Neck Carcinoma Research Articles

Aspergillus Species and Human Papillomavirus Infections in Epithelial Tumors of Nasal and Paranasal Cavities

Background: There are diverse lesions originating from the paranasal sinuses and nasal cavity. Tobacco use, alcohol consumption, and malnutrition have been identified to play a role in the development of head and neck carcinomas. Recently, fungi and viruses have been recognized as potential causes of nasal cavity and paranasal tumors. Objectives: This study aimed at specifying the prevalence of Aspergillus and human papillomavirus (HPV) infections in the epithelial tumors of nasal cavity and paranasal sinuses. Methods: In this cross-sectional study, 57 paraffin-embedded tissue samples of malignant and benign lesions of the paranasal sinuses and nasal cavity were evaluated for the presence of Aspergillus and HPV DNA by nested polymerase chain reaction (nPCR) technique with specific primers. Results: Despite the absence of angular hyphae (acute angle) of the fungus on histopathological slides, overall, 10 (17.54%) out of 57 paraffin-embedded samples were found to be positive for Aspergillus species. However, HPV-DNA was not found in any of the samples. Conclusions: Our data suggest that fungal infections (especially aspergillosis) as an etiological factor can be contributed to the development of sinonasal cancer and, therefore, they should be considered in the management of patients with sinonasal cancer. In addition, PCR can provide an alternative to culture-dependent identification methods.

Prognostic value of systemic immune-inflammation index in head and neck carcinoma patients undergoing definitive radio(chemo)therapy

ABSTRACT 
 Background: 
 The aim of this study is to investigate the prognostic effect of the systemic immune-inflammation index (SII) in non-surgically managed head and neck carcinoma patients who underwent definitive radio(chemo)therapy.
 Methods: 
 Twenty four patients who were all treated with radio(chemo)terapy with curative intent for head and neck cancer (HNC) were included in the study. All patients were analyzed in terms of age at diagnosis, gender, body mass index, stage, radiotherapy dose/ fraction, chemotherapy (CT), pre-treatment complete blood count parameters, the pre-treatment systemic immune-inflammation index, local relapse, distant failure, overall survival (OS), and disease-free survival (DFS).
 Results:
 SII index was observed to be higher in locally advanced patients than in stage I/II patients (p=0.004). In addition, as a result of the evaluation made with ROC (receiver operating characteristic) analysis, it was observed that the SII index had a diagnostic value in predicting locally advanced disease (AUC:0.867, 95% CI :0.721-1.00, p=0.002). DFS and OS rates were 79% and 90% at a median follow-up of 9 months.
 Conclusions:
 The systemic immune-inflammation index predicts more advanced disease in non-surgically managed head and neck cancer patients. It can be considered as a biomarker that can contribute to the management of definitive radio(chemo)therapy.

MiR-4521 perturbs FOXM1-mediated DNA damage response in breast cancer.

Introduction: Forkhead (FOX) transcription factors are involved in cell cycle control, cellular differentiation, maintenance of tissues, and aging. Mutation or aberrant expression of FOX proteins is associated with developmental disorders and cancers. FOXM1, an oncogenic transcription factor, is a promoter of cell proliferation and accelerated development of breast adenocarcinomas, squamous carcinoma of the head, neck, and cervix, and nasopharyngeal carcinoma. High FOXM1 expression is correlated with chemoresistance in patients treated with doxorubicin and Epirubicin by enhancing the DNA repair in breast cancer cells. Method: miRNA-seq identified downregulation of miR-4521 in breast cancer cell lines. Stable miR-4521 overexpressing breast cancer cell lines (MCF-7, MDA-MB-468) were developed to identify miR-4521 target gene and function in breast cancer. Results: Here, we showed that FOXM1 is a direct target of miR-4521 in breast cancer. Overexpression of miR-4521 significantly downregulated FOXM1 expression in breast cancer cells. FOXM1 regulates cell cycle progression and DNA damage response in breast cancer. We showed that miR-4521 expression leads to increased ROS levels and DNA damage in breast cancer cells. FOXM1 plays a critical role in ROS scavenging and promotes stemness which contributes to drug resistance in breast cancer. We observed that breast cancer cells stably expressing miR-4521 lead to cell cycle arrest, impaired FOXM1 mediated DNA damage response leading to increased cell death in breast cancer cells. Additionally, miR-4521-mediated FOXM1 downregulation perturbs cell proliferation, invasion, cell cycle progression, and epithelial-to-mesenchymal progression (EMT) in breast cancer. Discussion: High FOXM1 expression has been associated with radio and chemoresistance contributing to poor patient survival in multiple cancers, including breast cancer. Our study showed that FOXM1 mediated DNA damage response could be targeted using miR-4521 mimics as a novel therapeutic for breast cancer.

