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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]

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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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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Transoral robotic surgery (TORS) has become a common surgical approach for the treatment of both benign and malignant conditions of the oropharynx. While the newer da Vinci Xi platform has largely replaced the previous Si model in many institutions, the reported outcomes with this system in head and neck surgery are limited. We report the feasibility of using the da Vinci Xi platform for managing oropharyngeal cancer and obstructive sleep apnea in a low-volume center. This retrospective review from a consecutive case series includes demographic, procedural, and outcome data from all patients who underwent TORS using the da Vinci Xi platform at a single institution over a 5-year period from 2019 to 2023. Thirty-five patients (19 males and 16 females) underwent TORS for a variety of indications. No patients were excluded from the study. There were no mortalities, readmissions, or severe complications directly related to the primary surgery. Our case series demonstrates that TORS is feasible with the da Vinci Xi system even in low-volume centers and supports the existing data suggesting that the Xi platform has an acceptable safety profile. [ABSTRACT FROM AUTHOR]

Head and neck cancers affect speech, swallowing, and breathing, presenting physical and psychosocial challenges for patients. Understanding risk factors, symptoms, importance of early detection, and treatment options is essential for effective management and improved outcomes. [ABSTRACT FROM AUTHOR]

Background: Post‐treatment surveillance recommendations for oropharyngeal cancer do not vary with p16 status despite the differences in outcomes. The optimal algorithm personalizing follow‐up for these patients remains undefined. Here, we evaluate the feasibility and utility of incorporating electronic patient‐reported outcomes (ePROs) and circulating tumor DNA (ctDNA) into routine surveillance for patients treated for p16+ oropharynx cancer. Methods: A prospective registry was developed in which ePROs and ctDNA were incorporated into routine surveillance among patients with oropharynx cancer. ePROs were emailed monthly for 1 year and blood HPV ctDNA testing was performed every 3–6 months. The primary objective was to assess patient compliance with ePRO‐based surveillance with adequate compliance defined as ≥85% of patients completing monthly ePROs. Sensitivity, specificity, and positive/negative predictive values to detect recurrence were calculated for ePROs, HPV ctDNA, or the combination. Results: Of 122 patients who initially expressed interest, 76 completed the electronic consent process and 44/76 (58%) were compliant with monthly surveys over 1 year; thus adequate compliance was not achieved. Technical difficulties associated with ePRO receipt through email largely limited participation. Provider feedback was significantly associated with heightened ePRO compliance. One hundred and six patients had ctDNA testing with a mean number of three tests per patient. Sensitivity to detect recurrence was 75% for the combination of ePROs and ctDNA. Conclusion: Despite lower than anticipated compliance with ePROs, our findings show promise for incorporation of HPV ctDNA into surveillance paradigms for HPV‐related oropharynx cancer with suggestions of methods to optimize ePRO formats for personalized surveillance. [ABSTRACT FROM AUTHOR]

Background: Transoral surgical resectability (TOS) is a prognostic factor for patients with HPV+ T1‐2 oropharyngeal squamous cell carcinoma (OPSCC) disease undergoing radiotherapy (RT), but it is unclear whether this holds for HPV‐negative (HPV‐) patients. We aimed to compare outcomes of potential TOS‐candidates vs. non‐TOS candidates, among patients who underwent RT/CRT for early T‐stage HPV‐ OPSCC. Methods: For patients treated with RT/CRT for early T‐stage HPV‐negative OPSCC between 2014 and 2021, pretreatment imaging was reviewed by four head‐and‐neck surgeons, masked to clinical outcomes, to assess primary‐site suitability for TOS. Extracapsular extension (ECE) was assessed by a head‐and‐neck neuroradiologist. We compared outcomes based on surgical resectability relating to: (1) the primary site tumor alone, and (2) the primary site plus the absence/presence of ECE (overall assessment). Kaplan–Meier curves for overall survival (OS), disease‐specific survival (DSS), and progression‐free survival (PFS) were compared using the log‐rank test. Results: Seventy patients were included in the analysis. The primary site was TOS‐favorable in 46/70 (66%). Based on the overall assessment, 41/70 (58.6%) were TOS‐favorable. The 3‐year OS, DSS and PFS for primary site TOS‐favorable versus unfavorable were OS: 76.9% versus 37.4%; DSS: 78.1% versus 46.2%, PFS: 69.9% versus 41.3%, (log‐rank test = 0.01, 0.03, 0.04; respectively). Additionally, patients with an overall assessment of TOS favorability demonstrated better survival outcomes compared with TOS‐unfavorable patients (OS: 77.3% vs. 46.2%; DSS: 78.2% vs. 56.5%, PFS: 72.3% vs. 42.1%, log‐rank test = 0.01, 0.04, 0.01; respectively). Conclusion: Patients with TOS‐favorable HPV‐negative early T‐stage OPSCC have superior survival outcomes than TOS‐unfavorable patients. [ABSTRACT FROM AUTHOR]

