FDG uptake in the cervical muscles after neck dissection: imaging features and postoperative natural course on 18F­FDG­PET/CT.

PURPOSE: This study aimed to assess the imaging features and postoperative natural course of 18F-fluorodeoxyglucose (FDG) uptake in the cervical muscles after neck dissection. MATERIALS AND METHODS: This study included 83 patients who underwent preoperative and postoperative 18F-FDG-PET/CT and were diagnosed with head and neck malignancy after neck dissection. Postoperative 18F-FDG-PET/CT was performed within 5 years after neck dissection. Preoperative and postoperative FDG uptake of the trapezius, sternocleidomastoid, scalene, pectoralis major, and deltoid muscles was visually assessed. Increased postoperative uptake was visually defined as higher postoperative FDG uptake than the preoperative one in the corresponding muscle. The maximum standardized uptake value (SUVmax) was measured in cases with increased postoperative uptakes. RESULTS: Increased postoperative uptakes were observed in 43 patients (52%). The trapezius (31/83, 37%), sternocleidomastoid (19/83, 23%), and scalene (12/83, 14%) muscles were involved, as opposed to the pectoralis major and deltoid muscles were not. Increased postoperative uptakes were observed on the dissected side in all 43 patients. Significant differences between SUVmax estimated from the mixed-effects model and postoperative months were observed in the trapezius muscle (Coefficient (ß) = -0.038; 95% confidence interval (CI): [-0.047, -0.028]; p < 0.001) and sternocleidomastoid muscle (ß = -0.015; 95% CI: [-0.029, -0.001]; p = 0.046). CONCLUSIONS: Increased postoperative uptakes in the cervical muscles were observed on the dissected side in approximately half of the patients after neck dissection. The SUVmax in the trapezius and sternocleidomastoid muscles decreased after surgery over time.

Prognostic value of radiological T category using conventional MRI in patients with oral tongue cancer: comparison with pathological T category.

PURPOSE: This study aimed to compare the radiological tumor (T)-category using multiparametric MRI with the pathological T category in patients with oral tongue squamous cell carcinoma (OTSCC) and to examine which is a better predictor of prognosis. METHODS: This retrospective study included 110 consecutive patients with surgically resected primary OTSCC who underwent preoperative contrast-enhanced MRI. T categories determined by maximum diameter and depth of invasion were retrospectively assessed based on the pathological specimen and multiparametric MRI. The MRI assessment included the axial and coronal T1-weighted image (T1WI), axial T2-weighted image (T2WI), coronal fat-suppressed T2WI, and axial and coronal fat-suppressed contrast-enhanced T1WI (CET1WI). Axial and coronal CET1WI measurements were divided into two groups: measurements excluding peritumoral enhancement (MEP) and measurements including peritumoral enhancement. The prognostic values for recurrence and disease-specific survival after radiological and pathological T categorization of cases into T1/T2 and T3/T4 groups were compared. RESULTS: The T category of MEP on coronal CET1WI was the most relevant prognostic factor for recurrence [hazard ratio (HR) = 3.30, p = 0.001] and the HR was higher than the HR for pathological assessment (HR = 2.26, p = 0.026). The T category determined by MEP on coronal CET1WI was also the most relevant prognostic factor for disease-specific survival (HR = 3.12, p = 0.03), and the HR was higher than the HR for pathological assessment (HR = 2.02, p = 0.20). CONCLUSION: The T category determined by MEP on the coronal CET1WI was the best prognostic factor among all radiological and pathological T category measurements.

Translational research in head and neck cancer: Molecular and immunological updates.

Head and neck squamous cell carcinoma (HNSCC) has a poor prognosis. Each year, approximately 880,000 patients are newly diagnosed with HNSCC worldwide, and 450,000 patients with HNSCC die. Risk factors for developing HNSCC have been identified, with cigarette smoking, alcohol consumption, and viral infections being the major factors. Owing to the prevalence of human papillomavirus infection, the number of HNSCC cases is increasing considerably. Surgery and chemoradiotherapy are the primary treatments for HNSCC. With advancements in tumor biology, patients are eligible for novel treatment modalities, namely targeted therapies, immunotherapy, and photoimmunotherapy. Because this area of research has rapidly progressed, clinicians should understand the basic biology of HNSCC to choose an appropriate therapy in the upcoming era of personalized medicine. This review summarized recent developments in tumor biology, focusing on epidemiology, genetic/epigenetic factors, the tumor microenvironment, microbiota, immunity, and photoimmunotherapy in HNSCC, as well as how these findings can be translated into clinical settings.

