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Background: Ear and temporal bone squamous cell carcinoma (ETBSCC) is a rare and aggressive malignant tumor with minimal clinicopathological studies. The object of this study was to retrospectively evaluate the predictive effect of clinicopathological variables on the 5-year overall survival (OS) rate of ETBSCC patients in a single tertiary medical center in Tianjin, China., Methods: A cohort of 44 patients with diagnosed ETBSCC from December 2012 to August 2022 were retrospectively studied. Univariate and multivariate analysis were, respectively, performed for the assessment of clinicopathological predictors, including sex, age, history of chronic suppurative otitis media (CSOM), lesion side, diameter, the choice of surgical approach, parotidectomy, neck dissection, adjuvant therapies, T stage, lymph node metastasis, tumor grade, margin, perineural invasion (PNI), and Ki-67 index., Results: Seventeen females and 27 males were included, with the mean age of 65 years old, ranging from 36 to 89 years. The 5-year OS rate was 43% (mean 51 months, 95% confidence interval [CI] = 39-64). Significant prediction of a worse prognosis for 5-year OS rate was observed under univariate analysis for advanced T stage, positive margin, identified PNI, and higher Ki-67 index, respectively. Advanced T stage was confirmed to be an independent prognostic factor strongly affecting 5-year OS rate among this cohort of patients using a multivariate cox proportional hazard model., Conclusion: We found that clinicopathological parameters, especially postoperative pathological parameters, play a critical role in predicting the prognosis of ETBSCC patients., (© 2024 Wiley Periodicals LLC.)

Background: Hypopharyngeal cancer, constituting 3%-5% of head and neck cancers, predominantly presents as squamous cell carcinoma, with a 5-year overall survival rate of approximately 40%. Treatment modalities for locally advanced cases include chemoradiotherapy; however, the role of upfront neck dissection (UND) remains controversial. This study aimed to investigate the effect of UND on definitive radiotherapy in locally advanced hypopharyngeal carcinoma., Methods: This retrospective analysis included consecutive patients with locally advanced hypopharyngeal squamous cell carcinoma who were treated in our department between January 2007 and June 2023. All patients underwent definitive radiotherapy (dRT) at a total dose of 70 Gy in 35 fractions. The patients were categorized into two groups: dRT (radiotherapy with or without chemotherapy) and UND-dRT (surgical neck dissection followed by radiotherapy). Univariate Cox models and multivariate analyses were conducted to investigate the independent prognostic factors for overall survival and locoregional control rate., Results: This study included 115 patients, predominantly male (109/115), with a median age of 66 years. Clinical stage and chemotherapy distribution differed significantly between the dRT and UND-dRT groups. The 3-year overall survival and locoregional control rates for all patients were 63.8% and was 63.3%, respectively. The UND-dRT group exhibited a trend toward improved locoregional control, although this difference was not statistically significant. The multivariate analysis revealed that UND was an independent factor significantly associated with improved overall survival and locoregional control., Conclusion: This study provided evidence supporting the effectiveness of UND in conjunction with definitive radiotherapy for locally advanced hypopharyngeal carcinoma. Future research should focus on validating and refining these findings through well-designed prospective multicenter trials., (© 2024 The Author(s). Head & Neck published by Wiley Periodicals LLC.)

Purpose: This study aims to analyze the clinicopathological characteristics and survival outcomes of tongue cancer in the pediatric population, a topic with limited existing data, using a population-based cohort., Methods: Pediatric patients diagnosed with tongue cancer from 1975 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Survival rates were assessed using Kaplan-Meier analysis. Univariate survival analysis was conducted with the log-rank test, while multivariate analysis involved Cox proportional-hazards regression to identify factors influencing overall survival (OS). A predictive nomogram was developed based on Cox regression findings., Results: In total, 97 pediatric patients with tongue cancer were identified, with a median age at diagnosis of 15 years (range: 1-19 years). Tumors were classified as squamous cell carcinoma (45.4%), rhabdomyosarcoma (RMS) (13.4%), and others (41.2%). Of the patients, squamous cell carcinoma was more common in older children, whereas rhabdomyosarcoma was more common in younger children. The Cox proportional hazard regression revealed that histology and surgery were significant independent predictors of overall survival. The chance of death increased with no surgery. Moreover, patients with squamous cell carcinoma or rhabdomyosarcoma have a poorer survival percentage than patients with other subtypes., Conclusions: Tongue cancer in children is rare and associated with poor survival outcomes. This study highlights the significance of tumor histology and surgical intervention in determining overall survival, offering valuable insights for clinical decision-making in pediatric tongue cancer., (© 2024 Wiley Periodicals LLC.)

Background: Despite advances in treatment, residual or recurrent tumors after definitive (chemo) radiotherapy for laryngeal and hypopharyngeal squamous cell carcinoma (SCC) remain a challenge in clinical management and require accurate and timely detection for optimal salvage therapy. This study aimed to compare the diagnostic value of Fluorine 18 ( 18 F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) and diffusion-weighted magnetic resonance imaging (DW-MRI) in detecting residual or recurrent tumors after definitive (chemo) radiotherapy for laryngeal and hypopharyngeal SCC., Methods: A prospective study was conducted on 30 patients who presented with new symptoms after definitive (chemo) radiotherapy for laryngeal (n = 21) and hypopharyngeal (n = 9) carcinoma. Both 18 F-FDG PET/CT and DW-MRI were performed and histopathologic analysis served as the standard of reference., Results: Histopathology showed 20 patients as positive and 10 as negative for tumors. 18 F-FDG PET/CT detected all tumors correctly but was falsely positive in one case. DW-MRI detected tumors in 18 out of 20 positive patients and correctly excluded tumors in all negative patients. The sensitivity and specificity of 18 F-FDG PET/CT were 100% and 90%, respectively, while the values for DW-MRI were 90% and 100%, respectively., Conclusions: The study concludes that 18 F-FDG PET/CT is slightly superior to DW-MRI in detecting residual or recurrent tumors after definitive (chemo) radiotherapy for laryngeal and hypopharyngeal SCC. The combined use of 18 F-FDG PET/CT and DW-MRI can potentially improve specificity in therapy response evaluation., (© 2024 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background: The purpose of this study was to provide further insights into whether age and/or sex are associated with prognosis in oral tongue squamous cell carcinoma., Methods: This was a retrospective cohort study utilizing hospital registry data from 2006 to 2016 obtained from the National Cancer Database. Identified patients were divided into various cohorts based on age, sex, and staging. A descriptive analysis was performed using chi-square tests and overall survival rates were estimated using Kaplan-Meier method., Results: A total of 17 642 patients were included in the study. The 5-year overall survival rates were 82.0% (95% CI: 79.8%-84.0%) in younger patients versus 67.5% (95% CI: 66.7%-68.3%, p-value <0.0001) older patients. The median overall survival for females was 143.4 months (95% CI: 133.2-NA) versus 129.8 (95% CI: 125.4-138.7, p-value <0.0001) in males., Conclusions: Our analysis suggests that younger age and female sex are both predictors of improved survival in oral tongue squamous cell carcinoma., (© 2024 Wiley Periodicals LLC.)

