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Dentists are well-positioned to discuss oral health issues related to Human Papillomavirus (HPV) and recommend the HPV vaccine to their patients, mainly because the HPV virus causes oropharyngeal cancers.. We assessed Los Angeles (LA) County dentists opinions on discussing HPV-related oral health issues and recommending the HPV vaccine to their patients. We tested if opinions differed between dentists whose primary patient population was only adults versus children and adults. We mailed a 19-item survey to 2000 randomly sampled LA County dentists for this cross-sectional study. The primary outcome variable was a summary opinion score of 7 opinion statements. We ran descriptive, bivariate comparisons and adjusted linear regression models. Overall, 261 dentists completed the survey. A majority (58.5%) worried they would lose patients if they recommended the vaccine; 49% thought dentists were not appropriate to educate, counsel, or advise on HPV-related issues; 42% were concerned about the safety of the vaccine; and 40% did not feel comfortable recommending the vaccine. The mean summary opinion score was 21.4 ± 5.4 for the total sample. Regression analysis showed no differences in opinions between dentists whose primary patient population was only adults versus children and adults (Coefficient = 0.146, p = 0.83). Overall, the responding dentists were not very favorable about discussing oral health-related HPV issues and recommending the HPV vaccine to their patients. Additionally, the overall opinions were similar between dentists whose primary patient population was only adults versus children and adults.

OBJECTIVE: Salivary duct carcinoma (SDC) is a rare and aggressive salivary gland malignancy. Herein, we present the largest single-institution review of SDC to date. METHODS: This is a retrospective cohort study of all histologically confirmed cases of SDC seen at our institution from January 1, 2002, to August 1, 2022. Patient demographics, treatment, histological characteristics, tumor staging, and outcomes were extracted from the electronic medical record. Kaplan-Meier and Cox regression survival analyses were performed. RESULTS: This study included 119 patients with a mean age of 66.2 years. Most primary tumors arose from the parotid gland (72.3%), and 23.5% were noted to be carcinoma ex-pleomorphic adenoma. 57.1% of patients presented with regional lymph node metastasis, whereas 23.5% presented with distant disease. Kaplan-Meier analysis demonstrated a 62.4% 5-year overall survival (OS) and a 69.0% 5-year disease-specific survival (DSS). Univariate analyses indicated that presence of regional lymph node disease (p

Simple Summary: This study compared salivary gland volume changes and dry mouth symptom in 78 oropharyngeal cancer patients treated with IMRT alone or IMRT/IMPT combination. Ipsilateral parotid and submandibular glands showed significant volume reductions due to higher radiation doses, with the parotid stabilizing after an initial decline and the submandibular gland continuing to decline until 24 months. Contralateral salivary glands received lower doses, demonstrating recovery to baseline volumes by 48 months. Dry mouth symptom affected 60.3% of patients within 6 months, decreasing to 41.0% by 12 months, with no significant differences between groups. Volume reduction was greater in patients with dry mouth symptom. No significant differences in salivary gland volume changes or dry mouth symptom were observed between the two RT techniques, suggesting that the delivered dose to the salivary glands is the critical determinant rather than the RT modality. Background/Objectives: We aimed to compare the salivary gland volume changes following intensity-modulated radiation therapy (IMRT) alone versus IMRT/intensity-modulated proton therapy (IMPT) combination in oropharyngeal cancer (OPC). Methods: We retrospectively reviewed 78 OPC patients who underwent definitive RT with ipsilateral neck irradiation. RT techniques were either IMRT alone or IMRT/IMPT combination. Salivary gland volumes over time in relation to dry mouth symptom were evaluated. Results: Patients' characteristics were well balanced between groups. The mean dose to the ipsilateral parotid gland (PG) was significantly lower in IMRT alone than in IMRT/IMPT combination, while those to the contralateral PG and submandibular glands (SMGs) were significantly higher in IMRT alone. The volume ratio of ipsilateral PG showed an initial sharp decline, reaching 0.74, and stabilized thereafter. The ipsilateral SMG showed a continuous decline until 24 months and reached approximately 0.47 by 48 months. The contralateral PG/SMG showed initial decline and subsequent recovery to the initial volume by 48 months. There were no significant differences in salivary gland volume changes between groups. Within 6 months, 60.3% of patients experienced dry mouth symptom, and the dry mouth incidence decreased to 41.0% in 12 months and remained stable thereafter. There were no significant differences in dry mouth symptom between groups. The volume reduction in the ipsilateral salivary glands was greater in patients with dry mouth symptom. Conclusions: No significant differences in salivary gland volume changes and dry mouth symptom were apparent between groups. The critical factor in salivary gland volume change was the delivered dose to the salivary glands, not the RT techniques. [ABSTRACT FROM AUTHOR]

Simple Summary: Oropharyngeal cancers are increasingly caused by infections with high-risk types of human papillomavirus (HPV). Although the survival rates are high for this type of cancer, survivors suffer from treatment-related toxicities and long-term reduced quality of life. Some progress has been made towards precision treatment based on individual risk profiles; however, there is still room for improvement in this area, as molecular markers are not yet utilized. Here, we review current stratification approaches for HPV-associated oropharyngeal cancers, including recent de-escalation trials and candidate molecular biomarkers for risk stratification. The rising incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) necessitates advancements in risk stratification to optimize treatment outcomes and improve the quality of life for patients. Despite its favorable prognosis compared to HPV-negative OPSCC, current clinical staging and biomarkers, such as p16 status, are limited in their ability to distinguish between high- and low-risk patients within HPV-associated OPSCC. This limitation results in the overtreatment of low-risk patients, exposing them to unnecessary toxicity, and the undertreatment of high-risk patients who require more aggressive interventions. This review critically evaluates current stratification methods, including clinical assessments, de-escalation trials, and candidate molecular biomarkers for risk stratification. Emerging approaches such as immune markers, viral genomic integration patterns, and other molecular markers offer promising avenues for enhanced prognostic accuracy. By integrating advanced risk stratification methods, tailored treatment approaches may one day be developed to balance oncologic efficacy with reduced treatment-related morbidity. This review underscores the need for continued research into predictive biomarkers and adaptive treatment strategies to better address the diverse risk profiles of HPV-associated OPSCC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: The human papilloma virus, commonly known as HPV, is the most common sexually transmitted infection in the world. In fact, a majority of sexually active people are at substantial risk for acquiring an HPV infection of some type in their life. Risk factors associated with young adults are substantial given that sexual activity is common in this group. This study evaluated awareness and knowledge of HPV in a large group of young adult college students. Despite a good level of general awareness in the study population, we found significant gaps which may place this population at a greater relative risk. However, risk could be mitigated to some extent through vaccination for HPV. However, considerable variability was observed in our sample of college students. Consequently, there is a need for continued education related to HPV, its associated risks, and the value of vaccination for HPV. Background/Objectives: The human papillomavirus (HPV) is a prevalent sexually transmitted infection that is a known cause of morbidities such as genital warts and cancers of the cervix, anus, and oropharynx. Non-cervical HPV-related cancers have been a developing problem in North America, increasing in incidence by up to 225% in some instances over a span of two decades. Methods: This study investigated levels of awareness and knowledge of HPV, oropharyngeal cancer (OPC), and the HPV vaccine using a self-administered web-based survey designed specifically for this research. University students (n = 1005) aged 18–30 completed a 42-item questionnaire that included demographic information, awareness questions, and a series of "true/false/I don't know" knowledge questions. Results: The data gathered revealed that participants had relatively high levels of awareness. However, many respondents had significant gaps in their knowledge of HPV, OPC, and the HPV vaccine. Collectively, the data indicate that awareness and knowledge of HPV and the value of vaccination may place younger individuals at risk for HPV-related infections. Conclusions: Although a relatively high level of awareness concerning HPV was observed, the gaps in knowledge suggest that further efforts are necessary to educate young adults. While all risk factors cannot be reduced, the present data may guide future efforts directed toward better education on HPV and related health concerns and associated risks. [ABSTRACT FROM AUTHOR]

