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ObjectivesWe characterize functional outcomes in head and neck cancer of unknown primary (CUP) based on primary site identification.MethodsIn this retrospective study, CUP cases were categorized as known primaries (KP) if a tumor was localized after diagnostic workup or persisting unknown primaries (UP). Age, sex, HPV status, diagnostic methods, and treatments regimens were collected. Pretreatment and short-term posttreatment (3-6 months after completion of treatment) weights, PHQ-9, Eating Assessment Tool (EAT-10), and Voice Handicap Index (VHI-10) scores were compared between UP and KP.ResultsAmong 67 CUP patients, 35 (52.2%) had identified primaries (91.4% oropharyngeal and 8.6% nasopharyngeal). KP patients were younger (58 vs. 64, p = 0.04) and more likely to be HPV-positive (88.6% vs. 50%, p = 0.002). Overall detection rates were 16.7% for PET/CT, 34.7% for direct laryngoscopy, and 46.6% for transoral robotic oropharyngectomy. Diagnostic workup was not significantly different between groups. Patients with KP received smaller intermediate radiation dose volumes (436.5 vs. 278.9 cc, p = 0.03) and lower doses to the cricopharyngeal muscle (41.6 vs. 24.6 Gy, p = 0.03).Pretreatment weights, PHQ-9, EAT-10, and VHI-10 scores did not differ between groups. However, posttreatment, UP had greater relative weight loss (-14.1% vs. -7.6%, p = 0.032), higher EAT-10 scores (12.5 vs. 3, p = 0.004), and higher PHQ-9 scores (6 vs. 1.4, p = 0.017). Specifically, UP reported more stressful swallowing, difficulty swallowing solids and pills, and swallowing affecting public eating.ConclusionKP patients experienced less weight loss, depression, and reduced swallowing dysfunction, highlighting an early functional benefit of primary tumor identification likely driven by reduced radiation treatment volumes.Level of evidence4 Laryngoscope, 134:701-707, 2024.

INTRODUCTION: Most patients with HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) have an excellent response to chemoradiation, and trials are now investigating de-escalated treatment. However, up to 25% of patients with HPV-positive OPSCC will experience recurrence, and up to 5% will even progress through primary treatment. Currently, there are no molecular markers to identify patients with poor prognosis who would be harmed by de-escalation. Herein we report the clinical and genomic characteristics of persistent HPV-positive OPSCC after definitive platinum-based chemoradiation therapy. METHODS: Patients with HPV-positive OPSCC treated with curative intent platinum-based chemoradiation between 2007 and 2017 at two institutions and with a persistent locoregional disease were included. We evaluated clinical characteristics, including smoking status, age, stage, treatment, and overall survival. A subset of five patients had tissue available for targeted exome DNA sequencing and RNA sequencing. Genomic analysis was compared to a previously published cohort of 47 treatment-responsive HPV+ OPSCC tumors after batch correction. Mutational landscape, pathway activation, and OncoGPS tumor states were employed to characterize these tumors. RESULTS: Ten patients met the inclusion criteria. The tumor and nodal stages ranged from T1 to T4 and N1 to N2 by AJCC 8th edition staging. All patients were p16-positive by immunohistochemistry, and eight with available in situ hybridization were confirmed to be HPV-positive. The 1-year overall survival from the time of diagnosis was 57%, and the 2-year overall survival was 17%. TP53 mutations were present in three of five (60%) persistent tumors compared to 2% (one of 47) of treatment-responsive HPV-positive tumors (p = 0.008). Other genes with recurrent mutations in persistent HPV-positive OPSCC tumors were NF1, KMT2D, PIK3C2B, and TFGBR2. Compared to treatment-responsive HPV-positive tumors, persistent tumors demonstrated activation of DNA Repair and p53, EMT, MYC, SRC, and TGF-beta signaling pathways, with post-treatment samples demonstrating significant activation of the PI3K-EMT-Stem pathways compared to pretreatment samples. CONCLUSION: Chemoradiation-resistant HPV-positive OPSCC occurs infrequently but portends a poor prognosis. These tumors demonstrate higher rates of p53 mutation and activation of MYC, SRC, and TGF-beta pathways. A comparison of tumors before and after treatment demonstrates PI3K-EMT-Stem pathways post-treatment in HPV-positive tumors with persistent disease after platinum-based chemoradiation.

