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PD-L1 is a glycoprotein present on antigen-presenting cells and malignant cells and activates the PD-L1 receptor on cells surfaces, leading to T-cell anergy and death. The objective of this study was to assess PD-L1 tumoral expression in 50 patients with oral squamous cell carcinoma, define its prognostic value, and investigate its association with 2-year overall survival, locoregional recurrence, distant metastasis, and a number of other clinicopathological parameters. In a 24-month prospective observational study, involving 50 oral cavity squamous cell carcinoma patients, PD-L1 tumoral expression was evaluated using semiquantitative immunohistochemistry analysis by an experienced pathologist. PD-L1 expression of ≥ 6% of tumor cells was associated with poor survival outcome and determined to be a pertinent clinical cutoff value. PD-L1 expression of ≥ 6% was significantly associated with a number of clinicopathological parameters in our study of 50 patients with OSCC. Pathological nodal staging (P = 0.00), lympho-vascular invasion (P = 0.03), extra-nodal extension (P = 0.04), overall staging (P = 0.01), locoregional recurrence (P = 0.00), and distant metastasis (P = 0.00) all showed statistically significant associations. Our study concluded a significant correlation with decreased 2-year overall survival and 2-year disease free survival by using the Kaplan- Meier survival plot for overall survival (p = 0.02) and (p = 0.0002), respectively. The presence of ≥ 6% PD-L1 (CD274) tumoral expression was found to be significantly associated with 2-year overall survival (OS), locoregional recurrence (LRC), distant metastasis (DM), and various clinicopathological parameters. Tumoral PD-L1 was found as a discrete prognostic biomarker which showed significant association with tumor aggressiveness. [ABSTRACT FROM AUTHOR]

Head and neck cancers are considered to be the most common cancers in developing countries, especially in Southeast Asia. In India, it accounts for one-fourth of male cancers and one-tenth of female cancers. An attempt was made to study head and neck cancer trends in the Dibrugarh district of Assam, North-East India, India. All sites viz., oral cavity and mobile tongue, oropharynx, hypopharynx, larynx, nasopharynx and others were considered separately for both the sexes to carry out the present analysis. Using the data from the Population-Based Cancer Registry, Upper Assam, Dibrugarh, annual crude incidence rate and age-specific rate were calculated for the period from 2003 to 2016. Mann–Kendall and Sen's Slope non-parametric analysis were applied to examine the trend in the percentages of Head and Neck cancers. The most frequent incidence site for HN cancers was the hypopharynx (33.50%). The disease was common among the males (78.87%) compared to the female (21.13%) population in Dibrugarh district. HN cancers are more prone to the age group 50–70 years (60.93%) compared to the individuals with less than 50 years (26.51%). Combining all the sites of HN cancers in male showed a significant decrease in incidence, whereas in female increasing trend was noted over a period of time. A slight decline in the percentage of head and neck cancer was documented in Dibrugarh when we combined both sexes. The results obtained from the current investigation will laid the scientific framework for proper planning and organization of prevention, diagnosis and treatment of HN cancers in Dibrugarh district, Assam. [ABSTRACT FROM AUTHOR]

Introduction: Head and neck cancer (HNC) is a significant global health burden, with late presentation leading to complex treatment. While human papillomavirus (HPV) infection has been implicated in HNC, data from low‐ and middle‐income countries (LMICs) are limited. In this study, we investigated the prevalence and role of HPV in head and neck cancers diagnosed in Rwanda. Methods: A retrospective cross‐sectional study was conducted using Rwanda Cancer Registry from January 2011 through December 2020. p16 immunohistochemistry as a surrogate for HPV was performed on a randomly selected case. p16‐positive cases were genotyped. Results: A total of 1001 patients with HNC were identified; 82% (n = 819) had squamous cell carcinoma. The mean age at diagnosis was 51.1 years, with a majority being males (58%). Oral cavity and lip (27%) were the most common primary cancer sites. Stage was unknown in most cases (75%, n = 747). HIV status was known in 33% (n = 334) of patients with 10% (n = 33) HIV‐positive; 22% of 202 randomly selected cases were p16‐positive; 34% of the p16‐positive cases were oropharynx. PCR analysis of p16‐positive cases showed 19% HPV positivity, and HPV16 was the most common high‐risk HPV strain, and 55.5% were recorded HPV‐positive by PCR. Conclusions: HNC cases in Rwanda have been increasing from 2011 to 2020, with a significant portion being HPV‐positive. Strategies to implement routine testing for p16, especially in oropharynx cancer patients, improved preservation of tissue samples, collection of comprehensive information including cancer risk factors, staging, and treatment are needed in Rwanda. [ABSTRACT FROM AUTHOR]

Background:During the planning of 3D conformal radiotherapy for head and neck tumors, it is crucial to prioritize the dosage that reaches sensitive organs such as the thyroid gland. This is because there is a significant likelihood of developing thyroid dysfunction after radiotherapy, which can greatly impact the patient's quality of life. So, we aimed to evaluate thyroid gland function in H&N cancer patients after head and neck radiotherapy to correlate the relation between the RT dose and thyroid gland dysfunctions. Methods: This prospective study was conducted in Clinical Oncology and Nuclear Medicine Department in Zagazig University Hospitals on 30 patients with head and neck carcinoma who presented to Clinical Oncology department to receive either definitive or adjuvant conformal three dimensional radiotherapy with or without concurrent chemotherapy. Results: At 6 months of follow up, 73.3% had normal thyroid function while 26.7% had subclinical hypothyroidism and none had overt clinical hypothyroidism. However, at 12 months the rates of normal thyroid function dropped to 50% while subclinical hypothyroidism remained stable at 23.3% and now 26.7% demonstrated progression to clinical hypothyroidism. Conclusions: There is a high risk of radiation-induced thyroid dysfunction, particularly clinical hypothyroidism, in head and neck cancer patients receiving radiotherapy. [ABSTRACT FROM AUTHOR]

This study explored the soluble forms of PD-1 and sPD-L1/2 in serum and urine of patients with head and neck cancer (HNCs) and associated the data with clinical state and 5-year survival. The sPD-1 and sPD-L1/2 levels were evaluated by ELISA in sufferers (N=110) and normal controls (N=82). Patients in the case group were more likely to be male smokers or former smokers. Compared with the normal control group, the serum levels of sPD-1, sPD-L1 and sPD-L2 and the urine level of sPD-L1 in patients with HNCs were increased. Furthermore, sPD-1 and sPD-L1 serum levels existed a positive connection, and sPD-1 and sPD-L2 serum levels positively correlated in HNCs sufferers. The urine sPD-1 and sPD-L1 had a positive relationship. sPD-1 serum levels had a positive connection with urine sPD-1, sPD-L1 urine levels had a positive relationship with sPD-L1, and sPD-L2 serum levels positively connected to urine sPD-L2. Lower serum sPD-1 and sPD-L1/L2 were associated with disease progression and survival at the examination time. sPD-1 and sPD-L1/L2 serum levels above median were markedly related to a decreased probability of 5-years OS in patients with HNCs. The sPD-1 and sPD-L1/2 were complementary markers representing clinical condition and illness outcomes for HNCs patients. The sPD-L1 might accelerate the characterization of high-risk patients with disapproving illness outcomes. sPD-1 and sPD-L1/2 could be easily accessed through liquid biopsy. The incorporation of them as indicators for risk evaluation throughout treatment scheduling and follow-up seems to be an appreciated method. [ABSTRACT FROM AUTHOR]

Simple Summary: Ultrahigh-dose-rate therapy, known as FLASH radiotherapy (RT), is an emerging cancer treatment technique that offers similar tumor control to conventional RT but with the enhanced protection of normal tissue through the FLASH-sparing effect. Preclinical studies on animals and cell lines show promising results. This is significant for patients with recurrent tumors and reirradiation cases, where conventional RT has high toxicity rates. FLASH-RT can potentially improve tumor control while reducing side effects and preserving quality of life. Among the FLASH modalities, proton therapy stands out for its superior dosimetric and delivery characteristics, making it a safe and effective option for human malignancies. Despite its potential, proton Bragg peak FLASH for HN cancer remains underexplored, and this review highlights the novel proton conformal FLASH techniques, which allow for high-quality plans while minimizing radiation exposure to critical organs at risk (OARs) for HN cancer reirradiation. Ultrahigh-dose-rate therapy, also known as FLASH radiotherapy (RT), is an emerging technique that is garnering significant interest in cancer treatment due to its potential to revolutionize therapy. This method can achieve comparable tumor control to conventional-dose-rate RT while offering the enhanced protection of normal tissue through the FLASH-sparing effect. This innovative technique has demonstrated promising results in preclinical studies involving animals and cell lines. Particularly noteworthy is its potential application in treating head and neck (HN) cancers, especially in patients with challenging recurrent tumors and reirradiation cases, where the toxicity rates with conventional radiotherapy are high. Such applications aim to enhance tumor control while minimizing side effects and preserving patients' quality of life. In comparison to electron or photon FLASH modalities, proton therapy has demonstrated superior dosimetric and delivery characteristics and is a safe and effective FLASH treatment for human malignancies. Compared to the transmission proton FLASH, single-energy Bragg peak FLASH is a novel delivery method that allows highly conformal doses to targets and minimal radiation doses to crucial OARs. Proton Bragg peak FLASH for HN cancer has still not been well studied. This review highlights the significance of proton FLASH in enhancing cancer therapy by examining the advantages and challenges of using it for HN cancer reirradiation. [ABSTRACT FROM AUTHOR]