Background: Human papilloma virus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is rising in prevalence and is associated with better survival than HPV-negative OPSCC. In surgically treated HPV-negative OPSCCs, adverse pathologic features such as positive surgical margins, extra-nodal extension (ENE) and perineural invasion are well described to portend worse clinical outcomes. These adverse pathological features, however, are not validated prognostic markers among surgically treated HPV-positive OPSCCs. To that end, we pooled all available evidence to address the prognostic significance of these histologic features. Patients and Methods: This meta-analysis was performed according to PRISMA guidelines. PubMed, Web of Science and Embase databases were systematically searched for articles evaluating 13 known adverse histopathological prognostic factors of surgically treated HPV-associated OPSCC. Data analysis was done using R v4.0.5. Results: A total of 32 studies (n = 31,535) fulfilled the inclusion criteria. ENE and advanced pT stage were associated with poorer overall survival (OS) [hazard ratio (HR):1.80, 95% confidence interval (CI) [1.59–2.03], p < 0.0001, HR: 3.28, 95% CI [2.20–4.87], p = 0.0025]; disease-specific survival (DSS) (HR: 3.14, 95% CI [1.20–8.26], p = 0.0327, HR: 3.49, 95% CI [2.45–4.96], p = 0.0043) and disease-free survival (DFS) (HR: 2.03, 95% CI [1.05–3.94], p = 0.0397, HR: 3.66, 95% CI [2.81–4.77], p = 0.0001) respectively. The presence of lymphovascular invasion (HR: 1.46, 95% CI [1.22–1.75], p = 0.0018) and positive margins (HR: 1.50, 95% CI [1.185–1.899], p = 0.0069) significantly worsen OS. Conclusion: ENE, advanced pT stage, positive margins and lymphovascular invasion were adverse histologic prognostic marker among surgically treated HPV-positive OPSCC. The presence of these factors should be carefully evaluated in order to select the optimal patients for surgical treatment. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to use Mendelian randomisation to identify the causal relationship between a spectrum of 41 inflammatory cytokines and the development of oropharyngeal cancer. Methods: This study investigated genetic variants that have been associated with oral and oropharyngeal cancer using data from a large GWAS. Inflammatory cytokine data were obtained from 8293 asymptomatic individuals. The study primarily used inverse variance weighted and MR-Egger methods to determine the causal relationship between inflammatory cytokines and cancer incidence, complemented by a series of sensitivity analyses including MR-Egger, simple mode, weighted mode, weighted median and leave-one-out approaches. Results: Our study demonstrates that higher levels of interleukin-7 (IL-7) and interleukin-5 (IL-5) slightly increase the odds of oropharyngeal cancer by 0.07% [OR: 1.0007, p = 0.005] and 0.04% [OR: 1.0004, p = 0.015], corresponding to a modest increase. Similarly, increased PDGF-bb and CTACK levels are modestly associated with increased odds of oral and oropharyngeal cancer by 0.22% [OR: 1.0022, p = 0.031] and 0.17% [OR: 1.0017, p = 0.043], respectively. Conclusion: This investigation posits that IL-5 and IL-7 may be pertinent factors in the etiology of Oropharyngeal cancer, while PDGF bb and CTACK are likely implicated in the pathogenesis of both oral and oropharyngeal cancers. [ABSTRACT FROM AUTHOR]

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cause of cancer death globally, with newly diagnosed oropharyngeal squamous cell carcinoma (OPSCC) cases rising to 54,000 in the US alone in the year 2022. Recently, human papilloma virus (HPV) infection was more prevalent in OPSCC patients than the traditionally known carcinogens such as tobacco or alcohol. HPV 16 is the most common causative HPV strain, which is found in 5–10% of HNSCC patients. HPV 16's E6 and E7 oncoproteins bind and inactivate p53 and retinoblastoma (Rb) tumor-suppressing genes. This causes aberrant over-expression of the cell cycle inhibitor gene, p16, leading to tumorigenesis. Leica Biosystems (LBS) has developed a p16 antibody (6H12 clone) for qualitatively identifying the p16 protein in formalin-fixed paraffin-embedded (FFPE) tissue by immunohistochemical staining. This method comparison study tested the concordance rates between ready-to-use (RTU) LBS p16/LBS RTU p16 antibody and Roche Tissue Diagnostics (RTD) CINtec p16 Histology immunohistochemical (IHC) assays by measuring overall agreement (OA), average positive agreement (APA), and average negative agreement (ANA) rates in 170 OPSCC FFPE cases. Interobserver agreement of the 2 assays and LBS RTU p16 comparison with the standard HPV molecular assays (DNA ISH and PCR) were also assessed. Methods: One hundred and seventy (170) unique oropharyngeal cancer cases were stained for qualitative analysis by the LBS p16 antibody on BOND III. This assay was compared to Ventana's RTD E6H4 (CINtec) clone on Benchmark XT. A stained core was considered p16 positive if the Histoscore (H score) was ≥ 140 and negative if H < 140. Results: Across the pathologists, the agreement rate between the 2 assays ranged from OA, 98.7 – 98.8%, ANA, 98.8 -98.9%, and APA, 98.6%. For LBS RTU p16, the interobserver agreement was OA, 98.7%, ANA, 98.8%, and APA, 98.6%; while for RTD CINtec p16 assay, the concordance was OA, 98.7%, ANA, 98.8% and APA, 98.6%. In comparison to the HPV molecular testing, DNA ISH, and PCR, across pathologists, LBS p16 clone (LBS RTU p16) showed a concordance rate of 85.8-86.9% and 87.6-88.8%, respectively. Conclusion: LBS p16 monoclonal antibody demonstrated high concordance with CINtec p16 IHC assay across all the endpoints, suggesting a potential use of LBS RTU p16 clone in detecting p16 protein in oropharyngeal cancer cases. [ABSTRACT FROM AUTHOR]