Background: Human papillomavirus (HPV) infection has become an important etiological driver of oropharyngeal squamous cell carcinoma (OPSCC), leading to unique tumor characteristics. However, the interplay between HPV-associated tumor cells and tumor microenvironment (TME) remains an enigma. Methods: We performed a single-cell RNA-sequencing (scRNA-seq) on HPV-positive (HPV+) and HPV-negative (HPV‒) OPSCC tumors, each for three samples, and one normal tonsil tissue. Ex vivo validation assays including immunofluorescence staining, cell line co-culture, and flow cytometry analysis were used to test specific subtypes of HPV+ tumor cells and their communications with T cells. Results: Through a comprehensive single-cell transcriptome analysis, we uncover the distinct transcriptional signatures between HPV+ and HPV‒ OPSCC. Specifically, HPV+ OPSCC tumor cells manifest an enhanced interferon response and elevated expression of the major histocompatibility complex II (MHC-II), potentially bolstering tumor recognition and immune response. Furthermore, we identify a CXCL13+CD4+ T cell subset that exhibits dual features of both follicular and pro-inflammatory helper T cells. Noteworthily, HPV+ OPSCC tumor cells embrace extensive intercellular communications with CXCL13+CD4+ T cells. Interaction with HPV+ OPSCC tumor cells amplifies CXCL13 and IFNγ release in CD4+T cells, fostering a pro-inflammatory TME. Additionally, HPV+ tumor cells expressing high MHC-II and CXCL13+CD4+ T cell prevalence are indicative of favorable overall survival rates in OPSCC patients. Conclusions: Together, our study underscores a synergistic inflammatory immune response orchestrated by highly immunogenic tumor cells and CXCL13+CD4+ T cells in HPV+ OPSCC, offering useful insights into strategy development for patient stratification and effective immunotherapy in OPSCC. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) infection is a causative factor in the occurrence and progression of oropharyngeal squamous cell carcinoma (OPSCC). In recent years, clinical studies have found that HPV‐positive OPSCC patients may present a better prognosis than HPV‐negative patients, yet the underlying causes are unclear. This study aimed to investigate the relevance of HPV infection and the prognosis of OPSCC. On this basis, we aimed to establish a prediction model to accurately predict the prognosis and guide clinical practice. We analysed the records of 233 patients with OPSCC. Cox regression was applied to identify factors associated with survival. Moreover, variables with significant discrepancies were integrated into a nomogram model to predict prognosis. The results showed that HPV was an independent prognostic factor for OS and PFS. Immunoglobulin Heavy Constant Mu (IGHM) mRNA was significantly upregulated in patients with HPV‐positive OPSCC. Crucially, IGHM expression was associated with better prognosis. The receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis both confirmed that the prognostic model exhibits good performance. In summary, HPV infection were independent prognostic factors for OPSCC. IGHM may be the key contributors to the prognostic differences in HPV‐associated OPSCC. This nomogram model was able to accurately predict the prognosis of patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Oropharyngeal Squamous Cell Carcinoma (OPSCC) represents a significant fraction of head and neck cancers, with a challenging five-year survival rate of only 50%. Key risk factors include tobacco and alcohol consumption and infection with human papillomavirus (HPV), particularly HPV16. Distinct biological differences exist between HPV-positive and HPV-negative OPSCC, including differences in mutation patterns and gene expression profiles. This study focuses on aldo-keto reductases (AKRs), specifically AKR1C2, which are involved in cellular stress management and detoxification processes, particularly in cisplatin-resistant tumors. This study investigates the role of AKR1C2 in HPV-positive OPSCC and its effect on patient outcomes. The findings indicate that increased levels of AKR1C2 are linked to unfavorable prognosis, particularly in male patients, while higher levels in female patients indicate a favorable prognosis. Head and Neck Squamous Cell Carcinoma (HNSCC), particularly Oropharyngeal Squamous Cell Carcinoma (OPSCC), is a major global health challenge due to its increasing incidence and high mortality rate. This study investigates the role of aldo-keto reductase 1C2 (AKR1C2) in OPSCC, focusing on its expression, correlation with Human Papillomavirus (HPV) status, oxidative stress status, and clinical outcomes, with an emphasis on sex-specific differences. We analyzed AKR1C2 expression using immunohistochemistry in formalin-fixed, paraffin-embedded tissue samples from 51 OPSCC patients. Additionally, we performed RT-qPCR in cultured HPV16-E6*I and HPV16-E6 overexpressing HEK293 cell lines (p53WT). Statistical analyses were performed to assess the correlation between AKR1C2 expression and patient data. Our results indicate a significant association between increased AKR1C2 expression and higher AJCC classification (p = 0.009) as well as positive HPV status (p = 0.008). Prognostic implications of AKR1C2 varied by sex, whereby female patients with high AKR1C2 expression had better overall survival, whereas male patients exhibited poorer outcomes. Additionally, AKR1C2 expression was linked to HPV status, suggesting a potential HPV-specific regulatory mechanism. These findings underscore the complex interplay among AKR1C2, HPV, and patient sex, highlighting the need for personalized treatment strategies for OPSCC. Targeted inhibition of AKR1C2, considering sex-specific differences, may enhance therapeutic outcomes. Future research should investigate these mechanisms to enhance treatment efficacy. [ABSTRACT FROM AUTHOR]

Background: First aim was to compare ddPCR assays of ctHPVDNA with p16 IHC and qualitative HPV PCR. Second aim was to carry out longitudinal blood sampling to test for association of ctHPVDNA with histological confirmed recurrence. Third aim was to perform a multidimensional assessment which included: (1) clinical features; (2) ctHPVDNA; (3) MRI‐based tumor size measurements of primary tumor (PT) and cervical lymph node metastases (CLNM). Methods: Plasma samples were collected before treatment and during follow‐up, and ddPCR assay comprising E6 of HPV16 and HPV 33 and HPV 35 was used. Results: Present study was conducted at diagnosis in 117 patients and revealed a ctHPVDNA sensitivity of 100% (95% CI 95.5–100) and a specificity of 94.4 (95% CI 81.3–99.3), positive predictive value (PPV) of 94.4 (95% CI 81.3–99.3), and negative predictive value (NPP) of 100% (95% CI 89.7–100). During follow‐up ctHPVDNA had a sensitivity of 100% (95% CI 72.1–100)% and specificity of 98.4% (95% CI 91.7–100)%, PPV% of 90.9% (95% CI 62.3–98.4) and NPV% of 100% (95% CI 94.3–100) for ability to detect recurrence. Correlation between both the CLNM volume and the sum of PT and CLNM volume was observed. Conclusions: ctHPVDNA was superior to p16 in identification of HPV‐OPSCC at diagnosis. Introduction of ctHPVDNA, beyond diagnostic setting, represents a great opportunity to improve follow‐up protocol of OPSCC patients. [ABSTRACT FROM AUTHOR]

Objective: As the majority of oropharyngeal squamous cell carcinoma (OPSCC) is diagnosed in males, outcomes among females are not well‐characterized. We identify sex‐specific factors in OPSCC to refine female prognostication. Study Design: Retrospective cohort. Setting: National Cancer Database (NCDB). Methods: OPSCC cases from the 2004 to 2019 NCDB were identified. Sociodemographic, clinical, and treatment characteristics (including timing between diagnosis and treatment administration) were compared between sexes. Multivariable Cox proportional hazard regression models were constructed to characterize survival in overall and female‐only cohorts. Similar multivariable binomial logistic regression and survival models were constructed to assess odds of treatment delays and their effects on survival, respectively. Results: A total of 192,973 OPSCC patients were identified; 36,695 (19%) were female. Females had more human papillomavirus (HPV) negative, lower clinical T and N stage, and higher comorbidity disease. Females experienced lower survival in HPV negative (hazard ratio, HR = 1.11, P <.001) but not HPV‐positive disease. Females were more likely to have any treatment initiated over the median of 28 days (odds ratio, OR = 1.04, P =.014) or delays in adjuvant radiotherapy initiation over 6 weeks (OR = 1.11, P =.032). Treatment delay over 60 days (HR = 1.17, P =.016) and delay in adjuvant therapy initiation (HR = 1.24, P =.02) were associated with worse survival among females. Conclusion: In one of the largest analyses of OPSCC, females had poorer survival than males, specifically in HPV‐negative disease, despite presentation with less advanced disease. Notably, delays in any treatment initiation and adjuvant radiotherapy initiation were more likely in HPV‐negative women and associated with worse survival, highlighting potential systemic weaknesses contributing to poor prognosis among females. [ABSTRACT FROM AUTHOR]

