UNASSIGNED: Head and neck cancer is common in several parts of the world. It is sixth most prevalent neoplasms in the world. Approximately 900 000 cases diagnosed worldwide per year. It has good prognosis when timely diagnosed and treated appropriately.
UNASSIGNED: This was a retrospective study carried out in the Department of ENT-HNS of Shree Birendra Hospital, Chhauni, Kathmandu from May 2022 to April 2023. All histopathologically proven malignant cases of head and neck region were included in the study. Data were entered in Microsoft excel and managed in SPSS version 22. Analysis was done in the form of percentage and proportion and represented as table where necessary. The study has been registerd in clinical trials and has been reported in line with the STROCSS criteria.
UNASSIGNED: Total 76 patients were analyzed. Age ranged from 17 to 84 years and the most common age group presenting with head and neck cancer was 61-80 years. The most common malignancy was laryngeal cancer (34%) followed by thyroid malignancies (29%). Squamous cell carcinoma was the commonest histological type (48%). Surgery with postoperative radiotherapy (RT)/radioactive iodine (RAI) was found to be the commonest treatment modality.
UNASSIGNED: Head and neck cancers are not uncommon and majority of patients present late with advanced stage cancer. Hence, public awareness, early diagnosis with cost-effective treatment and regular follow-up are needed to improve outcomes of these patients in our society.

Background and Objectives: Nucleotide Excision Repair (NER), the most extensively researched DNA repair mechanism, is responsible for repairing a variety of DNA damages, and Xeroderma Pigmentosum (XP) genes participate in NER. Herein, we aimed to update the previous results with a meta-analysis evaluating the association of XPA, XPB/ERCC3, XPF/ERCC4, and XPG/ERCC5 polymorphisms with the susceptibility to HNC. Materials and Methods: PubMed/Medline, Web of Science, Scopus, and Cochrane Library databases were searched without any restrictions until 18 November 2023 to find relevant studies. The Review Manager 5.3 (RevMan 5.3) software was utilized to compute the effect sizes, which were expressed as the odds ratio (OR) with a 95% confidence interval (CI). Results: Nineteen articles were involved in the systematic review and meta-analysis that included thirty-nine studies involving ten polymorphisms. The results reported that the CC genotype of rs17655 polymorphism showed a significantly decreased risk of HNC in the recessive model (OR: 0.89; 95%CI: 0.81, 0.99; p-value is 0.03). In addition, the CT genotype (OR: 0.65; 95%CI: 0.48, 0.89; p-value is 0.008) of the rs751402 polymorphism was associated with a decreased risk, and the T allele (OR: 1.28; 95%CI: 1.05, 1.57; p-value is 0.02), the TT (OR: 1.74; 95%CI: 1.10, 2.74; p-value is 0.02), and the TT + CT (OR: 2.22; 95%CI: 1.04, 4.74; p-value is 0.04) genotypes were associated with an increased risk of HNC. Conclusions: The analysis identified two polymorphisms, rs17655 and rs751402, as being significantly associated with the risk of HNC. The study underscored the influence of various factors, such as the type of cancer, ethnicity, source of control, and sample size on these associations.

UNASSIGNED: Cancer is an important part of the global burden of childhood diseases. Head and neck carcinoma in children is rare and related research is limited. This study aimed to investigate the clinicopathological features of childhood head and neck carcinoma.
UNASSIGNED: Forty-two cases of childhood head and neck carcinoma treated in our institution were reviewed and analyzed.
UNASSIGNED: Median age overall was 11 years. Twenty-three patients (54.8%) were male and 19 (45.2%) were female. Parotid gland location was most common (54.8%). Mucoepidermoid carcinoma and squamous cell carcinoma were the most common histological types (57.1% and 11.9%, respectively). Two patients had a history of bone marrow transplantation and two had a history of odontogenic keratocyst. The recurrence rate after treatment was 8.6%.
UNASSIGNED: Early diagnosis and treatment and close follow-up of childhood head and neck carcinoma are warranted to prevent recurrence and improve clinical outcome.

