respectively. Standardized incidence ratios (SIR) and excess absolute risk (EAR) per 100,000 person-years at risk were calculated to quantify the risk of HNC among immigrants relative to the general Finnish population., Results: The overall risk of any HNC was not increased among first-generation male immigrants (SIR 1.00, 95% CI: 0.88-1.15), but significantly elevated for cancer of the pharynx (SIR 1.56, 95% CI: 1.22-1.95), and larynx (SIR 1.38, 95% CI: 1.02-1.83) and decreased for lip (SIR 0.38, 95% CI: 0.20-0.67). The increased risk of pharyngeal cancer was highest among male immigrants from Asia Pacific (SIR 4.21, 95% CI: 2.02-7.75). First-generation immigrant women had a significantly reduced risk of any HNC (SIR 0.45, 95% CI: 0.37-0.55), which remained even after stratification by site. We observed no increased risk of any HNC among the children of first-generation immigrants., Conclusion: Healthcare professionals need to recognize the groups at higher HNC risk. Efforts to address the main etiological risk factors, such as smoking, are needed among the selected immigrant populations, that haven't yet reached similar decreasing trends, as in for example smoking, as the main population.NOVELTY AND IMPACTCurrently, globally, over 280 million people live outside their country of birth. Limited data exist regarding head and neck cancer (HNC) burden among immigrants who may have distinct characteristics and hence different incidence rates from the general population. Immigrant studies can provide novel data by shedding light on risk alterations and the pace of acculturation of different populations.

Background: The overall assessment of tumor-infiltrating lymphocytes (TILs) evaluated using hematoxylin and eosin (HE) staining has been recently studied in oropharyngeal squamous cell carcinoma (OPSCC)., Methods: We conducted a systematic review of Scopus, Ovid Medline, PubMed, Web of Science, and Cochrane Library to retrieve studies assessing TILs in HE-stained sections of OPSCC. We used fixed-effect models and random-effect models to estimate the pooled hazard ratios (HRs) and confidence intervals (CIs) for disease-free survival (DFS), overall survival (OS) and disease-specific survival (DSS)., Results: Eleven studies were identified that had analyzed the prognostic significance of TILs in OPSCC using HE-stained specimens. Our meta-analyses showed that a high infiltration of TILs was significantly associated with improved DFS (HR 0.39, 95%CI 0.24-0.65, P = 0.0003), OS (HR 0.38, 95%CI 0.29-0.50, P < 0.0001), and DSS (HR 0.32, 95%CI 0.19-0.53, P < 0.0001)., Conclusion: Findings of our meta-analysis support a growing body of evidence indicating that assessment of TILs in OPSCC using HE-stained sections has reliable prognostic value. The clinical significance of such assessment of TILs has been reported repeatedly in many studies on OPSCC. The assessment is cost-effective, feasible, easy to transfer from lab to clinic, and therefore can be incorporated in daily practice., (Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Purpose: Hypopharyngeal carcinoma (HPC) is typically diagnosed at late stages, the patients tend to have serious co-morbidities, distant relapses are frequent, and the related mortality remains high. The treatment paradigm of HPC has remarkably changed from primary surgical approach toward definitive, platinum-based concomitant chemoradiotherapy (CRT). Our aim was to analyze the HPC treatment approaches and outcome in a nationwide series and to make a comparison with a previously published corresponding nationwide patient cohort from the period 1990-1999., Methods: We retrospectively reviewed all patients diagnosed with HPC at the five university hospitals in Finland between 2005 and 2014., Results: The cohort comprised 231 patients. Treatment with curative intent was offered for 175 (76%) patients and consisted of definitive radiotherapy (RT) or CRT in 156 (89%) patients, while 20 (11%) patients had primary surgery with or without adjuvant RT or CRT. The 5-year estimates for overall survival (OS) and disease specific survival (DSS) for the whole study group were 22.7% and 36.5%, respectively. For patients treated with curative intent, the 5-year estimates for OS and DSS were 29.4% and 44.3%, respectively., Conclusions: The treatment approach of HPC in Finland has changed thoroughly, as in the 1990s, 63% of HPC patients with curative treatment intent underwent primary surgery with or without RT, while in the current study, the primary treatment approach was non-surgical in 89% of the patients. However, the survival figures have not changed and remain dismal, but most of the few surviving patients now can retain their larynx., (© 2022. The Author(s).)