Lethal ventricular arrhythmia due to entrectinib-induced Brugada syndrome: a case report and literature review.

Entrectinib, a multikinase inhibitor of ROS1 and tropomyosin receptor kinases, is recommended to treat ROS1-positive metastatic non-small cell lung cancer (NSCLC). In a previous study, entrectinib-related cardiotoxicity occurred in 2% of patients; however, lethal arrhythmias remain understudied. We encountered a case of fatal arrhythmia due to drug-induced Brugada syndrome caused by entrectinib. An 81-year-old Japanese male with lung adenocarcinoma harboring ROS1-fusion gene was treated with entrectinib. The patient developed lethal arrhythmias three days after drug initiation, including ventricular tachycardia with Brugada-like electrocardiogram changes. Echocardiography and coronary angiography revealed no evidence of acute coronary syndrome or myocarditis. Following the termination of entrectinib, the electrocardiogram abnormality improved within 12 days. Hence, paying special attention to and monitoring electrocardiogram changes is necessary. In addition, it is also necessary to consider early therapeutic interventions and discontinuation of the drug in cases of drug-induced Brugada syndrome.

Adjustment of creatinine clearance for carboplatin dosing in Calvert's formula and clinical efficacy for lung cancer.

BACKGROUND: The Cockcroft-Gault formula is commonly used as a substitute for glomerular filtration rate (GFR) in Calvert's formula for carboplatin dosing, where adjusting serum creatinine measured using the enzymatic method with 0.2 mg/dL has been suggested in Japan. However, the effects of these adjustments on efficacy in patients with non-small-cell lung cancer remain unknown. METHODS: We conducted a post hoc analysis of the PREDICT1 study (CJLSG1201), a multicenter prospective observational trial of carboplatin-pemetrexed. Glomerular filtration rate values in Calvert's formula were back-calculated from the administered dosages of carboplatin and the reported value of the target area under the curve. We estimated the serum creatinine adjustments and divided the patients into crude and adjusted groups. RESULTS: Patients in the crude group (N = 169) demonstrated similar efficacy to those in the adjusted group (N = 104) in progression-free survival (PFS) and overall survival (OS) (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.76-1.35; p = 0.916 vs. HR, 0.87; 95% CI, 0.65-1.17; p = 0.363), with higher grade 3-4 hematologic toxicity. Among patients aged ≥75 years, the crude group (N = 47) showed superior efficacy compared with the adjusted group (N = 17) in PFS and OS (HR, 0.37; 95% CI, 0.20-0.69; p = 0.002 vs. HR, 0.43; 95% CI, 0.23-0.82; p = 0.010). CONCLUSIONS: Serum creatinine adjustment may be associated with similar efficacy compared to the crude serum creatinine value. In older patients, the adjustment should be cautiously applied owing to the potential for reduced efficacy.

Comprehensive Genome profile testing in head and neck cancer.

OBJECTIVE: Head and neck cancer (HNC) is a tumor occurring in various primary sites with limited chemotherapy options for its treatment. Recently, comprehensive genomic profiling (CGP) testing has become clinically widespread. In this study, we examined the utility of CGP in diagnosing and treating HNC. METHODS: This study included 29 patients with HNC who underwent CGP testing at the Gifu University Hospital between December 2019 and April 2022. We analyzed the types of gene mutations and tumor mutational burden (TMB) based on the CGP results. Squamous cell carcinoma accounted for 55.2%, and other cancers accounted for 44.8%. And we investigated the correlation of prognosis with gene mutations and TMB. RESULTS: Gene mutations were detected in TP53(48.3%), CDKN2A (27.6%), CDKN2B (17.2%), NOTCH1 (17.2%), PIK3CA (17.2%), ARID1A (13.8%), and NF1 (13.8%). TP53, CDKN2A and CDKN2B mutations significantly decreased survival rate in HNC. Five cases (17.2%) were TMB-high and 82.8% were TMB-low. In SCC cases treated with immune checkpoint inhibitors, TMB-high had better Overall survival than TMB-low. And all patients with TMB-high were oropharyngeal cancer. CONCLUSION: Although there were no cases in which effective treatment was actually performed based on the results of CGP, many gene mutations have been detected and several gene mutations correlated with prognosis. Furthermore, TMB can be used as a biomarker to predict the therapeutic effects of immune checkpoint inhibitors in cases of SCC.