Background: Cancer immune responses are generated in secondary lymphoid organs, such as the lymph nodes and tonsils. In the current study, transcriptional profiles of peritumoral tonsillar tissues (PTTs) from oropharyngeal cancers (OPCs) were assessed and compared with those of inflammatory tonsils and regional lymph nodes (rLNs). Methods: RNA samples of PTTs and rLNs from 13 OPCs, and 4 inflammatory tonsils were subjected to microarray analysis, and differentially expressed genes (DEGs) identified from 730 nCounter Panel immune-related genes. Gene Set enrichment Analysis (GSEA) was used for DEG profiling of PTTs and rLNs between lymph node metastasis-negative and metastasis-positive cases. The top 20 genes, as ranked by GSEA metric scores, were extracted and subjected to principal component analysis (PCA). The correlation of each patient's PCA score with lymph node status was assessed by Receiver Operating Characteristics (ROC) analysis. Results: Comparing DEG analyses of PTTs with those of inflammatory tonsils and rLNs revealed 144 and 45 upregulated genes, respectively. ClueGO, a widely used Cytoscape plug-in, revealed activated pathways in PTTs, including lymphocyte proliferation (followed by T cell activation involved in the immune response) and positive regulation of leukocyte migration (followed by antimicrobial humoral immune response mediated by antimicrobial peptides) as the most significantly enriched immune system process functions in the gene ontology when comparing inflammatory tonsils and rLNs. The area under the ROC curves of PTTs and rLNs were 0.806 and 0.389, and were significant by DeLong's test (p = 0.025). Conclusion: PTTs exhibit unique immunological features distinguishing them from inflammatory tonsils and rLNs. Gene expression analysis of PTTs is useful for investigating the mechanism of OPC lymphatic spread, even compared with analysis of rLNs. [ABSTRACT FROM AUTHOR]

In exploring adjuvant therapies for head and neck cancer, hyperthermia (40–45 °C) has shown efficacy in enhancing chemotherapy and radiation, as well as the delivery of liposomal drugs. Current hyperthermia treatments, however, struggle to reach large deep tumors uniformly and non-invasively. This study investigates the feasibility of delivering targeted uniform hyperthermia deep into the tissue using a non-invasive ultrasound spherical random phased array transducer. Simulations in 3D patient-specific models for thyroid and oropharyngeal cancers assessed the transducer's proficiency. The transducer consisting of 256 elements randomly positioned on a spherical shell, operated at a frequency of 1 MHz with various phasing schemes and power modulations to analyze 40, 41, and 43 °C isothermal volumes and the penetration depth of the heating volume, along with temperature uniformity within the target area using T10, T50, and T90 temperatures, across different tumor models. Intensity distributions and volumetric temperature contours were calculated to define moderate hyperthermia boundaries. The results indicated the array's ability to produce controlled heating volumes from 1 to 48 cm3 at 40 °C, 0.35 to 27 cm3 at 41 °C, and 0.1 to 8 cm3 at 43 °C. The heating depths ranged from 7 to 39 mm minimum and 52 to 59 mm maximum, measured from the skin's inner surface. The transducer, with optimal phasing and water-cooled bolus, confined the heating to the targeted regions effectively. Multifocal sonications also improved the heating homogeneity, reducing the length-to-diameter ratio by 38% when using eight foci versus a single one. This approach shows potential for treating a range of tumors, notably deep-seated and challenging oropharyngeal cancers. [ABSTRACT FROM AUTHOR]

Outcomes for patients with locally advanced head and neck cancer (HNC) treated with curative intent remain disappointing, with 5-year survival rates at 50%. Most recurrences occur within the first 2 years after treatment, providing a window of opportunity to identify patients with molecular residual disease (MRD). A tissue-agnostic test for MRD detection in patients with human papillomavirus (HPV) positive and negative HNC, where tissue is often scarce, is needed. Patients with stage I-IVB HNC, including patients positive and negative for HPV, were enrolled and peripheral blood plasma was collected longitudinally at diagnosis and ∼3, 12, and 24 months after curative intent treatment. The full cohort includes 325 patients with 1155 samples. Samples were split into distinct sets to train and validate a classifier capable of identifying MRD using a tissue-agnostic genome-wide methylome enrichment platform. The primary endpoint was recurrence-free survival (RFS). With a median follow-up of 60 months, patients in the blinded validation set with MRD positivity experienced significantly worse RFS with a hazard ratio (HR) of 35.7 [95% confidence interval (CI) 10.8-117.8; P < 0.0001]. For patients with HPV negativity, HR was 42.3 (95% CI 9.8-182.3; P < 0.0001); for patients with HPV-positive oropharyngeal cancer, HR was 24.1 (95% CI 3.0-196.8; P < 0.0001). Moreover, the lead time between MRD positivity and clinical recurrence was up to 14.9 months, with a mean lead time of 4.1 months. Surveillance sensitivity was 91% (95% CI 77% to 97%) and specificity was 88% (95% CI 80% to 93%). Here we validate the clinical performance characteristics of a tissue-agnostic genome-wide methylome enrichment assay for MRD detection in patients with HNC. The MRD detection test showed high sensitivity for identifying recurrence at high specificity across different anatomical sites, HPV status, and treatment regimens, highlighting the broad applicability for MRD detection in patients with HNC. • A tissue-agnostic assay for MRD detection in HNC, independent of HPV status is needed. • A blinded clinical validation of a locked classifier showed significant differences in RFS stratified by MRD positivity. • Recurrence ahead of clinical presentation or imaging with a lead time up to 14.9 months was demonstrated (mean 4.1 months). • Similar performances were observed across anatomical sites, HPV status, and treatments, highlighting broad applicability. [ABSTRACT FROM AUTHOR]

Propose: To investigate the performance of image registration methods for structure delineation in head and neck (H&N) cancer patients. Methods and materials: This retrospective study randomly recruited 22 patients who had been irradiated in the H&N region between January 2016 and February 2024. The sample group included nasopharyngeal carcinoma (NPC) and oropharyngeal cancer (OPC) patients. The treatment planning structures were delineated as images of computed tomography simulation (CTsim) and were set as the ground-truth. The latest CT diagnostic (CTdiag) image sets of these selected patients were imported into third-party software for delineation. The structures of CTdiag were delineated using an artificial intelligence method except for the target. The performance of rigid and deformable image registration methods (RIR and DIR, respectively) between these two image sets were evaluated using dice similarity coefficient (DSC) and Hausdorff distance (HD). The performance evaluation scores were also compared between NPC and OPC. Result: The DSC revealed a significant difference in all structures between RIR and DIR, whereas the HD showed no significant difference on the target and the larynx. In terms of a comparison of treatment regions, OPC appeared to sustain the greatest benefit from DIR. Conclusion: Image registration can provide the benefit of structure delineation, particularly when employing the DIR method. Although the DIR method may not offer a high degree of performance in terms of target delineation, it could effectively serve as a delineation guideline in this process. [ABSTRACT FROM AUTHOR]

Purpose: To report a single‐institutional experience with hypofractionated radiation therapy alone for human papillomavirus (HPV)‐positive oropharyngeal cancer. Methods and materials: A total of 101 consecutive patients were treated by radiation therapy alone using a regimen of 66 Gy in 30 fractions (60 patients) or 70 Gy in 33 fractions (41 patients) for newly diagnosed p16‐positive squamous cell carcinoma of the oropharynx. Sixty‐seven patients (67%) were never smokers. Results: The 3‐year actuarial rates of overall survival, local‐regional control, and progression‐free survival were 94%, 93%, and 89%, respectively. Among never‐smokers, the 3‐year rates of overall survival and local–regional control were 98% and 100%, respectively. The grade 3+ acute toxicity rate was 21%, with the most commonly observed side effects related to mucositis. Conclusion: Hypofractionated radiation alone resulted in excellent outcomes for patients with HPV‐positive oropharyngeal cancer. A prospective clinical trial investigating this modality in the setting of de‐escalation is currently underway. [ABSTRACT FROM AUTHOR]