Background: Free tissue transfer reconstruction carries significant complication rates in surgical head and neck oncology. A registry-based approach offers a possibility to investigate the factors affecting increased morbidity and early mortality, that is, death within 6 months of treatment., Methods: A retrospective registry review was conducted on a series of 317 consecutive microvascular free tissue transfers in head and neck cancer patients performed during 2013-2017 at the Helsinki University Hospital (Helsinki, Finland). All surviving patients had a minimum follow-up of 2 years (range 24-84 months)., Results: Overall, 36 (11.4%) early deaths occurred in this series. In multivariable logistic regression analysis, patients aged 75 years and older ( p = 0.019), Adult Comorbidity Evaluation-27 (ACE-27) score of 3 ( p = 0.048), tumor class T3 ( p = 0.005), lymph node class N2 ( p = 0.014), or thrombocyte count of 360 (× 10 9 L) or more ( p = 0.001) were more likely to die within 6 months of surgery. Of these 36 patients, 27 (75%) had a complication warranting hospital care and most ( n = 22, 61%) had several complications., Conclusions: Early postoperative mortality most frequently affects patients aged 75 years and above, with a high ACE-27 score, advanced tumor stage, or high thrombocyte count. Therefore, preoperative assessment and patient selection should have a crucial role in this patient population.

Background/aim: The oral bacteria involved in the development of periodontitis alter the tissue conditions and modify immune responses in a way that may also influence tumor development. We investigated the prevalence of R gingipain (Rgp), a key virulence factor of the oral pathobiont Porphyromonas gingivalis, and the tissue-destructive enzymes matrix metalloproteinase 8 (MMP-8) and 9 (MMP-9) in 202 unselected consecutive oropharyngeal squamous cell carcinoma (OPSCC) samples. We further investigated the relationships between these factors and human papillomavirus (HPV) status, Treponema denticola chymotrypsin-like proteinase (Td-CTLP) immunoexpression, clinical parameters, and patient outcome., Patients and Methods: Clinicopathological data were derived from university hospital records. Rgp, MMP-8, and MMP-9 immunoexpression was evaluated by immunohistochemistry; the immunohistochemistry of Td-CTLP and HPV has been described earlier for this patient series. Cox regression analysis including death by causes other than OPSCC as a competing risk served to assess sub distribution hazard ratios., Results: In multivariable survival analysis, positive tumoral MMP-9 immunoexpression predicted poor prognosis among all patients [sub distribution hazard ratio (SHR)=2.4; confidence interval (CI)=1.2-4.4, p=0.008], and especially among those with HPV-negative OPSCC (SHR=3.5; CI=1.7-7.3, p=0.001). Positive immunoexpression of Rgp in inflammatory cells was associated with favorable outcome among all patients (SHR=0.5, CI=0.2-0.9, p=0.021) and among those with HPV-negative disease (SHR=0.4, CI=0.2-0.9, p=0.022)., Conclusion: Our results suggest that tumoral MMP-9 may be related to poor outcome in OPSCC, especially in HPV-negative disease, while Rgp immunoexpression in inflammatory cells is associated here with better disease-specific survival (DSS)., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The clinical significance of tertiary lymphoid structures (TLSs) is not well-documented in early oral tongue squamous cell carcinoma (OTSCC)., Methods: A total of 310 cases of early (cT1-2N0) OTSCC were included in this multicenter study. Assessment of TLSs was conducted on hematoxylin and eosin-stained sections. TLSs were assessed both in the central part of the tumor and at the invasive front area., Results: The presence of TLSs associated with improved survival of early OTSCC as presented by Kaplan-Meier survival analyses for disease-specific survival (P = 0.01) and overall survival (P = 0.006). In multivariable analyses, which included conventional prognostic factors, the absence of TLSs associated with worse disease-specific survival with a hazard ratio (HR) of 1.96 (95% CI 1.09-3.54; P = 0.025) and poor overall survival (HR 1.66, 95% CI 1.11-2.48; P = 0.014)., Conclusion: Histological evaluation of TLSs predicts survival in early OTSCC. TLSs showed superior prognostic power independent of routine WHO grading and TNM staging system., (© 2022. The Author(s).)