Patients with recurrent or metastatic head and neck cancers (R/M HNCs) are prone to developing resistance after immunotherapy. This retrospective real-world study aims to investigate whether the addition of anlotinib can reverse resistance to PD-1 inhibitors (PD-1i) and evaluate the efficacy and safety of this combination in R/M HNCs. Main outcomes included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety. Potential biomarkers included PD-L1 expression, lipid index, and genomic profiling. Twenty-one patients with R/M HNCs were included, including 11 nasopharyngeal carcinoma (NPC), five head and neck squamous cell carcinoma (HNSCC), three salivary gland cancers (SGC), and two nasal cavity or paranasal sinus cancers (NC/PNC). Among all patients, ORR was 47.6% (95% CI: 28.6–66.7), with 2 (9.5%) complete response; DCR was 100%. At the median follow-up of 17.1 months, the median PFS and OS were 14.3 months (95% CI: 5.9-NR) and 16.7 months (95% CI:8.4-NR), respectively. The median DOR was 11.2 months (95% CI: 10.1-NR). As per different diseases, the ORR was 45.5% for NPC, 60.0% for HNSCC, 66.7% for SGC, and 50.0% for NC/PNC. Most treatment-related adverse events (TRAEs) were grade 1 or 2 (88.9%). The most common grades 3–4 TRAE was hypertension (28.6%), and two treatment-related deaths occurred due to bleeding. Therefore, adding anlotinib to the original PD-1i could reverse PD-1 blockade resistance, with a favorable response rate, prolonged survival, and acceptable toxicity, indicating the potential as a second-line and subsequent therapy choice in R/M HNCs. [ABSTRACT FROM AUTHOR]

Background: Head and neck cancers (HNC) present diagnostic challenges due to multifocal disease manifestations, posing difficulties in distinguishing between metastatic disease and second primary malignancies (SPM). This complexity underscores the need for advanced diagnostic approaches. Emerging technologies, such as next‐generation sequencing (NGS) and molecular classifier assays, show promise in providing precise insights into the diverse etiologies of HNC. Method: In this article, we employed NGS and molecular classifier assays to delve into three distinct clinical cases. The objective was to showcase the instrumental role of these technologies in facilitating accurate diagnoses and differentiating between metastatic disease and SPM in HNC cases. Results: The results of this series highlight the effectiveness of NGS and molecular classifier assays in enhancing diagnostic accuracy for HNC and contributing to the precise differentiation of disease etiologies. The utilization of these advanced technologies proved instrumental in avoiding unnecessary interventions and paved the way for more targeted and effective treatment strategies. Conclusion: Our findings underscore the necessity of incorporating advanced molecular testing technologies into the diagnostic and therapeutic approaches for HNC, thereby championing a more nuanced and effective approach to managing these complex cases. [ABSTRACT FROM AUTHOR]

Abstract Although the relationship between allergies and cancer has been investigated extensively, the role of allergies in head and neck cancer (HNC) appears less consistent. It is unclear whether allergies can independently influence the risk of HNC in the presence of substantial environmental risk factors, including consumption of alcohol, betel quid, and cigarettes. This study aims to find this association. We examined the relationship between allergies and HNC risk in a hospital-based case–control study with 300 cases and 375 matched controls. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals, controlling for age, sex, tobacco smoking and opium usage history, alcohol consumption, and socioeconomic status. Our study showed a significant reduction in the risk of HNC associated with allergy symptoms after adjusting for confounders. The risk of HNC was greatly reduced among those with any type of allergy (OR 0.42, 95% CI 0.28, 0.65). The ORs were considerably reduced by 58–88% for different kinds of allergies. The risk of HNC reduction was higher in allergic women than in allergic men (71% vs. 49%). Allergies play an influential role in the risk of HNC development. Future studies investigating immune biomarkers, including cytokine profiles and genetic polymorphisms, are necessary to further delineate the relationship between allergies and HNC. Understanding the relationship between allergies and HNC may help to devise effective strategies to reduce and treat HNC.

The aim of this study was to explore the relationship between the EAT-Lancet diet (ELD) and head and neck cancers (HNCs) in 101,755 Americans enrolled in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Prospective cohort study. ELD score was calculated to assess participant's adherence to ELD. Cox hazard regression models were utilised to evaluate the association of ELD and dietary components with HNC risk. Restricted cubic spline (RCS) plots were employed to explore the linearity of the relationships. Predefined subgroup analyses and sensitivity analyses were performed to identify potential effect modifiers and to assess the stability of the findings, respectively. After a mean follow-up of 8.84 years, 279 cases of HNCs, including 169 cases of oral cavity and pharyngeal cancers and 110 cases of laryngeal cancer were recorded. This study observed a dose–response negative correlation between ELD and HNCs (hazard ratio [HR] Q4 vs Q1 : 0.52; 95% confidence interval [CI]: 0.34, 0.80; P -trend = 0.003; HR per SD increment : 0.80; 95% CI: 0.71, 0.91), and oral cavity and pharyngeal cancers (HR Q4 vs Q1 : 0.52; 95% CI: 0.31, 0.88; P -trend = 0.008; HR per SD increment : 0.78; 95% CI: 0.66, 0.92). Analysis using RCS plots indicated a significant linear association between adherence to the ELD and reduced risk of HNCs and oral cavity and pharyngeal cancers (P -nonlinearity > 0.05). Subgroup analysis did not reveal significant interaction factors (P -interaction > 0.05), and sensitivity analysis confirmed the robustness of this study. Additionally, negative correlations were found between the consumption of fruits and whole grains and HNCs (fruits: HR Q4 vs Q1 : 0.58; 95% CI: 0.40, 0.84; P -trend = 0.010; whole grains: HR Q4 vs Q1 : 0.51; 95% CI: 0.26, 0.97; P -trend = 0.004). Adherence to ELD contributes to the prevention of HNCs. [ABSTRACT FROM AUTHOR]

Background. Peri-operative interventional radiotherapy (POIRT) entails tumor resection, catheter implantation in the same surgery, and irradiation within the peri-operative period. It allows for maximal tumor burden reduction, better tumor bed identification, more flexible implant geometry, highly conformal irradiation, and treatment delay minimization. We reviewed the published local control, survival, toxicity, and quality of life (QOL) outcomes with POIRT for head and neck cancers (HNCs) in primary and re-irradiation settings. Materials and Methods. A systematic search of PubMed, Scopus, Science Direct, and other databases, supplemented by bibliography scanning and hand-searching, yielded 107 titles. Fifteen unique articles were eligible, five of which were merged with more updated studies. Of the ten remaining studies, four reported on primary POIRT, and seven reported on reirradiation POIRT. Given data heterogeneity, only qualitative synthesis was performed. Results. Primary POIRT in early tongue cancer results in 6-year recurrence-free (RFS) and overall survival (OS) of 92% for both; in advanced HNCs, the 9-year RFS and OS rates are 52% and 55%. Grade 1–2 toxicity is very common; grade 3–4 toxicity is rare, but grade 5 toxicity has been reported. POIRT re-irradiation for recurrent HNCs results in 5y RFS and OS rates of 37–55% and 17–50%; better outcomes are achieved with gross total resection (GTR). QOL data are lacking. Conclusions. Primary POIRT is safe and effective in early tongue cancers; its use in other HNC sites, especially in advanced disease, requires careful consideration. Re-irradiation POIRT is most effective and safe when combined with GTR; toxicity is significant and may be limited by careful case selection, implant planning and execution, use of smaller fraction sizes, and adherence to homogeneity constraints. Study Registration Number. PROSPERO Registry Number CRD42024548294. [ABSTRACT FROM AUTHOR]