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Background: We have previously developed a candidate therapeutic HPV DNA vaccine (pBI-11) encoding mycobacteria heat shock protein 70 linked to HPV16/18 E6/E7 proteins for the control of advanced HPV-associated oropharyngeal cancer (NCT05799144). While naked DNA vaccines are readily produced, stable, and well tolerated, their potency is limited by the delivery efficiency. Here we compared three different IM delivery strategies, including intramuscular (IM) injection, either with a needle alone or with electroporation at the injection site, and a needle-free injection system (NFIS), for their ability to elicit gene expression and to improve the potency of pBI-11 DNA vaccine. Results: We found that electroporation after IM injection significantly increases gene expression from a luciferase-encoding DNA construct compared to IM injection alone or NFIS. We also showed that single administration of pBI-11 DNA via electroporation-mediated delivery generates the greatest increase in HPV antigen-specific CD8 + T cell-mediated immune responses, resulting in the most potent antitumor effect compared to the other two methods. We further compared the response to three repeat immunizations via each of these different methods. We found that electroporation-mediated delivery of pBI-11 DNA generates the greatest HPV antigen-specific CD8 + T cell immune responses and therapeutic antitumor effects compared to the other two methods. Monitoring of mouse behaviors and body weight, and necropsy indicated that electroporation-mediated delivery of clinical grade pBI-11 DNA vaccine was well-tolerated and presented no evident local or systemic toxicity. Conclusions: These findings provide rationale for clinical testing of pBI-11 DNA vaccine delivered by electroporation for the control of HPV16/18-associated infections and/or cancers. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explored how diffusion-weighted MRI (DW-MRI) differs in oropharyngeal cancer (OPC) based on HPV status before and during radiation therapy. MRI data from 178 OPC patients were analyzed and showed that HPV-positive tumors had lower initial ADC values and specific texture features than HPV-negative tumors. During treatment, the change in ADC values was higher in HPV-positive tumors compared with HPV-negative tumors. These findings highlight the potential of DW-MRI as a non-invasive biomarker for HPV status. Background: This study aimed to explore the differences in quantitative diffusion-weighted (DW) MRI parameters in oropharyngeal squamous cell carcinoma (OPC) based on Human Papillomavirus (HPV) status before and during radiotherapy (RT). Methods: Echo planar DW sequences acquired before and during (chemo)radiotherapy (CRT) of 178 patients with histologically proven OPC were prospectively analyzed. The volumetric region of interest (ROI) was manually drawn on the apparent diffusion coefficient (ADC) map, and 105 DW-MRI radiomic parameters were extracted. Change in ADC values (Δ ADC) was calculated as the difference between baseline and during RT at week 4, normalized by the baseline values. Results: Pre-treatment first-order 10th percentile ADC and Gray Level co-occurrence matrix (GLCM)-correlation were significantly lower in HPV-positive compared with HPV-negative tumors (82.4 × 10−5 mm2/s vs. 90.3 × 10−5 mm2/s, p = 0.03 and 0.18 vs. 0.30, p < 0.01). In the fourth week of RT, all first-order ADC values were significantly higher in HPV-positive tumors (p < 0.01). Δ ADC mean was significantly higher for the HPV-positive compared with the HPV-negative OPC group (95% vs. 55%, p < 0.01). A predictive model for HPV status based on smoking status, alcohol consumption, GLCM correlation, and mean ADC and 10th percentile ADC values yielded an area under the curve of 0.77 (95% CI 0.70–0.84). Conclusions: Our results highlight the potential of DW-MR imaging as a non-invasive biomarker for the prediction of HPV status, although its current role remains supplementary to pathological confirmation. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explores whether radiation therapy at the primary tumor site improves survival in patients with oropharyngeal cancer with distant metastasis limited to one anatomic site. We used data from a large national database to examine over 1000 patients, many of whom also received systemic therapy. Our findings suggest that radiation treatment to the primary cancer site can extend survival in patients, regardless of human papillomavirus status. This research may help guide treatment options for patients with limited metastatic oropharyngeal cancer, potentially improving survival outcomes in this group. Background/Objectives: Limited metastatic squamous cell carcinoma of the oropharynx (OPC) lacks clear management guidelines, especially for HPV-associated disease. The objective of this study was to investigate if primary site radiotherapy (RT) benefits overall survival in limited metastatic OPC. Methods: Utilizing the National Cancer Database (NCDB), patients aged 18–90 with OPC presenting as cM1 with limited metastatic disease to one distant site were identified. Propensity score matching, Cox-proportional hazards models, and Kaplan–Meier estimates were employed to assess factors associated with overall survival. Results: In this study, 1056 patients were included with metastases involving bone (19.0%), brain (0.8%), lung (52.9%), liver (10.1%), and lymph nodes (20.4%). Treatment modalities included 54.6% receiving primary site RT, 45.4% receiving no RT, and 69.9% undergoing systemic therapy. For HPV-positive patients, RT (HR 0.64, p = 0.0026) and receipt of chemotherapy (HR = 0.57, p = 0.0057) were associated with improved overall survival, while bone and lung metastases were associated with decreased survival (HR = 1.75 and 1.39, p = 0.0041 and 0.041, respectively). In HPV-negative cases, survival also correlated with RT (HR = 0.65, p = 0.0047), receipt of chemotherapy (HR = 0.45, p < 0.001), clinical T4 disease (HR = 1.99, p = 0.012), presence of bone metastases (HR = 2.52, p < 0.001), lung metastases (HR = 1.49, p = 0.035), and lymphovascular invasion (HR = 1.10, p < 0.001). Overall, patients who received RT showed increased median overall survival from 9.9 to 16.1 months (p < 0.001) compared to those who did not. When stratified by RT and HPV status, there was higher median survival for both HPV-positive (from 17.1 to 24.9 months, p < 0.001) and HPV-negative patients (from 8.4 to 12.9 months, p = 0.0016) who received RT compared to those who did not. Conclusions: Primary-site radiotherapy may positively impact overall survival in limited metastatic OPC, irrespective of HPV status. [ABSTRACT FROM AUTHOR]

Denmark, alongside other Scandinavian countries, the United States, Canada, and the United Kingdom, has high prevalence of human papillomavirus (HPV). Our oropharyngeal squamous cell carcinoma (OPSCC) database includes all diagnosed cases in Eastern Denmark during a period of more than two decades. We investigated the incidence, survival, and recurrence of patients with OPSCC with combined p16‐ and HPV testing covering a consecutive 21‐year period. Age‐adjusted incidence rate (AAIR) per 100,000, survival models, and Cox proportional‐hazards model were employed. Two thousand eight hundred thirty‐four patients were included (57.5% HPV positive (HPV+)/p16 positive (p16+), 33.7% HPV negative (HPV‐)/p16 negative (p16−), 4% HPV+/p16−, and 4.8% HPV−/p16+). The AAIR for all patients increased from 1.8 to 5.1 per 100,000 from 2000 to 2020 linked to an increasing AAIR of HPV+/p16+ OPSCCs from 0.9 to 3.5 per 100,000 from 2000 to 2020. The AAIR for the HPV−/p16− OPSCCs decreased from 1.6 to 1.4 from 2017 to 2020. HPV+/p16+ OPSCCs had a higher 5‐year overall survival (OS) of 79.2% compared to the other subgroups (HPV+/p16− OS: 50.4%; HPV−/p16+ OS: 49.4%; HPV−/p16− OS: 35.1%). The AAIR of the total OPSCC group increased from year 2000 to 2020, driven by a rise in the HPV+/p16+ group. A decreasing incidence rate was observed for the HPV−/p16− OPSCCs from 2017 to 2020. The OS for HPV+/p16+ OPSCCs was significantly higher compared to all other HPV/p16 subgroups. Therefore, we recommend testing for combined HPV and p16 status in patients with OPSCC when selecting patients for clinical trials, especially in case of de‐escalating/escalating. [ABSTRACT FROM AUTHOR]