Background: Human papilloma virus (HPV) related cancers of the oropharynx are rapidly increasing in incidence and may soon represent the majority of all head and neck cancers. Improved monitoring and surveillance methods are thus an urgent need in public health. Main text: The goal is to highlight the current potential and limitations of liquid biopsy through a meta analytic study on ctHPVDNA and TTMV-HPVDNA. It was performed a Literature search on articles published until December 2023 using three different databases: MEDLINE, Embase, and Cochrane Library. Studies that evaluated post-treatment ctHPVDNA and TTMV-HPVDNA in patients with HPV + OPSCC, studies reporting complete data on the diagnostic accuracy in recurrence, or in which the number of true positives, false positives, true negatives, and false negatives was extractable, and methods of detection of viral DNA clearly defined. The meta-analysis was conducted following the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) reporting guidelines. The aim of this meta-analysis was to evaluate the sensitivity, specificity, and accuracy of ctHPVDNA and TTMV by ddPCR to define its efficacy in clinical setting for the follow up of HPV-OPSCC. Conclusion: The 12 studies included in the meta-analysis provided a total of 1311 patients for the analysis (398 valuated with ctHPVDNA and 913 with TTMV-HPVDNA). Pooled sensitivity and specificity were 86% (95% CI: 78%-91%) and 96% (95% CI: 91%-99%), respectively; negative and positive likelihood ratios were 0.072 (95% CI: 0.057–0.093) and 24.7 (95% CI: 6.5–93.2), respectively; pooled DOR was 371.66 (95% CI: 179.1–918). The area under the curve (AUC) was 0.81 (95% CI, 0.67–0.91). Liquid biopsy for the identification of cell free DNA might identify earlier recurrence in HPV + OPSCC patients. At the present time, liquid biopsy protocol needs to be standardized and liquid biopsy cannot yet be used in clinical setting. In the future, a multidimensional integrated approach which links multiple clinical, radiological, and laboratory data will contribute to obtain the best follow-up strategies for the follow-up of HPV-OPSCC. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC), particularly oropharyngeal squamous cell carcinoma (OPSCC), is an increasingly prevalent pathology worldwide, especially in developed countries. For diagnosing HPV in HNSCC, the combination of p16 immunohistochemistry (IHC) and polymerase chain reaction (PCR) offers high sensitivity and specificity, with p16 IHC being a reliable initial screen and PCR confirming HPV presence. Advanced techniques like next-generation sequencing (NGS) and RNA-based assays provide detailed insights but are primarily used in research settings. Regardless of HPV status, standard oncological treatments currently include surgery, radiation, and/or chemotherapy. This conventional approach does not account for the typically better prognosis of HPV-positive HNSCC patients, leading to increased chemo/radiation-induced secondary morbidities and reduced quality of life. Therefore, it is crucial to identify and detect HPV positivity and other molecular characteristics of HNSCC to personalize treatment strategies. This comprehensive review aims to summarize current knowledge on various HPV detection techniques and evaluate their advantages and disadvantages, with a focus on developing methodologies to identify new biomarkers in HPV-positive HNSCC. The review discusses direct and indirect HPV examination in tumor tissue, DNA- and RNA-based detection techniques, protein-based markers, liquid biopsy potentials, immune-related markers, epigenetic markers, novel biomarkers, and emerging technologies, providing an overall insight into the current state of knowledge. [ABSTRACT FROM AUTHOR]

Abstract Background Human papilloma virus (HPV) related cancers of the oropharynx are rapidly increasing in incidence and may soon represent the majority of all head and neck cancers. Improved monitoring and surveillance methods are thus an urgent need in public health. Main text The goal is to highlight the current potential and limitations of liquid biopsy through a meta analytic study on ctHPVDNA and TTMV-HPVDNA. It was performed a Literature search on articles published until December 2023 using three different databases: MEDLINE, Embase, and Cochrane Library. Studies that evaluated post-treatment ctHPVDNA and TTMV-HPVDNA in patients with HPV + OPSCC, studies reporting complete data on the diagnostic accuracy in recurrence, or in which the number of true positives, false positives, true negatives, and false negatives was extractable, and methods of detection of viral DNA clearly defined. The meta-analysis was conducted following the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) reporting guidelines. The aim of this meta-analysis was to evaluate the sensitivity, specificity, and accuracy of ctHPVDNA and TTMV by ddPCR to define its efficacy in clinical setting for the follow up of HPV-OPSCC. Conclusion The 12 studies included in the meta-analysis provided a total of 1311 patients for the analysis (398 valuated with ctHPVDNA and 913 with TTMV-HPVDNA). Pooled sensitivity and specificity were 86% (95% CI: 78%-91%) and 96% (95% CI: 91%-99%), respectively; negative and positive likelihood ratios were 0.072 (95% CI: 0.057–0.093) and 24.7 (95% CI: 6.5–93.2), respectively; pooled DOR was 371.66 (95% CI: 179.1–918). The area under the curve (AUC) was 0.81 (95% CI, 0.67–0.91). Liquid biopsy for the identification of cell free DNA might identify earlier recurrence in HPV + OPSCC patients. At the present time, liquid biopsy protocol needs to be standardized and liquid biopsy cannot yet be used in clinical setting. In the future, a multidimensional integrated approach which links multiple clinical, radiological, and laboratory data will contribute to obtain the best follow-up strategies for the follow-up of HPV-OPSCC.