Purpose: Dry eye syndrome (DES) is a familiar sequelae of radiation therapy (RT) for head and neck cancers (HNC). Ocular surface changes such as DES occur due to injury to the conjunctival epithelium, goblet cells, corneal surface, lacrimal glands, and meibomian glands. This study aimed at the evaluation and early detection of changes in ocular surface parameters in patients receiving RT for extraocular HNC. Methods: Forty-two eyes of 21 patients undergoing HNC RT were evaluated. Radiation technique and dose of radiation to the lens and eye were recorded. Subjects were evaluated for meibomian gland changes by meiboscore grading, ocular surface disease index (OSDI) questionnaire, Schirmer's test, tear film break-up time (TBUT), and slit-lamp examination before RT, immediately post RT, and 6 weeks post RT. A comparison of the ipsilateral eye on the irradiated side to the contralateral eye was done. Results: A significant reduction in TBUT was seen immediately post RT and 6 weeks post RT (P < 0.001 and 0.008, respectively), with an increase in meiboscore at both visits (P < 0.001). An OSDI score of >13 was seen in 23.80% of patients post RT, with a significant difference from baseline (P < 0.001). On comparing ipsilateral and contralateral eye groups, a significant difference from baseline was seen in TBUT (P < 0.001 and 0.033, respectively) and meiboscore (P < 0.001 for both eyes). A significant change of >1 second in TBUT and >1.7 in meiboscore was seen with a mean dose of around 8 Gy to the lens. Conclusion: All patients undergoing HNC RT should be followed up for ocular surface and meibomian gland changes. The contralateral eye should also be evaluated. Patients receiving lower doses to the ocular structures should also be kept under follow-up. [ABSTRACT FROM AUTHOR]

Increased serum lactate dehydrogenase (LDH) activity is considered as a marker of cellular necrosis and serves as a metabolomic diagnostic marker in several types of cancer including head and neck squamous cell carcinoma (HNSCC). LDH, an enzyme involved in the glycolytic cycle, is correlated not only with the activation of oncogenes such as HIF-α and Myc, but also with effects such as tumor proliferation and metastasis. Serum alkaline phosphatase (ALP) is a marker of cell differentiation and tumor induction. Albumin-to-alkaline phosphatase ratio (AAPR) could be an advantageous biomarker due to its easily accessible dynamics and cost-effectiveness. Elevated values of AAPR could be associated with longer overall survival (OS) in cases with solid tumors. Diabetes mellitus (DM) could influence the outcome of patients with HNSCC by contributing to insulin resistance and chronic inflammation, and by being involved in various aspects of carcinogenesis, disease progression and metastasis. However, the use of antihyperglycemic medications (metformin) can have beneficial effects by inhibiting tumor metabolic pathways. The biomarker role of LDH and AAPR in HNSCC patients with DM has been less evaluated. The purpose of the study was to assess the prognostic value of pretreatment serum lactate dehydrogenase (LDH) and albumin-to-alkaline phosphatase ratio (AAPR) in predicting the duration of non-surgical oncological treatment and glycemic control in cases of head and neck cancers patients with DM, including cases selected from the database of the oncology clinic and oncology outpatient clinic of the Craiova County Hospital. Both LDH and AAPR can be used as pre-treatment biomarkers predictive of treatment response, or prognostic tools included in complex multi-parametric models in HNC associated with DM. However, given the impact of short-term glycemic control on the LDH level, it is necessary to evaluate these biomarkers after assessing and controlling for DM, and with the recommended cut-off value set around 0.5. Due to the limited number of cases, it is necessary to validate the results in multicentric trials with a larger number of patients (Tab. 5, Ref. 50). Text in PDF www.elis.sk [ABSTRACT FROM AUTHOR]

Background: Patients during radiotherapy due to head and neck cancers experience a lot of side effects which may have a considerable impact on the patients’ ability to meet individual daily energy demands by means of oral diet. Methods: The study included 104 head and neck cancer patients who qualified for radical radiotherapy. Radical treatment takes 6 weeks and every week the patients were assessed for dietary intake. The subjects were covered with the constant care of a dietician, received FSMP (food for special medical purposes), and, if necessary, enteral nutrition. Results: In the first week of treatment, the patients, from the kitchen diet alone, met 91.5% of the energy demand, while in the last week of treatment, only 40.9%. After introducing the FSMP or enteral nutrition, the patients met 120% of the demand in the first week of therapy and 95% in the last week, respectively. The patients who followed the dietary recommendations were characterized by significantly lower weight loss (3.07 kg) compared to non-adherent patients (5.56 kg). Conclusions: The used therapy significantly contributed to decreasing nutritional intake in the subsequent weeks of treatment. On the other hand, incorporating FSMP in the diet and enteral nutrition with industrial diets significantly increased the fulfilled energy demand of patients. [ABSTRACT FROM AUTHOR]

Background: Chemoradiation in head and neck carcinoma (HNC) shows significant anatomical resulting in erroneous dose deposition in the target or the organ at risk (OAR). Adaptive radiotherapy (ART) can overcome this. Timing of significant target and OAR changes with dosimetric impact; thus, most suitable time and frequency of ART is unclear. Methods: This dosimetric study used prospective weekly non‐contrast CT scans in 12 HNC patients (78 scans). OARs and TVs were manually contoured after registration with simulation scan. Dose overlay done on each scan without reoptimization. Dosimetric and volumetric variations assessed. Results: Commonest site was oropharynx. Gross Tumor Volume (GTV) reduced from 47.5 ± 19.2 to 17.8 ± 10.7 cc. Nodal GTV reduced from 15.7 ± 18.8 to 4.7 ± 7.1 cc. Parotid showed mean volume loss of 35%. T stage moderately correlated with GTV regression. Conclusion: Maximum GTV changes occurred after 3 weeks. Best time to do single fixed interval ART would be by the end of 3 weeks. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction Head and neck cancer (HNC) is a significant global health burden, with late presentation leading to complex treatment. While human papillomavirus (HPV) infection has been implicated in HNC, data from low‐ and middle‐income countries (LMICs) are limited. In this study, we investigated the prevalence and role of HPV in head and neck cancers diagnosed in Rwanda. Methods A retrospective cross‐sectional study was conducted using Rwanda Cancer Registry from January 2011 through December 2020. p16 immunohistochemistry as a surrogate for HPV was performed on a randomly selected case. p16‐positive cases were genotyped. Results A total of 1001 patients with HNC were identified; 82% (n = 819) had squamous cell carcinoma. The mean age at diagnosis was 51.1 years, with a majority being males (58%). Oral cavity and lip (27%) were the most common primary cancer sites. Stage was unknown in most cases (75%, n = 747). HIV status was known in 33% (n = 334) of patients with 10% (n = 33) HIV‐positive; 22% of 202 randomly selected cases were p16‐positive; 34% of the p16‐positive cases were oropharynx. PCR analysis of p16‐positive cases showed 19% HPV positivity, and HPV16 was the most common high‐risk HPV strain, and 55.5% were recorded HPV‐positive by PCR. Conclusions HNC cases in Rwanda have been increasing from 2011 to 2020, with a significant portion being HPV‐positive. Strategies to implement routine testing for p16, especially in oropharynx cancer patients, improved preservation of tissue samples, collection of comprehensive information including cancer risk factors, staging, and treatment are needed in Rwanda.

Abstract Background Human papillomavirus (HPV) is increasingly recognized as a significant risk factor in the development of head and neck cancers (HNCs), with varying prevalence and impact. This study aims to systematically review and analyze the prevalence of HPV in HNCs in India, providing insights into regional variations. Methods A comprehensive literature search was carried out using PubMed, Embase, and Web of Science up to November 10, 2023. Inclusion criteria focused on original research reporting HPV-positive cases among HNC patients in India. We used Nested-Knowledge software, for screening, and data extraction. The modified Newcastle-Ottawa Scale was used for quality assessment of included studies. We pooled the prevalence of HPV among HNC patients and performed a random-effects model meta-analysis using R software (version 4.3). Results The search yielded 33 studies, encompassing 4654 HNC patients. The pooled prevalence of HPV infection was found to be 33% (95% CI: 25.8–42.6), with notable heterogeneity (I² = 95%). Analysis of subgroups according to geographical location indicated varying prevalence rates. Specifically, the prevalence was 47% (95% CI: 32.2–62.4) in the eastern regions and 19.8% (95% CI: 10.8–33.4) in the western regions. No evidence of publication bias was detected. Conclusion The observed considerable regional disparities on the prevalence of HPV in HNC patients in India emphasizes the need for integrated HPV vaccination and screening programs in public health strategies. The findings underline the necessity for further research to explore regional variations and treatment responses in HPV-associated HNCs, considering the impact of factors such as tobacco use and the potential benefits of HPV vaccination.

