Neck Cancer Research Articles

Highlights of the 2024 ASCO Annual Meeting: radiotherapy of head and neck cancer

At the 2024 Annual Meeting of the American Society of Clinical Oncology (ASCO), several important studies on radiotherapy for head and neck squamous cell carcinoma (HNSCC) were presented. There were two Chinese phaseIII trials on treatment escalation for locally advanced nasopharyngeal carcinoma: adjuvant immune checkpoint inhibition with camrelizumab after induction chemotherapy and cisplatin-based chemoradiotherapy (RCT) in the DIPPER trial reached the primary endpoint of improved event-free survival (EFS) but did not improve overall survival (OS). Simultaneous and adjuvant administration of the angiogenesis inhibitor endostar in addition to cisplatin-based RCT for locally advanced nasopharyngeal carcinoma led to asignificant improvement in progression-free survival (PFS) and OS. Another major focus was on treatment optimization and deintensification for oropharyngeal cancer (OPC): using intensity-modulated proton therapy (IMPT), aphaseIII trial demonstrated noninferiority in definitive RCT for OPC compared to photon-based intensity-modulated radiotherapy (IMRT). In adjuvant treatment of human papillomavirus-positive (HPV+) OPC, the long-term results of the E3311 phaseII study confirmed that individually deintensified radiotherapy is feasible. Lee etal. showed with the results of aphaseII study that HPV+ OPC might be treatable with chemoradiotherapy to atotal dose of only 30 Gy if no hypoxia is detected in the 18F‑fluoromisonidazole positron-emission tomography-computed tomography (F-MISO-PET) scan. Both the deintensified treatment of HPV+ OPC as well as additive immune checkpoint and angiogenesis inhibition in chemoradiotherapy of nasopharyngeal carcinoma require further studies before they can be recommended in clinical practice.

Recurrence Detection by Hybrid [18F]FDG-PET in Advanced Head and Neck Squamous Cell Carcinoma.

In the clinical management of advanced stage head and neck squamous cell carcinoma, the use of hybrid [18F]FDG-PET imaging is well established. However, there is ongoing debate regarding the optimal frequency of hybrid PET scans to be included in follow-up protocols, particularly if the initial post-therapeutic scan is negative. We conducted a single-center 10-year retrospective study involving all patients who underwent hybrid PET scans for the follow-up of advanced stage head and neck cancer. A total of 285 patients were included. Out of 199 patients with a negative 3-month hybrid PET, 15% subsequently developed a recurrence during further follow-up. Notably, 90% of these recurrences were detected by hybrid PET. Fifteen percent of patients with a negative 3-month hybrid PET experienced a recurrence. Given that the majority of recurrences were detected by hybrid PET scans, there is a compelling argument for incorporating regular repetitive scans during follow-up.

Diving into hot topics of salivary gland carcinoma management—an EORTC young and early career investigator survey

IntroductionRecently, the ASCO and ESMO guidelines on salivary gland carcinomas (SGCs) have been released. However, several crucial points lack strong recommendations due to low or intermediate quality of evidence. To better address these “grey zones” in the guidelines, we conducted a survey among the European Organization for Research and Treatment of Cancer (EORTC) Head and Neck Cancer Group (HNCG) members on behalf of the EORTC young and early career investigators.Materials and methodsThe survey included 29 questions addressing diagnostic and therapeutic issues related to SGC patients and was shared among 539 members of the EORTC HNCG. Responses were collected from December 2022 to March 2023. The primary aim was to evaluate the decision-making criteria guiding physicians in areas with low evidence in SGC guidelines.ResultsWith a response rate of 19%, the survey received input from 102 respondents, mainly medical oncologists (45%). Among those with pathological high-risk features, 35% and 30% of respondents opted for chemoradiotherapy (CRT) in the definitive and adjuvant settings, respectively. For patients with R0 resection of highly aggressive SGC at the pT1–2 stage, 37% proposed a close follow-up, while 38% proposed adjuvant lymph-node field RT. In cases of pT3–4 stage, 48% proposed adjuvant lymph-node field RT in all cases, and 44% proposed it based only on risk factors. The most important factors guiding the decision to give adjuvant RT after salvage surgery for locoregional relapse include previous radiotherapy, margin status, and the presence of extranodal extension. When faced with combined positivity to HER2 and AR, responses regarding the choice of first-line palliative treatment were heterogeneous.ConclusionsInternational guidelines lack strong recommendations in several fields of SGC diagnosis and treatment due to insufficient high-quality data, resulting in heterogeneity in physicians’ treatment decision (e.g., adjuvant lymph-node field RT and their low concordance with guidelines, such as the use of concomitant CRT). The survey demonstrated the need for prospective clinical trial data to address these gaps in the future.