Background: Evaluate whether extranodal extension (ENE) extent impacts outcomes in patients with oral cavity squamous cell carcinoma (OCSCC)., Methods: From an institutional database, patients with OCSCC and pathologic ENE who received adjuvant treatment were included. Surgical slides were reviewed to confirm ENE extent. Multivariable Cox regression was used to relate patient/treatment characteristics with disease-free survival (DFS) and overall survival (OS). ENE was analyzed as both a dichotomous and continuous variable., Results: A total of 113 patients were identified. Between major (>2 mm) versus minor ENE (≤2 mm), there was no significant difference in DFS (HR 1.18, 95%CI 0.72-1.92, p = 0.51) or OS (HR 1.17, 95%CI 0.70-1.96, p = 0.55). There was no significant association between ENE as a continuous variable and DFS (HR 0.97 per mm, 95%CI 0.87-1.4, p = 0.96) or OS (HR 0.96 per mm, 95%CI 0.83-1.11, p = 0.58)., Conclusion: No significant relationship was seen between ENE extent and DFS or OS in individuals with OCSCC., (© 2024 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background: There are no large studies reporting oncological or survival outcomes for patients diagnosed with perineural spread (PNS) of cutaneous squamous cell carcinoma (cSCC) via the ophthalmic nerve (V 1 ). Where orbital exenteration may be necessary for curative treatment, it is critical to have survival data with which the morbidity associated with surgical treatment can be justified. Furthermore, with the emerging treatment option of immunotherapy, current standard of care outcomes are needed to help guide future trial design and eventually changed management guidelines., Objective: To determine the oncological and survival outcomes observed in patients with PNS of cSCC via V 1 ., Materials and Methods: Retrospective analysis of prospectively maintained cohort of patients with PNS of cSCC via V1 treated in a tertiary Australian head and neck oncology/skull base referral center. Consecutive sample of 53 patients managed between March 1, 1999 and April 30, 2020. Follow-up closure date was September 1, 2021. Curative-intent surgery, curative-intent radiotherapy, or palliative care was undertaken. Endpoints included five-year overall, disease-specific, and disease-free survival from the date of treatment., Results: Five-year Kaplan-Meier overall survival was 61.9% (95% CI 46.2%-74.3%), with disease-specific survival of 74.6% (95% CI 58.8%-85.3%), and disease-free survival 62.1% (95% CI 46.5%-74.3%). Survival was superior in patients treated via surgery and adjuvant radiotherapy than in those receiving surgery alone or definitive radiotherapy. Survival was superior among patients with less advanced disease as assessed by the Williams zonal staging system; patients with Zone 1 disease had disease-specific survival of 94.1% at 5 years with 82.5% disease-free survival., Discussion: Five-year oncological and survival outcomes in this cohort were favorable. Superior survival was observed in patients treated with curative-intent surgery and adjuvant radiotherapy. Less extensive disease as delineated by the Williams zonal staging system was associated with improved survival., Conclusion: Surgical resection with adjuvant radiotherapy confers favourable oncological and survival outcome in patients with V1 PNS, particularly with early disease limited to Zone 1., (© 2024 The Author(s). Head & Neck published by Wiley Periodicals LLC.)

Objective: Our objective is to assess the oncologic outcomes of observation, elective neck dissection (END), and elective neck irradiation (ENI) in the neck management of head and neck cutaneous squamous cell carcinoma (HNcSCC) with parotid metastasis (P+) and to evaluate the quality of life (QoL) of patients who received END or ENI., Methods: Patients with P+ HNcSCC were retrospectively enrolled. The impact of observation, END, and ENI on regional control (RC) and overall survival (OS) was analyzed using Cox proportional hazards model with presentation via hazard ratio (HR) with a 95% confidence interval (CI). QoL was evaluated using the University of Washington Quality of Life questionnaire., Results: A total of 134 patients were included in our analysis. In the Cox model for RC, both END and ENI had decreased HRs of 0.27 (95% CI: 0.15-0.69) and 0.34 (95% CI: 0.18-0.86), respectively, in comparison with observation. In the Cox model for OS, both END (p = 0.001, HR: 0.22, 95% CI: 0.10-0.72) and ENI (p = 0.006, HR: 0.30, 95% CI: 0.17-0.83) were superior to observation. In patients with three or more positive parotid lymph nodes, END resulted in significantly better RC (p < 0.001) and OS (p = 0.001) compared with ENI. The two groups were found to be comparable in all 12 domains of the University of Washington Quality of Life questionnaire., Conclusion: In the neck management of P+ HNcSCC, observation is not recommended. END is the preferred option, but ENI is an alternative method without compromise to survival or QoL, except in cases with three or more metastatic parotid lymph nodes., (© 2024 Wiley Periodicals LLC.)

Background: Hypopharyngeal carcinoma is likely to spread to the lymph nodes, but there is no established strategy for management in transoral surgery., Methods: We compared oncologic and functional outcomes in a retrospective multicenter study of patients who underwent transoral surgery for hypopharyngeal carcinoma between 2015 and 2021., Results: Two-hundred and thirty-two patients were included. Comparing patients with and without adjuvant radiotherapy, 3-year regional recurrence-free survival (RRFS) was not significantly different in pN2b and pN2c, but was significantly worse in pN3b without adjuvant radiotherapy. In patients without neck dissection, the 3-year RRFS was 85.6%, 76.8%, and 70.0% for T1, T2, and T3 primary lesions, respectively, and was significantly worse for T2 or higher (p = 0.035)., Conclusions: In the absence of extracapsular invasion, regional control did not deteriorate without adjuvant therapy. If prophylactic neck dissection is not performed, careful follow-up is necessary if the primary lesion is T2 or greater., (© 2024 Wiley Periodicals LLC.)