Human Papillomavirus (HPV) is the most prevalent sexually transmitted infection, posing a significant public health concern with HPV-associated oropharyngeal cancer emerging as the most common HPV-associated cancer (HPV-aOC). Risky sexual behaviours, notably, oral sex emerge as a critical risk factor for HPV-aOC. Despite its profound impact, there exists a poor awareness of the connection between HPV and oropharyngeal cancer, coupled with suboptimal vaccine uptake. By elucidating the nexus between sexual behaviour and HPV-aOC, this paper aims to foster a paradigm shift towards modified sexual activity, ultimately leading to a reduced risk of HPV-aOC. This study also advocates for multi-faceted approaches such as the use of protective barriers, reducing the number of oral sex partners, increasing awareness through public health education, and augmenting vaccine uptake to limit the prevalent risks of HPV-aOC. Through these concerted efforts, it is envisaged that the incidence and prevalence of HPV-aOC can be mitigated. [ABSTRACT FROM AUTHOR]

Simple Summary: This review elucidates the manner in which artificial intelligence (AI) is transforming the diagnosis and staging of squamous cell carcinomas of the oropharynx (OPSCC). The review examines the potential utilization of AI in discerning the status of human papillomavirus (HPV) in OPSCCs. AI is primarily employed in the analysis of imaging data and the interpretation of histological specimens. While the outcomes are encouraging, they require further validation before they can be adopted in clinical practice. Human papillomavirus (HPV) infection is sexually transmitted and commonly widespread in the head and neck region; however, its role in tumor development and prognosis has only been demonstrated for oropharyngeal squamous cell carcinoma (HPV-OPSCC). The aim of this review is to analyze the results of the most recent literature that has investigated the use of artificial intelligence (AI) as a method for discerning HPV-positive from HPV-negative OPSCC tumors. A review of the literature was performed using PubMed/MEDLINE, EMBASE, and Cochrane Library databases, according to PRISMA for scoping review criteria (from 2017 to July 2024). A total of 15 articles and 4063 patients have been included. Eleven studies analyzed the role of radiomics, and four analyzed the role of AI in determining HPV histological positivity. The results of this scoping review indicate that AI has the potential to play a role in predicting HPV positivity or negativity in OPSCC. Further studies are required to confirm these results. [ABSTRACT FROM AUTHOR]

To analyze mortality from head and neck cancer (HNC) in the State of Santa Catarina from 1979 to 2023. Ecological study of data available in the Mortality Atlas of the National Cancer Institute and in the Mortality Information System. Approximately 13,309 deaths due to HNC were recorded in the Mortality Atlas, considering the period from 1979 to 2021 and 11,027 deaths recorded in SIM in the period from 1996 to 2023. The profile of these patients consisted predominantly of subjects aged 60–69 years old, male, white, married and with 1–3 years of education. Regarding types of cancer, most deaths occurred from laryngeal cancer, followed by oropharyngeal cancer. There is a need to improve health services, with an emphasis on diagnosis of the highest risk profiles, prevention and health promotion with publicity campaigns. [ABSTRACT FROM AUTHOR]

Lipoma is the most common soft tissue benign tumor in the body. It can occur in the head and neck area as well. Fibrolipoma is a variant of lipoma that contains fibrous tissue. Fibrolipomas of the head and neck are relatively rare, and their presentation depends largely on their size and location; some slowly growing tumors might go unnoticed until they reach significant size and become symptomatic. Here, we report a case of 64-year-old male who presented with large pedunculated oropharyngeal fibrolipoma that originated from the posterior oropharyngeal wall and extended downward into the postcricoid area and cervical esophagus. It was excised transorally using rigid endoscope, and ACE Harmonic scalpel was utilized to excise this 16.7 cm long mass. The postoperative pain was minimal, the surgical site showed complete healing, and oral diet was resumed easily in 5 days. [ABSTRACT FROM AUTHOR]

Cancers represent the primary cause of mortality among people living with HIV (PLWH). However, comprehensive nationwide data regarding cancer incidence remains limited. Our objective was to evaluate the incidence rates of cancers, particularly those associated with human papillomavirus (HPV), within a nationwide study cohort. Using data from the Estonian Health Insurance Fund and the National Cancer Registry from 2004 to 2021, we calculated standardized incidence ratios (SIRs) for various cancer types among PLWH to compare to the general population with special emphases on HPV-associated cancers. A total of 7011 individuals (65.7% men) diagnosed with HIV were identified. HPV-associated cancers accounted for 21.4% of all incident cancer cases among PLWH. SIRs for HPV-associated cancers were 3.7 [95% confidence interval (CI) 2.2–6.2] among men living with HIV (MLWH) and 5.7 (95% CI 4.0–7.9) among women living with HIV (WLWH). In MLWH, the highest SIRs were for penile 12.5 (95% CI 4.0–38.7), followed by oropharyngeal 3.6 (95% CI 1.7–7.6) and anal–rectal cancers 2.7 (95% CI 1.1–6.4) in comparison to the general population. In WLWH, an increased incidence of cervical (SIR = 5.8, 95% CI 3.9–8.5), oropharyngeal (SIR = 6.1, 95% CI 1.5–24.3), and anal–rectal (SIR = 3.6, 95% CI 1.2–11.2) cancers was observed. A significantly increased risk of AIDS-defining and non-AIDS-defining cancers is reported. We demonstrate a substantially heightened risk of HPV-associated cancers among PLWH compared to the general population, underscoring the imperative for intensified screening and scaled-up vaccination along with improvement in adherence to antiretroviral therapy. [ABSTRACT FROM AUTHOR]

One main advantage of proton therapy versus photon therapy is its precise radiation delivery to targets without exit dose, resulting in lower dose to surrounding healthy tissues. This is critical, given the proximity of head and neck tumors to normal structures. However, proton planning requires careful consideration of factors, including air-tissue interface, anatomic uncertainties, surgical artifacts, weight fluctuations, rapid tumor response, and daily variations in setup and anatomy, as these heterogeneities can lead to inaccuracies in targeting and creating unwarranted hotspots to a greater extent than photon radiation. In addition, the elevated relative biological effectiveness at the Bragg peak's distal end can also increase hot spots within and outside the target area. The purpose of this study was to evaluate for a difference in positron emission tomography (PET) standard uptake value (SUV) after definitive treatment, between intensity modulated proton therapy (IMPT) and intensity modulated photon therapy (IMRT). In addition, we compared the biologic dose between PET areas of high and low uptake within the clinical target volume–primary of patients treated with IMPT. This work is assuming that the greater SUV may potentially result in greater toxicities. For the purposes of this short communication, we are strictly focusing on the SUV and do not have correlation with toxicity outcomes. To accomplish this, we compared the 3- and 6-month posttreatment fluorodeoxyglucose PET scans for 100 matched patients with oropharyngeal cancer treated definitively without surgery using either IMPT (n = 50) or IMRT (n = 50). Our study found a significant difference in biologic dose between the high- and low-uptake regions on 3-month posttreatment scans of IMPT. However, this difference did not translate to a significant difference in PET uptake in the clinical target volume–primary at 3 and 6 months' follow-up between patients who received IMPT versus IMRT. Studies have proposed that proton's greater relative biological effectiveness at the Bragg peak could lead to tissue inflammation. Our study did not corroborate these findings. This study's conclusion underscores the need for further investigations with ultimate correlation with clinical toxicity outcomes. [ABSTRACT FROM AUTHOR]