Prognostic Factors of Pretreatment Magnetic Resonance Imaging for Predicting Clinical Outcome in Patients With Parotid Gland Cancer.

PURPOSE: This study aimed to assess the utility of pretreatment magnetic resonance imaging (MRI) in predicting the clinical outcomes of patients with parotid gland cancer. METHODS: A total of 43 patients with histopathologically confirmed primary parotid gland cancer, who underwent pretreatment MRI, were enrolled in this study. All images were retrospectively reviewed, and MRI features were evaluated as possible prognostic factors influencing the progression-free survival (PFS) using the Kaplan-Meier method and Cox proportional hazards regression model. Cox regression analysis was used to estimate the hazard ratios (HRs) with 95% confidence interval (95% CI) values. RESULTS: Kaplan-Meier survival analysis showed that old age (>73 years, P < 0.01), large maximum tumor diameter (>33 mm, P < 0.01), low apparent diffusion coefficient value (≤1.29 ×10 -3 mm 2 /s, P < 0.01), ill-defined margin ( P < 0.01), skin invasion ( P < 0.01), regional nodal metastasis ( P < 0.01), heterogeneous enhancement ( P < 0.05), and high signal intensity ratio on gadolinium-enhanced fat-suppressed T1-weighted images (>2.017, P < 0.05) were significant predictors of worse PFS. Cox proportional hazards regression analysis revealed that regional nodal metastasis (HR, 32.02; 95% CI, 6.42-159.84; P < 0.01) and maximum tumor diameter (HR, 1.04; 95% CI, 1.01-1.08; P < 0.05) were independent predictors of PFS. CONCLUSION: Pretreatment MRI parameters could be prognostic factors of patients with parotid gland cancer. In particular, the maximum tumor diameter and regional nodal metastasis, which were closely associated with T and N classifications, were important prognostic factors in predicting the PFS.

MRI findings of sporadic/simple lymphoepithelial cyst of the parotid gland.

PURPOSE: This study aimed to determine the MRI features of sporadic/simple lymphoepithelial cyst (SLEC) of the parotid gland. METHODS: Ten patients (seven men, three women; mean age, 60 years; age range, 38-77 years) with histopathologically and clinically proven SLEC of the parotid gland who underwent MRI before surgical resection were enrolled in this study. No enrolled patient had HIV infection or Sjögren syndrome. MRI findings of SLEC were retrospectively assessed. RESULTS: We confirmed 10 SLECs larger than 10 mm with a mean maximum diameter of 26.6 mm (range, 12-42 mm). Nine patients (90%) had a single cyst, and one (10%) had a large cyst accompanied by small cysts (<10 mm) within the ipsilateral parotid gland. Eight SLECs (80%) were unilocular, and two (20%) were bilocular, with complete septa. Among seven SLECs (70%) with internal septa, five unilocular SLECs (50%) had incomplete septa. Six SLECs (60%) had eccentric cyst wall thickening, and five (50%) were surrounded by small solid nodules that were isointense relative to lymph node. On T1-weighted images, all cyst contents were homogeneously hyperintense relative to cerebrospinal fluid. CONCLUSION: SLECs of the parotid gland are usually single unilocular lesions. Internal septa, eccentric cyst wall thickening, and small solid nodules surrounding the lesion were often observed. Cyst contents are always homogeneously hyperintense on T1-weighted images.

High-performance glass filters for capturing and culturing circulating tumor cells and cancer-associated fibroblasts.

Various liquid biopsy methods have been developed for the non-invasive and early detection of diseases. In particular, the detection of circulating tumor cells (CTCs) and cancer-associated fibroblasts (CAFs) in blood has been receiving a great deal of attention. We have been developing systems and materials to facilitate such liquid biopsies. In this study, we further developed glass filters (with various patterns of holes, pitches, and non-adhesive coating) that can capture CTCs, but not white blood cells. We optimized the glass filters to capture CTCs, and demonstrated that they could be used to detect CTCs from lung cancer patients. We also used the optimized glass filters for detecting CAFs. Additionally, we further developed a system for visualizing the captured cells on the glass filters. Finally, we demonstrated that we could directly culture the captured cells on the glass filters. Based on these results, our high-performance glass filters appear to be useful for capturing and culturing CTCs and CAFs for further examinations.