Background: Differences in pretreatment body mass index (BMI) have been associated with survival in squamous cell carcinoma of head and neck (SCCHN). We examined effects of BMI on survival in SCCHN patients after stratifying patients by tumor human papillomavirus (HPV) status and subsite., Methods: Totally 2204 SCCHN patients in a prospective study were included in this secondary analysis. Multivariable Cox models were used to evaluate associations between pretreatment BMI and overall survival, disease-specific survival, and disease-free survival., Results: BMI was significantly higher among patients with HPV-positive tumors than HPV-negative tumors. BMI >25 kg/m 2 was associated with improved survival, while BMI <18.5 kg/m 2 was associated with reduced survival, particularly in patients with HPV-positive oropharyngeal cancer tumors., Conclusions: This exploratory analysis suggests that pretreatment BMI could be an independent prognostic factor of survival outcomes in SCCHN patients, particularly in patients with HPV-positive oropharyngeal cancer tumors. Further prospective investigations are warranted., (© 2024 Wiley Periodicals LLC.)

Background: An international multidisciplinary panel of experts aimed to provide consensus guidelines describing the optimal intratumoral and intranodal injection of NBTXR3 hafnium oxide nanoparticles in head and neck squamous cell carcinoma (HNSCC) of the oral cavity, oropharynx, and cervical lymph nodes and to review data concerning safety, feasibility, and procedural aspects of administration., Methods: The Delphi method was used to determine consensus. A 4-member steering committee and a 10-member monitoring committee wrote and revised the guidelines, divided into eight sections. An independent 3-member reading committee reviewed the recommendations., Results: After two rounds of voting, strong consensus was obtained on all recommendations. Intratumoral and intranodal injection was deemed feasible. NBTXR3 volume calculation, choice of patients, preparation and injection procedure, potential side effects, post injection, and post treatment follow-up were described in detail., Conclusions: Best practices for the injection of NBTXR3 were defined, thus enabling international standardization of intratumoral nanoparticle injection., (© 2024 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background: This study assessed a palliative radiotherapy regimen using daily radiation over 4 days for three courses in inoperable head and neck cancers, emphasizing oral primary cancers., Methods: Retrospective data of 116 patients treated with a daily dose of 3.6-3.7 Gy in four fractions over 4 days to a total of three courses, with a 2-week gap after every course, were analyzed for survival outcomes. A subgroup analysis was done for oral cancer., Results: Ninety-nine (85%) completed three courses. Overall subjective response rate was 77%. Median overall survival and progression-free survival were 12 months (95% confidence interval [CI]: 8-20) and 8 months (95% CI: 6-10), with numerically higher overall survival in oral cancer. The treatment was well tolerated, with no on-treatment hospitalization or grade 3-4 toxicities., Conclusion: The modified QUAD SHOT regimen is practical for palliation in head and neck cancers., (© 2024 Wiley Periodicals LLC.)

Background: Massive oropharyngeal bleeding post-chemoradiotherapy is a life-threatening condition that requires emergent management., Methods: This retrospective case series included 11 patients with oropharyngeal squamous cell carcinoma who suffered from massive bleeding during or following treatment with definitive chemoradiotherapy. Details of acute and definitive management of oropharyngeal bleeding are reported., Results: Nine of 11 hemorrhagic events occurred a mean (SD) of 88.6 days (53.6) after radiotherapy. Airway intubation and embolization were performed in 10 of 11 patients, followed by surgery in 7 of 11 patients. The most commonly embolized vessels were the external carotid and lingual arteries. At the time of discharge, 3 of 11 patients had a tracheostomy, and 7 of 11 continued to use a gastrostomy tube. Four patients died., Conclusions: Hemorrhagic complications in oropharyngeal cancer treatment require emergent responses. Developing a workflow for coordination between multidisciplinary teams can maximize probability of survival and decrease morbidity., (© 2024 Wiley Periodicals LLC.)

The aim of this systematic review is to shed light on the role of tumor budding (TB) in the biology, behavior, and prognosis of head and neck squamous cell carcinoma (HNSCC). A search was run in PubMed, Scopus, and Embase databases following PRISMA guidelines. After full-text screening and application of inclusion/exclusion criteria, 36 articles were included. Several investigations support the prognostic role of TB, which might play a role in selecting rational treatment strategies. To achieve this goal, further research is needed for greater standardization in TB quantification. Although TB is not included as a negative prognostic factor in the current management guidelines, it might be reasonable to consider a closer follow-up for HNSCC cases with high histopathological evidence of TB., (© 2023 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background: Human papillomavirus association has changed the landscape of treatment for oropharyngeal squamous cell carcinoma; it remains to be seen whether current post-treatment surveillance schedules are effective., Objective: Evaluate whether post-treatment surveillance of oropharyngeal cancer through FDG-PET imaging is modified by human papillomavirus association., Methods: A prospective cohort analysis of retrospective data was conducted for patients undergoing treatment of oropharyngeal cancer between 2016 and 2018. This study was conducted at a single large tertiary referral center in Brisbane, Australia., Results: Two-hundred and twenty-four patients were recruited for the purposes of the study, 193 (86%) with HPV-associated disease. In this cohort FDG-PET had a sensitivity of 48.3%, specificity of 72.6%, positive predictive value of 23.7%, and negative predictive value of 88.8% in detecting disease recurrence., Conclusions: FDG-PET in HPV-associated oropharyngeal cancer has significantly lower positive predictive value when compared to non-HPV-associated oropharyngeal cancer. Caution should be used when interpreting positive post-treatment FDG-PET., (© 2023 Wiley Periodicals LLC.)

Background: Distant metastasis (DM) development in Oropharyngeal Squamous Cell Carcinoma (OPSCC) represents an important prognostic factor. The identification of a phenotype of metastatic patients may better define therapeutic and follow-up programs., Methods: We included 408 patients with OPSCC, non-metastatic at the time of diagnosis, and treated with curative intent. The Overall Survival (OS) analyses were performed and the impact of developing DM on survival was analyzed through Cox proportional-hazard regression model., Results: 57 (14%) patients develop DM. 302 (74%) were p16+ OPSCC and 35 of them experienced DM. Advanced clinical stage, smoking, p16-status, response to primary treatment, and loco-regional relapse influence the DM rate. Only in the p16+ group, DM onset results in a greater impact on OS (p < 0.0001). Lung metastases have a better OS compared to non-pulmonary ones (p = 0.049)., Conclusion: This retrospective study shows a possible stratification of OPSCC patients based on the risk of the development of DMs., (© 2023 Wiley Periodicals LLC.)