Therapeutic implication of chimeric antigen receptor T-cell therapy for head and neck squamous cell carcinoma.

Therapeutic implication of chimeric antigen receptor T-cell therapy for head and neck squamous cell carcinoma.

SPECTRUM OF MALIGNANT LESIONS IN HEAD AND NECK REGION: A TERTIARY CARE HOSPITAL BASED STUDY FROM NORTH EAST INDIA

Introduction: Most head and neck region malignancies arise in the epithelium of oral cavity, larynx, pharynx, nasal cavity and paranasal sinuses. Most of head and neck carcinomas are squamous cell carcinoma. It is the 6th most common carcinoma in the world according to Union for International Cancer control. AIM: To evaluate the spectrum of malignant lesions in head and neck region and to look for the associated risk factors. Methodology: A one year retrospective study was carried out in the Department of Pathology in collaboration with the Department of ENT, from Feb 2022 to Jan 2023, where 140 parafn embedded tissue blocks of head and neck biopsies were collected from the archives of the department. Results: A total 140 cases were included of which 104 (74.3%) were males and 36 (25.7%) were females. Male to female ratio = 2.8:1. The most affected age group is 51-60 years. The most important risk factor is betel nut consumption followed by tobacco chewing. The most common site involved is the oropharynx followed by tongue. Most of the carcinomas are moderately differentiated squamous cell carcinomas. Conclusion: Head and neck malignancies are quite common in Northeastern region of India, so wehave performed this study to evaluate the spectrum of malignant lesions in head and neck region. Its association with risk factors are also studied for the prevention, early detection, early treatment intervention and withdrawal from risk habits for improving the wellbeing of the people in the society

Evaluation of dosimetric and volumetric changes in target volumes and organs at risk during adaptive radiotherapy in head and neck cancer: A prospective study

BackgroundDuring radiation therapy for head and neck malignancies, most patients experience significant anatomical alterations due to loss of weight, changes in tumor volumes, and immobilization issues. Adaptive radiotherapy adapts to the patient's actual anatomy through repetitive imaging and replanning. In the present study, dosimetric and volumetric changes in target volumes and organs at risk during adaptive radiotherapy in head and neck cancer was evaluated. Material and methodsThirty-four locally advanced Head and neck carcinoma patients with histologically proven Squamous Cell Carcinoma for curative treatment were included. Rescan was done at the end of 20 fractions of treatment. All quantitative data were analyzed with paired t-Test and Wilcoxon Signed Rank (Z) test. ResultsMost patients had oropharyngeal carcinoma (52.9%). There were significant volumetric changes in all the parameters - GTV-primary (10.95, p < 0.001), GTV- nodal (5.81, p = 0.001), PTV High Risk (26.1, p < 0.001), PTV – Intermediate Risk (46.9, p = 0.006), PTV – Low Risk (43.9, p = 0.003), lateral neck diameter (0.9, p < 0.001), right parotid volumes (6.36, p < 0.001) and left parotid volumes (4.93, p < 0.001). Dosimetric changes in the organs at risk were non-significant. ConclusionAdaptive replanning has been seen to be labour intensive. However, the changes in the volumes of both target and the OARs credit a mid-treatment replanning to be done. Long term follow-up is required to assess locoregional control after adaptive radiotherapy in head and neck cancer.

Insight on common forms of cutaneous head and neck carcinoma (Review).