Cancer driver genes (CDGs) and the driver mutations disrupt the homeostasis of numerous critical cell activities, thereby playing a critical role in tumor initiation and progression. In this study, integrative bioinformatics analyses were performed based on a series of online databases, aiming to identify driver genes with high frequencies of mutations in head and neck cancers. Higher myeloma overexpressed (MYEOV) genetic variation frequency and expression level were connected to a poorer prognosis in head and neck cancer patients. MYEOV was dramatically upregulated within head and neck tumor samples and cells. Consistently, MYEOV overexpression remarkably enhanced the aggressiveness of head and neck cancer cells by promoting colony formation, cell invasion, and cell migration. Conversely, MYEOV knockdown attenuated cancer cell aggressiveness and inhibited tumor growth and metastasis in the oral orthotopic tumor model. In conclusion, MYEOV is overexpressed in head and neck cancer, with greater mutation frequencies correlating to a poorer prognosis in head and neck cancer patients. MYEOV serves as an oncogene in head and neck cancer through the promotion of tumor cell colony formation, invasion, and migration, as well as promoting tumor growth and metastasis in the oral orthotopic tumor model. [ABSTRACT FROM AUTHOR]

Head and neck cancers (HNCs), primarily head and neck squamous cell carcinoma (HNSCC), are associated with high‐risk human papillomavirus (HR HPV), notably HPV16 and HPV18. HPV status guides treatment and predicts outcomes, with distinct molecular pathways in HPV‐driven HNSCC influencing survival rates. HNC incidence is rising globally, with regional variations reflecting diverse risk factors, including tobacco, alcohol, and HPV infection. Oropharyngeal cancers attributed to HPV have significantly increased, particularly in regions like the United States. The HPV16 genome, characterized by oncoproteins E6 and E7, disrupts crucial cell cycle regulators, including tumor protein p53 (TP53) and retinoblastoma (Rb), contributing to HNSCC pathogenesis. P16 immunohistochemistry (IHC) is a reliable surrogate marker for HPV16 positivity, while in situ hybridization and polymerase chain reaction (PCR) techniques, notably reverse transcription‐quantitative PCR (RT‐qPCR), offer sensitive HPV detection. Liquid‐based RT‐qPCR, especially in saliva, shows promise for noninvasive HPV detection, offering simplicity, cost‐effectiveness, and patient compliance. These molecular advancements enhance diagnostic accuracy, guide treatment decisions, and improve patient outcomes in HNC management. In conclusion, advances in HPV detection and molecular understanding have significant clinical management implications. Integrating these advancements into routine practice could ultimately improve patient outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Since the last update of GEC-ESTRO (Groupe Européen de Curiethérapie - European Society for Therapeutic Radiology and Oncology) recommendations for head and neck (HN) brachytherapy in 2017, advances in understanding and management of HN cancers have influenced brachytherapy. We conducted a scoping review to depict the evolution of HN brachytherapy research and practice, and identify emerging topics since the previously published guidelines. Material and methods: Systematic literature search was performed in PubMed, EBSCOhost, Europe PMC, and Google Scholar databases for articles on HN brachytherapy from 2017 onwards; the search was last done on June 29, 2023. We included primary studies on HN brachytherapy in English, complemented by bibliography scanning of secondary studies. Iterative team approach was employed in data extraction and charting. Quantitative and qualitative analyses and narrative synthesis were performed. Results: Systematic search yielded 215 unique articles. A total of 132 primary studies were included: 112 on clinical outcomes (retrospective cohorts in majority, n = 72), and 22 were simulation and dosimetric studies. China consistently produced the most research output per year. The most studied sites were the oral cavity (n = 84), oropharynx (n = 37), and salivary glands (n = 20). While most reported on high-dose-rate brachytherapy (n = 57), there was resurgence of studies on low-dose-rate (LDR) brachytherapy (n = 50) in the form of permanent seed implants. In the latter, CT (n = 50) and template (n = 27) guidance were described. While majority discussed definitive brachytherapy, 18 reported on perioperative brachytherapy. Several reported on 3D printing for template and applicator design (n = 11) as well as new approaches to dose calculation or dose optimization algorithms (n = 2). Conclusions: The current scoping review identified recent trends in HN brachytherapy, such as application in other HN sites, use of LDR seed implants, perioperative brachytherapy, and 3D printing in template design. Data from these recent publications provide a foundation for further investigations, which can generate evidence for succeeding guidelines. [ABSTRACT FROM AUTHOR]

Background: Moderately advanced and technically unresectable oral cavity cancers have a poor prognosis. Neoadjuvant chemotherapy might be beneficial in such patients by reducing tumour bulk and allowing definitive surgery. Aim: To evaluate the response of neoadjuvant chemotherapy in moderately advanced technically unresectable oral cavity cancers. Methodology: Prospective observational study - secondary data analysis of patients with moderately advanced oral cavity cancer, which were treated with neoadjuvant chemotherapy (NACT) during the period November 2014-April 2016. Data was analysed for information on patient characteristics, chemotherapy received, toxicity, clinical response rates, local treatment offered and pathological response rates. The statistical analysis was performed with SPSS version 20. Results: 30 patients, with a median age of 52 years were analyzed. Buccal mucosa was the most common sub site (50%). Three drug regimen was utilized in all patients. Resectability was achieved in 14 patients (46.67%). Febrile neutropenia was seen in 3 patients (10%). The overall response rate was 31%. Conclusion: NACT was effective in converting moderately advanced technically unresectable oral cavity cancers to operable disease in approximately 47% of patients. Post NACT, there is significant association between clinical and pathological findings of response rates. There is no increase in surgical complication rates following NACT. [ABSTRACT FROM AUTHOR]