HPV and p53 status as precision determinants of head and neck cancer response to DNA-PKcs inhibition in combination with irradiation.

Major risk factors of head and neck squamous cell carcinoma (HNSCC) are tobacco use and human papillomavirus (HPV). HPV E6 oncoprotein leads to p53 degradation, whereas HPV-negative cancers are frequently associated with TP53 mutations. Peposertib is a potent and selective, orally administered small-molecule inhibitor of the catalytic subunit of the DNA-dependent kinase (DNA-PKcs), a key regulator of non-homologous end joining (NHEJ). NHEJ inhibition along with irradiation (IR)-induced DNA double-strand breaks has the potential to increase antitumor treatment efficacy. Here, we investigated the responses of a panel of HNSCC models with distinct HPV and p53 status to treatments with IR, DNA-PKcs inhibition, and their combination in-vitro and in-vivo. IR-induced DNA damage combined with peposertib administration shortly before IR results in decreased cell viability and proliferation and causes DNA repair delay in all studied HNSCC cell lines. However, our data confirm that the actual cell fate upon this treatment is determined by cellular p53 and/or HPV status. Cells lacking functional p53 due to its degradation by HPV or due to a loss-of-function mutation are arrested in the G2/M phase of the cell cycle and eliminated by apoptosis whereas p53-proficient HNSCC cell lines preferentially undergo senescence. This is also recapitulated in-vivo, where HPV+ UD-SCC-2 xenografts display stronger and more durable responses to the combined treatment as compared to p53 wild-type UM-SCC-74A tumors. In conclusion, DNA-PKcs inhibitor peposertib should be further studied as a potential radiosensitizer for HNSCCs, taking into consideration the genetic background and the HPV status of a particular tumor.

Chronotherapy in head and neck cancer: A systematic review and meta-analysis.

Optimizing the timing of radiotherapy and chemotherapy tailored to the body's biological clock (i.e., chronotherapy) might improve treatment efficacy and reduce side effects. This systematic review evaluated the effect of chrono-radiotherapy and chrono-chemotherapy on treatment efficacy, toxicity and adverse events in head and neck cancer (HNC) patients from prospective and retrospective studies published between the date of database inception until March 2024. The primary outcome measures for chrono-radiotherapy were treatment efficacy and incidence of grade ≥3 oral mucositis, and the main outcome measures for chrono-chemotherapy were objective response rate (ORR) and overall toxicity and adverse events. Of 7349 records identified, 22 studies with 3366 patients were included (chrono-radiotherapy = 9 and chrono-chemotherapy = 13). HNC patients who underwent chrono-radiotherapy had 31% less risk of developing severe oral mucositis (grade ≥3) compared to evening radiotherapy (risk ratio: 0.69, 95% CI: 0.53-0.90, p < 0.05). Further, HNC patients who underwent chrono-chemotherapy using platinum-based and antimetabolite agents had 73% less risk of lower ORR compared to nontime-stipulated chemotherapy (risk ratio: 0.27, 95% CI: 0.09-0.84, p < 0.05). In addition, HNC patients who underwent chrono-chemotherapy had 41% less risk of lower overall toxicity and adverse events in comparison to nontime-stipulated chemotherapy (risk ratio: 0.59, 95% CI: 0.47-0.72, p < 0.05). In conclusion, chrono-chemotherapy studies showed evidence of improved treatment efficacy, while in chrono-radiotherapy it was maintained. Chrono-radiotherapy and chrono-chemotherapy studies provide evidence of reduced toxicity and adverse events. However, optimized circadian-based multicentric clinical studies are needed to support chrono-radiotherapy and chrono-chemotherapy in managing HNC.

Managing esophageal squamous cell carcinoma after cervical radiotherapy for a head and neck cancer: esophagectomy remains a viable option.