To improve the outcome and quality of life for patients with head and neck carcinoma, an increasing amount of research has been performed on the particularities of this type of cancer and its treatment methods. Starting from clinical aspects, including histology and imaging features, up-to-date studies from different parts of the world have determined new data leading to a better understanding of the mechanisms behind the disease and proposed new treatment protocols. The head and neck areas are predisposed to almost all skin neoplasms, most commonly those related to ultraviolet exposure. Squamous cell carcinoma and basal cell carcinoma account for almost 90% of non-melanoma skin cancers in this region; therefore, reviewing the literature on cutaneous carcinomas of the head and neck area and sharing particular aspects of their physiopathology are beneficial for a great number of patients.

Synchronous Presentation of Right Parotid Branchial Cleft Cyst and Left Neck HPV-Associated Cystic Metastatic Squamous Cell Carcinoma: A Diagnostic Quandary.

Branchial cleft cyst arising within the parotid space is considered an extremely rare phenomenon. In contrast, cystic squamous cell carcinoma in the lateral neck is not an uncommon presentation of HPV-related head and neck cancer. Although they have singly been narrated in literature, simultaneous expression of these anomalies has yet to be reported. We describe a case of synchronous presentation of branchial cleft cyst of the right parotid gland and cystic metastatic squamous cell carcinoma of the left neck. These findings are discussed in light of the challenges in fine needle aspiration biopsy of cystic masses, and the risk of two distinct pathologic entities presenting as cysts in the head and neck.

PATTERN OF NECK LYMPH NODE METASTASIS AND FACTORS AFFECTING THE LYMPH NODE METASTASIS IN SQUAMOUS CELL CARCINOMAS OF HEAD AND NECK

Background: Head and neck cancer exhibits metastases to cervical lymph nodes through certain lymphatic drainage routes. The 5-year survival rate for patients with neck metastases reduces depending on the number and level of nodes involved. To assess the patterns of lymph Objective: node metastasis for squamous cell carcinoma of head and neck and analyse the prognostic factors of cervical node status and highlight their effect on treatment and prognosis. The study entailed a cross sectional analysis of Method: 66 patients with squamous cell carcinoma of head and neck radiologically or pathologically proven. Data collected and was analysed by a chi square test using SPSS (version 20). Of the 66 clinically Results: node-positive patients, 18 had bilateral lymph node metastasis and 48 had ipsilateral LNM. In all primary sites pattern of lymph drainage was followed except for in 1 case of carcinoma larynx where metastasis was to level II and IV without involvement of level III. We Conclusion: concluded majority of the HNSCC cases followed normal pattern of drainage and in individuals with oral cavity and oropharynx SCC, the incidence of bilateral neck LNMs are high particularly to level II of contralateral side. With higher stage of the disease and long duration of symptoms chances of lymph node metastasis is high thus worsening the prognosis. Bilateral neck dissection is recommended for primary surgical treatment, with the exception of early stages, when ipsilateral neck dissection may be performed

Low dose weekly Carboplatin (AUC: 2) with radiation is an acceptable alternative for weekly cisplatin with radiation in the treatment of advanced head neck carcinoma: An observational study

Low dose weekly Carboplatin (AUC: 2) with radiation is an acceptable alternative for weekly cisplatin with radiation in the treatment of advanced head neck carcinoma: An observational study

HPV-related multiphenotypic sinonasal carcinoma, HPV type 35-related: a case report

Most HPV-related head and neck carcinomas arise in the oropharynx, but can also arise in the sinonasal tract. The entity now referred to as HPV-related multiphenotypic sinonasal carcinoma (HMSC) was previously known as HPV-related carcinoma with adenoid cystic carcinoma-like features. This tumour is characterised by an association with high-risk HPV subtypes (commonly type 33), a sinonasal location and histologic phenotype resembling both adenoid cystic carcinoma and surface derived squamous cell carcinoma.

Assessment of quality of life after soft tissue resection of head and neck carcinoma and reconstruction with double-paddle peroneal artery perforator free flap