Introduction: This study compared the submental surface electromyography (sEMG) duration and amplitude during dry swallowing between irradiated head and neck cancer (HNC) survivors and age-matched normal individuals. Further, the relationship between submental and infrahyoid sEMG in the irradiated HNC group was explored. Method: Forty participants (20 HNC survivors and 20 age-matched normal individuals) participated in this study. The HNC survivors had completed organ preservation cancer treatment (at least 1-month post-treatment). They were on a complete oral diet without enteral supplementation (FOIS score> 4). Submental and infrahyoid sEMG activity was calculated for three trials of saliva swallow for each participant using sEMG. The duration and amplitude parameters considered were: onset duration – duration from the onset of swallowing to the maximum amplitude, offset duration – duration from the maximum amplitude to the end of the swallowing activity, total duration, and maximum amplitude. Results: The study found that irradiated HNC survivors exhibited prolonged temporal measures, particularly in the offset duration, which suggested a delayed descent of the hyolaryngeal complex during swallowing. Additionally, the HNC group showed a positive correlation between submental and infrahyoid sEMG. Furthermore, it was observed that the rate of increase in the duration of submental sEMG during subsequent swallowing was greater in HNC survivors which could be due to reduced salivation. Conclusion: Compared to age-matched normal individuals, irradiated HNC survivors manifest alterations in the submental muscle activities during dry swallowing as measured using sEMG. The temporal and amplitude changes are likely to have arisen as a consequence of postradiation changes. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to observe the curative effect of radioactive 125I seed implantation in treating inoperable or refused operation head and neck cancer. Methods: Data from 132 patients with head and neck malignant tumors underwent computed tomography-guided radioactive 125I seed implantation from April 2004 to August 2020 were analyzed retrospectively. The Kaplan-Meier method was used to calculate the local control and survival rates. The logarithmic rank test and the Cox proportional risk model were used for univariate and multivariate analysis, respectively. Results: A total of 132 patients were enrolled. All tumors were confirmed to be malignant through pathological analysis. Herein, we revealed that the seeds were implanted at the primary tumor site (23 cases, representing 17.4%), recurrent (9 cases, representing 6.8%), or metastatic lymph nodes (100 cases, representing 75.8%). Three months after the operation, 96 patients were evaluated as effective, whereas 36 patients were considered ineffective. The median local control time was 16 months; the local rates at 6, 12, 18, and 24 months were observed to be 75%, 47%, 35%, and 22%, respectively. The study reports a median survival period (OS) of 15 months. Additionally, the survival rates at 6, 12, 18, and 24 months were 61%, 42%, 31%, and 27%, respectively. Regarding side effects, skin or mucosal toxicity occurred in 14 patients. Grade I skin toxicity occurred in seven cases (5.3%), grade IV skin toxicity in one case (0.8%), grade I mucosal ulcer in four cases (3.0%), and grade I dry mouth in four cases (3.0%). The multivariate analysis showed that short-term efficacy and tumor site were independent prognostic factors (P < 0.001, 0.006, respectively). Additionally, the multivariate analysis showed that the independent OS influencing factors included D90, the longest tumor diameter, and short-term efficacy (P = 0.017, 0.001, <0.001). Conclusion: Radioactive 125I seed implantation is a safe and effective salvage therapy for patients with inoperable or refused operation head and neck cancer. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the utility of long duration (10 min) acquisitions compared to standard 4 min scans in the evaluation of head and neck cancer (HNC) using a long-axial field-of-view (LAFOV) system in 2-[18F]FDG PET/CT. Methods: HNC patients undergoing LAFOV PET/CT were included retrospectively according to a predefined sample size calculation. For each acquisition, FDG avid lymph nodes (LN) which were highly probable or equivocal for malignancy were identified by two board certified nuclear medicine physicians in consensus. The aim of this study was to establish the clinical acceptability of short-duration (4 min, C40%) acquisitions compared to full-count (10 min, C100%) in terms of the detection of LN metastases in HNC. Secondary endpoints were the positive predictive value for LN status (PPV) and comparison of SUVmax at C40% and C100%. Histology reports or confirmatory imaging were the reference standard. Results: A total of 1218 records were screened and target recruitment was met with n = 64 HNC patients undergoing LAFOV. Median age was 65 years (IQR: 59–73). At C40%, a total of 387 lesions were detected (highly probable LN n = 274 and equivocal n = 113. The total number of lesions detected at C100% acquisition was 439, of them 291 (66%) highly probable LN and 148 (34%) equivocal. Detection rate between the two acquisitions did not demonstrate any significant differences (Pearson's Chi-Square test, p = 0.792). Sensitivity, specificity, PPV, NPV and accuracy for C40% were 83%, 44%, 55%, 76% and 36%, whilst for C100% were 85%, 56%, 55%, 85% and 43%, respectively. The improved accuracy reached borderline significance (p = 0.057). At the ROC analysis, lower SUVmax was identified for C100% (3.5) compared to C40% (4.5). Conclusion: In terms of LN detection, C40% acquisitions showed no significant difference compared to the C100% acquisitions. There was some improvement for lesions detection at C100%, with a small increment in accuracy reaching borderline significance, suggestive that the higher sensitivity afforded by LAFOV might translate to improved clinical performance in some patients. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) approaches have been introduced in various disciplines but remain rather unused in head and neck (H&N) cancers. This survey aimed to infer the current applications of and attitudes toward AI in the multidisciplinary care of H&N cancers. From November 2020 to June 2022, a web-based questionnaire examining the relationship between AI usage and professionals' demographics and attitudes was delivered to different professionals involved in H&N cancers through social media and mailing lists. A total of 139 professionals completed the questionnaire. Only 49.7% of the respondents reported having experience with AI. The most frequent AI users were radiologists (66.2%). Significant predictors of AI use were primary specialty (V = 0.455; p < 0.001), academic qualification and age. AI's potential was seen in the improvement of diagnostic accuracy (72%), surgical planning (64.7%), treatment selection (57.6%), risk assessment (50.4%) and the prediction of complications (45.3%). Among participants, 42.7% had significant concerns over AI use, with the most frequent being the 'loss of control' (27.6%) and 'diagnostic errors' (57.0%). This survey reveals limited engagement with AI in multidisciplinary H&N cancer care, highlighting the need for broader implementation and further studies to explore its acceptance and benefits. [ABSTRACT FROM AUTHOR]

Simple Summary: Head and neck squamous cell carcinoma is one of the most common cancers that arises in the upper aerodigestive tract. Patients suffering from this cancer have a high mortality risk, mainly due to local recurrence, resistance to chemo- and radiotherapy, and metastasis. The more aggressive behavior of this tumor is associated with epithelial–mesenchymal transition, a process described in both physiological, primarily during embryonic development, and pathological situations, including the progression of other types of tumors. Epithelial-to-mesenchymal transition is governed by various transcription factors that regulate target gene expression and play a role in the resistance to contemporary head and neck cancer therapies. This review presents the current knowledge of the main transcription factors involved in mesenchymal conversion and discusses their role in head and neck squamous cell carcinoma treatment. The main protein markers associated with this cancer type are also presented. Head and neck cancers (HNCs) are heterogeneous and aggressive tumors of the upper aerodigestive tract. Although various histological types exist, the most common is squamous cell carcinoma (HNSCC). The incidence of HNSCC is increasing, making it an important public health concern. Tumor resistance to contemporary treatments, namely, chemo- and radiotherapy, and the recurrence of the primary tumor after its surgical removal cause huge problems for patients. Despite recent improvements in these treatments, the 5-year survival rate is still relatively low. HNSCCs may develop local lymph node metastases and, in the most advanced cases, also distant metastases. A key process associated with tumor progression and metastasis is epithelial–mesenchymal transition (EMT), when poorly motile epithelial tumor cells acquire motile mesenchymal characteristics. These transition cells can invade different adjacent tissues and finally form metastases. EMT is governed by various transcription factors, including the best-characterized TWIST1 and TWIST2, SNAIL, SLUG, ZEB1, and ZEB2. Here, we highlight the current knowledge of the process of EMT in HNSCC and present the main protein markers associated with it. This review focuses on the transcription factors related to EMT and emphasizes their role in the resistance of HNSCC to current chemo- and radiotherapies. Understanding the role of EMT and the precise molecular mechanisms involved in this process may help with the development of novel anti-cancer therapies for this type of tumor. [ABSTRACT FROM AUTHOR]

Purpose: Recent breakthroughs in natural language processing and machine learning, exemplified by ChatGPT, have spurred a paradigm shift in healthcare. Released by OpenAI in November 2022, ChatGPT rapidly gained global attention. Trained on massive text datasets, this large language model holds immense potential to revolutionize healthcare. However, existing literature often overlooks the need for rigorous validation and real-world applicability. Methods: This head-to-head comparative study assesses ChatGPT's capabilities in providing therapeutic recommendations for head and neck cancers. Simulating every NCCN Guidelines scenarios. ChatGPT is queried on primary treatments, adjuvant treatment, and follow-up, with responses compared to the NCCN Guidelines. Performance metrics, including sensitivity, specificity, and F1 score, are employed for assessment. Results: The study includes 68 hypothetical cases and 204 clinical scenarios. ChatGPT exhibits promising capabilities in addressing NCCN-related queries, achieving high sensitivity and overall accuracy across primary treatment, adjuvant treatment, and follow-up. The study's metrics showcase robustness in providing relevant suggestions. However, a few inaccuracies are noted, especially in primary treatment scenarios. Conclusion: Our study highlights the proficiency of ChatGPT in providing treatment suggestions. The model's alignment with the NCCN Guidelines sets the stage for a nuanced exploration of AI's evolving role in oncological decision support. However, challenges related to the interpretability of AI in clinical decision-making and the importance of clinicians understanding the underlying principles of AI models remain unexplored. As AI continues to advance, collaborative efforts between models and medical experts are deemed essential for unlocking new frontiers in personalized cancer care. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell cancers (HNSCCs) represent a diverse group of tumors emerging within different mucosal surfaces of the oral cavity, nasopharynx, oropharynx, larynx, and hypopharynx. HNSCCs share common clinical risk factors and genomic features, including smoking, alcohol, age, male sex, aneuploidy, and TP53 mutations. Viral initiating and contributing events are increasingly recognized in HNSCCs. While both Epstein-Barr Virus (EBV) and human papilloma virus (HPV) are observed, EBV is more frequently associated with nasopharyngeal cancers whereas HPV is associated with oropharyngeal cancers. HNSCCs are associated with high tumor mutational burden and loss of tumor suppressor gene function, especially in TP53 and X-linked genes. Multiple lines of evidence suggest that HNSCCs are subject to immunologic surveillance and immune-induced evolutionary pressure that correlate with negative clinical outcomes. This review will discuss genomic mechanisms related to immune-mediated pressures and propose prognostic and therapeutic implications of detectable immune escape mechanisms that drive tumorigenesis and disease progression.