Background: Oral potentially malignant disorders (OPMD) are associated with the risk of malignant transformation (MT) into oral cavity carcinoma (OCC). Oral lichen planus (OLP) is one of the most common OPMDs in western countries. Although there is a substantial amount of research on progression to cancer, a specific analysis of the clinical characteristics and prognosis of cancer developed in patients with a history of OLP versus patients without a history of OLP has not been investigated so far., Methods: Retrospective evaluation of 82 patients treated for OCC with a known history of OLP compared to a representative sample of 82 patients treated for OCC without a known history of LP. Comparative analyses were performed on age at presentation, sex, TNM staging, clinical characteristics, pathology characteristics, 2- and 5-year overall survival (OS), and disease-free survival (DFS)., Results: It was shown that patients with a history of LP were significantly younger at first presentation than patients without a history of LP (mean age difference 6.7 years, 95% CI 3.1-10.3, p < 0.05). Also, patients with a history of OLP were in higher proportion females. The main pathological stage at presentation was significantly lower in the OLP group (p < 0.05). The 2-year survival analysis showed that DFS and OS were significantly lower in patients without a known history of OLP, with a hazard ratio (HR) of 3.1 (95% CI 1.4-6.8) and HR of 2.6 (95% CI 1.3-5.3), respectively. The 5-year survival analysis showed that DFS and OS were significantly lower in patients without a known history of OLP, with a hazard ratio of 3.1 (95% CI 1.6-6.2) and of 2.9 (95% CI 1.5-5.6), respectively., Conclusions: Cancer arising from OLP has peculiar characteristics compared to cancer in naïve patients. It most commonly affects younger patients, women, and nonsmokers. It is usually diagnosed at earlier stages and appears to have less aggressive behavior at presentation. Moreover, when 2- and 5-year survival is analyzed, it appears that patients in OLP group have an overall and a disease-free survival advantage. These results suggest that cancer from OLP is less aggressive and thus has a potential biological difference with cancer arising in non-OLP patients. Further clinical and basic investigations are needed to confirm the results of this study., (© 2023 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background: The literature on modern-era outcomes of oropharyngeal squamous carcinoma (OPSCC) in India is limited., Materials and Methods: We analyzed records of consecutive patients with OPSCC treated using a curative SIB IMRT regimen of 66 Gy/30#/6 weeks., Results: One hundred fifteen patients from July 2011 to December 2018 were analyzed. Twenty of 69 patients tested positive for p16. In p16 positive patients, the K-M probability of being disease free and alive at 2 years, with at least one follow-up 3 months after treatment, was 83% (median not reached) compared with 48% if p16 was unknown/negative. Patients staged as IVB p16 negative had a 2-year DFS of 25%. Patients unfit for cisplatin and consequently received other agents had 2-year DFS estimated at 20%., Conclusions: Intensity-modulated radiation therapy (IMRT) with simultaneous integrated boost (SIB) and concurrent chemotherapy was feasible, with toxicity and disease control comparable to available literature. AJCC Stage IVB p16 negative disease had notably poor outcome., (© 2023 Wiley Periodicals LLC.)

Background: Radiomics represents an emerging field of precision-medicine. Its application in head and neck is still at the beginning., Methods: Retrospective study about magnetic resonance imaging (MRI) based radiomics in oral tongue squamous cell carcinoma (OTSCC) surgically treated (2010-2019; 79 patients). All preoperative MRIs include different sequences (T1, T2, DWI, ADC). Tumor volume was manually segmented and exported to radiomic-software, to perform feature extraction. Statistically significant variables were included in multivariable analysis and related to survival endpoints. Predictive models were elaborated (clinical, radiomic, clinical-radiomic models) and compared using C-index., Results: In almost all clinical-radiomic models radiomic-score maintained statistical significance. In all cases C-index was higher in clinical-radiomic models than in clinical ones. ADC provided the best fit to the models (C-index 0.98, 0.86, 0.84 in loco-regional recurrence, cause-specific mortality, overall survival, respectively)., Conclusion: MRI-based radiomics in OTSCC represents a promising noninvasive method of precision medicine, improving prognosis prediction before surgery., (© 2023 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background: Although strongly associated with tobacco and alcohol use, many oral cavity squamous cell carcinoma (OCSCC) cases occur in patients without exposure to either, known as "never-smoker, never-drinkers" (NSND). We aimed to compare clinical outcomes between NSND and tobacco/alcohol-exposed populations and to define demographic characteristics of NSND., Methods: We performed a retrospective, single-institution cohort study of 672 OCSCC patients. Cox models were used to estimate differences in overall survival (OS) and recurrence-free survival (RFS) between NSND and tobacco/alcohol-exposed patients while adjusting for confounders., Results: NSND represented 25.6% of our cohort and were older, more female, and more economically advantaged. Among NSND, oral tongue tumors dominated in younger patients, while alveolar ridge tumors dominated in elderly patients. Multivariate survival analysis revealed no differences in OS or RFS between NSND and tobacco/alcohol-exposed patients., Conclusion: When adjusted for independent biologic features, clinical outcomes in OCSCC are similar between NSND and tobacco/alcohol-exposed patients., (© 2022 Wiley Periodicals LLC.)

Esophageal basaloid squamous cell carcinoma (bSCC) is a subtype of squamous cell carcinoma (SCC) with a different behavior and poor prognosis. Exploring bSCC's molecular characteristics and treatment strategies are of great clinical significance. We performed multi-omics analysis of paired bSCC and common SCC (cSCC) using whole exome sequencing and a NanoString nCounter gene expression panel. Immunohistochemistry was used for verification of candidate biomarkers. Different treatment response was analyzed on both patients receiving neoadjuvant treatment and late-stage patients. The common genetically-clonal origin of bSCC and cSCC was confirmed. No significant differences between their genetic alterations or mutation spectra were observed. Mutation signature 15 (associated with defective DNA damage repair) was less prominent, and tumor mutational burden (TMB) was lower in bSCC. bSCC with an RNA expression pattern resembling cSCC had a better survival than other bSCCs. Moreover, bSCC showed significant upregulation of expression of genes associated with angiogenesis response, basement membranes, and epithelial-mesenchymal transition, and downregulation of KRT14 (squamous differentiation) and CCL21 (associated with immune response). Immunohistochemistry for SFRP1 was shown to be highly sensitive and specific for bSCC diagnosis (p < 0.001). In addition, bSCC receiving neoadjuvant immuno-chemotherapy had a worse pathological response than bSCC receiving neoadjuvant chemotherapy (but without statistical significance), even in bSCC positive for PD-L1. Our results demonstrated the molecular characteristics of esophageal bSCC as a subtype with a distinct RNA expression pattern and immune characteristics, but no specific genetic mutations. We provided a useful biomarker, SFRP1, for diagnosis. After outcome analysis for six bSCCs with neoadjuvant immunotherapy treatment and four late-stage bSCCs with immunotherapy, we found that immunotherapy may not be an effective treatment option for most bSCCs. This may also provide a clue for the same subtypes of lung and head and neck cancer. Our study highlighted the heterogeneity among bSCC patients, and might explain the conflicting results of bSCC outcomes in existing studies. © 2022 The Pathological Society of Great Britain and Ireland., (© 2022 The Pathological Society of Great Britain and Ireland.)