We aimed to assess the quality of life for head and neck carcinoma (HNC) patients who underwent soft tissue resection and reconstruction with double-paddle peroneal artery perforator (DPAP) free flap. The quality of life was assessed by means of the University of Washington quality of life (UW-QOL) and the 14-item Oral Health Impact Profile (OHIP-14) questionnaires at 12 months postoperatively. Data from 57 patients were retrospectively analysed. Out of these, 51 patients were at TNM stage III or IV. Finally, 48 patients finished and returned the two questionnaires. In the UW-QOL questionnaire, the mean (SD) higher scores were pain 76.5 (6.4), shoulder 74.3 (9.6), and activity 71.6 (6.1), whereas the lower scores were chewing 49.7 (5.2), taste 51.1 (7.7), and saliva (56.7 (7.4). In the OHIP-14 questionnaire, the higher-scoring domains were psychological discomfort (69.3 (9.6) and psychological disability 65.2 (5.8), whereas the lower-scoring domains were handicap 28.7 (4.3) and physical pain 30.4 (8.1). The DPAP free flap significantly improved appearance, activity, shoulder, mood, psychological discomfort, and handicap compared with pedicled pectoralis major myocutaneous flap reconstruction. In conclusion, DPAP free flap for reconstruction of tissue defects after soft tissue resection of HNC significantly improved the patients' QOL compared to pedicled pectoralis major myocutaneous flap reconstruction.

Systematic Review and Meta-Analysis on Angiotensin Converting Enzyme 2 in Head and Neck Region.

The objective of this systematic review was to investigate the expression of angiotensin converting enzyme 2 (ACE 2) in the head and neck region. We examined the evidence of the association of ACE 2 expression in oral tissues, salivary glands, and head and neck carcinoma. We searched Pub Med/Medline, Biorxiv, and Google Scholar to identify relevant literature. Studies reporting ACE 2 expression in human oral tissues and with a focus on head and neck carcinoma samples were included. From 110 studies, we extracted 15 studies analyzing the distribution and expression of ACE 2 in different head and neck tissues - olfactory mucosa and nasopharynx n=5, oral mucosa n=5, salivary gland n=5, head and neck squamous cell carcinoma patients n=3. ACE 2 was found to be expressed at a 4.43-fold increase in the head and neck region (OR, 4.43; 95% CI, 3.76-5.22; I2= 97%, Ph=<0.00001) when compared with controls (other tissues except for head and neck region). RNA expression of ACE 2 was 60% higher in head and neck squamous cell carcinoma patients than that in the normal tissues (OR=0.60, 95% CI, 0.04-9.26, Ph=0.00001). In conclusion, the meta-analysis of the studies indicated that ACE 2 is highly expressed in olfactory mucosa, nasopharynx, oral mucosa, and salivary glands. Furthermore, the results indicate that ACE 2 expression is increased in patients with head and neck cancer.

Fisetin, a dietary flavonoid, increases the sensitivity of chemoresistant head and neck carcinoma cells to cisplatin possibly through HSP90AA1/IL-17 pathway.

Cisplatin (DDP) resistance is a bottleneck in the treatment of head and neck cancer (HNC), leading to poor prognosis. Fisetin, a dietary flavonoid, has low toxicity and high antitumor activity with unclear mechanisms. We intended to predict the targets of fisetin for reversing DDP-resistance and further verify their expressions and roles. A network pharmacology approach was applied to explore the target genes. The hub genes were screened out and subjected to molecular docking and experimental verification (in vivo and in vitro). Thirty-two genes common to fisetin and DDP-resistance were screened, including three hub genes, namely HSP90AA1, PPIA, and PTPRS. Molecular docking suggested that fisetin and the candidate proteins could bind tightly. HSP90AA1 was identified as the key gene. Administration of fisetin increased the sensitivity of chemoresistant cells (Cal27/DDP and FaDu/DDP) to DDP, accompanied by the downregulation of HSP90AA1 and IL-17. HSP90AA1 silencing increases the sensitivity of DDP-resistant cells to DDP, which was mediated by IL-17. In summary, fisetin might inhibit the chemoresistance of HNC cells to DDP by targeting the HSP90AA1/IL-17 pathway. Several hub genes might be the targets of fisetin for reversing DDP-resistance in HNC cells and might also serve as prognostic factors and therapeutic targets for HNC.

Prognostic Model and Nomogram for Early-Onset Adenoid Cystic Carcinoma of Head and Neck: A Retrospective SEER-Based Analysis.