Head and neck squamous cell carcinoma (HNSCC) exhibits significant genetic heterogeneity and primarily concerns the oral cavity and oropharynx. These cancers occur more frequently in men with a 5-year survival rate below 50%. Major risk factors include human papilloma virus (HPV) (notably type 16), Epstein-Barr virus, tobacco, alcohol, and poor oral hygiene with approximately 4.5% of global cancers linked to HPV. Notably, differences in the microbiome between healthy individuals and patients with head and neck cancers (HNCs) have been identified. Recent studies highlight the significance of certain oral microbes in risk assessment and the potential of the microbiome as a biomarker for HNCs. Additionally, role of the microbiome in metastasis has been acknowledged. Treatment for HNCs includes local methods, such as surgery and radiotherapy, and systemic approaches, such as immunotherapy. Numerous side effects accompany these treatments. Emerging research suggests the beneficial role of preoperative immunonutrition and probiotics in patient outcomes, emphasizing the influence of the microbiome on treatment efficacy. This review explores the reciprocal effects of HNC treatment and the gut microbiome using radiotherapy, brachytherapy, surgery, immunotherapy, and chemotherapy. [ABSTRACT FROM AUTHOR]

Radiotherapy (RT) is an integral part of many cancer treatment protocols. Chronic radiation-induced dermatitis (CRD) is a cutaneous toxicity that occurs in one-third of all patients treated with this method. CRD is usually observed several months after completion of treatment. Typical symptoms of CRD are telangiectasia, skin discoloration, atrophy, thickening, and cutaneous fibrosis. There are currently no data in the literature on the evaluation of the dermoscopic features of CRD. The aim of this prospective study was the identification of clinical and dermoscopic features in a group of 32 patients with head and neck cancer (HNC) in whom CRD developed after RT. CRD was assessed at 3, 6, and 12 months after RT in 16, 10, and 10 patients, respectively. CRD was assessed at one time point and two time points in 28 and 4 patients, respectively. The control included skin areas of the same patient not exposed to RT. The dataset consisted of 36 clinical and 216 dermoscopic photos. Clinical evaluation was performed according to the RTOG/EORTC radiation-induced dermatitis scale. The highest score was grade 2 observed in 21 patients. Clinical observations revealed the presence of slight and patchy atrophy, pigmentation change, moderate telangiectasias, and some and total hair loss. Dotted vessels, clustered vessel distribution, white patchy scale, perifollicular white color, white structureless areas, brown dots and globules, and white lines were the most frequently noted features in dermoscopy. Three independent risk factors for chronic toxicity, such as age, gender, and surgery before RT, were identified. The dermoscopic features that had been shown in our study reflect the biological reaction of the skin towards radiation and may be used for the parametrization of CRD regarding its intensity and any other clinical consequences in the future. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we have explored the impact of a promising new cancer treatment modality called proton therapy (PT) and compared it to traditional X-ray based photon therapy (XRT) for head and neck cancers. Proton therapy is effective because it can be delivered with precision, thus causing fewer side effects. We demonstrate in this study that, when using proton therapy, there was a significant reduction (75%) in the production of small extracellular vesicles, commonly known as exosomes, from cancer cells, which usually suppress the immune system. XRT did not reduce exosome production. Exosomes from both PT and XRT had similar inhibitory effects on immune cells. Our findings suggest that proton therapy might be better at reducing the immune-suppressing effects of cancer exosomes by producing fewer of them. Proton therapy (PT) is emerging as an effective and less toxic alternative to conventional X-ray-based photon therapy (XRT) for patients with advanced head and neck squamous cell carcinomas (HNSCCs) owing to its clustered dose deposition dosimetric characteristics. For optimal efficacy, cancer therapies, including PT, must elicit a robust anti-tumor response by effector and cytotoxic immune cells in the tumor microenvironment (TME). While tumor-derived exosomes contribute to immune cell suppression in the TME, information on the effects of PT on exosomes and anti-tumor immune responses in HNSCC is not known. In this study, we generated primary HNSCC cells from tumors resected from HNSCC patients, irradiated them with 5 Gy PT or XRT, and isolated exosomes from cell culture supernatants. HNSCC cells exposed to PT produced 75% fewer exosomes than XRT- and non-irradiated HNSCC cells. This effect persisted in proton-irradiated cells for up to five days. Furthermore, we observed that exosomes from proton-irradiated cells were identical in morphology and immunosuppressive effects (suppression of IFN-γ release by peripheral blood mononuclear cells) to those of photon-irradiated cells. Our results suggest that PT limits the suppressive effect of exosomes on cancer immune surveillance by reducing the production of exosomes that can inhibit immune cell function. [ABSTRACT FROM AUTHOR]

Background/Aim: Radiotherapy (RT) outcomes are generally reported based on stage, patient background, and concomitant chemotherapy. This study aimed to investigate the effects of the prescribed dose to gross tumor volume (GTV) and the calculation algorithm on local control in definitive RT for head and neck (H&N) cancers using follow-up images after RT. Patients and Methods: This study included 154 patients with H&N cancers treated by Volumetric Modulated Arc Therapy at the Kobe City Medical Center General Hospital. Patients were classified into those receiving definitive RT (70 Gy of irradiation) and those not receiving it. Follow-up images were used to categorize the patients into the responders and non-responders groups. In the non-responders group, follow-up images were imported into the treatment planning system, and the contours of the residual or recurrent areas (local failure) were extracted and fused with computed tomography-simulated images for treatment planning. Dose evaluation parameters included maximum dose, dose administered to 1% of the volume, dose administered to 50% of the volume, dose administered to 99% of the volume (D99%), and minimum dose (Dmin) administered to the GTV. The doses to the GTV were compared between responders and non-responders. Results: D99% exhibited significant differences between local failure and responders and between local failure and nonresponders. Dmin showed significant differences between responders and non-responders and between responders and local failure. Conclusion: This study emphasizes the importance of verifying dose distribution in all slices of treatment planning, highlighting the need for precise assessment of the dose to the GTV in head and neck cancers. [ABSTRACT FROM AUTHOR]

Background: The purpose of this retrospective cohort study is to describe the association between the history of tonsillectomy and the risk of oropharyngeal squamous cell carcinoma (OPSSC), using a large cohort of patients. Materials and methods: We performed a retrospective cohort study with 3620 patients diagnosed with OPٍSCC from 2010 to 2021. We utilized the University of Florida patients' registry i2b2 system. Three subsets of OPSSC were defined, base of tongue(BOT) cancer, tonsillar cancer, and other OPSSC. Tumor demographics and history of tonsillectomy were collected. Odds ratio for OPSSC were assessed utilizing a logistic regression model with adjusting for gender, race, and age. P < 0.05 was deemed significant. Results: Of the 3620 OPSSC patients were BOT cancer (N = 964), tonsillar cancer (N = 995), and other OPSSC (N = 1661). There was a statistically significant reduction in tonsillar cancer and BOT cancer odds ratio in patients with a history of tonsillectomy vs. patients without tonsillectomy (0.086 and 0.117), respectively, with a P value <.0001. The odds ratio of OPSSC in patients with a history of tonsillectomy vs. patients without tonsillectomy is 1.031. Conclusion: This study showed that the OPSSC and previous history of tonsillectomy are associated. Our results showed a significant reduction in BOT and tonsillar cancer risk in patients with a history of tonsillectomy and an insignificant decrease in other OPSSC. This study could emphasize the importance of the development of future clinical trials to investigate the role of prophylactic tonsillectomy as a secondary preventive strategy to reduce OPSSC. [ABSTRACT FROM AUTHOR]