Usefulness of intraoperative monitoring for mesenteric lymph node metastasis in transplanted free jejunum.

We herein report a rare case of a patient with hypopharyngeal squamous cell carcinoma (SCC) who presented with recurrent metastasis in the mesenteric lymph node of a transplanted jejunum. Removal of the metastatic lymph node required resection of the nutrient vessels which risked the current state of the transplanted jejunum. Importantly, although the nutrient vessels were resected, the jejunum did not become necrotic. This case and another similar case indicate that it may be possible to predict the viability of a transplanted jejunum where jejunal nutrient vessels must subsequently be resected. Key indicators for jejunal survival include determining jejunal blood flow by intraoperative indocyanine green fluorescence imaging, confirming good jejunal color and observation of peristaltic movement by intraoperative blood flow blockage of nutrient vessels. In conclusion, if intraoperative indocyanine green fluorescence imaging in the entire jejunum can be confirmed, there is a high possibility that the jejunum can be well preserved. The clinical presentation and clinical course are described with a proposed new schema of the resectable site of the transplanted jejunal mesentery.

Current status of diffusion-weighted imaging in differentiating parotid tumors.

Recently, diffusion-weighted imaging (DWI) is an essential magnetic resonance imaging (MRI) protocol for head and neck imaging in clinical practice as it plays an important role in lesion detection, tumor extension evaluation, differential diagnosis, therapeutic effect prediction, therapy evaluation, and recurrence diagnosis. Especially in the parotid gland, several studies have already attempted to achieve accurate differentiation between benign and malignant tumors using DWI. A conventional single-shot echo-planar-based DWI is widely used for head and neck imaging, whereas advanced DWI sequences, such as intravoxel incoherent motion, diffusion kurtosis imaging, periodically rotated overlapping parallel lines with enhanced reconstruction, and readout-segmented echo-planar imaging (readout segmentation of long variable echo-trains), have been used to characterize parotid tumors. The mean apparent diffusion coefficient values are easily measured and useful for assessing cellularity and histological characteristics, whereas advanced image analyses, such as histogram analysis, texture analysis, and machine and deep learning, have been rapidly developed. Furthermore, a combination of DWI and other MRI protocols has reportedly improved the diagnostic accuracy of parotid tumors. This review article summarizes the current state of DWI in differentiating parotid tumors.

Two cases of flow void sign of temporal bone metastasis from follicular thyroid carcinoma.

This report describes CT and MRI findings of temporal bone metastasis from follicular thyroid carcinoma in two cases. Both of these had large, osteolytic, hypervascular masses of the temporal bone, accompanied by internal scattered bone fragments and extraosseous mass formation on unenhanced and contrast-enhanced CT images. In the first case, several dilated and tortuous vessels within the markedly hypervascular mass were observed on the arterial phase of dynamic contrast-enhanced CT images. Compared with the signal intensity of the cerebellum, temporal bone masses showed slightly hypo- to slightly hyperintense on T1-weighted images and slightly hypo- to moderately hyperintense on T2-weighted images. Both cases had flow voids in abnormally dilated vessels within the mass on T1- and T2-weighted images. Thyroid follicular carcinoma rarely metastasizes the temporal bone and presents with an osteolytic hypervascular mass with flow void sign.

Posterior ischemic optic neuropathy following postoperative bleeding and internal jugular vein compression.

Perioperative blindness, especially posterior ischemic optic neuropathy (PION), is an uncommon but potentially devastating complication. We report a case of a 65-year-old male patient who underwent laryngopharyngectomy, bilateral neck dissection, and free jejunum flap reconstruction, but then experienced PION in his right eye following postoperative bleeding and bilateral internal jugular veins (IJVs) compression. Despite systemic corticosteroid therapy, his visual recovery prognosis was poor. The specific mechanism responsible for PION remains unclear, and no therapy has been shown to improve this condition. As such, prevention of perioperative PION remains the only available strategy. Surgeons should be aware of this rare potential complication and its risk factors and strive to avoid it. As postoperative bleeding and IJV compression are one of important risk factors for PION, avoiding these are critical.

Nonsurgical Treatment Strategies for Elderly Head and Neck Cancer Patients: An Emerging Subject Worldwide.