Adenoid cystic carcinoma of head and neck (ACCHN) is an uncommon head and neck cancers, whose predilection age is 40 to 60. Some studies have revealed that early-onset cancers, such as colorectal cancers and esophageal adenocarcinoma, might present some unique clinicopathological features and have different prognosis with late-onset ones. However, little is known about the early-onset ACCHN. This study aimed to develop a prognostic nomogram for overall survival (OS) of patients younger than 40 with ACCHN. Cases with ACCHN from 1975 to 2016 were retrieved from SEER-18 program. Demographic, clinical, and survival outcomes data of patients were identified for further analysis. The caret package was used to randomly divide early-onset patients into a training cohort and a validation cohort. A prognostic nomogram was constructed based on the univariate and multivariate Cox analysis. The discriminative ability and calibration power of the nomogram was evaluated by the concordance index (C-index), calibration curve, and receiver operating characteristic (ROC) curve. A total of 5858 cases with ACCHN were selectively retrieved from SEER program in this study. The number of patients younger than 40, which was defined as early-onset ACCHN in this study, was 825. Based on the outcomes of multivariate analysis, tumor size, chemotherapy, surgery, and stage were selected for the construction of nomogram to predict 10-year OS. The C-index was 0.792 (95%CI 0.760-0.823) and 0.776 (95%CI 0.720-0.832) in the training and validation set, respectively. The area under the ROC curve values were 0.875 (95%CI 0.810-0.940) and 0.833(95%CI 0.754-0.912). The calibration plot indicated that this nomogram had proper calibration in both the training and validation cohorts. A novel prognostic nomogram for early-onset ACCHN was constructed and validated in this study. This nomogram could be applied for assisting clinicians to more accurately assess the prognosis of young patients, which might facilitate clinical decision-making and subsequent follow-up.

Psychological impact after treatment in patients with head and neck cancer.

Cancer is the second cause of death all over the world and it causes considerable morbidity, disability, and treatment sequela, which often lead to post-treatment pain and disfigurement. This study aims to evaluate such physical sequelae, and their psychological, (cognitive and emotional), impact, in a cohort of patients treated for Head and Neck (HNC) cancer, in search for methods to help such patients deal effectively with the psychological effects of their cancer treatments adverse consequences. The sample consists of 56 subjects, 47 men and 9 women, ranging from 47 years to 86 years of age, who were treated for head and neck cancers at Spanish Public General Hospital in the Otolaryngology Unit, Surgery Section. Two types of questionnaires were used in the study: the Questionnaire of Sequelae after Treatment of head and neck carcinoma and the State-Trait Anxiety Inventory (STAI-E and R). With respect to anxiety, the study found high levels of state anxiety which was significantly associated with the degree of perception of social stigma but was not associated with the post-treatment sequelae themselves nor with the level of discomfort that such symptomatic sequelae produced. The presence of a post-surgical stoma with cannula, increased patient's stigma (both components: external rejection and self-rejection) and state anxiety ratings, while there was no difference in state anxiety between cannulated and non-cannulated patients. There are few differences between men and women in terms of the presence of anxiety and their responses are similar in terms of the after-effects of surgery. Our study confirmed that current treatments for Head and Neck carcinoma generate adverse symptomatic sequela that impose significant psychological and physical burden for these patients. We will discuss the various pathways for preventive intervention that these findings open up.

Radiotherapy Increases aMMP-8-Levels and Neutrophil/Lymphocyte Ratio Rapidly in Head and Neck Cancer Patients: A Pilot Study.

Radiotherapy for head and neck carcinoma (HNC) has both curative and palliative purposes. This study investigated mouthrinse aMMP-8 levels, molecular forms of MMP-8, blood neutrophil counts and neurophil/lymphocyte ratios before and 3 weeks after HNC radiotherapy started. Thirteen HNC patients undergoing radiotherapy were included. Mouthrinse samples (before and 3 weeks after HNC radiotherapy had started) were assayed quantitatively by aMMP-8 point-of-care-kit (PerioSafe®/ORALyzer®) and by western immunoblot. Total neutrophil counts and neutrophil/lymphocyte ratios were evaluated in the hemogram results. Three weeks after HNC radiotherapy started, significant increases in aMMP-8 levels and neutrophil/lymphocyte ratios were observed. No significant difference was found in total neutrophil counts. Elevations of the activated and fragmented MMP-8 levels after HNC radiotherapy application were observed on western immunoblot analysis. The increase in the aMMP-8 levels and neutrophil/lymphocyte ratios indicate inflammation both locally and systemically suggesting increased risk for periodontitis due to the HNC radiotherapy.