Background: The evaluation of immune response can aid in prediction of cancer behaviour. Here, we assessed the prognostic significance of tumour-infiltrating lymphocytes (TILs) in oropharyngeal squamous cell carcinoma (OPSCC)., Methods: A total of 182 patients treated for OPSCC were included in this study. Assessment of TILs was conducted on tumour sections stained with standard haematoxylin and eosin (HE) staining. We used the scoring criteria proposed by the International Immuno-Oncology Biomarker Working Group., Results: The multivariable analysis showed that TILs associated with disease-specific survival with a hazard ratio (HR) of 2.13 (95% CI 1.14-3.96; P = 0.017). Similarly, TILs associated significantly with overall survival with HR of 1.87 (95% CI 1.11-3.13; P = 0.018). In a sub-analysis of HPV-positive and HPV-negative cases separately, TILs showed a significant prognostic value in both groups (P < 0.05)., Conclusion: The evaluation of TILs as proposed by the International Immuno-Oncology Biomarker Working Group is a simple and promising method in prediction of survival of OPSCC. It is easily applicable and after further validation can be implemented in the routine pathological report as a basic immune parameter., (© 2022. The Author(s).)

Abstract: Plexiform variants of neurofibromas and schwannomas are rare and typically arise in superficial soft tissues in the head and neck region. The treatment of these tumors is challenging and no generally accepted guidelines exist for their optimal management. The purpose of this study was to review the management and longterm prognosis of head and neck plexiform neurofibromas and schwannomas at 2 tertiary care academic hospitals in Finland over a 31-year period. The pathology files were searched for plexiform neurofibromas and schwannomas between the years 1990 and 2020. The case notes were reviewed for full management details. Two plexiform schwannomas and 6 plexiform neurofibromas were identified. Five of the 6 plexiform neurofibromas were managed operatively. All patients with a surgically managed plexiform neurofibroma underwent multiple operations. Sclerotherapy abolished 1 patient's cutaneous plexiform neurofibromas. The management of plexiform neurofibromas and plexiform schwannomas remains challenging. Sclerotherapy may offer a promising management option for cutaneous plexiform neurofibromas., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by Mutaz B. Habal, MD.)

Purpose: The prognosis of glottic T1a laryngeal squamous cell carcinoma (LSCC) is excellent with both transoral laser surgery (TLS) and radiation therapy (RT). Our aim was to compare TLS and RT treatment results in a randomized study., Methods and Materials: Of 56 male patients with glottic T1a LSCC, 31 were randomized for TLS and 25 for RT. Survival and larynx preservation data were collected from medical records., Results: Five-year overall survival (OS) was 87%, disease-specific survival (DSS) was 97%, and recurrence-free survival (RFS) was 81% in patients treated with TLS. Five-year OS was 92%, DSS was 100%, and RFS was 88% in patients treated with RT. The primary treatment method was not associated with OS, RFS, or DSS in a log-rank test. The larynx preservation rate was similar in both groups (TLS, 97%; RT, 92%; P = .575)., Conclusions: In a prospective randomized setting oncological outcomes of both treatment modalities (TLS or RT) for T1a LSCC were similar., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Head and neck squamous cell carcinomas (HNSCCs) arising in the mucosal linings of the upper aerodigestive tract are highly heterogeneous, aggressive, and multifactorial tumors affecting more than half a million patients worldwide each year. Classical etiological factors for HNSCC include alcohol, tobacco, and human papillomavirus (HPV) infection. Current treatment options for HNSCCs encompass surgery, radiotherapy, chemotherapy, or combinatorial remedies. Comprehensive integrative genomic analysis of HNSCC has identified mutations in TP53 gene as the most frequent of all somatic genomic alterations. TP53 mutations are associated with either loss of wild-type p53 function or gain of functions that promote invasion, metastasis, genomic instability, and cancer cell proliferation. Interestingly, disruptive TP53 mutations in tumor DNA are associated with aggressiveness and reduced survival after surgical treatment of HNSCC. This review summarizes the current evidence and impact of TP53 mutations in HNSCC., (© 2022 Wiley Periodicals LLC.)