Human papilloma virus (HPV), primarily type 16 (less commonly type 18), is associated with oropharyngeal squamous cell carcinoma (OPSCC). According to literature data, between 25 and 70 % of all cases of this cancer are linked to HPV infection. In the USA and some countries of the European Union, HPV-associated OPSCC comprises 60-70 % of all cases of head and neck squamous cell carcinoma. HPV-associated OPSCC is characterized by more favorable prognosis and higher survival compared to HPV-negative OPSCC. These types of this pathology are differently characterized in the 8th edition Tumor, Nodus and Metastasis (TNM). Significant differences in survival and disease prognosis led to studies aimed at deintensification of standard OPSCC treatment to minimize adverse events without the loss of effectiveness. Despite more favorable clinical progression, in 15 % of patients with HPV-associated OPSCC even after standard therapy recurrences and/or regional/distant metastases are observed which lead to unfavorable prognosis. Modern treatment schemes for recurrent/metastatic head and neck squamous cell carcinoma include immunotherapy, results of which also depend on HPV-status of the tumor. While clinical trials studying effectiveness of immune drugs include patients with HPV-positive tumors, data on treatment outcomes are contradictory, and molecular mechanisms of HPV effect on the immune response are not fully understood.The article summarizes the data on the effect of positive HPV status on the effectiveness of immunotherapy in patients with progressing/metastatic head and neck squamous cell carcinoma.

Abstract Background The proportional trends of HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) according to various factors have not been analyzed in detail in previous studies. We aimed to evaluate the trends of HPV-associated OPSCC in the United States. Methods This retrospective cohort study included 13,081 patients with OPSCC from large population-based data using Surveillance, Epidemiology, and End Results (SEER) 2010–2017 database, 17 Registries. Patients were diagnosed with OPSCC primarily in the base of tongue (BOT), posterior pharyngeal wall (PPW), soft palate (SP), and tonsil and were tested for HPV infection status. We analyzed how the proportional trends of patients with OPSCC changed according to various demographic factors. Additionally, we forecasted and confirmed the trend of HPV (+) and (−) patients with OPSCC using the autoregressive integrated moving average (ARIMA) model. Results The proportion of patients who performed the HPV testing increased every year, and it has exceeded 50% since 2014 (21.95% and 51.37% at 2010 and 2014, respectively). The HPV-positive rates tended to increase over past 7 years (66.37% and 79.32% at 2010 and 2016, respectively). Positivity rates of HPV were significantly higher in OPSCC located in the tonsil or BOT than in those located in PPW or SP. The ARIMA (2,1,0) and (0,1,0) models were applied to forecast HPV (+) and (−) patients with OPSCC, respectively, and the predicted data generally matched the actual data well. Conclusion This large population-based study suggests that the proportional trends of HPV (+) patients with OPSCC has increased and will continue to increase. However, the trends of HPV (+) and (−) patients differed greatly according to various demographic factors. These results present a direction for establishing appropriate preventive measures to deal with HPV-related OPSCC in more detail.

Abstract Background Despite the better prognosis associated with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), some patients experience relapse and succumb to the disease; thus, there is a need for biomarkers identifying these patients for intensified treatment. Leucine-rich repeats and immunoglobulin-like domain (LRIG) protein 1 is a negative regulator of receptor tyrosine kinase signaling and a positive prognostic factor in OPSCC. Studies indicate that LRIG1 interacts with the LIM domain 7 protein (LMO7), a stabilizer of adherence junctions. Its role in OPSCC has not been studied before. Methods A total of 145 patients diagnosed with OPSCC were enrolled. Immunohistochemical LMO7 expression and staining intensity were evaluated in the tumors and correlated with known clinical and pathological prognostic factors, such as HPV status and LRIG1, CD44, Ki67, and p53 expression. Results Our results show that high LMO7 expression is associated with significantly longer overall survival (OS) (p = 0.044). LMO7 was a positive prognostic factor for OS in univariate analysis (HR 0.515, 95% CI: 0.267–0.994, p = 0.048) but not in multivariate analysis. The LMO7 expression correlated with LRIG1 expression (p = 0.048), consistent with previous findings. Interestingly, strong LRIG1 staining intensity was an independent negative prognostic factor in the HPV-driven group of tumors (HR 2.847, 95% Cl: 1.036–7.825, p = 0.043). Conclusions We show for the first time that high LMO7 expression is a positive prognostic factor in OPSCC, and we propose that LMO7 should be further explored as a biomarker. In contrast to previous reports, LRIG1 expression was shown to be an independent negative prognostic factor in HPV-driven OPSCC.

Abstract Several studies have emphasised how positive and negative human papillomavirus (HPV+ and HPV−, respectively) oropharyngeal squamous cell carcinoma (OPSCC) has distinct molecular profiles, tumor characteristics, and disease outcomes. Different radiomics-based prediction models have been proposed, by also using innovative techniques such as Convolutional Neural Networks (CNNs). Although some of these models reached encouraging predictive performances, there evidence explaining the role of radiomic features in achieving a specific outcome is scarce. In this paper, we propose some preliminary results related to an explainable CNN-based model to predict HPV status in OPSCC patients. We extracted the Gross Tumor Volume (GTV) of pre-treatment CT images related to 499 patients (356 HPV+ and 143 HPV−) included into the OPC-Radiomics public dataset to train an end-to-end Inception-V3 CNN architecture. We also collected a multicentric dataset consisting of 92 patients (43 HPV+ , 49 HPV−), which was employed as an independent test set. Finally, we applied Gradient-weighted Class Activation Mapping (Grad-CAM) technique to highlight the most informative areas with respect to the predicted outcome. The proposed model reached an AUC value of 73.50% on the independent test. As a result of the Grad-CAM algorithm, the most informative areas related to the correctly classified HPV+ patients were located into the intratumoral area. Conversely, the most important areas referred to the tumor edges. Finally, since the proposed model provided additional information with respect to the accuracy of the classification given by the visualization of the areas of greatest interest for predictive purposes for each case examined, it could contribute to increase confidence in using computer-based predictive models in the actual clinical practice.

Background. Oropharyngeal squamous cell carcinoma (OPSCC) is characterized by late-stage diagnosis and high rate of mortality. Combined modality treatment including preoperative chemoradiotherapy (CRT) is the standard of care for OPSCC. The search for criteria for predicting the efficacy of preoperative chemoradiotherapy with a view to prescribe it to those patients for whom it is really indicated and will be effective remains challenging. The aim of the study was to identify serum actin-binding proteins that can predict preoperative therapy efficacy in patients with OPSCC. Material and methods. Blood serum from 45 patients with stage II–IV OPSCC was studied. all patients received preoperative chemotherapy with paclitaxel and carboplatin. Radiation therapy in a standard mode was given 2 weeks after chemothetapy. serum levels of actin-binding proteins (CAP1, fascin, ezrin, gelsolin, and profiling) were determined before treatment using ELISA. Results. complete or partial response to preoperative CRT was achieved in 27 patients. Disease progression or stabilization was observed in 18 patients. A comparison of the serum levels of actin-binding proteins before treatment with those obtained after preoperative CRT showed that the serum level of ezrin was lower in patients who did not respond to preoperative CRT than in patients with partial or complete response to therapy. ROC-analysis showed that the serum level of ezrin of less than 2.50 ng/ml can predict the tumor response to CRT as unfavorable (less than 75 % according to the RECIST scale). The sensitivity was 72 % and the specificity was 71 %. Conclusion. Determination of the serum level of ezrin in patients with OPSCC has a predictive value in relation to preoperative chemoradiotherapy.