Hybrid nano-architectures loaded with metal complexes for the co-chemotherapy of head and neck carcinomas.

Head and neck squamous cell carcinomas (HNSCCs) are a complex group of malignancies that affect different body sites pertaining to the oral cavity, pharynx and larynx. Current chemotherapy relies on platinum complexes, the major exponent being cisplatin, which exert severe side effects that can negatively affect prognosis. For this reason, other metal complexes with less severe side effects are being investigated as alternatives or adjuvants to platinum complexes. In this context, exploiting (supra)additive effects by the concurrent administration of cisplatin and emerging metal complexes is a promising research strategy that may lead to effective cancer management with reduced adverse reactions. Here, the combined action of cisplatin and a ruthenium(II) η6-arene compound (RuCy), both as free molecules and loaded into hybrid nano-architectures (NAs), has been assessed on HPV-negative HNSCC models of increasing complexity: 2D cell cultures, 3D multicellular tumor spheroids, and chorioallantoic membranes (CAMs). Two new NAs have been established to explore all the delivery combinations and compare their ability to enhance the efficacy of cisplatin in the treatment of HNSCCs. A significant supra-additive effect has been observed in both 2D and 3D models by one combination of treatments, suggesting that cisplatin is particularly effective when loaded on NAs, whereas RuCy performs better when administered as a free compound. Overall, this work paves the way for the establishment of the next co-chemotherapeutic approaches for the management of HNSCCs.

Salivary protein candidates for biomarkers of oral disorders in people with a crack cocaine use disorder

The use of cocaine and its main derivative, crack, can cause some systemic effects that may lead to the development of some oral disorders. To assess the oral health of people with a crack cocaine use disorder and identify salivary protein candidates for biomarkers of oral disorders. A total of 40 volunteers hospitalized for rehabilitation for crack cocaine addiction were enrolled; nine were randomly selected for proteomic analysis. Intraoral examination, report of DMFT, gingival and plaque index, xerostomia, and non-stimulated saliva collection were performed. A list of proteins identified was generated from the UniProt database and manually revised. The mean age (n=40) was 32 (±8.88; 18-51) years; the mean DMFT index was 16±7.70; the mean plaque and gingival index were 2.07±0.65 and 2.12±0.64, respectively; and 20 (50%) volunteers reported xerostomia. We identified 305 salivary proteins (n=9), of which 23 were classified as candidate for biomarkers associated with 14 oral disorders. The highest number of candidates for biomarkers was associated with carcinoma of head and neck (n=7) and nasopharyngeal carcinoma (n=7), followed by periodontitis (n=6). People with a crack cocaine use disorder had an increased risk of dental caries and gingival inflammation; less than half had oral mucosal alterations, and half experienced xerostomia. As possible biomarkers for 14 oral disorders, 23 salivary proteins were identified. Oral cancer and periodontal disease were the most often associated disorders with biomarkers.

Effect of Triphaladi Choornam Mouthwash and Chlorhexidine Gluconate Mouthwash in Radio-Chemotherapy Induced Oral Mucositis in NonMetastatic Squamous Cell Carcinoma of Head and Neck: A Comparative Study

Background: The cases of lung and mouth cancer have boomed in the last decade due to various reasons, the major one being tobacco consumption. In non-metastatic squamous cell cancer of the head and neck, oral mucositis becomes prominent, especially during chemo or radiotherapy. Such patients also often suffer from stomatitis, xerostomia and pharyngitis. Materials and methods: This comparative study comprises of 36 patients undergoing chemo and radiotherapy. Here, 18 patients each are randomly allocated in two groups. One group receiving the existing prophylactic treatment i.e., chlorhexidine gluconate mouthwash and the other group received, Triphaladi choornam for gargling. Both the groups were asked to perform gargling, from the first day of radiation therapy to 21 days thereafter. Analytical tools: The effectiveness of both mouthwashes was compared for their healing potential and quality of life by WHO oral mucositis scale and Patient Reported Oral Mucositis Symptoms (PROMS)scale respectively. Conclusion: The reduction in mucositis and betterment of quality of life was significant in the group which received ayurvedic mouthwash compared to the prophylactic treatment group.