HPV viral E6 and E7 onco‐proteins play a well‐known role in carcinogenesis. Host genomic alterations also play a key role in the development of HPV‐related oropharyngeal cancer and have been under‐recognized. We describe a case series of 6 metastatic/locoregionally recurrent HPVOPSCC patients with FGFR alterations. HPVOPSCC presents with distinct pattern of spread both temporally and sites of recurrence compared to non‐HPV‐related oropharyngeal cancer. Identification and reporting of genomic alterations in HPV are crucial to the understanding of disease biology and could aid in development of novel therapeutics for these patients. In addition, use of circulating tumor DNA may lead to early detection and supplement imaging in the follow up of these patients. Loco‐regional treatments may also play a key role in the management of metastatic HPV OPSCC depending on the pattern of presentation. Our case series highlights all these novelties that could lead to better treatment outcomes. [ABSTRACT FROM AUTHOR]

Introduction: This study provides an epidemiological description of cancer in the lip, oral cavity, and oropharynx in the South and South‐East Asia region. Methods: The number of new cases and deaths was extracted from the GLOBOCAN 2020 and the CI5 series. We present age‐standardized incidence and mortality rates per 100,000 inhabitants. To assess temporal trends, we estimated the annual percent change. Results: The incidence rates (ASR) for lip and oral cavity cancer in South and South‐East Asia were highest in Taiwan (30.2), Sri Lanka (16.5), India (14.8), and Pakistan (13.2) among males. For oropharyngeal cancer, the highest rates were found in Taiwan (4.7), Bangladesh, Sri Lanka, and India (4.3, 2.9, and 2.6, respectively). Incidence rates were consistently higher in males compared to females. Overall, trends in lip and oral cavity cancer incidence were either stable or decreasing in most of the populations evaluated. In India, an increase in rates among males contrasted with a decline among females over the study period. Conclusion: Incidence and mortality rates of oral cavity cancer in South and South‐East Asia are among the highest globally. Our results suggest an optimistic trend of reduction in oral cavity rates in the region, despite an increase in rates among Indian males. [ABSTRACT FROM AUTHOR]

Background Human papillomavirus (HPV)+ oropharynx cancer (OPC) has a more favorable prognosis than HPV-negative disease, but the impact of specific HPV genotype and phylogenic clade on patient outcomes is not well understood and has profound implications for treatment de-intensification. Methods The objective of this single-institution cohort study was to investigate the association of HPV genotype (16 vs high-risk non-16) and clade (A9 vs A7) with OPC outcomes. The primary endpoints were overall survival (OS) and event-free survival (EFS) in patients with M0 disease treated with curative intent. Results The cohort included 598 patients (87% HPV16, 98% A9). Compared to those with HPV16 OPC, individuals with non-HPV16 OPC had a higher age, comorbidity index, and proportion of non-whites, HIV+ patients, T4 tumors, and stage IV disease (AJCC 7th edition). Non-HPV16 genotype was associated with worse OS in univariate (HR = 2.17, 95% CI, 1.24-3.80, P  = .0066), but not in multivariate analysis (HRadj = 0.84, 95% CI, 0.43-1.62, P  = .5921). A7 clade was associated with worse OS in univariate (HR = 4.42, 95% CI, 1.60-12.30, P  = .0041), but not in multivariate analysis (HRadj = 2.39, 95% CI, 0.57-9.99, P  = .2325). Neither HPV genotype (HR = 1.60, 95% CI, 0.99-2.60, P  = .0566) nor phylogenic clade (HR = 2.47, 95% CI, 0.91-6.72, P  = .0761) was associated with EFS. Conclusion Non-HPV16 genotype and A7 clade were associated with worse OS and trended toward worse EFS in univariate analyses. The survival differences were more pronounced by phylogenic clade than by HPV16 status, suggesting that the former may be a more useful classification for future studies. However, neither HPV16 status nor phylogenic clade was prognostic when adjusting for patient and tumor covariates, raising the question as to whether possible differences in outcomes are related to distinct clinical profiles rather than inherent viral properties. [ABSTRACT FROM AUTHOR]