UNASSIGNED: Basal information of head and neck small-cell carcinoma (HNSmCC) including epidemiology, primary site, treatment, and prognosis remains sparse due to its rarity. We report here a multicenter retrospective study on the diagnosis, treatment, and outcomes of patients with HNSmCC.
UNASSIGNED: This study involved 47 patients with HNSmCC from 10 participating institutions. Eight patients were excluded for whom no pathological specimens were available (n = 2) and for discrepant central pathological judgements (n = 6). The remaining 39 patients were processed for data analysis.
UNASSIGNED: As pretreatment examinations, computed tomography (CT) was performed for the brain (n = 8), neck (n = 39), and chest (n = 32), magnetic resonance imaging (MRI) for the brain (n = 4) and neck (n = 23), positron emission tomography-CT (PET-CT) in 23 patients, bone scintigraphy in 4, neck ultrasonography in 9, and tumor markers in 25. Primary sites were oral cavity (n = 1), nasal cavity/paranasal sinuses (n = 16), nasopharynx (n = 2), oropharynx (n = 4), hypopharynx (n = 2), larynx (n = 6), salivary gland (n = 3), thyroid (n = 2), and others (n = 3). Stages were II/III/IV-A/IV-B/IV-C/Not determined = 3/5/16/6/5/4; stage IV comprised 69%. No patient had brain metastases. First-line treatments were divided into 3 groups: the chemoradiotherapy (CRT) group (n = 27), non-CRT group (n = 8), and best supportive care group (n = 4). The CRT group included concurrent CRT (CCRT) (n = 17), chemotherapy (Chemo) followed by radiotherapy (RT) (n = 5), and surgery (Surg) followed by CCRT (n = 5). The non-CRT group included Surg followed by RT (n = 2), Surg followed by Chemo (n = 1), RT alone (n = 2), and Chemo alone (n = 3). The 1-year/2-year overall survival (OS) of all 39 patients was 65.3/53.3%. The 1-year OS of the CRT group (77.6%) was significantly better compared with the non-CRT group (31.3%). There were no significant differences in adverse events between the CCRT group (n = 22) and the Chemo without concurrent RT group (n = 9).
UNASSIGNED: Neck and chest CT, neck MRI, and PET-CT would be necessary and sufficient examinations in the diagnostic set up for HNSmCC. CCRT may be recommended as the first-line treatment. The 1-year/2-year OS was 65.3%/53.3%. This study would provide basal data for a proposing the diagnostic and treatment algorithms for HNSmCC.

Background Head and neck carcinomas are one of the most common malignancies in developing countries including India. Most patients are treated with radiotherapy. Although post-radiotherapy hypothyroidism is a known complication, data regarding its incidence and factors influencing it are scarce. This study aimed to determine the incidence of post-radiotherapy hypothyroidism in head and neck carcinoma patients treated with radiotherapy and the factors influencing it. Methodology Patients with head and neck carcinomas treated with radiotherapy as one of the modalities were included in this study. Thyroid function tests were done, and quality of life questionnaires were completed before treatment and during follow-up. Dose-volume histogram (DVH), demographic data, and disease-related parameters were compared. Results Out of the 95 patients screened, 14 were found to be hypothyroid prior to the commencement of radiotherapy and were excluded. With a median follow-up duration of 34 weeks, 29.6% developed hypothyroidism, with 19% developing it in the first year. On univariate and multivariate analysis of the DVH of the thyroid gland, volume receiving 50 Gy (V50), dose received to 50% volume (D50), and the mean dose (more than 50 Gy) were found to be significantly associated with hypothyroidism. Conclusions Hypothyroidism is a significant comorbid factor in Indian patients with head and neck carcinomas. The incidence of post-radiotherapy hypothyroidism is significant and occurs early compared to the western population leading to significant deterioration in the quality of life. Parameters such as the volume of the thyroid gland, V50, D50, and mean dose to the thyroid gland influence the incidence of hypothyroidism. The use of appropriate constraints can significantly prevent radiotherapy-induced hypothyroidism.

Mammalian target of rapamycin (mTOR) regulates cellular functions by integrating intracellular signals and signals from the tumor microenvironment (TME). The PI3K-AKT-mTOR pathway is activated in 70% of head and neck squamous cell carcinoma (HNSCC) and associated with poor prognosis. This phase I-II study investigated the effect of mTOR inhibition using weekly everolimus (30 mg for dose level 1, 50 mg for dose level 2) combined with weekly induction chemotherapy (AUC2 carboplatin and 60 mg/m2 paclitaxel) in treatment-naïve patients with locally advanced T3-4/N0-3 HNSCC. Patients received 9 weekly cycles before chemoradiotherapy. Objectives were safety and antitumor activity along with tissue and blood molecular biomarkers. A total of 50 patients were enrolled. Among 41 evaluable patients treated at the recommended dose of 50 mg everolimus weekly, tolerance was good and overall response rate was 75.6%, including 20 major responses (≥50% reduction in tumor size). A significant decrease in expression of p-S6K (p-value: 0.007) and Ki67 (p-value: 0.01) was observed in post-treatment tumor tissue. Pro-immunogenic cytokine release (Th1 cytokines IFN-γ, IL-2, and TNF-β) was observed in the peripheral blood. The combination of everolimus and chemotherapy in HNSCC was safe and achieved major tumor responses. This strategy favorably impacts the TME and might be combined with immunotherapeutic agents.