Consistent with the increasing rate of head and neck cancers among elderly adults, there has been an increase in the rate of those receiving nonsurgical treatments to maintain their function and quality of life. However, various problems, such as poor tolerance to chemoradiotherapy-related toxicity, are of greater concern in elderly adults than in younger individuals. In this review, we describe adverse events that should be particularly noted in elderly patients and provide an overview of countermeasures in nonsurgical treatments. We mainly focus on cisplatin-based chemoradiotherapy-the primary treatment for head and neck squamous cell carcinoma (HNSCC). Furthermore, we review the molecular targeted drugs and immune checkpoint inhibitors for elderly patients with HNSCC. Although the number of older patients is increasing worldwide, clinical trials aimed at determining the standard of care typically enroll younger or well-conditioned elderly patients. There is still very little evidence for treating elderly HNSCC older patients, and the question of optimal treatment needs to be explored.

A Case of Thyroid Carcinoma Showing Thymus-Like Differentiation With Breast Cancer Susceptibility Gene 2 Mutation: A Case Report and Literature Review.

Carcinoma showing thymus-like differentiation (CASTLE) is a rare malignant tumor that originates from ectopic thymic or residual embryonic tissues. CASTLE is specified as a synonym for intrathyroidal thymic carcinoma. The patient is a 66-year-old male. Surgery was performed on the thyroid tumor with tracheal infiltration, and pathological examination revealed CASTLE. Multidisciplinary treatment, including chemoradiotherapy, was performed for recurrent tumors, and he has been alive for 90 months since the initial treatment. The cancer genome panel identified mutations in AT-rich interaction domain 1A(ARID1A)and breast cancer susceptibility gene 2 (BRCA2), but there were no available clinical trials or recommended drugs. BRCA2 may be involved in CASTLE. Herein, we review the literature and report the treatment method and gene mutation for recurrent metastatic cases of CASTLE, for which standard treatment has not been established.

Metabolic profiling analysis of head and neck squamous cell carcinoma.

OBJECTIVE: Tumor cells can acquire a large amount of energy and structural components by reprogramming energy metabolism; moreover, metabolic profiles slightly differ according to cancer type. This study compared and assessed the metabolic profile of head and neck squamous cell carcinoma (HNSCC) and normal tissues, which were collected from patients without cancer. SUBJECTS AND METHODS: Overall, 23 patients with HNSCC and 6 patients without cancer were included in the analysis. Metabolomic profiles were analyzed using capillary electrophoresis-mass spectrometry. Gene expression was evaluated using real-time reverse transcription-polymerase chain reaction. RESULTS: Glycolysis, the pentose phosphate pathway, tricarboxylic acid cycle, and glutamine metabolism were upregulated in HNSCC tissues based on gene expression analysis. HNSCC could then have enhanced energy production and structural component. The levels of lactate, succinate, glutathione, 2-hydroxyglutarate, and S-adenosylmethionine, considered as oncometabolites, increased and these had accumulated in HNSCC tissues. CONCLUSIONS: The level of metabolites and the expression of enzymes differ between HNSCC and normal tissues. Reprogramming metabolism in HNSCC provides an energy source as well as structural components, creating a system that offers rapid proliferation, progression, and is less likely to be eliminated.

MET-Induced CD73 Restrains STING-Mediated Immunogenicity of EGFR-Mutant Lung Cancer.

Immunotherapy has shown limited efficacy in patients with EGFR-mutated lung cancer. Efforts to enhance the immunogenicity of EGFR-mutated lung cancer have been unsuccessful to date. Here, we discover that MET amplification, the most common mechanism of resistance to third-generation EGFR tyrosine kinase inhibitors (TKI), activates tumor cell STING, an emerging determinant of cancer immunogenicity (1). However, STING activation was restrained by ectonucleosidase CD73, which is induced in MET-amplified, EGFR-TKI-resistant cells. Systematic genomic analyses and cell line studies confirmed upregulation of CD73 in MET-amplified and MET-activated lung cancer contexts, which depends on coinduction of FOSL1. Pemetrexed (PEM), which is commonly used following EGFR-TKI treatment failure, was identified as an effective potentiator of STING-dependent TBK1-IRF3-STAT1 signaling in MET-amplified, EGFR-TKI-resistant cells. However, PEM treatment also induced adenosine production, which inhibited T-cell responsiveness. In an allogenic humanized mouse model, CD73 deletion enhanced immunogenicity of MET-amplified, EGFR-TKI-resistant cells, and PEM treatment promoted robust responses regardless of CD73 status. Using a physiologic antigen recognition model, inactivation of CD73 significantly increased antigen-specific CD8+ T-cell immunogenicity following PEM treatment. These data reveal that combined PEM and CD73 inhibition can co-opt tumor cell STING induction in TKI-resistant EGFR-mutated lung cancers and promote immunogenicity. SIGNIFICANCE: MET amplification upregulates CD73 to suppress tumor cell STING induction and T-cell responsiveness in TKI-resistant, EGFR-mutated lung cancer, identifying a strategy to enhance immunogenicity and improve treatment.