The aim of this review is to assess the utility of circulating HPV tumor DNA (ctHPVDNA) clearance in the monitoring of molecular residual disease in HPV-related oropharyngeal squamous cell carcinoma (OPSCC) patients. Recently, ctHPVDNA in patient plasma was found to be a promising biomarker for HPV OPSCC. Changes in this biomarker appear to be associated with treatment response and may be useful for identifying molecular residual disease. A review of the literature was performed using PubMed/MEDLINE, EMBASE, and Cochrane Library databases according to the PRISMA criteria for scoping reviews (from 2017 to July 2024). A total of 5 articles and 562 patients have been included. Three studies examine the role of ctHPVDNA clearance in CRT, while the remaining two studies consider surgery as a treatment option. The results of this scoping review indicate that ctHPVDNA has a potential role to serve as a valuable biomarker in the assessment of molecular residual disease. Further studies are required to confirm the efficacy of this marker for stratifying this group of patients. [ABSTRACT FROM AUTHOR]

Background and aims: Nuclear protein testis (NUT) carcinoma (NC) is a rare and highly aggressive tumour characterised by chromosomal rearrangement of the nuclear protein testis family member 1 (NUTM1) gene, also known as the NUT gene. NC occurs mainly in the head and neck, mediastinum and lung. In general, primary NC in the oral cavity is extremely rare and reported sporadically. Methods: A total of 111 formalin‐fixed and paraffin‐embedded specimens of poorly differentiated oral and oropharyngeal tumours were collected from 10 hospitals. NUT protein IHC staining was performed on these samples, and fluorescence in‐situ hybridisation (FISH) and RNA sequencing detection were further carried out for NUT IHC‐positive cases. Results: The expression of NUT protein in tumour cells was detected in five cases (five of 111, 4.5%). The tumours in these cases were located in the oral floor, lip, base of the tongue, gingiva and hard palate. FISH detection results showed BRD4::NUT rearrangement in three patients and a non‐BRD4::NUT rearrangement pattern in two patients. RNA sequencing results confirmed BRD4::NUT rearrangement in two cases. Conclusions: To our knowledge, this is the first and largest retrospective study of oral NC, and we found that NC is easily misdiagnosed as poorly differentiated oral squamous cell carcinoma (SCC) or poorly differentiated carcinoma. The morphology and immunophenotype of four NC cases were similar to SCC, and abrupt keratinisation was observed in three cases. Therefore, it is necessary to detect NUT protein for NC screening in oral malignant tumours with these morphologies, especially for young patients who are more likely to be misdiagnosed with other types of cancer. [ABSTRACT FROM AUTHOR]

Computed tomography (CT) of the chest is routinely performed as part of head and neck cancer (HNC) staging. Pulmonary nodules incidentally encountered present a clinical dilemma, as they may indicate early malignancy. Clinically indeterminant nodules are those that cannot be classed as definitively malignant or benign. This study aimed to assess the outcomes of pulmonary nodules detected on initial staging chest CT in a consecutive cohort of patients with oral and oropharyngeal squamous cell carcinoma (SCC). A retrospective cohort study of newly diagnosed oral or oropharyngeal SCC patients with pulmonary nodules identified on staging chest CT at a single institution was conducted. Pulmonary nodules were categorised as benign, indeterminant, or malignant. Indeterminant nodules underwent further investigations with either repeat imaging or needle biopsy to exclude malignancy. Descriptive and bivariate statistics were used to evaluate the association between pulmonary metastasis and patient demographics, disease characteristics, and nodular features. P values of ≤ 0.05 were considered statistically significant. Of 579 patients diagnosed with HNC who had undergone staging chest CT between 2010 and 2015, 154 had pulmonary nodules. Indeterminant pulmonary nodules at staging in 26 patients (16.9%) were later confirmed to be lung metastases. Pulmonary nodules of subsolid type found in patients with N2/N3 disease were significantly more likely to be metastatic. Isolated pulmonary nodules in the right lung were more likely to be benign. A HNC-specific protocol for the management of incidental pulmonary nodules should now be developed to guide the interval and duration of required clinical and radiological surveillance, taking into account the disease characteristics and nodular features. [ABSTRACT FROM AUTHOR]

Background: Lymphatic mapping with SPECT–CT has been demonstrated to accurately define lymphatic drainage patterns in oropharyngeal cancer but there has yet to be a study demonstrating its feasibility across multiple institutions. Methods: Twelve adult patients with lateralized oropharyngeal carcinoma (T1‐T3) who were planned for definitive or adjuvant radiotherapy without contralateral nodal disease underwent injection of 99‐m technetium sulfur colloid followed by static planar lymphoscintigraphy to verify tracer migration, and SPECT–CT acquired at 30 ± 15 min (optional) and 3 h (±1 h) (mandatory time‐point). Results: All 12 patients completed the study with 7/12 patients having the injections performed under local anesthetic and 5 patients requiring general anesthetic. There were no tracer migration failures and there were no serious adverse events or complications encountered. Four out of 12 patients (33%) showed contralateral drainage patterns. Conclusions: Lymphatic mapping with SPECT–CT of lateralized oropharyngeal squamous cell carcinoma can be performed safely across multiple institutions. [ABSTRACT FROM AUTHOR]

Objective: The present study challenges the appropriateness of considering invasion of the palatoglossus muscle (PGM) as a criterion for staging oropharyngeal squamous cell carcinoma (OPSCC) as T4. Study Design: Retrospective observational study. Setting: Tertiary University Hospital. Methods: This retrospective study included nonmetastatic OPSCC patients treated with curative intent at the University of Trieste, Italy from 2015 to 2021. Patients were categorized into 4 groups: (1) tumors classified as T1‐T2 by both International Cancer Control (UICC) and American Joint Committee on Cancer (AJCC)‐TNM; (2) T1‐T2 tumors upgraded to T4 solely by UICC due to oropharyngeal PGM infiltration; (3) T1‐T2 tumors upgraded to T4 by both UICC and AJCC due to oral PGM infiltration; (4) tumors classified as T3‐T4 by both UICC and AJCC. Kaplan‐Meier analysis estimated overall survival (OS) and disease‐free survival (DFS). Multivariable Cox models, adjusted for clinical factors, assessed the impact of palatoglossus invasion on outcomes over 5 years. Results: A total of 121 consecutive patients with primary OPSCC were included (median [interquartile range] age 65 years [58‐74]; 63% male). While patients with upgraded T4 category due to infiltration of the oral portion of the PGM exhibited a prognosis superimposable on that of other patients with advanced stage disease, those with upgraded T4 category due to infiltration of the oropharyngeal portion of the PGM displayed OS and DFS comparable to T1‐T2 patients. Conclusion: Our findings highlight that invasion of the oropharyngeal portion of the PGM may not be a suitable criterion for staging OPSCC as T4. Further research involving larger and independent patient cohorts is strongly encouraged to corroborate these observations. [ABSTRACT FROM AUTHOR]