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Background/Aim: Parotid oncocytomas typically present as benign, unilateral, slow-growing, painless, and solitary masses that are histologically firm and multilobulated. They are often misdiagnosed as pleomorphic adenomas, hemangiomas, or other forms of oncocytosis. However, in our case, the parotid oncocytomas initially mimicked bilateral parotid gland metastasis of advanced oropharyngeal cancer. Here, we present a case of oropharyngeal cancer with bilateral parotid oncocytomas treated with chemoradiotherapy (CCRT). Case Report: We report the case of a 74-year-old man with a sore throat, neck pain, right earache, oropharyngeal cancer, and bilateral parotid gland oncocytoma. Head and neck computed tomography and magnetic resonance imaging (MRI) showed soft-tissue swelling in the right tonsillar fossa and several enlarged level II neck lymph nodes. MRI revealed enhancing masses in both parotid glands, initially suspected to be metastatic lymph nodes. A biopsy of the right palatine tonsil confirmed squamous cell carcinoma with human papilloma virus-16 positivity. A positron emission tomography scan was performed, and biopsyproven malignant lesions were observed in the right tonsillar region with metastatic lymph nodes in the right and left neck. Focal hypermetabolism was observed in the parotid glands, suspected to be pathological lesions such as metastatic intraparotid lymph node or Warthin's tumor. An ultrasonographyguided biopsy of the left parotid gland confirmed an oncocytoma. Based on these results, the patient was scheduled for CCRT. After pathological confirmation of parotid oncocytoma, CCRT was administered, excluding the parotid glands within the radiotherapy field. Conclusion: This is a case of bilateral parotid gland oncocytoma mimicking oropharyngeal cancer. [ABSTRACT FROM AUTHOR]

Background/Aim: Radiotherapy (RT) for advanced oropharyngeal cancer (OPC) is effective, especially when combined with chemotherapy (CRT). However, its success can vary depending on factors, such as tumor stage, HPV infection (p16 status), and the patient's nutritional and immune status. This study examined the controlling nutritional status (CONUT) score and tumor immunity as predictive factors for treatment outcomes in OPC, aiming to develop a personalized risk score. Patients and Methods: A retrospective analysis was conducted on 84 patients with OPC treated with definitive RT or CRT, and survival outcomes were compared based on various factors, including BMI, CONUT score, CD8 expression, and HLA class II expression. Results: We observed better overall survival (OS) rates in CD8-positive patients and those with higher HLA class II expression. The univariate analysis identified stage, p16 status, BMI, CONUT score, and CD8 expression as significantly associated with OS. In multivariate analysis, stage, BMI, and CONUT score remained significant predictors of OS. A risk scoring system was developed based on stage, p16 status, BMI, CONUT score, and CD8 expression. Patients were categorized into low-risk and high-risk groups, with significantly better survival in the low-risk group. Conclusion: A combined risk score incorporating clinical, nutritional, and immune factors can improve the prediction of treatment outcomes for OPC patients. This risk stratification may enable personalized treatment plans and improve OS rates. [ABSTRACT FROM AUTHOR]

Introduction: Oral cavity cancer (OCC), primarily oral squamous cell carcinoma (OSCC), is a growing concern in Europe, particularly among younger populations. Preventable lifestyle factors and social determinants of health contribute significantly to the disease burden. Limited access to healthcare and delayed diagnoses further complicate treatment and reduce survival rates. Methods: This systematic literature review adhered to PRISMA guidelines to explore trends in OSCC epidemiology, etiology, diagnosis, treatment, and survival across Europe. A comprehensive search strategy using PubMed, GLOBOCAN data, and the EUROCARE-5 study identified relevant articles focusing on human populations in Europe with a primary interest in OSCC epidemiology. Only peer-reviewed publications in English with full-text access were included. Results: This study investigated the burden of OSCC across Europe, revealing variations in incidence, mortality, and prognosis. Eastern and Central Europe displayed the highest burden. Males exhibited a significantly higher risk compared to females. Age-related disparities existed in life expectancy and time to achieve favorable outcomes. HPV emerged as a growing risk factor for oropharyngeal cancer. Public health strategies should target modifiable risk factors and improve early detection. Conclusion: This review reveals concerning disparities in European OSCC. Region, sex, and age all influence burden and prognosis. Future research should focus on controlling risk factors and personalized medicine to optimize treatment. This will lead to a Europe with reduced OSCC incidence and demonstrably better patient outcomes. [ABSTRACT FROM AUTHOR]