Immune-modified Glasgow prognostic score: A new prognostic marker for head and neck cancer.

BACKGROUND: The modified Glasgow prognostic score (mGPS) includes C-reactive protein and serum albumin levels and is a useful prognostic tool for malignant tumors. The immune system affects cancer progression and recurrence and treatment response. We hypothesized that increasing the lymphocyte count improves mGPS, and we created a new prognostic marker termed immune-mGPS (imGPS). METHODS: This study included 461 patients with head and neck squamous cell carcinoma (HNSCC). The imGPS was calculated as the conventional mGPS with one additional point for a low lymphocyte count (<1250/µL). RESULTS: Addition of the lymphocyte count to mGPS significantly increased the area under the time-dependent receiver operating characteristic curve for overall and progression-free survivals. The added predictive abilities of this tool were supported by improvement in both net reclassification and integrated discrimination. CONCLUSION: imGPS is a more accurate predictor of clinical outcome in patients with HNSCC than mGPS.

Bilateral Recurrent Laryngeal Nerve Paralysis Manifesting as Long COVID.

Management with ventilation is used for severe cases of coronavirus disease 2019 (COVID-19). After extubation, recurrent laryngeal nerve paralysis due to various factors may occur. Almost all cases of paralysis develop unilaterally; however, bilateral recurrent laryngeal nerve paralysis occurs rarely. Such cases may be fatal due to upper air obstruction, and patients are forced to adhere to restrictions after a tracheotomy. The present case illustrates bilateral recurrent laryngeal nerve paralysis that occurred 48 hours after withdrawal from the ventilator. A 75-year-old woman with a history of hypertension came to our hospital with a history of fever and cough for five days. She was diagnosed with pneumonia due to COVID-19 via polymerase chain reaction using her saliva, and ground-glass opacity was found in both lung fields on chest X-ray and computed tomography (CT). Mechanical ventilation, steroids, remdesivir, and baricitinib were administered. The patient's fever and oxygenation status improved with these treatments, and she was weaned from the ventilator on the eighth day of hospitalization. She had no symptoms immediately. However, 48 hours after extubation, bilateral recurrent laryngeal nerve paralysis was suspected. Thus, oral intubation was immediately introduced and a tracheostomy was performed. Vocal cord movement disorders continued for eight weeks, and during that period, the patient displayed hoarseness and suffered from dysphagia. We considered that nerve disorders from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in addition to the compression by the endotracheal tube, caused bilateral recurrent laryngeal nerve paralysis. The neural injury by SARS-CoV-2 may prolong and manifest as "Long COVID."

Neoadjuvant Immunotherapy Strategies in HPV-Related Head-and-Neck Cancer.

Purpose of review: Herein, we review current evidence and future directions of neoadjuvant immunotherapy in HPV-related head and neck squamous cell carcinoma (HNSCC) by describing published data and ongoing clinical trials. Recent findings: Although HNSCCs have shown response to immune checkpoint inhibitors in recurrent/metastatic disease, a limited number of patients benefit from this treatment. There is an expanding interest in clarifying the clinical benefit of immunotherapy in earlier stage disease setting including at initial presentation. Neoadjuvant immunotherapy for HPV-related HNSCCs represents a rational approach, as these cancers bear strong viral antigens. Summary: The majority of patients with HPV-related HNSCC have good prognosis and treatment de-intensification strategies are under evaluation to decrease toxicity and maintain efficacy. On the other hand, a subset of patients with HPV-related HNSCC have a poorer prognosis and additional treatment options are need to improve outcome. Multiple clinical trials are ongoing to evaluate whether neoadjuvant immunotherapy will achieve these goals.