Background: Knowledge of the prognostic factors and performance of machine learning predictive models for 2-year cancer-specific survival (CSS) is limited in the head and neck cancer (HNC) population., Methods: Data from our facilities' oncology information system (OIS) collected for routine practice (OIS dataset, n = 430 patients) and research purposes (research dataset, n = 529 patients) were extracted on adults diagnosed between 2000 and 2017 with squamous cell carcinoma of the head and neck., Results: Machine learning demonstrated excellent performance (area under the curve, AUC) in the whole cohort (AUC = 0.97, research dataset), larynx cohort (AUC = 0.98, both datasets), and oropharynx cohort (AUC = 0.99, both datasets). Tumor site and T classification were identified as predictors of 2-year CSS in both datasets. Hypothyroidism and fitness for operation were further identified in the research dataset., Conclusions: Datasets extracted from an OIS for routine clinical practice and research purposes demonstrated high utility for informing 2-year head and neck CSS., (© 2022 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background: Accurate epidemiological and outcomes data regarding cutaneous squamous cell carcinoma (cSCC) extending to the temporal bone is lacking., Methods: Retrospective analysis of 167 Australian patients with primary and peri-temporal bone cSCC., Results: cSCC extending from secondary subsites (93.4%) was 14 times more frequent than primary temporal bone SCC (6.6%). For patients who underwent curative surgery ± post-operative radiotherapy (n = 146, 87.4%), 5-year disease-free survival, locoregional recurrence-free survival, disease-specific survival, and overall survival was 53.0%, 59.4%, 67.9%, and 44.7%, respectively. External ear and pre-auricular tumors, salvage surgery, tumor size (≥40 mm medial-lateral), nodal disease, and involved margins were negative predictors of survival in multivariable analysis., Conclusion: In regions of high sun exposure, cSCCs extending to the temporal bone are more common than primary cancers. Outcomes are improved with clear margins, justifying the need for radical resection. Further research regarding pre-auricular cancers is required given poorer associated survival outcomes., (© 2022 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background: To retrospectively investigate the prognostic role of baseline 18 F-FDG PET/CT in squamous cell carcinoma (SCC) of the paranasal sinuses., Methods: Clinical features and PET/CT semiquantitative parameters of 49 patients were collected. Anova and Kruskall-Wallis tests were used to assess the relationship between these parameters. Kaplan-Meier, univariate, and multivariate analysis were performed to search for independent prognostic factors for progression free (PFS) and overall survival (OS)., Results: Mean PFS was 29.95 months (SD 29.36) with relapse/progression of disease occurring in 18 patients; mean OS was 33.40 (SD 27.78) months with death occurring in 15 patients. Presence of nodal metastasis (14 subjects) was correlated with standardize uptake value (SUV) max, SUVmean, SUV/blood-pool ratio, SUV/liver ratio, metabolic tumor volume, and total lesion glycolysis. SUVmax, SUVmean, and presence of nodal metastasis resulted as independent prognostic factors for OS., Conclusion: 18 F-FDG PET/CT semiquantitative parameters confirmed their prognostic role for SCC of paranasal sinuses., (© 2022 Wiley Periodicals LLC.)

Background: Immune checkpoint inhibitors have shown promising antitumour activity. Application in head and neck cutaneous squamous cell carcinoma (cSCC) large nerve perineural spread (PNS) is limited., Methods: Retrospective review of 13 patients with PNS receiving anti-PD-1 therapy from September 2017 to May 2021 is presented. Primary endpoints were objective response (complete or partial response) and median time to progression, determined by Head and Neck Multi-Disciplinary Team (MDT) and independent radiology review of magnetic resonance imaging (MRI) and/or computed tomography/positron emission tomography (CT/PET)., Results: Objective response was observed in 9/13 patients (69%), with complete response in 6 (46%) and partial response in 3 patients (23%). Median time to response was 2.1 months (IQR 1.8-2.7 months). There were 3 (23%) patients with progressive disease, with median time to progression of 3.5 months. There were no grade 3-4 treatment related adverse events., Conclusions: This case series supports developing evidence for anti-PD-1 checkpoint inhibitor therapy for perineural spread, supporting future prospective clinical trials in this patient population., (© 2022 Wiley Periodicals LLC.)

To perform a systematic review focusing on the prognosis of oral cavity squamous cell carcinoma (OSCC) in young patients (≤40 years old) compared to older (>40 years old). Four databases were used in our search strategy. First, all titles were systematically organized using the Covidence platform online. In the second phase, 118 full texts of potentially eligible studies were analyzed by reviewers independently and in pairs. Twelve studies were considered eligible for data extraction. The relapse was higher in the young than in controls (pooled relative risk (RR) = 1.31; 95% CI [1.10-1.56]). The 5-year disease-free survival (DFS) was worse in young group (pooled hazard ratio (HR) = 0.73; 95% CI [0.63-0.85]) but the 5-year overall survival (OS) estimate was similar between the groups (pooled HR = 0.84; 95% CI [0.70-1.00]). While the 5-year OS was similar between groups, the number of relapses and 5-year DFS were worse in patients with OSCC ≤40 years old., (© 2021 Wiley Periodicals LLC.)

Background: Patients with oropharyngeal cancer who undergo transoral robotic surgery (TORS) and have high-risk features generally receive adjuvant chemoradiotherapy or trimodality therapy (TMT). The notion that TMT leads to high toxicity is largely based on studies that included human papilloma virus (HPV)-negative cancers and/or nonrobotic surgery; we sought to describe outcomes in HPV-associated oropharyngeal squamous cell cancer (HPV + OPSCC) undergoing TORS-TMT., Methods: In consecutive patients with HPV + OPSCC receiving TMT at an academic center from 2010 to 2017, survival was estimated using Kaplan-Meier methodology, and toxicities were ascertained via chart review., Results: In our cohort of 178 patients, 5-year survival was 93.6%. Feeding tube rates were 25.8% at therapy completion and 0.7% at 1 year. Rates of grade ≥ 3 kidney injury, anemia, and neutropenia in cisplatin-treated patients were 2.7%, 3.4%, and 11.0%, respectively., Conclusions: Patients with HPV + OPSCC who underwent TORS-TMT had excellent survival and low rates of toxicity and feeding tube dependence. These outcomes compare favorably to historical cohorts treated with definitive chemoradiotherapy., (© 2021 Wiley Periodicals LLC.)