Objectives: This study used multilevel social determinants of health (SDoH) models to determine how SDoH influence different sexes of patients diagnosed with HPV-positive oropharyngeal squamous cell cancers (OPSCC) across the US. Methods: This was a retrospective cohort study assessing HPV-confirmed patients with oropharyngeal squamous cell cancers from 2010 to 2018 using census-level Yost Index socioeconomic status (SES) score and rurality–urbanicity measures alongside individual-level race–ethnicity while stratifying by biological sex. Age-adjusted multivariate regressions were performed for survival, treatment receipt, and delay of treatment initiation (of 3+ months). Results: Across 14,076 OPSCC-HPV-positive patients, delay of treatment uniquely featured positive predictors for males of black race–ethnicity (OR, 2.07; 95% CI, 1.68–2.54) and poor Yost SES (1.43; 1.24–1.65). Five-year all-cause mortality uniquely showed positive predictors of females of black race–ethnicity (2.74; 1.84–4.71) and of males with poor Yost SES (1.98; 1.79–2.19). Three-year all-cause mortality shared positive predictors across sexes but were exacerbated in females of black race–ethnicity (2.50; 1.82–3.44) compared to males (2.23; 1.91–2.60); this was reversed for poor Yost SES (male, 1.92, 1.76–2.10; female, 1.60, 1.32–1.95). Surgery showed negative predictors of black race–ethnicity that displayed worsened effects in females (0.60, 0.44–0.79) versus males (0.75, 0.66–0.86). First-line radiation receipt uniquely featured negative predictors for males of black race–ethnicity (0.73; 0.62–0.86) with poor Yost SES (0.74; 0.68–0.82). Conclusions: Comprehensive models of multilevel SDoH displayed exacerbated disparity effects of community-level SES in males and black race–ethnicity among female HPV-positive OPSCC patients. These objective comparisons of specific SDoH factors inform providers and policy direction on how to strategically target the most pertinent SDoH factors affecting a rapidly growing cancer population. [ABSTRACT FROM AUTHOR]

Simple Summary: Oropharyngeal squamous cell carcinoma (OPSCC) and its treatments often result in dysphagia, necessitating prolonged use of a nasogastric (NG) tube. NG tube removal rates in patients with OPSCC were compared between two strategies (induction chemotherapy followed by surgery versus induction chemotherapy followed by chemoradiation therapy). The outcomes related to swallowing function and NG tube dependence were shared with clinical physicians for guidance. Objectives: This retrospective observational study investigated to determine whether surgery or chemoradiation therapy after induction chemotherapy leads to better swallow function for oropharyngeal cancer patients. Methods: We documented the treatment paths and results of 267 patients with oropharyngeal squamous cell cancer (OPSCC). By quantifying nasogastric (NG) tube usage, surgery after induction chemotherapy (IC–surgery), and chemoradiation therapy after induction chemotherapy (IC-CRT) could be compared to determine the effectiveness of each. Cancer stages were also recorded concerning treatment options. The differences in NG tube usage IC–surgery and IC-CRT groups were compared. The NG tube dependence rates were also presented. Results: The prognosis and tube dependence differed significantly between the two groups. The IC–surgery had a better prognosis compared to IC-CRT for oropharyngeal cancer. The findings indicated that NG tube dependence was greater in advanced tumor stage 4 compared to stages 1–3, and NG tube dependence rates were higher for patients who underwent chemoradiation therapy after induction chemotherapy. Swallowing function was better in the IC–surgery group compared to the IC-CRT group. Conclusions: Higher NG tube retention rates and NG dependence are found in OPSCC patients who choose CRT as their treatment and also in the advanced-stage group. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the performance of vision transformer‐derived image embeddings for distinguishing between normal and neoplastic tissues in the oropharynx and to investigate the potential of computer vision (CV) foundation models in medical imaging. Methods: Computational study using endoscopic frames with a focus on the application of a self‐supervised vision transformer model (DINOv2) for tissue classification. High‐definition endoscopic images were used to extract image patches that were then normalized and processed using the DINOv2 model to obtain embeddings. These embeddings served as input for a standard support vector machine (SVM) to classify the tissues as neoplastic or normal. The model's discriminative performance was validated using an 80–20 train‐validation split. Results: From 38 endoscopic NBI videos, 327 image patches were analyzed. The classification results in the validation cohort demonstrated high accuracy (92%) and precision (89%), with a perfect recall (100%) and an F1‐score of 94%. The receiver operating characteristic (ROC) curve yielded an area under the curve (AUC) of 0.96. Conclusion: The use of large vision model‐derived embeddings effectively differentiated between neoplastic and normal oropharyngeal tissues. This study supports the feasibility of employing CV foundation models like DINOv2 in the endoscopic evaluation of mucosal lesions, potentially augmenting diagnostic precision in Otorhinolaryngology. Level of Evidence: 4 Laryngoscope, 134:4535–4541, 2024 [ABSTRACT FROM AUTHOR]