Objectives: Cisplatin is combined with radiotherapy for advanced head and neck squamous cell carcinoma (HNSCC). While providing a beneficial effect on survival, it also causes side effects and thus is an important target when considering treatment de-escalation. Currently, there are no biomarkers to predict its patient-selective therapeutic utility. In this study, we examined the role of the stem cell factor OCT4 as a potential biomarker to help clinicians stratify HNSCC patients between radiotherapy and chemoradiotherapy., Materials and Methods: OCT4 immunohistochemical staining of a population-validated tissue microarray (PV-TMA) (n = 166) representative of a standard HNSCC patients was carried out, and 5-year survival was analyzed. The results were validated using ex vivo drug sensitivity analysis of HNSCC tumor samples, and further cross-validated in independent oropharyngeal (n = 118), nasopharyngeal (n = 170), and vulvar carcinoma (n = 95) clinical datasets. In vitro, genetically modified, patient-derived HNSCC cells were used., Results: OCT4 expression in HNSCC tumors was associated with radioresistance. However, combination therapy with cisplatin was found to overcome thisradioresistance in OCT4-expressing HNSCC tumors. The results were validated by using several independent patient cohorts. Furthermore, CRISPRa-based OCT4 overexpression in the HNSCC cell line resulted in apoptosis resistance, and cisplatin was found to downregulate OCT4 protein expression in vitro. Ex vivo drug sensitivity analysis of HNSCC tumors confirmed the association between OCT4 expression and cisplatin sensitivity., Conclusion: This study introduces OCT4 immunohistochemistry as a simple and cost-effective diagnostic approach for clinical practice to identify HNSCC patients benefitting from radiosensitization by cisplatin using either full or reduced dosing., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Patients with head and neck cancer (HNC) are usually confronted with functional changes due to the malignancy itself or its treatment. These factors typically affect important structures involved in speech, breathing, chewing, swallowing, and saliva production. Consequently, the intake of food will be limited, which further contributes to loss of body weight and muscle mass, anorexia, malnutrition, fatigue, and anemia. This multifactorial condition can ultimately lead to cancer cachexia syndrome. This study aims to examine the treatment of cachexia in HNC patients., Methods: We systematically searched OvidMedline, PubMed, Scopus, and Web of Science for articles examining the treatment of cachexia in HNC., Results: A total of nine studies were found, and these suggested interventions including nutritional, pharmacologic, therapeutic exercise, and multimodal approaches. The nutritional intervention includes essential components such as dietary counseling, oral nutritional supplements, and medical nutritional support. Individualized nutritional interventions include oral, enteral (feeding tubes i.e., percutaneous endoscopic gastrostomy [PEG], nasogastric tube [NGT]) and parenteral nutrition. The pharmacologic interventions aim at increasing the appetite and weight of cachectic patients. Therapeutic exercise and increased physical activity can help to enhance the synthesis of muscle protein, reducing inflammation and the catabolic effects of cachexia syndrome., Conclusion: Owing to the multifactorial nature of this syndrome, it is expected that the management approach should be multi-interventional. Early implementation of these interventions may help to improve survival and quality of health and life of cachectic HNC patients., (© 2022. The Author(s).)

Background: Early diagnosis of head and neck cancer (HNC) will improve patient outcomes. The low incidence of HNC renders its detection challenging for a general practitioner (GP) in primary health care (PHC)., Patients and Methods: To examine these challenges, our cohort consisted of all patients visiting PHC centres in the City of Helsinki in 2016. We chose 57 ICD-10 codes representing a sign or symptom resulting from a possible HNC and compared data for all new HNC patients., Results: A total of 242,211 patients (499,542 appointments) visited PHC centres, 11,896 (5%) of whom presented with a sign or symptom possibly caused by HNC. Altogether, 111 new HNCs were diagnosed within the Helsinki area, of which 40 (36%) were referred from PHC. The median delay from the initial PHC visit to the referral to specialist care was 5 days, whereby 88% of patients were referred within one month., Conclusions: Despite the low incidence of HNC and the large number of patients presenting with HNC-related symptoms, GPs working in PHC sort out potential HNC patients from the general patient group in most cases remarkably effectively. KEY MESSAGES For every head and neck cancer (HNC) patient encountered in the primary health care, a general practitioner (GP) will meet approximately 6000 other patients, 100 of whom exhibit a sign or a symptom potentially caused by a HNC. Despite the low incidence of HNC, GPs referred patients to specialist care effectively, limiting the median delay from the initial appointment to referral to only 5 days.