Background: Regional metastasis of head and neck cutaneous squamous cell carcinoma (HNcSCC) can be seen in either parotid and/or cervical lymph nodes. The aim of this study was to assess whether there was a difference in prognosis between parotid and cervical nodal metastases., Methods: Patients with regional metastasis from HNcSCC were identified from an institutional database. Disease-specific (DSS) and overall survival (OS) were calculated using the Kaplan-Meier method and Cox proportional hazards models., Results: Five hundred and thirty-five patients were identified with median follow-up of 26.4 months (3-255 months). Two hundred and thirty-five patients had parotid metastasis, 96 patients had neck metastasis, and 204 patients had both. On multivariable analysis, any regional metastasis to the neck when compared to parotid alone conferred worse DSS (HR 1.8, p = 0.007) and OS (HR 1.3, p = 0.024)., Conclusion: Regional metastasis of HNcSCC to the neck confers worse outcomes compared to metastasis to the parotid alone., (© 2021 Wiley Periodicals LLC.)

Standard of care for high-risk cutaneous squamous cell carcinoma (cSCC) is surgical excision of the primary lesion with clear margins when possible, and additional resection of positive margins when feasible. Even with negative margins, certain high-risk factors warrant consideration of adjuvant therapy. However, which patients might benefit from adjuvant therapy is unclear, and supporting evidence is conflicting and limited to mostly small retrospective cohorts. Here, we review literature from the last decade regarding adjuvant radiation therapy and systemic therapy in high-risk cSCC, including recent and current trials and the role of immune checkpoint inhibitors. We demonstrate evidence gaps in adjuvant therapy for high-risk cSCC and the need for prognostic tools, such as gene expression profiling, to guide patient selection. More large-cohort clinical studies are needed for collecting high-quality, evidence-based data for determining which patients with high-risk cSCC may benefit from adjuvant therapy and which therapy is most appropriate for patient management., (© 2021 Castle Biosciences, Inc. Head & Neck published by Wiley Periodicals LLC.)

Hemorrhage in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) may be attributed to chemotherapy and local tumor irradiation. Evidence of the relationship between hemorrhage in R/M HNSCC and targeted therapies, including epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) inhibitors, or immune checkpoint inhibitors, is limited. We aimed to identify epidemiological and clinical data related to the occurrence of hemorrhage in R/M HNSCC and to explore its relationship with various therapies. We describe information obtained from literature searches as well as data extracted from a commercial database and a database from the author's institution (Istituto Nazionale dei Tumori of Milan). Evidence suggests that most bleeding events in R/M HNSCC are minor. Clinical trial safety data do not identify a causal association between hemorrhage and anti-EGFR agents or immune checkpoint inhibitors. In contrast, anti-VEGF agents are associated with increased, and often severe/fatal, hemorrhagic complications., (© 2021 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Oral tongue squamous cell carcinoma (OTSCC) is a quite peculiar disease from an anatomical and biological standpoint. An increasing amount of literature highlights the existence of a small subset of T1-T2N0 OTSCC, properly resected on a margin-dependent basis, which conversely proved higher than expected rates of loco-regional/distant failure and disease-specific mortality. These specific high-risk tumors might not have a margin-dependent disease and could possibly benefit from a more aggressive upfront loco-regional treatment, especially addressing the so-called T-N tract. Widespread adoption of a histopathological risk model would allow early recognition of these high-risk diseases and, consequently, intensification of the traditional treatment strategies in that specific niche. We reviewed the available knowledge trying to shed light on the potential determinants of the dismal prognosis of these high-risk OTSCC, with special reference to the role of overlooked T-N tract involvement and possible alternatives in terms of elective neck management and risk stratification., (© 2021 Wiley Periodicals LLC.)

Background: The purpose of this study is to describe human epidermal growth factor 2 (HER2) overexpression in head and neck squamous cell carcinoma (HNSCC) and re-evaluate its potential as a target for HER2-directed immunotherapies., Methods: A retrospective cohort of patients with HNSCC receiving curative treatment was identified, and HER2 expression evaluated in archival tissue by immunohistochemistry and correlated with clinicopathological characteristics. HER2 expression data were also determined for HNSCC patients in The Cancer Genome Atlas., Results: Nineteen percent of HNSCC and 39% of oropharyngeal HNSCC (OPSCC) were HER2 positive. HER2 expression positively correlated with nodal metastasis (p = 0.035). Patients with HER2-positive tumors had decreased overall survival (p = 0.012), including within the human papilloma virus-positive OPSCC subgroup (p = 0.007)., Conclusions: A substantial fraction of HNSCC overexpresses HER2 protein, suggesting it may be a suitable target for antigen-directed immunotherapy. HER2 expression and its correlation with survival vary across HNSCC subsites, making it unsuitable as a prognostic marker., (© 2021 Wiley Periodicals LLC.)

Background: Human papilloma virus testing for oropharyngeal squamous-cell carcinoma has been recommended by the National Comprehensive Cancer Network since 2012. We examine disparities, reported rates of human papillomavirus (HPV) testing, and the impact on these findings of limitations with the variable in database registries., Methods: The HPV variable was queried for patients with oropharyngeal squamous carcinoma (OPSCC) from 2013 to 2016 in National Cancer Data Base (NCDB) and Surveillance, Epidemiology, and End Results (SEER). Multivariable regression was used to identify disparities based on sociodemographic variables. Sensitivity analyses were used to investigate limitations of the variable., Results: Despite limitations in the HPV variable in the databases, there was less than 100% adherence to recommended testing, and there were significant disparities in multiple sociodemographic variables. For example, in NCDB 70% of white versus 60.4% of black patients were tested (odds ratio [OR] 0.75, confidence interval [CI] 0.66-0.85, p ≤ 0.0001); in SEER 59.8% of white and 47.6% of black patients were tested (OR 0.73, CI 0.67-0.81; p ≤ 0.0001)., Conclusions: Disparities exist among patients undergoing testing for HPV-associated OPSCC and adherence to guideline recommended HPV testing has been suboptimal. In addition, the HPV variable definition, especially as it relates to p16 positivity, and use in these two registries should be improved., (© 2021 Wiley Periodicals LLC.)