Managing esophageal squamous cell carcinoma (ESCC) in patients with a history of cervical radiotherapy for a head and neck cancer (HNC) often requires a careful evaluation of esophagectomy due to concerns regarding complications and prognosis. This study evaluates the periesophagectomy and oncological outcomes of such patients. Patients diagnosed with ESCC between January 2010 and August 2023 and who had undergone esophagectomy with cervical anastomosis were retrospectively reviewed. Patients were categorized into two groups based on the presence (group 1) or absence (group 2) of a history of radiotherapy for as HNC. After 1: 2 propensity score matching, the perioperative and oncological outcomes, including overall survival (OS) and recurrence-free survival (RFS), were evaluated. A total of 481 patients, 32 in group 1 and 449 in group 2, were included. After matching, group 1 patients and 64 patients in the group 2 were analyzed. All the patients in group 1 were males, and their mean age was 56years. The median radiation dose was 69Gy. The rates of anastomosis leakage, pneumonia, respiratory failure, and reoperation were comparable between the two groups. However, vocal cord palsy occurred more frequently in group 1, particularly in those with recurrent laryngeal nerve lymph node dissection (37.5%). The 3-year OS (69.6% vs. 75.2%; p = 0.26) and RFS (50.8% vs. 55.9%; p = 0.63) were similar between groups 1 and 2. In conclusion, perioperative and oncological outcomes were comparable between ESCC patients with and without prior HNC radiotherapy, supporting esophagectomy as a feasible option.

Effects of spot size errors in DynamicARC pencil beam scanning proton therapy planning.

Spot size stability is crucial in pencil beam scanning (PBS) proton therapy, and variations in spot size can disrupt dose distributions. Recently, a novel proton beam delivery method known as DynamicARC PBS scanning has been introduced. The current study investigates the dosimetric impact of spot size errors in DynamicARC proton therapy for head and neck (HNC), prostate, and lung cancers.&#xD;Approach: Robustly optimized DynamicARC proton therapy plans were created for HNC (n=4), prostate (n=4), and lung (n=4) cancer patients. Spot size errors of ±10%, ±15%, and ±20% were introduced, and their effects on target coverage (D95% and D99%), homogeneity index (HI), and organ-at-risk (OAR) doses were analyzed across different cancer sites.&#xD;Main Results: HNC and lung cancer plans showed greater vulnerability to spot size errors, with reductions in target coverage of up to 4.8% under -20% spot size errors. Dose homogeneity was also more affected in these cases, with HI degrading by 0.12 in lung cancer. Prostate cancer demonstrated greater resilience to spot size variations, even under errors of ±20%. For spot size errors ±10%, the oral cavity, parotid glands, and constrictor muscles experienced Dmean deviations within ±1.2%, while deviations were limited to ±0.5% for D10% of the bladder and rectum and ±0.3% for V20Gy(RBE) of the lungs. The robustness analysis indicated that lung cancer plans were most susceptible to robustness reductions caused by spot size errors, while HNC plans demonstrated moderate sensitivity. Conversely, prostate cancer plans demonstrated high robustness, experiencing only minimal reductions in target coverage.&#xD;Significance: While the ±10% spot size tolerance is appropriate in the majority of the cases, lung cancer plans may require more stringent criteria. As DynamicARC becomes clinically available, measuring spot size errors in practice will be essential to validate these findings and refine tolerance thresholds for clinical use.

Integrated analysis of single-cell, spatial and bulk RNA-sequencing identifies a cell-death signature for predicting the outcomes of head and neck cancer

Integrated analysis of single-cell, spatial and bulk RNA-sequencing identifies a cell-death signature for predicting the outcomes of head and neck cancer

Radiomics Features from Positron Emission Tomography with [18F] Fluorodeoxyglucose Can Help Predict Cervical Nodal Status in Patients with Head and Neck Cancer

Radiomics Features from Positron Emission Tomography with [18F] Fluorodeoxyglucose Can Help Predict Cervical Nodal Status in Patients with Head and Neck Cancer

Finnish translation and linguistic validation of the FACE-Q Head and Neck Cancer Module.

Head and neck cancer (HNC) and its treatment can result in permanent changes to a patient's appearance, speaking, eating, and psychosocial well-being. To better assess the impact of the disease on HNC patients, the FACE-Q Head and Neck Cancer Module, a health-related quality-of-life instrument, was developed. The aim of this study was to produce and linguistically validate a Finnish version of the module. The module was translated into Finnish following the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) guidelines. A total of 51 patients who had undergone tumour resection and reconstruction of the oral cavity, tonsil, or tongue area between 2019 and 2021 were approached for a pilot study. They completed the translated module and provided feedback on any linguistic issues. Adjustments were made based on the pilot study comments. The FACE-Q Head and Neck Cancer Module translated well into Finnish. Twenty-one (41%) patients participated in the survey, 12 men (57%) and nine women (43%) with a median age of 66 years (range 48-89 years). The median time since surgery was 3 years (range 1-4 years). Based on the feedback from the pilot study participants, one word was changed, and one question was rewritten. Otherwise, no deficiencies were identified in the language of the module. In summary, this study produced a linguistically valid Finnish version of the FACE-Q Head and Neck Cancer Module, enabling its application in evaluating the health-related quality-of-life among Finnish HNC patients who have undergone reconstructive surgery.