Introduction: Pectoralis major myo-cutaneous (PMMC) flap continues to be a widely used tool to reconstruct oral cavity defects. But an unreliable and unstable vascular supply can lead to complications like flap loss, Oro-cutaneous fistula and wound dehiscence. Preservation of the lateral thoracic artery (LTA) has been suggested to improve the vascularity of the skin paddle. The present study aspires to compare the complications and flap related outcomes after preserving or sacrificing the LTA while reconstructing oral cavity defects with bi-folded PMMC flap. Materials and Methods: Retrospective analysis of the data of 61 male patients who were reconstructed with bi-folded PMMC flaps between January 2022 and September 2022 was done. 36 patients were reconstructed using a PMMC flap where the LTA was sacrificed, whereas in 25 patients the LTA was preserved. Data was analyzed in terms of patient factors and flap related complications. Results: The overall complication rate including major/minor complications was 44.26% with flap detachment at 22.95% being the commonest complication observed. 13.11% patients developed an Oro-cutaneous fistula and partial and complete flap loss were seen in 9.83% and 4.91% respectively. LTA preservation was significantly associated with only decreased flap detachment rates (p value < 0.05). No significant association was noticed between other flap related complications and LTA preservation. Conclusion: Reconstructing larger defects with a PMMC flap where the LTA is preserved can help improve the vascularity of the flap and decrease various major/minor flap related complications. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral Mucositis, a debilitating side effect of radio and chemotherapy for head and neck cancers, involves inflammation and ulceration of the mucous membranes in the oral cavity. This condition often leads to severe pain, difficulty in eating, and compromised quality of life for cancer patients. The use of natural compounds such as polyphenols has shown promise in preventing and alleviating Oral Mucositis as they possess anti-inflammatory, antioxidant, and healing properties, capable of mitigating the adverse effects of chemo and radiotherapy on the oral mucosa. The recent literature suggests that integrating these natural compounds into treatment regimens may help manage Oral Mucositis, offering a potential adjuvant therapy to improve a patient's quality of life and overall well-being during cancer treatment. Oral Mucositis (OM) is the most common side effect due to chemotherapy and radiotherapy, which are the conventional treatment options for head and neck cancers. OM is a severe inflammatory condition characterized by multifactorial etiopathogenesis. It further negatively affects patients' quality of life by severe impairment of normal oral functions. Consequently, it is mandatory to identify new effective therapeutic approaches to both prevent and treat OM while also avoiding any recurrence. Polyphenols recently attracted the interest of the scientific community due to their low toxicity and wide range of biological activities making them ideal candidates for several applications in the odontostomatological field, particularly against OM. This review collects the in vivo studies and the clinical trials conducted over the past 13 years evaluating the preventive and curative effects of several polyphenolic compounds towards chemo- and radiotherapy-induced OM, both when administered alone or as a plant-extracted phytocomplex. The literature fully confirms the usefulness of these molecules, thus opening the possibility of their clinical application. However, polyphenol limitations (e.g., unfavourable physicochemical properties and susceptibility to degradation) have emerged. Consequently, the interest of the scientific community should be focused on developing innovative delivery systems able to stabilize polyphenols, thus facilitating topical administration and maximizing their efficacy. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC) is associated with high morbidity and mortality. New personalized treatment strategies represent an unmet medical need to improve the overall survival and the quality of life of patients, which are often limited by the toxicity of established multimodal treatment protocols. Several studies have reported an increased expression of the estrogen receptor 1 (ESR1) in HNSCC, but its potential role in the disease outcome of these tumors remains elusive. Using an integrative analysis of multiomics and clinical data from The Cancer Genome Atlas (TCGA)-HNSC, we established a prognostic risk model based on an ESR1-related 25-gene set. The prognostic value was confirmed in an independent cohort of HNSCC and other solid tumors from TCGA. Finally, we performed in silico drug sensitivity modeling to explore potential vulnerabilities for both risk groups. This approach predicted a higher sensitivity for HNSCC, with prominent ESR1 pathway activity under treatment with specific estrogen receptor modulators. In conclusion, our data confirm the involvement of ESR1-related pathway activity in the progression of a defined subset of HNSCC, provide compelling evidence that these tumors share a specific vulnerability to endocrine therapy, and pave the way for preclinical studies and clinical trials to demonstrate the efficacy of this new therapeutic option. [ABSTRACT FROM AUTHOR]

Background: In order to accurately accumulate delivered dose for head and neck cancer patients treated with the Adapt to Position workflow on the 1.5T magnetic resonance imaging (MRI)‐linear accelerator (MR‐linac), the low‐resolution T2‐weighted MRIs used for daily setup must be segmented to enable reconstruction of the delivered dose at each fraction. Purpose: In this pilot study, we evaluate various autosegmentation methods for head and neck organs at risk (OARs) on on‐board setup MRIs from the MR‐linac for off‐line reconstruction of delivered dose. Methods: Seven OARs (parotid glands, submandibular glands, mandible, spinal cord, and brainstem) were contoured on 43 images by seven observers each. Ground truth contours were generated using a simultaneous truth and performance level estimation (STAPLE) algorithm. Twenty total autosegmentation methods were evaluated in ADMIRE: 1–9) atlas‐based autosegmentation using a population atlas library (PAL) of 5/10/15 patients with STAPLE, patch fusion (PF), random forest (RF) for label fusion; 10–19) autosegmentation using images from a patient's 1–4 prior fractions (individualized patient prior [IPP]) using STAPLE/PF/RF; 20) deep learning (DL) (3D ResUNet trained on 43 ground truth structure sets plus 45 contoured by one observer). Execution time was measured for each method. Autosegmented structures were compared to ground truth structures using the Dice similarity coefficient, mean surface distance (MSD), Hausdorff distance (HD), and Jaccard index (JI). For each metric and OAR, performance was compared to the inter‐observer variability using Dunn's test with control. Methods were compared pairwise using the Steel‐Dwass test for each metric pooled across all OARs. Further dosimetric analysis was performed on three high‐performing autosegmentation methods (DL, IPP with RF and 4 fractions [IPP_RF_4], IPP with 1 fraction [IPP_1]), and one low‐performing (PAL with STAPLE and 5 atlases [PAL_ST_5]). For five patients, delivered doses from clinical plans were recalculated on setup images with ground truth and autosegmented structure sets. Differences in maximum and mean dose to each structure between the ground truth and autosegmented structures were calculated and correlated with geometric metrics. Results: DL and IPP methods performed best overall, all significantly outperforming inter‐observer variability and with no significant difference between methods in pairwise comparison. PAL methods performed worst overall; most were not significantly different from the inter‐observer variability or from each other. DL was the fastest method (33 s per case) and PAL methods the slowest (3.7–13.8 min per case). Execution time increased with a number of prior fractions/atlases for IPP and PAL. For DL, IPP_1, and IPP_RF_4, the majority (95%) of dose differences were within ± 250 cGy from ground truth, but outlier differences up to 785 cGy occurred. Dose differences were much higher for PAL_ST_5, with outlier differences up to 1920 cGy. Dose differences showed weak but significant correlations with all geometric metrics (R2 between 0.030 and 0.314). Conclusions: The autosegmentation methods offering the best combination of performance and execution time are DL and IPP_1. Dose reconstruction on on‐board T2‐weighted MRIs is feasible with autosegmented structures with minimal dosimetric variation from ground truth, but contours should be visually inspected prior to dose reconstruction in an end‐to‐end dose accumulation workflow. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral infection with high-risk human papillomaviruses is one of the known risk factors for oropharyngeal cancer. Human papillomavirus-related oropharyngeal cancer is a rising trend in many Western countries. Hong Kong is a vibrant Chinese cosmopolitan city in East Asia where data on the trend of change in human papillomavirus-related oropharyngeal cancer are not available. This study found that oropharyngeal cancer cases have increased persistently over the last three decades in Hong Kong, despite a notable decrease in other head and neck cancers such as the laryngeal cancer. By testing a series of cancer samples collected over the past several years, this study found that the proportion of oropharyngeal cancer infected with high-risk human papillomaviruses has increased substantially over the last decade. Strategies to prevent oral human papillomavirus infection and its associated diseases including oropharyngeal cancer are urgently needed. Research on the early detection of oropharyngeal cancer is a priority. The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is rising in the West, but little is known in Asia. This study elucidated changes in the incidence and HPV-positive portion of OPSCC in Hong Kong. Data from population-based cancer registry were used to analyze the incidence of OPSCC in association with other head and neck cancers. Archived tumor tissues were tested for HPV. From 1986 to 2020, there was a marked decrease in the incidence of nasopharyngeal and laryngeal cancers, but a persistent increase in OPSCC from 36 cases in 1986 to 116 cases in 2020. The average positive rate for high-risk HPV was 36.1% (112/310) among OPSCC diagnosed in 2010–2020. The HPV-positive rate in recent years was significantly higher than earlier cases (tonsil SCC: 64.7% (55/85) in 2016–2020 vs. 40.4% (19/47) in 2010–2015, p = 0.007). Patients with HPV-positive tonsil cancers were significantly younger than those negative (mean [SD]: 58.9 [9.9] vs. 64.3 [13.3] years, p = 0.006), but no significant difference was observed between genders. A persistent increase in the incidence of oropharyngeal cancer over the last few decades was observed in Hong Kong, which can be explained by the remarkable increase in HPV-positive tonsil cancers. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to compare conventional 3 field versus 5 field treatment planning techniques during 3-dimensional conformal radiotherapy(3D-CRT) in respect of OAR, PTV coverage, treatment response & toxicities in head and neck Cancer. Materials and methods: This study included 50 biopsy proven and registered patients of head and neck cancer. Twenty five patients randomized to each arm. Arm A- 3D- conformal radiotherapy by 3 field delivery technique. Arm B-- 3D- conformal radiotherapy by 5 field delivery technique. All patients were irradiated on linear accelerator with concurrent chemotherapy in form of 3 weekly Cisplatin. Target volumes and normal structures were manually contoured on the axial slices of the planning CT scan. Patients were evaluated at end of treatment, 1st, 3rd & 6th months follow up visits. Results: At the end of treatment 22 (88%) patient in 3 field and 23 (92%) patients in 5 field had complete response. At 6 months complete response was 76% and 80 % in Arm A and B respectively (p value=0.6836). Grade 3rd xerostomia was seen 12% Vs 4% in Arm A and B respectively (p value= 0.92) Mean V95 was 90.93 for conventional 3 field technique and 93.28 with 5 field technique (p value=0.08). Conclusion: 5 field 3D-CRT technique can be used to spare parotid and other OAR and better PTV coverage specially in larynx carcinoma, patient with N2 or less nodal involvement and not involving higher neck node level. [ABSTRACT FROM AUTHOR]