Background: Outcomes of oropharyngeal squamous cell carcinoma (OPSCC) after development of distant metastases (DM) in the context of human papillomavirus (HPV) tumor status remain controversial in the literature., Methods: OPSCC patients with DM treated between June 2015 and March 2019 were included from a prospectively enrolled database. Characteristics of DM including sites, episodes, and timing of disease were analyzed in addition to survival after DM., Results: Sixty-nine HPV-positive and 18 HPV-negative OPSCC patients with DM were included. The 2-year survival after DM was higher for HPV-positive patients (54.0% vs. 11.3%, p < 0.001). HPV-positive patients did not demonstrate greater episodes or sites of DM. Multiple sites of DM, early development of DM, and Charlson comorbidity Index were independently associated with worse survival after DM., Conclusions: While multiple sites, early DM, and comorbidities were poor prognostic factors, OPSCC patients with distant progression can have substantial survival after DM, including M1 patients., (© 2021 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background: Cutaneous squamous cell carcinomas (CSCC) involving the head and neck are common, but initial presentation or recurrence limited to the cranial nerves is rare., Methods: We conducted a retrospective study of 21 patients with clinical perineural invasion (PNI) from CSCC and no measurable disease by RECIST 1.1. Patients treated with radiotherapy or chemoradiotherapy were included., Results: The median time from symptom onset until diagnosis was 13.0 months (2.6-83.1). All patients received radiotherapy. Fourteen received concurrent systemic therapy. The median follow-up time was 30.5 months (1.1-106.0). Ten patients recurred, with the majority being locoregional. The 2-year overall survival rate was 85%. The median progression-free survival (PFS) was 21.5 months with an estimated 2-year PFS of 44.5% (95%CI: 22.3-66.8)., Conclusions: CSCCs with clinical PNI alone are difficult to diagnose and can have a long interval between appearance of symptoms and diagnosis. They can successfully be treated with chemoradiotherapy. However, many patients still suffer from locoregional recurrences., (© 2021 Wiley Periodicals LLC.)

Background: Head and neck spindle cell carcinoma (HNSpCC) is a rare histological variant associated with worse outcomes. Our objective was to identify clinicopathological factors associated with survival in patients with HNSpCC compared to patients with conventional head and neck squamous cell carcinoma (HNSCC)., Methods: Using clinical data from the Surveillance, Epidemiology, and End Results database, we performed a survival analysis in patients with HNSpCC or HNSCC between 2004 and 2016., Results: A total of 458 HNSpCC and 77 104 HNSCC were identified, including 17% and 16% female, respectively. Five-year disease-specific survival (DSS) was 63.90% and 73.90% in patients with HNSpCC and HNSCC, respectively. Sex (hazard ratio [HR] for females = 2.816; CI: 1.139-6.965; p = 0.025) was significantly associated with DSS in HNSpCC while no association was observed between sex and DSS in HNSCC., Conclusion: HNSpCC in women is a specific subgroup of HNSCC, which is associated with a poor prognosis., (© 2021 Wiley Periodicals LLC.)

Background: Some patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) do not receive guideline-recommended postoperative radiation therapy (PORT) following primary transoral robotic surgery (TORS)., Methods: Three-hundred and sixty-four patients with treatment-naïve, HPV-associated OPSCC were recommended to receive PORT based on clinicopathological features following TORS. Patients were stratified based on if they received PORT. Oncologic outcomes were compared., Results: The 3-year locoregional failure (LRF) was 32% in patients who did not receive PORT and 4% in patients who received PORT (P < .001). Despite increased LRF, avoiding PORT was not associated with increased 3-year distant metastasis rates (8% vs 4%, P = .56) or worse 3-year survival (95% vs 98%, P = .34). Recurrences in the surgery alone cohort varied between local and regional sites and were often successfully salvaged., Conclusions: Patients with HPV-associated OPSCC who do not receive indicated PORT have an increased risk of LRF but similar survival due to high salvage rates., (© 2020 Wiley Periodicals LLC.)

Background: Nomograms applying the 8th edition of the TNM staging system aimed at predicting overall (OS), disease-specific (DSS), locoregional recurrence-free (LRRFS) and distant recurrence-free survivals (DRFS) for oral tongue squamous cell carcinoma (OTSCC) are still lacking., Methods: A training cohort of 438 patients with OTSCC was retrospectively enrolled from a single institution. An external validation set of 287 patients was retrieved from two independent institutions., Results: Internal validation of the multivariable models for OS, DSS, DRFS and LRRFS showed a good calibration and discrimination results with optimism-corrected c-indices of 0.74, 0.75, 0.77 and 0.70, respectively. The external validation confirmed the good performance of OS, DSS and DRFS models (c-index 0.73 and 0.77, and 0.73, respectively) and a fair performance of the LRRFS model (c-index 0.58)., Conclusions: The nomograms herein presented can be implemented as useful tools for prediction of OS, DSS, DRFS and LRRFS in OTSCC., (© 2021 Wiley Periodicals LLC.)

Background: Cutaneous squamous cell carcinoma of the head and neck (CSCC-HN) appears to behave more aggressively in immunosuppressed patients. We aimed to investigate this hypothesis by comparing solid organ transplant recipients (SOTR) with CSCC-HN to immunocompetent patients., Methods: A retrospective comparative study was conducted for SOTR and immunocompetent patients who were treated for CSCC-HN., Results: A total of 177 SOTR and 157 immunocompetent patients with CSCC-HN were included. Lymph node metastases were more common in the SOTR group (9% vs 3%), and distant metastases occurred only in SOTR (3% of patients). SOTR had a higher rate of recurrences (19% vs 10%), which were mostly regional (7%) and distant (3%). The 2-year disease-specific survival of SOTR was lower (93% vs 100%)., Conclusions: SOTR with CSCC-HN has significantly worse outcomes compared to immunocompetent patients. Solid-organ transplantation should be regarded as a negative prognostic factor in patients with CSCC-HN., (© 2020 Wiley Periodicals LLC.)

Purpose: The number of elderly patients with head and neck squamous cell carcinoma (HNSCC) continues to grow. Management of this cohort remains poorly defined. We investigated treatment tolerability and clinical outcomes in this underrepresented population., Methods: We identified patients aged ≥70 with nonrecurrent, nonmetastatic HNSCC treated curatively from 2007-2018 and analyzed clinical covariates., Results: Two hundred and twenty patients with a median age of 75 (interquartile range:72-80) were identified. Age and comorbidities were not correlated with toxicity (P ≥ .05). Patients who experienced a treatment interruption had significantly greater weight loss (P = .042) and worse overall survival (OS) (P < .001), but not worse disease-specific survival (P = .45), or locoregional control (P = .21)., Conclusions: Treatment interruptions were associated with weight loss and worse OS, but not disease related outcomes, suggesting an interruption in the elderly may be a surrogate for another issue. In sum, our data should guide clinical trial design to benefit this growing, neglected cohort., (© 2020 Wiley Periodicals LLC.)