BACKGROUND: JCOG1015A1 is an ancillary research study to determine the organ-specific dose constraints in head and neck carcinoma treated with intensity-modulated radiation therapy (IMRT) using data from JCOG1015.
METHODS: Individual patient data and dose-volume histograms of organs at risk (OAR) were collected from 74 patients with nasopharyngeal carcinoma treated with IMRT who enrolled in JCOG1015. The incidence of late toxicities was evaluated using the cumulative incidence method or prevalence proportion. ROC analysis was used to estimate the optimal DVH cut-off value that predicted toxicities.
RESULTS: The 5-year cumulative incidences of Grade (G) 1 myelitis, ≥ G1 central nervous system (CNS) necrosis, G2 optic nerve disorder, ≥ G2 dysphagia, ≥ G2 laryngeal edema, ≥ G2 hearing impaired, ≥ G2 middle ear inflammation, and ≥ G1 hypothyroidism were 10%, 5%, 2%, 11%, 5%, 26%, 34%, and 34%, respectively. Significant associations between DVH parameters and incidences of toxicities were observed in the brainstem for myelitis (D1cc ≥ 55.8 Gy), in the brain for CNS necrosis (D1cc ≥ 72.1 Gy), in the eyeball for optic nerve disorder (Dmax ≥ 36.6 Gy), and in the ipsilateral inner ear for hearing impaired (Dmean ≥ 44 Gy). The optic nerve, pharyngeal constrictor muscle (PCM), and thyroid showed tendencies between DVH parameters and toxicity incidence. The prevalence proportion of G2 xerostomia at 2 years was 17 versus 6% (contralateral parotid gland Dmean ≥ 25.8 Gy vs less).
CONCLUSIONS: The dose constraint criteria were appropriate for most OAR in this study, although more strict dose constraints might be necessary for the inner ear, PCM, and brainstem.

Background and objective:N-acetyltransferases 1 and 2 (NAT1 and NAT2) genes have polymorphisms in accordance with slow and rapid acetylator phenotypes with a role in the development of head and neck cancers (HNCs). Herein, we aimed to evaluate the association of NAT1 and NAT2 polymorphisms with susceptibility to HNCs in an updated meta-analysis. Materials and methods: A search was comprehensively performed in four databases (Web of Science, Scopus, PubMed/Medline, and Cochrane Library until 8 July 2021). The effect sizes, odds ratio (OR) along with 95% confidence interval (CI) were computed. Trial sequential analysis (TSA), publication bias and sensitivity analysis were conducted. Results: Twenty-eight articles including eight studies reporting NAT1 polymorphism and twenty-five studies reporting NAT2 polymorphism were involved in the meta-analysis. The results showed that individuals with slow acetylators of NAT2 polymorphism are at higher risk for HNC OR: 1.22 (95% CI: 1.02, 1.46; p = 0.03). On subgroup analysis, ethnicity, control source, and genotyping methods were found to be significant factors in the association of NAT2 polymorphism with the HNC risk. TSA identified that the amount of information was not large enough and that more studies are needed to establish associations. Conclusions: Slow acetylators in NAT2 polymorphism were related to a high risk of HNC. However, there was no relationship between NAT1 polymorphism and the risk of HNC.

Immune checkpoint inhibitors for blocking the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis are now available for squamous cell carcinoma of the head and neck (HNSCC) in relapsing and/or metastatic settings. In this work, we compared the resulting combined positive score (CPS) of PD-L1 using alternative methods adopted in routine clinical practice and determined the level of diagnostic agreement and inter-observer reliability in this setting. The study applied 5 different protocols on 40 tissue microarrays from HNSCC. The error rate of the individual protocols ranged from a minimum of 7% to a maximum of 21%, the sensitivity from 79% to 96%, and the specificity from 50% to 100%. In the intermediate group (1 ≤ CPS < 20), the majority of errors consisted of an underestimation of PD-L1 expression. In strong expressors, 5 out of 14 samples (36%) were correctly evaluated by all the protocols, but no protocol was able to correctly identify all the \"strong expressors\". The overall inter-observer agreement in PD-L1 CPS reached 87%. The inter-observer reliability was moderate, with an ICC of 0.774 (95% CI (0.651; 0.871)). In conclusion, our study showed moderate interobserver reliability among different protocols. In order to improve the performances, adequate specific training to evaluate PD-L1 by CPS in the HNSCC setting should be coordinated.

UNASSIGNED: To date, no guidelines have been proposed for the ideal treatment of postoperative larynx squamous cell carcinoma (LSCC) patients with lymphovascular invasion due to a lack of similar studies. The present study was conducted to compare the survival and toxicity in LSCC patients with lymphovascular invasion receiving either postoperative radiotherapy (PORT) or postoperative chemoradiotherapy (POCRT). The results can be applied for more appropriate treatment of these patients.
UNASSIGNED: Three hundred eighty-eight eligible LSCC patients with lymphovascular invasion were enrolled in this retrospective study. Survival and treatment-related toxicities were compared in the POCRT and PORT group using propensity score matching (PSM) methodology (1:1).
UNASSIGNED: Five-year overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) of all patients were 48.7%, 58.2%, and 56.0%, respectively. Significantly, higher RFS rates (P=0.040) were found in the POCRT group than the PORT group in the PSM cohort. In the multivariate analysis, higher OS, DSS, and RFS rates were observed in the POCRT group than the PORT group (P=0.049, 0.024, and 0.011 respectively). Patients in the POCRT group presented more acute toxicities than those in the PORT group such as hematological toxicities (25.0% vs 0.9%, P<0.001) and mucositis (35.0% vs 19.1%, P=0.002).
UNASSIGNED: In the context of no ideal treatment for LSCC patients with lymphovascular invasion, the present study proposes POCRT as a preferable modality compared with PORT, as POCRT was associated with higher RFS rates. Higher RFS, DFS, and OS rates were also observed in the POCRT group in the multivariate analysis.