Impact of the coronavirus pandemic on the diagnosis and treatment of head and neck cancer

After the first appearance of COVID-19cases, the virus spread worldwide within afew months. This led to adecrease in medical consultations. The present study investigates whether this effect had an impact on the diagnosis and treatment of head and neck cancer during the period from 2018 to 2022. Data from the clinical cancer registration center (KKR) of Mecklenburg-Vorpommern from the 2020-2022 period were compared to those from the two previous years (2018, 2019). Demographic data, case numbers, diagnosis data, International Classification of Diseases (ICD) codes, and TNM classifications were recorded. COVID-19case numbers were obtained from the Robert Koch Institute (RKI). Data were analyzed using the Mann-Whitney Utest and Pearson's correlation. Atotal of 2332 patient cases could be included in this study. During the lockdown there was neither asignificant reduction in tumor diagnoses registered at the KKR nor acorrelation between COVID-19case numbers and tumor diagnoses. Significant differences were found in terms of Tcategory in the year 2022 compared to the pre-COVID years 2018 and 2019. Furthermore, there was ashift in the relative frequencies of some ICD-10codes. During the COVID-19 pandemic, no significant differences in tumor diagnoses were observed upon comparing the years 2018 to 2022. Contrary to the expectation of adecrease in case numbers during the pandemic due to the lockdown with an increase in tumor stages, areduction of the Tcategory could be found in 2022, and ashift in the relative frequencies of some ICD-10codes in the pandemic period was observed.

Revalidation of Proactive Gastrostomy Tube Placement Guidelines for Head and Neck Cancer Patients Receiving Helical Intensity-Modulated Radiotherapy

The Royal Brisbane and Women’s Hospital (RBWH) Swallowing and Nutrition Management Guidelines for Patients with Head and Neck Cancer were developed to enable evidence-based decision-making by the Head and Neck Multidisciplinary Team (H&amp;N MDT) regarding enteral nutrition support options. The purpose of this study was to revalidate these guidelines in a cohort of patients receiving helical intensity-modulated radiotherapy (H-IMRT) compared to a historical cohort who received primarily 3D-conformal radiotherapy. Eligible patients attending the RBWH H&amp;N MDT between 2013 and 2014 (n = 315) were assessed by the guidelines, with high-risk patients being recommended proactive gastrostomy tube placement. Data were collected on guideline adherence, gastrostomy tube insertions, the duration of enteral tube use and weight change. Sensitivity, specificity and positive predictive and negative predictive values were calculated and compared with the historical cohort. Overall guideline adherence was 84%, with 60% and 96% adherence to the high-risk and low-risk pathways, respectively. Seventy patients underwent proactive gastrostomy tube placement (n = 62 high-risk; n = 8 low-risk). Validation outcomes were sensitivity 73% (compared to 72%) and specificity 86% (compared to 96%). The guidelines yielded a high sensitivity and specificity, remaining valid in a cohort of patients treated with H-IMRT. Further studies are recommended to improve the sensitivity and understand the decrease in specificity in order to make ongoing guideline improvements.

A Review of Contemporary Image Guidance Techniques in Head and Neck Cancer.

Traditional head and neck cancer treatment involves open surgery, cytotoxic chemotherapy, and conventional radiotherapy planning. Emerging techniques aim to improve precision and reduce associated toxicity and functional impairment in current practice. This review article describes four such adaptations in image guidance, tailored to next generation therapies. This is a review of current literature, including feasibility studies from our cancer center, relating to: saline-aided intra-oral ultrasound-guided retropharyngeal biopsy; intra-oral ultrasound guided trans-oral robotic surgery (TORS); ultrasound-guided injection of "directly injectedtherapies"; and magnetic resonance imaging-guided radiotherapy. Presented within the context of the wider literature, initial local experience and data indicate good technical outcomes and patient tolerance, and low technical complications in all four image guidance techniques. Initial findings suggest a potentially important future role for these four image guidance techniques, on which next generation therapies are reliant. The broader implications on cross-disciplinary collaboration are also explored herein.