Objectives: To (1) assess perceptions of parents of patients ages 9–17 years regarding human papillomavirus (HPV) vaccine counseling and a same‐day HPV vaccine program, and (2) assess perceptions among dental staff who actively participated in the same administration program. Methods: We conducted a post‐evaluation, convenience survey of parents of patients aged 9–17 and dental staff at a large‐urban federally qualified healthcare center (FQHC) from July 25, 2022, to August 26, 2022. Parent and staff perceptions were assessed using validated instruments whenever possible. Data were analyzed descriptively. Results: Overall, 101 parents participated (response rate: 89%). Overall, 80 parents (74.3%) reported wanting to discuss diseases prevented by the HPV vaccine with their dental provider. Twenty parents (20%) reported receiving counseling on the HPV vaccine by their dentist; 95% (n = 19) of those parents reported it did not change their comfort with their provider and 60% (n = 12) reported their child received the vaccine that day. Overall, 44 dental staff members (32% DDS/DMD, 14% RDH‐BS‐Dental Hygiene, 55% Other) completed surveys (response rate: 100%). Of these, 39 (88.6%) were willing to recommend the HPV vaccine and participate in a referral program. Nearly all dentists and hygienists (95%) reported discussing the vaccine was within their scope of practice, and most (65%) agreed vaccine administration should be within their scope. Conclusion: In a single site convenience survey within an urban, federally qualified health care system, most parents, and dental staff perceived HPV vaccine counseling and administration favorably and clinically appropriate during routine dental visits. [ABSTRACT FROM AUTHOR]

Objective: Health care costs are disproportionately concentrated among a small number of patients. We sought to identify variables associated with high‐cost patients and high hospital concentration of high‐cost patients and to examine associations with short‐term outcomes in head and neck cancer (HNCA) surgery. Study Design: The Nationwide Inpatient Sample was used to identify 170,577 patients who underwent HNCA surgery in 2001–2011. High‐cost patients were defined as patients whose costs of care were in the top decile, and high‐concentration hospitals were defined as those whose percentage of high‐cost patients was in the top decile. Methods: Multivariable regression was used to evaluate associations between cost and patient and hospital variables, postoperative complications, and in‐hospital mortality. Results: Costs associated with high‐cost patients were 4.47‐fold greater than the remaining 90% of patients. High‐concentration hospitals treated 36% of all high‐cost patients. High‐cost patients were more likely to be non‐white (OR = 2.08 [1.45–2.97]), have oral cavity cancer (OR = 1.21 [1.05–1.39]), advanced comorbidity (OR = 1.53 [1.31–1.77]), Medicaid (OR = 1.93 [1.62–2.31]) or self‐pay payor status (OR = 1.72 [1.38–2.14]), income>50th percentile (OR = 1.25 [1.05–1.51]), undergo major procedures (OR = 3.52 [3.07–4.05]) and have non‐routine discharge (OR = 7.50 [6.01–9.35]). High‐concentration hospitals were more likely to be teaching hospitals (OR = 3.14 [1.64–6.05]) and less likely to be urban (OR = 0.20 [0.04–0.93]). After controlling for all other variables, high‐cost patients were associated with an increased odds of mortality (OR = 8.00 [5.89–10.85]) and postoperative complications (OR = 5.88 [5.18–6.68]). High‐concentration hospitals were associated with an increased odds of postoperative complications (OR = 1.31 [1.08–1.61]) but were not associated with increased mortality (OR = 0.98 [0.67–1.44]). Conclusions: High‐cost HNCA surgical patients are associated with increased postoperative morbidity and mortality, and are disproportionately concentrated at teaching hospitals. Level of Evidence: 4 Laryngoscope, 134:4971–4978, 2024 [ABSTRACT FROM AUTHOR]

Randomized trials have found that patients with locoregionally advanced p16+ oropharyngeal squamous cell carcinoma (OPSCC) do not benefit from treatment deintensification, even among favorable risk groups. Although various methods have been used to identify candidates for treatment deintensification, the optimal approach is unknown. We conducted a multi-institutional cohort study of 444 patients with previously untreated p16+ OPSCC undergoing definitive radiation therapy with or without systemic therapy between 2009 and 2022. We compared the following 2 approaches for identifying candidates for deintensification: (1) favorable versus unfavorable risk, using NRG-HN005 eligibility criteria, and (2) low versus high relative risk of cancer events, using the Head and Neck Cancer Intergroup predictive classifier ("omega score"). We tested differences in outcomes and systemic therapy allocation by risk group using multivariable Cox models, competing event models, and logistic regression, and compared characteristics of hypothetical deintensification trials using the 2 approaches. Progression-free survival events were defined as cancer recurrence (locoregional or distant) or death from any cause. Median follow-up time was 52 months; 120 patients (27.0%) were favorable risk; a different 120 patients had low omega score; 28 patients (6.3%) met both criteria; 184 patients (41.4%) had discordant classification. On ordinal logistic regression, decreasing omega score was associated with a statistically significantly lower odds of receiving intensive therapy (normalized odds ratio, 0.37 per SD; 95% CI, 0.24-0.57), with a greater magnitude than favorable risk group (odds ratio, 0.66; 95% CI, 0.44-0.99). Among patients receiving cisplatin and/or platinum-based induction (n = 374), favorable risk was associated with significantly improved progression-free survival (hazard ratio, 0.59; 95% CI, 0.36-0.99), whereas lower omega score was associated with a significantly decreased relative hazard for cancer events (relative hazard ratio, 0.18; 95% CI, 0.070-0.46). In simulations, selecting patients with low omega scores increased the efficiency of hypothetical noninferiority trials. Considering patients' relative risk of cancer events can help define optimal populations for treatment deintensification in p16+ OPSCC. [ABSTRACT FROM AUTHOR]

With the increasing proportion of human papilloma virus (HPV) infection in the pathogenic factors of oropharyngeal cancer, a series of changes have occurred in the surgical treatment. While the treatment mode has been improved, there are still many problems, including the inconsistency between diagnosis and treatment modes, the lack of popularization of reconstruction technology, the imperfect post-treatment rehabilitation system, and the lack of effective preventive measures. Especially in terms of treatment mode for early oropharyngeal cancer, there is no unified conclusion whether it is surgery alone or radiotherapy alone, and whether robotic minimally invasive surgery has better functional protection than radiotherapy. For advanced oropharyngeal cancer, there is greater controversy over the treatment mode. It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy, or a treatment mode of surgery combined with postoperative chemoradiotherapy. In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer, this expert consensus, based on the characteristics and treatment status of oropharyngeal cancer in China and combined with the international latest theories and practices, forms consensus opinions in multiple aspects of preoperative evaluation, surgical indication determination, primary tumor resection, neck lymph node dissection, postoperative defect repair, postoperative complication management prognosis and follow-up of oropharyngeal cancer patients. The key points include: ① Before the treatment of oropharyngeal cancer, the expression of P16 protein should be detected to clarify HPV status; ② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resection of oropharyngeal cancer. Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction; ③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months, it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment; ④ Early-stage oropharyngeal cancer patients may opt for either surgery alone or radiation therapy alone. For intermediate and advanced stages, HPV-related oropharyngeal cancer generally prioritizes radiation therapy, with concurrent chemotherapy considered based on tumor staging. Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma (including primary and recurrent) and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy; ⑤ For primary exogenous T1-2 oropharyngeal cancer, direct surgery through the oral approach or da Vinci robotic surgery is preferred. For T3-4 patients with advanced oropharyngeal cancer, it is recommended to use temporary mandibulectomy approach and lateral pharyngotomy approach for surgery as appropriate; ⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth >3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients, selective neck dissection of levels IB to IV is recommended. For cN+ HPV unrelated oropharyngeal cancer patients, therapeutic neck dissection in regions I-V is advised; ⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node, or imaging suggests continuous enlargement of lymph nodes, the patient should undergo neck dissection; ⑧ For patients with suspected extracapsular invasion preoperatively, lymph node dissection should include removal of surrounding muscle and adipose connective tissue; ⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps, with priority given to adjacent flaps, followed by distal pedicled flaps, and finally free flaps. The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