Objective: This study is aimed to evaluate the efficacy and safety of PD-1 inhibitors combined with neoadjuvant chemotherapy in patients with locally advanced hypopharyngeal and oropharyngeal cancer prior to surgical resection. Methods: This retrospective analysis included 42 patients diagnosed with locally advanced hypopharyngeal and oropharyngeal cancer. The efficacy, safety, survival, and laryngeal preservation rate were evaluated. Results: A total of 42 patients were included in this retrospective analysis, of whom 28 had hypopharyngeal cancer and 14 had oropharyngeal cancer. Of the 42 patients, 14 (33.3%) achieved a pathological complete response (PCR) at the primary site, 20 (47.6%) achieved a major pathological response (MPR), and 8 (19%) had an incomplete pathological response (IPR) at the primary lesion. A PCR at both the primary site and the neck lymph nodes was observed in 9 patients (21.4%). The laryngeal preservation rate was 92.9% (26/28) in patients with hypopharyngeal cancer. The median follow-up time was 10.5 months. The median progressionfree survival (PFS) was 26.42 months (95% CI, 23.416–29.424), and the median overall survival (OS) was 27.1 months (95% CI, 24.316–29.884). The 1-year PFS rate was 83.1%, and the 1-year OS rate was 85.9%. Conclusion: Combination therapy with PD-1 inhibitors and neoadjuvant chemotherapy has demonstrated superior efficacy and safety as a preoperative treatment for locally advanced hypopharyngeal and oropharyngeal cancer. Notably, this treatment regimen does not increase the risk of severe postoperative complications and has shown promising results in improving laryngeal preservation rates. [ABSTRACT FROM AUTHOR]

Cancer will continue to be a major source of morbidity and mortality globally during the foreseeable future. Human papillomavirus (HPV)‐related cancer is now a serious problem in both women and men. The most common HPV‐related cancer is cervical cancer in females and oropharyngeal cancer in males. Eastern Africa has a high age‐standardized incidence of HPV‐related cancers, followed in order by Southern Africa, Central Africa, and then the rest of Africa. Among Asian and Oceania countries, Fiji, Papua New Guinea, Solomon Islands, Indonesia, Maldives, and Myanmar have extremely high age‐standardized incidences and mortality. Oropharyngeal cancer is less common than cervical cancer, but the age‐standardized incidence, for both females and males, is higher in Western Europe, Northern Europe, North America, and Australia/New Zealand. Oropharyngeal cancer incidence rates differ significantly from the rates of cervical cancer within the same countries. In Asia and Oceania, the incidence of oropharyngeal cancer is particularly high among females in Bhutan, Bangladesh, and Australia, and it is highest among males in Bangladesh, New Caledonia, Australia, and French Polynesia. To a certain extent, cervical cancer can be reduced through the development of cervical screening programs and improvements in screening uptake. On the other hand, for oropharyngeal cancer, as of yet, no effective means of cancer screening has been established. Widespread uptake of HPV vaccine will contribute to the reduction of HPV‐related cancers in Asia and Oceania, but also in the rest of the world. [ABSTRACT FROM AUTHOR]