Background: To analyze the characteristics and survival patterns of patients with head and neck squamous cell carcinoma (SCC) who received palliative treatment during their first course of treatment., Methods: Cohort analysis utilizing the National Cancer Data Base (NCDB) of patients with a diagnosis of oral cavity/oropharyngeal, hypopharyngeal, and laryngeal SCC. Statistical analysis included multivariate logistic regression and Cox Hazard ratio modeling, and Kaplan-Meier survival analysis., Results: 165 081 patients were included, of which 2747 patients received palliative treatment. Patients who received palliative treatment tended to be ≥65 years old, black, Charlson/Deyo score ≥3, hypopharyngeal cancer, stage (III-IV), with Medicaid insurance (P < .05). Patients were more likely to be treated with palliative intent if they underwent chemotherapy/radiotherapy and declined surgery (P < .001) compared to patients who underwent surgery and declined chemotherapy/radiotherapy (P = .006)., Conclusions: Palliative care use in head and neck oncology is associated with older patients, non-whites, Medicaid patients, and nonsurgically treated patients., (© 2020 Wiley Periodicals LLC.)

Background: The 8th edition American Joint Committee on Cancer staging manual (AJCC8) introduced a separate staging system for head and neck cutaneous squamous cell carcinoma (HNcSCC) which parallels mucosal SCC and incorporates extranodal extension (ENE). This study aims to evaluate its prognostic utility., Methods: Univariate analysis of 1146 patients with metastatic HNcSCC from four Australian cancer centers was performed according to both AJCC 7th (AJCC7) and the 8th editions., Results: AJCC8 increased classification of 924 (80.6%) patients to either pN2a or pN3b and 341 patients (29.8%) from stage III to IV compared to AJCC7. The disease-specific survival (DSS) was not significantly different between pN1, pN2 or pN3a categories per AJCC8. Estimates of model performance for the AJCC8 pN staging revealed modest predictive capacity (Harrell's C of 0.62 for DSS)., Conclusions: The risk stratification according to pN classification of AJCC8 staging system performed poorly as a prognostic indicator., (© 2020 Wiley Periodicals LLC.)

Background: Identifying and linking barriers to access to head and neck cancer care, specifically provider density, to stage of diagnosis and survival outcomes is important to serve as a foundation for policy interventions., Methods: Retrospective cohort study using patients with head and neck squamous cell (HNSCC) in the Surveillance, Epidemiology, and End Results (SEER) database from 2007 to 2016 and Area Resource File. Primary outcomes included stage of presentation and cancer-specific 5-year survival and relation to provider density., Results: The initial cohort consisted of 18 342 patients with oral cavity, 21 809 oropharyngeal, 15 860 laryngeal, and 2887 patients with hypopharyngeal malignancy. Non-Hispanic Black race and being uninsured increased the odds of presenting with advanced stage HNSCC and increased hazard of death. There was no significant and consistent association identified between Health Service Areas provider density and advanced stage at diagnosis or cancer-specific 5-year mortality., Conclusions: Provider density of otolaryngologists and primary care physicians and dentists was not significantly associated with stage of presentation or cancer-specific survival for HNSCC while race and insurance status remained independent predictors for worse outcomes., (© 2020 Wiley Periodicals LLC.)

Head and neck (HN) squamous cell carcinoma (SCC) is the eighth most common human cancer worldwide. Besides tobacco and alcohol consumption, genetic and epigenetic alterations play an important role in HNSCC occurrence and progression. microRNAs (miRNAs) are small noncoding RNAs that regulate cell cycle, proliferation, development, differentiation, and apoptosis by interfering in gene expression. Expression profiling of miRNAs showed that some miRNAs are upregulated or downregulated in tumor cells when compared with the normal cells. The present review focuses on the role of miRNAs deregulations in HNSCC, enrolled in risk, development, outcome, and therapy sensitivity. Moreover, the influence of single nucleotide variants in miRNAs target sites, miRNAs seed sites, and miRNAs-processing genes in HNSCC was also revised. Due to its potential for cancer diagnosis, progression, and as a therapeutic target, miRNAs may bring new perspectives in HNSCC understanding and therapy, especially for those patients with no or insufficient treatment options., (© 2020 Wiley Periodicals LLC.)

Background: Aggressive dose de-escalated adjuvant radiation therapy (RT) in patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV(+)OPSCC)., Methods: Patients with HPV(+)OPSCC on a phase II clinical trial of primary surgery and neck dissection followed by dose de-escalated RT (N = 79) were compared with a cohort of patients who received standard adjuvant therapy (N = 115). Local recurrence-free, regional recurrence-free, distant metastases-free survival, and progression-free survival (PFS) were assessed., Results: Of 194 patients, 23 experienced progression at a median of 1.1 years following surgery (interquartile range [IQR] 0.7-2.0; range 0.3-5.4); 10 patients in the de-escalated cohort and 13 patients in the standard cohort. The 3-year PFS rate for the de-escalated cohort was 87%, and in the standard cohort was 90% (hazard ratio [HR] 1.18, 95% confidence interval (CI) [0.50-2.75])., Conclusion: Patients with HPV(+)OPSCC who undergo surgical resection and neck dissection and meet criteria for adjuvant therapy can undergo aggressive dose de-escalation of RT without increasing risk of progression locally, regionally or at distant sites., (© 2020 Wiley Periodicals LLC.)

Objective: To identify predictors of overall survival (OS) and to stratify patients according to significant prognostic variables., Methods: A retrospective study of 274 consecutive patients with primary Oral Cavity Squamous Cell Carcinoma. Kaplan-Meier, Cox proportional hazard models, and recursive partitioning analysis (RPA) were used for analysis of OS. These results were further validated using National Cancer Database cohort of 21 895 patients., Results: Median OS was 3.65 years. T-classification and N-classification, alcoholic beverages/week, age, and adjuvant treatment were significant predictors of OS. RPA identified high-risk subpopulations: N0-1 patients with CCI ≥ 4.5 and N2-3 patients ordered by those not receiving adjuvant treatment, those with T3-4 disease despite adjuvant therapy, and those having T1-2 disease with adjuvant therapy., Conclusions: This study utilized significant prognostic indicators and RPA to highlight the importance of age, N-classification, T-classification, comorbidity, and adjuvant therapy in conjunction with American Joint Committee on Cancer staging to improve preoperative counseling., (© 2020 Wiley Periodicals LLC.)