Objective: This study evaluated the significance of positron emission tomography/computed tomography (PET/CT) in detecting recurrences or other primary malignancies in patients treated for oro- and hypopharyngeal squamous cell carcinoma. Method: A retrospective analysis of the follow up of 132 patients was performed and 370 PET/CT scans were assessed for their accuracy. Results: All asymptomatic clinical occult recurrences were detected by PET/CT and accounted for 28 per cent of recurrences. Asymptomatic patients with metastases detected by PET/CT had a significant survival benefit compared to patients diagnosed in a symptomatic stage. For locoregional recurrence, no significant difference in overall survival could be demonstrated. In total, 33 primary malignancies were discovered, of which 48 per cent were first detected by PET/CT. The specificity and negative predictive value of the PET/CT scans had ranges of 85–100 and 83–100 per cent, respectively. Conclusion: The role of PET/CT scans in detecting primary malignancies, clinical occult recurrences and especially asymptomatic metastases was observed. [ABSTRACT FROM AUTHOR]

Background: The proportional trends of HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) according to various factors have not been analyzed in detail in previous studies. We aimed to evaluate the trends of HPV-associated OPSCC in the United States. Methods: This retrospective cohort study included 13,081 patients with OPSCC from large population-based data using Surveillance, Epidemiology, and End Results (SEER) 2010–2017 database, 17 Registries. Patients were diagnosed with OPSCC primarily in the base of tongue (BOT), posterior pharyngeal wall (PPW), soft palate (SP), and tonsil and were tested for HPV infection status. We analyzed how the proportional trends of patients with OPSCC changed according to various demographic factors. Additionally, we forecasted and confirmed the trend of HPV (+) and (−) patients with OPSCC using the autoregressive integrated moving average (ARIMA) model. Results: The proportion of patients who performed the HPV testing increased every year, and it has exceeded 50% since 2014 (21.95% and 51.37% at 2010 and 2014, respectively). The HPV-positive rates tended to increase over past 7 years (66.37% and 79.32% at 2010 and 2016, respectively). Positivity rates of HPV were significantly higher in OPSCC located in the tonsil or BOT than in those located in PPW or SP. The ARIMA (2,1,0) and (0,1,0) models were applied to forecast HPV (+) and (−) patients with OPSCC, respectively, and the predicted data generally matched the actual data well. Conclusion: This large population-based study suggests that the proportional trends of HPV (+) patients with OPSCC has increased and will continue to increase. However, the trends of HPV (+) and (−) patients differed greatly according to various demographic factors. These results present a direction for establishing appropriate preventive measures to deal with HPV-related OPSCC in more detail. [ABSTRACT FROM AUTHOR]

Background: Despite the better prognosis associated with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), some patients experience relapse and succumb to the disease; thus, there is a need for biomarkers identifying these patients for intensified treatment. Leucine-rich repeats and immunoglobulin-like domain (LRIG) protein 1 is a negative regulator of receptor tyrosine kinase signaling and a positive prognostic factor in OPSCC. Studies indicate that LRIG1 interacts with the LIM domain 7 protein (LMO7), a stabilizer of adherence junctions. Its role in OPSCC has not been studied before. Methods: A total of 145 patients diagnosed with OPSCC were enrolled. Immunohistochemical LMO7 expression and staining intensity were evaluated in the tumors and correlated with known clinical and pathological prognostic factors, such as HPV status and LRIG1, CD44, Ki67, and p53 expression. Results: Our results show that high LMO7 expression is associated with significantly longer overall survival (OS) (p = 0.044). LMO7 was a positive prognostic factor for OS in univariate analysis (HR 0.515, 95% CI: 0.267–0.994, p = 0.048) but not in multivariate analysis. The LMO7 expression correlated with LRIG1 expression (p = 0.048), consistent with previous findings. Interestingly, strong LRIG1 staining intensity was an independent negative prognostic factor in the HPV-driven group of tumors (HR 2.847, 95% Cl: 1.036–7.825, p = 0.043). Conclusions: We show for the first time that high LMO7 expression is a positive prognostic factor in OPSCC, and we propose that LMO7 should be further explored as a biomarker. In contrast to previous reports, LRIG1 expression was shown to be an independent negative prognostic factor in HPV-driven OPSCC. [ABSTRACT FROM AUTHOR]

Objectives In this feasibility study, we explored the combined use of circulating tumor human papillomavirus (HPV) DNA (ctHPVDNA) and HPV serology as diagnostic tests for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Methods Among patients with research-banked serum or plasma at diagnosis, IgG antibodies to oncoproteins from HPV types 16, 18, 31, 33, 35, 45, 52, and 58 were detected with multiplex serology. Positivity for HPV 16 was defined based on detection of combinations of anti-E6, E1, E2, and E7 and for other high-risk types on detection of anti-E6 and anti-E7. Circulating tumor HPV DNA was detected by custom digital droplet polymerase chain reaction (ddPCR) assays for HPV types 16, 18, 33, 35, and 45. p16 immunohistochemistry and high-risk HPV RNA in situ hybridization (ISH) using a cocktail of 18 high-risk HPV types were performed on tissue. Results Of 75 patients, 67 (89.3%) were HPV-associated (p16 and HPV RNA ISH positive) and 8 (10.7%) were HPV-independent. All 8 HPV-independent patients were seronegative and negative for ctHPVDNA (100% specificity). Serology was positive in 53 (79.1%) of 67 HPV-associated patients, while ddPCR was positive for ctHPVDNA in 59 (88.6%) of 67 HPV-associated patients. Requiring both tests to be positive resulted in a sensitivity of 50 (74.6%) of 67 while combining assays (either positive) improved sensitivity to 62 (92.6%) of 67. Conclusions Compared to HPV RNA ISH, HPV serology and ctHPVDNA are sensitive and highly specific biomarkers for HPV-associated OPSCC at the time of presentation. [ABSTRACT FROM AUTHOR]