Second Events After Curative-Intent Treatment for Lip Cancer: Navigating the Path of Follow-Up Care.

We aimed to investigate the pattern, risk, and treatment of subsequent events after curative-intent treatment of lip cancer. This retrospective cohort study included 313 patients treated for lip cancer from 2011 to 2021 in a tertiary oncological center. After a median follow-up time of 29.16 months, 145 (46.32%) patients presented with second primary tumors, 93% of which were skin carcinomas. Locoregional recurrence occurred in 7.9% of cases, with 2.5% with nodal recurrence. The 1-, 5-, and 10-year cumulative second primary tumor probabilities were 32.8%, 60.92%, and 70.92%, respectively. A higher risk was observed in elderly patients and basal cell carcinoma cases located on the cutaneous surface of the upper lip. Regional metastasis but not second primary tumors negatively impacted survival. Our study helps fill a literature gap, structuring specific recommendations regarding evaluations and follow-up protocols for patients with lip cancer. Since cutaneous second primary tumors were the most common second event, standard skin examination is key. Age and histology were significant predictors for second primary tumors. For cases of locally advanced lip squamous cell carcinoma, standard guidelines for head and neck cancer must be followed.

Targeting the EGFR and Spindle Assembly Checkpoint Pathways in Oral Cancer: A Plausible Alliance to Enhance Cell Death

Background/Objectives: Head and neck cancer (HNC) is among the most common cancer types globally, with its incidence expected to increase significantly in the coming years. Oral squamous cell carcinoma (OSCC), the predominant subtype, exhibits significant heterogeneity and resistance to treatment. Current therapies, including surgery, radiation, and chemotherapy, often result in poor outcomes for advanced stages. Cetuximab, an EGFR inhibitor, is widely used but faces limitations. This study explores the combined inhibition of EGFR and mitotic proteins to enhance treatment efficacy. Methods: We analyzed the effects of co-treating OSCC cells with small molecules targeting MPS-1 (BAY1217389), Aurora-B (Barasertib), or KSP (Ispinesib), alongside Cetuximab. The rationale is based on targeting EGFR-mediated survival pathways and the mitotic checkpoint, addressing multiple cell cycle phases and reducing resistance. Results: Our findings indicate that inhibiting MPS-1, Aurora-B, or KSP enhances Cetuximab’s therapeutic potential, promoting increased cancer cell death. Additionally, we examined EGFR, MPS-1, Aurora-B, and KSP expression in OSCC patient samples, revealing their clinicopathologic significance. Conclusions: This combinatorial approach suggests a promising strategy to improve treatment outcomes in OSCC.

Cancer-Specific Integrin Imaging With 68Ga-Trivehexin: A Potential Imaging for Accurate Staging of Thyroid Malignancy.

68Ga-Trivehexin is a novel radiotracer binding to "cancer-specific integrin αvβ6." 68Ga-Trivehexin has high specificity for tumor cells and, thus, has the potential to replace 18F-FDG PET/CT due to its limited specificity in the head and neck cancer. Here, we present one case of papillary thyroid carcinoma, where 68Ga-Trivehexin PET CT demonstrated accurate staging compared with 18F-FDG PET/CT.

Sinonasal Mucosal Melanoma Survival Outcomes, Recurrence Patterns, and Prognostic Factors: A Systematic Literature Review and Meta-analysis of Publications after 2000

Abstract Background Sinonasal mucosal melanoma (SNMM) comprises &lt;1% of all head and neck cancers but has one of the highest 5-year mortalities. Methods A systematic review and analysis using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta- Analyses) guidelines was conducted on SNMM survival, recurrence, and prognostic factors. Results A total of 2,379 abstracts were reviewed resulting in 90 studies describing 3347 SNMM patients. Patients were 49.65% male and 66.5 years old. Surgery plus radiation therapy, followed by surgery only, then radiation only were the most common treatments. Chemotherapy and immunotherapy were used in 418 patients and 101 respectively. The 2-, 3-, and 5-year overall survivals are 55.97, 40.09, and 30.35%, respectively. The 5-year disease-free survival and disease-specific survival are 25.56 and 38.04%. The 5-year local, regional, and distant recurrence-free survivals are 42.35, 81.64, and 44.65%. Mean survival after diagnosis was 26.99 months. Local (n = 650), regional (n = 226), and distant (n = 723) failure presented after 19.36, 6.35, and 12.42 months. Sites of metastasis were lung, liver, bone, brain, skin, kidney, and adrenal glands. Distant metastases, disease in the paranasal sinuses, and higher stage were noted to have worse survival outcomes. Positive margins did not significantly impact overall survival in 11/12 studies. Conclusion Overall survival over 20 years has remained poor with 70% of patients deceased in 5 years. About half of patients will develop distant failure and will thereafter rapidly decline. These data indicate need for advances in treatment of SNMM and new efforts with targeted immunotherapy offer a promising avenue toward improving survival outcomes.