The inherent variability in performing specific surgical procedures for head and neck cancer remains a barrier for accurately assessing treatment outcomes, particularly in clinical trials. While non-surgical modalities for cancer therapeutics have evolved to become far more uniform, there remains the challenge to standardize surgery. The purpose of this review is to identify the barriers in achieving uniformity and to highlight efforts by surgical groups to standardize selected operations and nomenclature. While further improvements in standardization will remain a challenge, we must encourage surgical groups to focus on strategies that provide such a level., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To provide expert opinion and consensus on salvage carbon dioxide transoral laser microsurgery (CO 2 TOLMS) for recurrent laryngeal squamous cell carcinoma (LSCC) after (chemo)radiotherapy [(C)RT]., Methods: Expert members of the European Laryngological Society (ELS) Cancer and Dysplasia Committee were selected to create a dedicated panel on salvage CO 2 TOLMS for LSCC. A series of statements regarding the critical aspects of decision-making were drafted, circulated, and modified or excluded in accordance with the Delphi process., Results: The expert panel reached full consensus on 19 statements through a total of three sequential evaluation rounds. These statements were focused on different aspects of salvage CO 2 TOLMS, with particular attention on preoperative diagnostic work-up, treatment indications, postoperative management, complications, functional outcomes, and follow-up., Conclusion: Management of recurrent LSCC after (C)RT is challenging and is based on the need to find a balance between oncologic and functional outcomes. Salvage CO 2 TOLMS is a minimally invasive approach that can be applied to selected patients with strict and careful indications. Herein, a series of statements based on an ELS expert consensus aimed at guiding the main aspects of CO 2 TOLMS for LSCC in the salvage setting is presented., (© 2021. The Author(s).)

Purpose: We assessed current policies and perceptions of enteral tube feeding in head and neck cancer (HNC) patients undergoing chemoradiotherapy (CRT). A web-based survey was used to compare the timing and method of tube feeding within and between the five Nordic countries, covering a population of 27 million., Methods: From each of the 21 Nordic university hospitals, one oncologist and one otorhinolaryngology-head and neck (ORL-HN) surgeon responded to a survey. The respondents were asked whether tube insertion before the onset of CRT, or during CRT as required (prophylactic vs. reactive) was preferred. The use of a pretreatment nutritional screening tool and the choice of feeding route (nasogastric vs. gastrostomy tube) were assessed. In total, we analyzed responses from 21 oncologists and 21 ORL-HN surgeons., Results: A tendency was observed towards decreasing the use of a PEG tube. Of the 21 university hospitals, only 2 (10%) reported using a prophylactic PEG tube in over half of HNC patients undergoing definitive CRT. The preferred method for reactive tube feeding was by a NG tube in 14 of 21 (67%), and by a PEG in 7 of 21 (33%). In general, both oncologists and ORL-HN surgeons were content with their current policy., Conclusions: The practices for enteral tube feeding in HNC management vary within and between the Nordic countries. We suggest that unified protocols for tube feeding should be developed for this patient population., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Cancers of the head and neck region often present with nodal involvement. There is a long-standing convention within the community of head and neck radiation oncology to irradiate both sides of the neck electively in almost all cases to include both macroscopic and microscopic disease extension (so called elective nodal volume). International guidelines for the selection and delineation of the elective lymph nodes were published in the early 2000s and were updated recently. However, diagnostic imaging techniques have improved the accuracy and reliability of nodal staging and as a result, small metastases that used to remain undetected and were thus in the past included in the elective nodal volume, will now be included in high-dose volumes. Furthermore, the elective nodal areas are situated close to the parotid glands, the submandibular glands and the swallowing muscles. Therefore, irradiation of a smaller, more selected volume of the elective nodes could reduce treatment-related toxicity. Several researchers consider the current bilateral elective neck irradiation strategies an overtreatment and show growing interest in a unilateral nodal irradiation in selected patients. The aim of this article is to give an overview of the current evidence about the indications and benefits of unilateral nodal irradiation and the use of SPECT/CT-guided nodal irradiation in squamous cell carcinomas of the head and neck., (© 2021 Wiley Periodicals LLC.)