Simple Summary: Human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) has a different disease course compared to HPV-negative (HPV−) OPSCC. This systematic review aims to investigate whether magnetic resonance imaging (MRI) can discriminate between HPV+ and HPV− OPSCC or predict HPV status in OPSCC patients using MRI. Our results show that parameters derived from structural MRI and diffusion-weighted MRI are able to discriminate between HPV+ and HPV− cases and predict HPV status with reasonable accuracy. Other MRI sequences have yet to prove their added value for the discrimination and prediction of HPV status in OPSCC patients. Machine learning studies that compared predictive models with and without clinical variables found that performance improved significantly when clinical variables were included in the model. Before the clinical implementation of MRI for HPV status determination, larger studies with external model validation using independent datasets are needed. Human papillomavirus (HPV) is an important risk factor for oropharyngeal squamous cell carcinoma (OPSCC). HPV-positive (HPV+) cases are associated with a different pathophysiology, microstructure, and prognosis compared to HPV-negative (HPV−) cases. This review aimed to investigate the potential of magnetic resonance imaging (MRI) to discriminate between HPV+ and HPV− tumours and predict HPV status in OPSCC patients. A systematic literature search was performed on 15 December 2022 on EMBASE, MEDLINE ALL, Web of Science, and Cochrane according to PRISMA guidelines. Twenty-eight studies (n = 2634 patients) were included. Five, nineteen, and seven studies investigated structural MRI (e.g., T1, T2-weighted), diffusion-weighted MRI, and other sequences, respectively. Three out of four studies found that HPV+ tumours were significantly smaller in size, and their lymph node metastases were more cystic in structure than HPV− ones. Eleven out of thirteen studies found that the mean apparent diffusion coefficient was significantly higher in HPV− than HPV+ primary tumours. Other sequences need further investigation. Fourteen studies used MRI to predict HPV status using clinical, radiological, and radiomics features. The reported areas under the curve (AUC) values ranged between 0.697 and 0.944. MRI can potentially be used to find differences between HPV+ and HPV− OPSCC patients and predict HPV status with reasonable accuracy. Larger studies with external model validation using independent datasets are needed before clinical implementation. [ABSTRACT FROM AUTHOR]

Background: Patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with radiation-based therapy suffer from short- and long-term toxicities that affect quality of life (QOL). Transoral robotic surgery (TORS) has an established role in the management of early OPSCC but adjuvant treatment is often indicated postoperatively due to the high incidence of nodal metastasis associated with advanced human papillomavirus (HPV)-related OPSCC. To overcome the need for adjuvant radiation therapy (RT), neoadjuvant chemotherapy followed by TORS and neck dissection (ND) is proposed. This study aimed to assess if QOL in HPV-associated OPSCC receiving neoadjuvant chemotherapy followed by TORS and ND returns to baseline within 12 months of completing treatment. Methods: A 12 month longitudinal study was carried out at McGill University Health Centre in Montreal, Canada, among a convenience sample of patients with American Joint Committee on Cancer Seventh Edition stage III and IVa HPV-related OPSCC who were treated with neoadjuvant chemotherapy followed by TORS and ND. QOL data were obtained pretreatment and at 1, 3, 6, and 12 months following treatment completion using the European Organisation for Research and Treatment of Cancer Core and Head and Neck extension modules. Paired t tests and mixed models for repeated measures analysis were used to assess changes in QOL from baseline to 12 months postoperatively and over time, respectively. Results: Nineteen of 23 patients (median age 58 years) who received the study treatment fulfilled the eligibility criteria. OPSCC subsites were palatine tonsil (n = 12) and base of tongue (n = 7). All 19 patients were treated per protocol and none required adjuvant RT as per pathology review and protocol requirements at a postoperative multidisciplinary team tumor board discussion. No significant differences were found when comparing 12 month QOL follow-up scores to pretreatment scores in measures that would likely be affected by RT [eg, swallowing (P =.7), social eating (P =.8), xerostomia (P =.9)]. Conclusion: In HPV-related OPSCC, neoadjuvant chemotherapy followed by TORS and ND as definitive treatment is associated with excellent QOL outcomes. Postoperative QOL scores returned to baseline by 3 months and were maintained for all measures, indicating a return to normal function. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) is associated with both benign and malignant disorders, such as genital warts and a variety of cancers, including oropharyngeal squamous cell carcinomas (OPSCCs). The current 9-valent HPV vaccine (Gardasil 9) protects against high-risk strains that have been shown to cause OPSCC, and widespread vaccination should reduce the rate of all HPV-associated cancers. HPV-related OPSCCs differ from non-HPV-related OPSCCs in their clinical presentations and responsiveness to treatment. To provide oral healthcare providers with a basis for effective communication with patients, this article will examine the evolution of the HPV vaccination schedule and the role of the HPV vaccine in the prevention of OPSCCs. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of cetuximab instead of cisplatin in combination with downstaging radiotherapy for papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma (HPV+ OPSCC). Design: Meta-analysis and systematic evaluation. Data sources: The PubMed, Embase, Web of Science, and Cochrane library databases were searched up to June 8, 2023, as well as Clinicaltrials.gov Clinical Trials Registry, China Knowledge Network, Wanfang Data Knowledge Service Platform, and Wiprojournal.com. Eligibility criteria for selecting studies: Randomized controlled trials reporting results of standard regimens of cetuximab + radiotherapy vs cisplatin + radiotherapy in treating HPV+ OPSCC were included. The primary outcomes of interest were overall survival (OS), progression-free survival (PFS), local regional failure rate (LRF), distant metastasis rate (DM), and adverse events (AE). Data extraction and synthesis: Two reviewers independently extracted data and assessed the risk of bias of the included studies. The HR and its 95% CI were used as the effect analysis statistic for survival analysis, while the OR and its 95% CI were used as the effect analysis statistic for dichotomous variables. These statistics were extracted by the reviewers and aggregated using a fixed-effects model to synthesise the data. Results: A total of 874 relevant papers were obtained from the initial search, and five papers that met the inclusion criteria were included; a total of 1,617 patients with HPV+ OPSCC were enrolled in these studies. Meta-analysis showed that OS and PFS were significantly shorter in the cetuximab + radiotherapy group of patients with HPV+ OPSCC compared with those in the conventional cisplatin + radiotherapy group (HR = 2.10, 95% CI [1.39–3.15], P = 0.0004; HR = 1.79, 95% CI [1.40–2.29], P < 0.0001); LRF and DM were significantly increased (HR = 2.22, 95% CI [1.58–3.11], P < 0.0001; HR = 1.66, 95% CI [1.07–2.58], P = 0.02), but there was no significant difference in overall grade 3 to 4, acute and late AE overall (OR = 0.86, 95% CI [0.65–1.13], P = 0.28). Conclusions: Cisplatin + radiotherapy remains the standard treatment for HPV+ OPSCC. According to the 7th edition AJCC/UICC criteria, low-risk HPV+ OPSCC patients with a smoking history of ≤ 10 packs/year and non-pharyngeal tumors not involved in lymphatic metastasis had similar survival outcomes with cetuximab/cisplatin + radiotherapy. However, further clinical trials are necessary to determine whether cetuximab + radiotherapy can replace cisplatin + radiotherapy for degraded treatment in individuals who meet the aforementioned characteristics, particularly those with platinum drug allergies. Prospero registration number: CRD42023445619. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective: To analyze, through literary research, the relation between oropharynx squamous cell carcinoma (SCC) and Human Papillomavirus (HPV), as well as associated epidemiological data and prognosis. Methods: This is a narrative review of literature, with investigation on PubMed, LiLACS, Scielo and BVS bases, as well as free search, from June/2021 to February/2022. The DeCS/MeSH descriptors used in Portuguese and English were: “HPV”, “Papillomavirus humano”, “Human Papillomavirus”, “Carcinoma de Células Escamosas Orofaríngeo”, “Oropharyngeal squamous cell Carcinoma” and “Carcinoma Escamocelular”. After all the refinement steps through the application of inclusion and exclusion criteria, a total of 26 studies were selected. Results: Oropharyngeal cancer is related to HPV-positive patients, and its incidence is higher in men. It presents a growing increase in young adults. However, the prognosis and survival rates are favorable. Conclusion: There is a growing relation between oropharynx SCC and HPV in young and adult males, which emphasizes the importance and need for efforts to improve diagnosis, treatment, and prevention of new cases. Further studies are needed to determine the epidemiological impact and this relation in the long term.