Background: Worldwide, the incidence of oropharyngeal squamous cell carcinoma (OPSCC) caused by human papillomavirus (HPV), a sexually transmitted virus, is increasing. This increase has yet to be demonstrated in an Irish cohort. Aims: To evaluate the number of OPSCC presentations locally, to stratify cases by HPV status and to estimate if any changes in the patient population had occurred over a 10-year period. Methods: A STROBE-compliant, retrospective evaluation of patients with OPSCC at St James's Hospital between 2012 and 2022 was performed. Patients with non-SCC histology, undocumented HPV status and residual or recurrent tumours were excluded. Results: We included 294 patients with a mean age of 60.4 years (95% CI 59.2–61.5 years) and 175 (59.5%) patients had HPV+ OPSCC. The number of new OPSCC diagnoses increased from 115 patients (39.1%) between 2012 and 2016 to 179 patients (60.9%) between 2017 and 2021. This was associated with an increased proportion of HPV-linked OPSCC (50.4% 2012–2016 vs. 65.4% 2017–2021, p = 0.011). Over time, more patients had a functionally limiting comorbidity (p = 0.011). The mean age of HPV+ OPSCC cases increased by 3.6 years (p = 0.019). Patients with HPV+ OPSCC had greater 2-year OS (83.9% vs. 54.9%; p < 0.001) and 2-year DFS (73.5% vs. 45.6%; p < 0.001). The 2-year OS and DFS did not change over time for HPV+ or HPV− patients. Conclusions: In our institution, the number of patients with OPSCC is increasing due to an escalation in cases associated with HPV. Population-level interventions such as vaccination programs may alter the current increase in the incidence of these tumours. [ABSTRACT FROM AUTHOR]

Background: Increased sexual activity is associated with higher human papillomavirus (HPV) rates; however, there is a lack of analysis comparing the sexual history of patients with HPV positive and HPV negative oropharyngeal cancer (OPC). Methods: In this meta‐analysis, PubMed, Scopus, and CINAHL were searched for articles that included patients with OPC and reported information regarding HPV status and either history of oral sex, number of sexual partners, or sexually transmitted infections (STI). Results: A total of 11 studies were included with 3296 patients with OPC. Patients with HPV positive OPC were more likely than patients with HPV negative OPC to report a history of oral sex (92%, 95% CI: 87.0–97.0 vs. 74.5%, 95% CI: 50.6–98.4, p < 0.0001), higher mean number of sexual partners (18.4 partners, 95% CI: 1.5–35.4 vs. 7.2 partners, 95% CI: 1.0–13.4, p < 0.0001), and more frequent history of STI (23.7%, 95% CI: 18.4–29.0 vs. 8.8%, 95% CI: 4.7–12.8, p = 0.0001). Conclusions: Compared to patients with HPV negative OPC, our analysis shows a larger proportion of patients with HPV positive OPC had participated in oral sex, had a higher number of sexual partners, and had a higher proportion of STI history. [ABSTRACT FROM AUTHOR]

Aims: To examine the prognostic value of F‐18 fluorodeoxyglucose (FDG) uptake in the bone marrow (BM) for disease recurrence and survival in patients with oropharyngeal squamous cell carcinoma (OP‐SCC). The secondary aims were to evaluate the prognostic value of PET/CT parameters for the primary oropharyngeal tumor and total tumor burden, and to assess the correlation between FDG uptake variables and serum inflammatory markers. Methods: This was an observational study of 91 patients with OP‐SCC who underwent pretreatment FDG‐PET/CT. The patients' blood samples were collected before treatment, and treatment was administered with the intention to cure. The median follow‐up time was 40 months. The PET parameters measured were SUVmeanBM for the assessment of BM FDG uptake, SUVmean, SUVmax, total lesion glycolysis (TLG), and metabolic tumor volume (MTV) for the evaluation of primary oropharyngeal tumor and total tumor burden. Blood samples were analyzed to determine each patient's white cell, red cell, and platelet cell counts, hemoglobin, and C‐reactive protein level. In a subgroup of 33 patients, blood serum was analyzed to evaluate the expression of serum immune proteins using a proximity extension assay (Olink Proteomics). Results: The univariate analysis revealed that SUVmeanBM and tumor‐specific parameters (SUVmaxtumor, SUVmeantotal, SUVmaxtotal, MTVtotal, TLGtotal) were significantly associated with recurrence‐free survival (RFS). After adjusting for age, sex, and stage only SUVmeanBM remained significantly associated with RFS. Spearman's correlation identified several correlations between PET parameters and inflammatory markers. Conclusions: Our results show that several FDG‐PET/CT parameters may have a prognostic value of treatment outcome in patients with OP‐SCC. However, SUVmeanBM was the only independent PET parameter that showed a prognostic value for RFS in the study cohort. Moreover, the study findings might suggest an association between systemic inflammation and the metabolic activity in the BM. [ABSTRACT FROM AUTHOR]