Background/purpose: The incidence of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) is increasing worldwide. HPV vaccines have shown efficacy in preventing diseases in both males and females. Therefore, there is a need to develop cost-effective strategies for HPV vaccines to prevent HPV-related OPC. This meta-analysis aimed to evaluate cost-effectiveness using the global mean of incremental cost-effectiveness ratios compared to the willingness-to-pay threshold and incremental net benefits (INBs) of HPV vaccination strategies between boys’ extension vaccine and girls only. These recommendations will be useful for countries that have not implemented universal HPV vaccines in national programs, such as Taiwan. Materials and methods: Studies evaluating the cost-effectiveness of HPV vaccination strategies in the prevention of OPC that included both sexes versus girls only were identified through the Cochrane Library, EMBASE, PubMed, ScienceDirect, and Web of Science databases on February 05, 2024, and a meta-analysis of pooled INBs was performed using a random-effects model. The outcome was an effective measurement of the OPC burden. The results are represented in USD (2024). Results: Fifteen model analyses were included. All the studies were conducted in high-income countries. The global mean of incremental cost-effectiveness ratio was $39,553 (95% CI, $27,008–66,641) per quality-adjusted life years gained, which was below the global mean of the willingness-to-pay threshold of $65,473 (95% CI, $52,138–83,755). Pooled INBs of $9370 (95% CI, $5046–13,695; P

Paraneoplastic acral vascular syndrome (PAVS) is a captivating enigma in the landscape of oncological pathology, characterized by vascular disturbances of the extremities. PAVS is linked to rapidly progressing trajectory and understanding the intricate interplay between cancer and this vascular dysfunction is imperative for timely diagnosis. We describe the case of a 45-year-old cachectic male who presented at the ICU with bilateral tumefied, cyanotic digits, accompanied by acute pain and numbness in both hands. A Digital Angiography described complete obstruction of the digital arteries. Imaging showed a laterocervical tumor mass with pulmonary metastases. This form of digital ischemia likely stems from endothelial dysfunction and prothrombotic effects induced by the tumor through a paraneoplastic mechanism. This case underscores the importance of recognizing acral vascular syndrome, prompting thorough investigation for an underlying malignancy. Ultimately, collective efforts aimed at enhancing our understanding of PAVS and optimizing its management hold promise for improving outcomes and alleviating the burden of this condition on affected patients.

Background Nearly 24,000 new cases of oropharyngeal cancers (OPCs) are reported per year in India, constituting 3.9% of cancers in all sites. By 2009, Human papilloma virus (HPV), in particular HPV-16, was established as an etiological factor and even a causative agent in OPCs being associated with up to 70% OPCs. Prior imaging-based studies have described certain differentiating factors between HPV-mediated and HPV-negative OPC, highlighting computed tomography and magnetic resonance characteristics that could help differentiate the two groups. Our study aimed to evaluate any imaging differences between HPV-mediated and non-HPV-mediated oropharyngeal malignancies in the Indian subcontinent population. Methods Seventy-nine patients from the Indian subcontinent who were referred to a tertiary center in southern India between the period of January 2019 to September 2020 (19 months) were included in the study. Imaging descriptors were documented by blinded radiologists, and univariate and multivariate analysis of various imaging descriptors and imaging differences between HPV-mediated and non-HPV cases were attempted to be identified. Results We found no statistically significant imaging differences between HPV-mediated and non-HPV-mediated oropharyngeal malignancies. The only epidemiologically significant difference in the two groups was that in women and nonsmokers, HPV-mediated malignancies were more common. Conclusion HPV-mediated and HPV-negative malignancies have similar primary tumor as well as nodal imaging characteristics. Previously cited differences in the two groups, in Western literature, could not be demonstrated in our population. It implores further research into whether downstaging of treatment and better prognosis of HPV-mediated malignancies is actually applicable in the Indian subcontinent setting.

The incidence of human papillomavirus (HPV) associated oropharyngeal cancer has increased to epidemic-like proportions in the United States and other industrialized nations. While significant progress has been made in the understanding of this disease with respect to its underlying biology and clinical behavior, numerous questions persist regarding treatment. It is now firmly established that patients with HPV-positive oropharyngeal cancer have a significantly improved prognosis as a result of their exquisite radiosensitivity compared to their HPV-negative counterparts and thus can be targeted with de-escalated approaches using reduced doses of radiation and/or chemotherapy. The fundamental goal of de-escalation is to maintain the high cure and survival rates associated with traditional approaches while reducing the incidence of both short- and long-term toxicity. Although the exact reason for the improved radiosensitivity of HPV-positive oropharyngeal carcinoma is unclear, prospective studies have now been published demonstrating that de-escalated radiation can successfully maintain the high rates of cure and preserve quality of life for appropriately selected patients with this disease. However, the selection criteria and specific means for de-escalation remain uncertain, and paradigms continue to evolve. Given that HPV-positive oropharyngeal cancer is increasingly recognized as a public health problem, the search for answers to many of these provocative questions has important societal implications and is the subject of this review. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Methods Results Conclusion Oropharyngeal squamous cell carcinoma (OP‐SCC) represents a public health problem and human papillomavirus (HPV) is one of the risk factors. Neutrophil extracellular traps (NET) are meshes of DNA strands and granule proteins. NET has been identified in diverse cancers, whether associated with viruses or not. However, there is no information on NET in OP‐SCC. We aimed to evaluate the NET release by neutrophils in the OP‐SCC microenvironment, stratified by HPV status.This cross‐sectional study analyzed OP‐SCC biopsy specimens diagnosed from 1997 to 2021. HPV status was determined by p16 immunohistochemistry and “in situ” hybridization. Neutrophils were detected by CD66b immunohistochemistry. Immunofluorescence was used to identify NET by co‐localization of myeloperoxidase (MPO) and citrullinated histone H3 (H3Cit). Bivariate statistics, Kaplan–Meier survival analysis, and the log‐rank test were performed.HPV‐positive and HPV‐negative OP‐SCC had similar CD66b + neutrophil infiltration (p > 0.05), but the release of NET was significantly increased in HPV‐positive compared to HPV‐negative OP‐SCC samples (p < 0.05). Overall survival was not impacted by NET indexes (p > 0.05).The presence of HPV may stimulate NET release in the OP‐SCC microenvironment. [ABSTRACT FROM AUTHOR]