Objective: To assess the proportion of adequate surgery in head and neck cancers. Study Design: Prospective longitudinal study. Place and Duration of Study: Medical Oncology Department, Jinnah Postgraduate Medical Center, Karachi Pakistan, from Jan to Dec 2020. Methodology: One fifty-nine patients aged over 20-65 years, of either gender with a confirmed diagnosis of squamous cell carcinoma of the Head and neck were included. Surgery was performed upfront in all patients without any preoperative/ induction chemotherapy. Data regarding socio-demographic and histopathology findings were noted. Surgery was labelled as inadequate when the number of resected lymph nodes recovered was less than 36, and the margins of the tumour were

BackgroundWhile immune checkpoint inhibitors (ICI) were approved for head and neck squamous cell carcinomas (HNSCCs), the response rate remains relatively low. Mechanisms underlying ICI unresponsiveness versus sensitivity are not fully understood.MethodTo better delineate differential responses to ICI treatment, we employed mouse SCC models, termed KPPA tumors that were caused by deleting p53 and hyperactivating PIK3CA, two most frequently mutated genes in human HNSCCs. We transplanted two KPPA tumor lines (TAb2 versus TCh3) into C57BL/6 recipients and examined the immune tumor microenvironment using flow cytometry. Furthermore, we employed single-cell RNA sequencing to identify the difference in tumor infiltrating lymphocytes (TILs).ResultsWe found that different KPPA tumors exhibited heterogeneous immune profiles pre-existing treatment that dictated their sensitivity or unresponsiveness to anti-PD-L1. Unresponsive TAb2 tumors were highly enriched with functional tumor-associated macrophages (TAMs), especially M2-TAMs. In contrast, sensitive TCh3 tumors contained more CD8 TILs with better effector functions. TAb2 tumor cells drastically expanded F4/80+ TAMs from bone marrow precursors, requiring CSF1 and VEGF. Consistently, a higher combined expression of VEGF-C and CSF1 predicts worse survival in PIK3CAAmp/TP53Mutated HNSCC patients. Unresponsive TAb2 tumors upregulated distinct signaling pathways that correlate with aggressive tumor phenotypes. While anti-PD-L1 did not affect the TME of TAb2 tumors, it significantly increased the number of CD8 TILs in TCh3 tumors.ConclusionsWe uncovered tumor-intrinsic differences that may underlie the differential responses to ICI by establishing and employing two SCC tumor lines, TAb2 vs. TCh3, both of which harbor TP53 deletion and PIK3CA hyperactivation. Our study indicates the limitation of stratifying cancers according to their genetic alterations and suggests that evaluating HNSCC tumor-intrinsic cues along with immune profiles in the TME may help better predict ICI responses. Our experimental models may provide a platform for pinpointing tumor-intrinsic differences underlying an immunosuppressive TME in HNSCCs and for testing combined immunotherapies targeting either tumor-specific or TAM-specific players to improve ICI efficacy.

The rising incidence of oropharyngeal squamous cell cancers (OPSCC) in the United States is largely attributed to HPV. Prophylactic HPV vaccines have demonstrated effectiveness against oral infection of HPV 16 and HPV 18. We review the global epidemiology and biology of HPV-related cancers as well as the development of HPV vaccines and their use worldwide. We also review the various strategies and challenges in development of therapeutic HPV vaccines.

Abstract Background Head and neck reconstructive surgeries needs free tissue transfer but it fails sometimes. As most of the flap failure occurs in first 24 h. Local rise in lactate level or glucose lactate ratio provides clear indicator of tissue ischemia and further recovery. The question is about systemic rise in lactate levels with failing flap. Hence, we aimed to use systemic lactate levels to indicate free flap failure. To correlate the systemic rise in serum lactate levels to free flap failure in head and neck reconstructive surgeries. The series of cases were targeted undergoing free fibular graft, posted electively for head and reconstructive surgery operated by same surgeon. Record of blood loss, need of blood transfusion and use of microspan was also done. Monitoring of arterial blood gas values mainly lactate and vitals were done. Results Out of 15 patients studied, only 2(13.3%) patients had flap re-exploration (group F). Twelve (80%) patients were of ASA class I. Lactate, pH, blood sugars, base deficits and hemoglobin and vitals studied over 24 h in two groups had no statistically significant difference in the two groups. Lactate rise was noted in all cases for first few hours after starting surgery but elevated values were not observed during hours of flap re-exploration. Conclusions We could not establish relation between systemic rise in lactate levels and flap re-exploration or flap failure but continuous acidosis can impact outcome. We need to be vigilant and need to have individualized approach for management.

Background and purpose: Radiotherapy (RT) is a mainstay component of treatment for patients with head and neck squamous cell carcinoma (HNSCC), but responses vary. As RT relies upon oxidative damage, antioxidant expression in response to RT-induced reactive oxygen species (ROS) could compromise treatment response. We aimed to examine local and systemic antioxidant responses to increased RT-induced ROS in relation to treatment success. Materials and methods: Nuclear factor erythroid 2-related factor 2 (NRF2), the main antioxidant transcription factor, was immunofluorescently stained in FaDu cells and in tumor biopsies of patients with oral cavity/oropharynx HNSCC before and after five fractions of RT. Besides, total antioxidant capacity (TAC) was analyzed in HNSCC tumor cells in vitro and in serum of HNSCC patients before, during, and after RT. Results: Data revealed an increase in NRF2 expression and TAC in head and neck cancer cells in vitro over the course of 5 daily fractions of 2 Gy. In accordance, also in patients’ tumors NRF2 expression increased, which was associated with increased serum TAC during RT. Increasing serum TAC was related to impaired local tumor control. Conclusion: Radiation induced NRF2 expression and upregulated TAC, which may compromise the effect of RT-induced ROS. Changes in serum TAC during RT could serve as a novel predictor of treatment outcome in HNSCC patients.Medical Ethics Review Committee (CMO) approval – CMO number: 2007/104.

Purpose: Dry eye syndrome (DES) is a familiar sequelae of radiation therapy (RT) for head and neck cancers (HNC). Ocular surface changes such as DES occur due to injury to the conjunctival epithelium, goblet cells, corneal surface, lacrimal glands, and meibomian glands. This study aimed at the evaluation and early detection of changes in ocular surface parameters in patients receiving RT for extraocular HNC. Methods: Forty-two eyes of 21 patients undergoing HNC RT were evaluated. Radiation technique and dose of radiation to the lens and eye were recorded. Subjects were evaluated for meibomian gland changes by meiboscore grading, ocular surface disease index (OSDI) questionnaire, Schirmer’s test, tear film break-up time (TBUT), and slit-lamp examination before RT, immediately post RT, and 6 weeks post RT. A comparison of the ipsilateral eye on the irradiated side to the contralateral eye was done. Results: A significant reduction in TBUT was seen immediately post RT and 6 weeks post RT (P < 0.001 and 0.008, respectively), with an increase in meiboscore at both visits (P < 0.001). An OSDI score of >13 was seen in 23.80% of patients post RT, with a significant difference from baseline (P < 0.001). On comparing ipsilateral and contralateral eye groups, a significant difference from baseline was seen in TBUT (P < 0.001 and 0.033, respectively) and meiboscore (P < 0.001 for both eyes). A significant change of >1 second in TBUT and >1.7 in meiboscore was seen with a mean dose of around 8 Gy to the lens. Conclusion: All patients undergoing HNC RT should be followed up for ocular surface and meibomian gland changes. The contralateral eye should also be evaluated. Patients receiving lower doses to the ocular structures should also be kept under follow-up.