Background: The five Nordic countries with a population of 27M people form a rather homogenous region in terms of health care. The management of Head and Neck Cancer (HNC) is centralized to the 21 university hospitals in these countries. Our aim was to survey the current status of organization of palliative care for patients with HNC in the Nordic countries as the field is rapidly developing., Materials and Methods: A structured web-based questionnaire was sent to all the Departments of Otorhinolaryngology-Head and Neck Surgery and Oncology managing HNC in the Nordic countries., Results: All 21 (100%) Nordic university hospitals responded to the survey. A majority (over 90%) of the patients are discussed at diagnosis in a multidisciplinary tumor board (MDT), but the presence of a palliative care specialist is lacking in 95% of these MDT's. The patients have access to specialized palliative care units (n = 14, 67%), teams (n = 10, 48%), and consultants (n = 4, 19%) in the majority of the hospitals., Conclusion: The present results show that specialized palliative care services are available at the Nordic university hospitals. A major finding was that the collaboration between head and neck surgeons, oncologists and palliative care specialists is not well structured and the palliative care pathway of patients with HNC is not systematically organized. We suggest that early integrated palliative care needs to be included as an addition to the already existing HNC care pathways in the Nordic countries.

Background: Oral cancer can show heterogenous patterns of behavior. For proper and effective management of oral cancer, early diagnosis and accurate prediction of prognosis are important. To achieve this, artificial intelligence (AI) or its subfield, machine learning, has been touted for its potential to revolutionize cancer management through improved diagnostic precision and prediction of outcomes. Yet, to date, it has made only few contributions to actual medical practice or patient care., Objectives: This study provides a systematic review of diagnostic and prognostic application of machine learning in oral squamous cell carcinoma (OSCC) and also highlights some of the limitations and concerns of clinicians towards the implementation of machine learning-based models for daily clinical practice., Data Sources: We searched OvidMedline, PubMed, Scopus, Web of Science, and Institute of Electrical and Electronics Engineers (IEEE) databases from inception until February 2020 for articles that used machine learning for diagnostic or prognostic purposes of OSCC., Eligibility Criteria: Only original studies that examined the application of machine learning models for prognostic and/or diagnostic purposes were considered., Data Extraction: Independent extraction of articles was done by two researchers (A.R. & O.Y) using predefine study selection criteria. We used the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) in the searching and screening processes. We also used Prediction model Risk of Bias Assessment Tool (PROBAST) for assessing the risk of bias (ROB) and quality of included studies., Results: A total of 41 studies were published to have used machine learning to aid in the diagnosis/or prognosis of OSCC. The majority of these studies used the support vector machine (SVM) and artificial neural network (ANN) algorithms as machine learning techniques. Their specificity ranged from 0.57 to 1.00, sensitivity from 0.70 to 1.00, and accuracy from 63.4 % to 100.0 % in these studies. The main limitations and concerns can be grouped as either the challenges inherent to the science of machine learning or relating to the clinical implementations., Conclusion: Machine learning models have been reported to show promising performances for diagnostic and prognostic analyses in studies of oral cancer. These models should be developed to further enhance explainability, interpretability, and externally validated for generalizability in order to be safely integrated into daily clinical practices. Also, regulatory frameworks for the adoption of these models in clinical practices are necessary., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The clinical significance of tumor-stroma ratio (TSR) has been examined in many tumors. Here we systematically reviewed all studies that evaluated TSR in head and neck cancer., Methods: Four databases (Scopus, Medline, PubMed and Web of Science) were searched using the term tumo(u)r-stroma ratio. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) were followed., Results: TSR was studied in nine studies of different subsites (including cohorts of nasopharyngeal, oral, laryngeal and pharyngeal carcinomas). In all studies, TSR was evaluated using hematoxylin and eosin staining. Classifying tumors based on TSR seems to allow for identification of high-risk cases. In oral cancer, specifically, our meta-analysis showed that TSR is significantly associated with both cancer-related mortality (HR 2.10, 95%CI 1.56-2.84) and disease-free survival (HR 1.84, 95%CI 1.38-2.46)., Conclusions: The assessment of TSR has a promising prognostic value and can be implemented with minimum efforts in routine head and neck pathology.