The growth pattern of oropharyngeal squamous cell carcinomas (OPSCC) varies from compact tumor cell aggregates to diffusely infiltrating tumor cell-clusters. The influence of the growth pattern on local tumor control and survival has been studied mainly for surgically treated oral cavity carcinomas on a visual basis. In this study, we used multiplex immunofluorescence staining (mIF) to examine the antigens pan-cytokeratin, p16INK4a, Ki67, CD271, PD-L1, and CD8 in pretherapeutic biopsies from 86 OPSCC. We introduce Tumor-stroma contact ratio (TSC), a novel parameter, to quantify the relationship between tumor cells in contact with the stromal surface and the total number of epithelial tumor cells. mIF tumor cores were analyzed at the single-cell level, and tumor-stromal contact area was quantified using the R package ''Spatstat''. TSC was correlated with the visually assessed invasion pattern by two independent investigators. Furthermore, TSC was analyzed in relation to clinical parameters and patient survival data to evaluate its potential prognostic significance.Higher TSC correlated with poor response to (chemo-)radiotherapy (r = 0.3, p < 0.01), and shorter overall (OS) and progression-free (PFS) survival (median OS: 13 vs 136 months, p < 0.0001; median PFS: 5 vs 85 months, p < 0.0001). Visual categorization of growth pattern according to established criteria of tumor aggressiveness showed interobserver variability increasing with more nuanced categories (2 categories: k = 0.7, 95 %-CI: 0.55 - 0.85; 4 categories k = 0.48, 95 %-CI: 0.35 - 0.61).In conclusion, TSC is an objective and reproducible computer-based parameter to quantify tumor-stroma contact area. We demonstrate its relevance for the response of oropharyngeal carcinomas to primary (chemo-)radiotherapy.

Head and Neck Squamous Cell Carcinoma (HNSCC) is one of the most common malignancies worldwide with most of the patients presenting in advanced stage. The associated high mortality and poor prognosis of the tumour has rendered the search for better therapeutic options than the traditional modalities of surgery, radiotherapy and chemotherapy. Immunotherapy targeting Programmed Cell Death Protein 1 / Programmed Cell Death Ligand 1 (PD-1/PD-L1) has been approved in recurrent/ metastatic HNSCC cases. PD-L1 expressing HNSCCs are likely to respond to immunotherapy. PD-L1 expression has been studied in peripheral blood utilising Circulating Tumour Cells (CTC) and soluble exosomes. Despite these non invasive techniques, PD-L1 expression has been most frequently assessed by immunohistochemistry (IHC) application on the Formalin Fixed Paraffin Embedded (FFPE) tissue of the tumour. Currently, many antibody clones and various IHC platforms are available for PD-L1, but only 22c3 has been approved by the Food and Drug Administration (FDA). Although, the availability of multiple options has made PD-L1 assessment possible and affordable at many centres worldwide, but various procedural, pre-analytical, and analytic issues have to be considered prior to the interpretation of immunoexpression of PD-L1. In this review, the authors aim to highlight the problem areas, and to understand the implications of PD-L1 expression in HNSCC. The authors propose recommendations for the optimal assessment of PD-L1 expression in HNSCC on IHC.