Prevalence of human papilloma virus in head and neck mucous squamous cell carcinoma and genotypes by location: an observational study.

Human papillomavirus (HPV) is a factor in oropharyngeal cancer, but data regarding other head and neck locations are scarce in France. The main objective of the study was to determine the prevalence of HPV in head and neck cancers at all locations. As a secondary objective, we aimed to investigate the HPV genotypes. We retrospectively included in a tertiary center between 2014 and 2020 mucosal squamous cell carcinomas of the head and neck in adult. First outcome was the prevalence of HPV cancer. Secondary outcomes were overall survival (OS) at 2 and 5 years and disease-free survival (DFS). A total of 508 patients were enrolled, resulting in 537 cases of mucous squamous cell carcinoma of the head and neck (n = 29 synchronous carcinomas). Clinical, pathological, and survival data were collected, and a double PCR for HPV with genotyping was performed on most of the samples. The HPV prevalence in the cohort was 28.2%, with HPV 16 being the predominant genotype (87%). However, HPV-positive status did not significantly improve OS at 2 and 5 years or DFS (P = 0.1, P = 0.64, and P = 0.07, respectively). It was also observed that HPV-positive patients had significantly fewer second tumor localizations (P < 0.01). The prevalence of HPV continues to rise, and the complexities surrounding HPV status and its association with clinical outcomes in head and neck squamous cell carcinoma highlight the impact of vaccination.

Education of Dental Hygienists and Dental Therapists Working With Head and Neck Cancer Patients in Oral and Maxillofacial Surgery Departments in the United Kingdom-A Quantitative Study.

To investigate Dental Hygienists' (DHs) and Dental Therapists' (DTs) current undergraduate and postgraduate education with regard to the treatment of head and neck cancer (HANC) in Oral & Maxillofacial Surgery (OMFS) departments in the United Kingdom. A purposive sample of DHs and DTs, who were employed, or had been previously employed, in OMFS departments in the United Kingdom were asked to complete an online questionnaire about their education in the care and management of patients with HANC. The questionnaire was sent to members of the British Society of Dental Hygiene and Therapy (BSDHT), and the British Association of Dental Therapy (BADT) and was also posted via online forums. The questionnaire received 55 responses (response rate 83%): 54 female respondents and 1 male. Thirty-one (56%) respondents had not undertaken any HANC training. However, on starting work in an OMFS department, nine (16%) respondents reported being provided with HANC training. The results suggest that the UK review and standardise the provision of HANC training in the DH and DT educational curricula. Furthermore, it is recommended that the DH and DT curricula, at both undergraduate and postgraduate level, should include psychology training.

Progress in Precision Medicine for Head and Neck Cancer.

This paper presents a comprehensive comparative analysis of biomarkers for head and neck cancer (HNC), a prevalent but molecularly diverse malignancy. We detail the roles of key proteins and genes in tumourigenesis and progression, emphasizing their diagnostic, prognostic, and therapeutic relevance. Our bioinformatic validation reveals crucial genes such as AURKA, HMGA2, MMP1, PLAU, and SERPINE1, along with microRNAs (miRNA), linked to HNC progression. OncomiRs, including hsa-miR-21-5p, hsa-miR-31-5p, hsa-miR-221-3p, hsa-miR-222-3p, hsa-miR-196a-5p, and hsa-miR-200c-3p, drive tumourigenesis, while tumour-suppressive miRNAs like hsa-miR-375 and hsa-miR-145-5p inhibit it. Notably, hsa-miR-155-3p correlates with survival outcomes in addition to the genes RAI14, S1PR5, OSBPL10, and METTL6, highlighting its prognostic potential. Future directions should focus on leveraging precision medicine, novel therapeutics, and AI integration to advance personalized treatment strategies to optimize patient outcomes in HNC care.