Introduction: HPV vaccination prevents most HPV-related cancers, yet uptake remains low. HPV is linked to an estimated 70% of oropharyngeal cancers (OPCs) in the US and outnumber cases of HPV-related cervical cancers. Not all OPCs can be detected through routine screening, making HPV vaccination a more effective primary prevention strategy. However, bridging primary and oral healthcare faces challenges due to a lack of referral networks between practices. The purpose of this study is to identify key infrastructure elements and policies, as well as HPV prevention strategies, among an academic practice network of dental clinics and partnering community health clinics in a southeastern state. Methods: Researchers held interviews with directors and focus groups with staff at six dental clinics and eight associated community clinics in a southeastern state. Interviews and focus groups at dental and community clinics were analyzed by two study team members using thematic analysis with Nvivo software. Results: A total of 90 participants participated in all focus groups and interviews (N = 14 interviews, 10 focus groups (5–13 participants per focus group). Most participants identified as white (58.9%) and female (70%), with an average age of 38.5 years. Researchers identified nine key study themes: three specific to the dental clinics' HPV conversations with patients, two related to community clinics' vaccine provision, and four involving the relationship between the dental and co-located community clinics. Dental clinic staff do not currently discuss HPV with patients. They are open to discussing HPV with patients but anticipate barriers that require preparation to overcome them. Community clinics have demonstrated previous success with HPV vaccination, but patients over the age of 18 face financial barriers to vaccination. Community clinics and dental clinics report that they do not currently have existing referral networks but are open to a referral system between practices if infrastructure is put into place to support it. Conclusions: Our findings indicate that there is interest in, and potential for, increased discussion of HPV with dental patients and collaboration between dental and community clinics for HPV vaccination referral. The results of this investigation can be used to develop intervention strategies to increase HPV vaccination through referrals between dental clinics and nearby community clinics. Ultimately, this work can reduce health inequities in HPV-related cancers, serve as a model for US dental practices, and possibly influence public health policy. [ABSTRACT FROM AUTHOR]

Background: Head and neck (HN) gross tumor volume (GTV) auto‐segmentation is challenging due to the morphological complexity and low image contrast of targets. Multi‐modality images, including computed tomography (CT) and positron emission tomography (PET), are used in the routine clinic to assist radiation oncologists for accurate GTV delineation. However, the availability of PET imaging may not always be guaranteed. Purpose: To develop a deep learning segmentation framework for automated GTV delineation of HN cancers using a combination of PET/CT images, while addressing the challenge of missing PET data. Methods: Two datasets were included for this study: Dataset I: 524 (training) and 359 (testing) oropharyngeal cancer patients from different institutions with their PET/CT pairs provided by the HECKTOR Challenge; Dataset II: 90 HN patients(testing) from a local institution with their planning CT, PET/CT pairs. To handle potentially missing PET images, a model training strategy named the "Blank Channel" method was implemented. To simulate the absence of a PET image, a blank array with the same dimensions as the CT image was generated to meet the dual‐channel input requirement of the deep learning model. During the model training process, the model was randomly presented with either a real PET/CT pair or a blank/CT pair. This allowed the model to learn the relationship between the CT image and the corresponding GTV delineation based on available modalities. As a result, our model had the ability to handle flexible inputs during prediction, making it suitable for cases where PET images are missing. To evaluate the performance of our proposed model, we trained it using training patients from Dataset I and tested it with Dataset II. We compared our model (Model 1) with two other models which were trained for specific modality segmentations: Model 2 trained with only CT images, and Model 3 trained with real PET/CT pairs. The performance of the models was evaluated using quantitative metrics, including Dice similarity coefficient (DSC), mean surface distance (MSD), and 95% Hausdorff Distance (HD95). In addition, we evaluated our Model 1 and Model 3 using the 359 test cases in Dataset I. Results: Our proposed model(Model 1) achieved promising results for GTV auto‐segmentation using PET/CT images, with the flexibility of missing PET images. Specifically, when assessed with only CT images in Dataset II, Model 1 achieved DSC of 0.56 ± 0.16, MSD of 3.4 ± 2.1 mm, and HD95 of 13.9 ± 7.6 mm. When the PET images were included, the performance of our model was improved to DSC of 0.62 ± 0.14, MSD of 2.8 ± 1.7 mm, and HD95 of 10.5 ± 6.5 mm. These results are comparable to those achieved by Model 2 and Model 3, illustrating Model 1′s effectiveness in utilizing flexible input modalities. Further analysis using the test dataset from Dataset I showed that Model 1 achieved an average DSC of 0.77, surpassing the overall average DSC of 0.72 among all participants in the HECKTOR Challenge. Conclusions: We successfully refined a multi‐modal segmentation tool for accurate GTV delineation for HN cancer. Our method addressed the issue of missing PET images by allowing flexible data input, thereby providing a practical solution for clinical settings where access to PET imaging may be limited. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) vaccine is an underutilized tool in cancer prevention. HPV vaccine completion rates in adolescents age 13 to 15 years remain low at 59%. The HPV vaccine can prevent more than 90% of cases of cancer caused by HPV, including cervical, oropharyngeal, anal, penile, vulvar, and vaginal. HPV vaccine is very safe and effective, as demonstrated by numerous large-scale studies. Practice-based strategies can improve vaccination rates, such as having providers give a strong presumptive recommendation for the vaccine, using motivational interviewing for hesitant families, and using electronic health record reminders to prompt providers to offer it, among other interventions. Offering HPV vaccine starting at age 9 years is another evidence-based strategy to improve HPV vaccine completion rates, which has been shown to be acceptable to both providers and parents. [Pediatr Ann. 2024;53(10):e372–e377.] [ABSTRACT FROM AUTHOR]

Background: High-risk human papillomaviruses are the causal agents of a subset of head and neck cancers. A previous transcriptomic analysis showed that cIAP2 protein, involved in cell survival and apoptosis, is upregulated in OKF6 oral cells that express HPV16 E6/E7. In addition, cIAP2 promotes radioresistance, a very important concern in HNC treatment. However, cIAP2 increase has not yet been evaluated in oropharyngeal carcinomas (OPCs), nor has been the role of cIAP2 in HNC radioresistance. Methods: We carried out a descriptive-analytical retrospective study in 49 OPCs from Chilean patients. We determined the expression of cIAP2 at transcript and proteins levels using reverse-transcriptase -polymerase chain reaction and immunohistochemistry, respectively. HPV and p16 expression were previously analyzed in these specimens. In addition, SCC-143 HNC cells ectopically expressing HPV16 E6/E7 were analyzed for cIAP2 expression and after transfection with a siRNA for HPV16 E6/E7 knocking down. Results: We found a statistically significant association between HPV presence and cIAP2 expression (p = 0.0032 and p = 0.0061, respectively). An association between p16 and cIAP2 levels was also found (p = 0.038). When SCC-143 cells were transfected with a construct expressing HPV16 E6/E7, the levels of cIAP2 were significantly increased (p = 0.0383 and p = 0.0115, respectively). Conversely, HPV16 E6 and E7 knocking down resulted in a decrease of cIAP2 levels (p = 0.0161 and p = 0.006, respectively). Finally, cIAP2 knocking down in HPV16 E6/E7 cells resulted in increased apoptosis after exposure to radiation at 4 and 8 Gy (p = 0.0187 and p = 0.0061, respectively). Conclusion: This study demonstrated for the first time a positive relationship between HPV presence and cIAP2 levels in OPCs. Additionally, cIAP2 knocking down sensitizes HNC cells to apoptosis promoted by radiation. Therefore, cIAP2 is a potential therapeutic target for radiation in HPV-driven HNC. [ABSTRACT FROM AUTHOR]