Objectives: Primary objective: describe rates of 30-days unplanned readmission following outpatient resection of oral cavity cancer. Secondary objective: evaluate for patient and treatment factors associated with readmission. Methods: Retrospective, dual-institution cohort study of 2 tertiary care referral centers involving adult patients undergoing resection of oral cavity cancer with plans for same-day discharge. Consecutive sample of 77 patients included. Primary outcome was unplanned readmission to emergency room or inpatient stay in the 30 days following surgery. Comparison testing was used between return and non-return groups. Results: Among 77 patients treated with outpatient surgery for oral cavity cancer, 19 (25%) returned to the hospital within 30 days. Among the reasons for return, 16 (80%) were directly related to surgery, and 4 (20%) were related to perioperative medical complications not directly related to a surgical site. Among the 25 patients also undergoing sentinel lymph node biopsy with their oral cavity resection, none returned to the hospital for neck-related complications. While most patients could be safely observed and discharged after return to the hospital, 8 patients (10%) required inpatient readmission. No significant differences between return and non-return groups were identified, although there was a trend toward shorter driving distance from hospital for the return group (47.6 miles vs. 69.5 miles, P = 0.097). Conclusion: Unplanned return to the hospital following outpatient oral cavity resection is prevalent and primarily driven by postoperative primary resection site concerns. Among patients selected for same day discharge, no definite population at highest risk of unplanned return was identified. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinomas (OSCC) signs and symptoms may be first identified by dental hygienists during routine extra and intra-oral examinations. A comprehensive extra-oral and intra-oral examination during regular dental hygiene assessment is paramount to identifying oral potentially malignant disorders (OPMD) and cancerous lesions for timely referral and treatment. Integrating a systematic list of questions during the medical and dental assessment along with careful visual and tactile examinations is critical to identifying OPMDs and cancerous lesions. Understanding the relationship between oropharyngeal squamous cell carcinomas (OPSCC) and Human Papilloma Virus (HPV) and how vaccination can prevent HPV-related OPSCC is critical to providing evidence-based recommendations and care. The purpose of this report is to provide an update on current epidemiological trends of OSCC and OPSCC rates in the United States (US) and provide the latest evidence on what dental hygienists must know to improve health outcomes and mitigate the consequences of undiagnosed cancer. This report considers enduring challenges with the annual rise in OPSCC rates and the public health burden of HPV-related cancers in the US. Emphasis on regular, quality continuing education about OSCC and OPSCC is emphasized along with recommendations for evidence-based training. [ABSTRACT FROM AUTHOR]

We sought to determine the diagnostic accuracy of radiomics features in predicting HPV status in oropharyngeal squamous cell carcinoma (SCC) compared to routine paraclinical measures used in clinical practice. Twenty-six articles were included in the systematic review, and thirteen were used for the meta-analysis. The overall sensitivity of the included studies was 0.78, the overall specificity was 0.76, and the overall area under the ROC curve was 0.84. The diagnostic odds ratio (DOR) equaled 12 (8, 17). Subgroup analysis showed no significant difference between radiomics features extracted from CT or MR images. Overall, the studies were of low quality in regard to radiomics quality score, although most had a low risk of bias based on the QUADAS-2 tool. Radiomics features showed good overall sensitivity and specificity in determining HPV status in OPSCC, though the low quality of the included studies poses problems for generalizability. [ABSTRACT FROM AUTHOR]

Purpose: Confocal Laser Endomicroscopy (CLE) is an imaging tool, that has demonstrated potential for intraoperative, real-time, non-invasive, microscopical assessment of surgical margins of oropharyngeal squamous cell carcinoma (OPSCC). However, interpreting CLE images remains challenging. This study investigates the application of OpenAI's Generative Pretrained Transformer (GPT) 4.0 with Vision capabilities for automated classification of CLE images in OPSCC. Methods: CLE Images of histological confirmed SCC or healthy mucosa from a database of 12 809 CLE images from 5 patients with OPSCC were retrieved and anonymized. Using a training data set of 16 images, a validation set of 139 images, comprising SCC (83 images, 59.7%) and healthy normal mucosa (56 images, 40.3%) was classified using the application programming interface (API) of GPT4.0. The same set of images was also classified by CLE experts (two surgeons and one pathologist), who were blinded to the histology. Diagnostic metrics, the reliability of GPT and inter-rater reliability were assessed. Results: Overall accuracy of the GPT model was 71.2%, the intra-rater agreement was κ = 0.837, indicating an almost perfect agreement across the three runs of GPT-generated results. Human experts achieved an accuracy of 88.5% with a substantial level of agreement (κ = 0.773). Conclusions: Though limited to a specific clinical framework, patient and image set, this study sheds light on some previously unexplored diagnostic capabilities of large language models using few-shot prompting. It suggests the model's ability to extrapolate information and classify CLE images with minimal example data. Whether future versions of the model can achieve clinically relevant diagnostic accuracy, especially in uncurated data sets, remains to be investigated. [ABSTRACT FROM AUTHOR]

Purpose: Treatment de-intensification for p16 + oropharyngeal squamous cell carcinoma (OPSCC) is an area of active research to reduce the side effects and improve patients' quality of life (QoL). In this paper we evaluated the Overall Survival (OS), the Disease-Free Survival (DFS) and the QoL of patients affected by p16 + OPSCC according to their prognostic stage group (PSG) and different treatments. Methods: Patients were selected retrospectively through our Electronic Tumor Board Database according to prespecified inclusion criteria. Basic data of eligible patients were recorded and analyzed. Then, OS and DFS were evaluated according to the PSG and the treatments performed. Patients alive completed three questionnaires: the QoL Questionnaire Core 30 (QLQ-C30), the QoL Questionnaire Head & Neck 43 (QLQ-HN43) and the MD Anderson Dysphagia Inventory (MDADI) questionnaire. Results: Sixty-one patients were included in this study. Eight patients died from the disease and the remaining 53 patients completed the 3 questionnaires. Fifteen (25%) patients were treated with upfront surgery, 6 (10%) patients with definitive radiotherapy and 40 (65%) patients with concomitant chemoradiotherapy. Comparing the DFS and the OS of PSG I patients by the different treatments performed, no statistically significant difference was identified. Patients treated with upfront surgery showed better outcomes in some aspects of their QoL. Conclusion: For p16 + OPSCC PSG I patients, upfront surgery can be considered a valid alternative to radiotherapy or chemoradiotherapy while maintaining a comparable DFS and OS and giving patients better results in terms of specific aspects of their QoL. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to compare treatment characteristics and outcomes between patients with HPV‐positive oropharyngeal squamous cell carcinoma (OPSCC) treated at hospitals of varying safety‐net burden status. Methods: Patients with cT1‐4, N0‐3, M0 HPV‐positive OPSCC who underwent definitive surgery or radiation were included. Patients were grouped based on their treating hospital safety‐net burden status, defined as the percentage of uninsured and Medicaid‐insured patients with OPSCC treated at the facility and stratified as low burden (LBH: 0–25th percentile), medium burden (MBH: 25th–75th percentile), or high burden (HBH: 75th–100th percentile). The primary outcome was primary treatment with surgery versus radiation, evaluated with multivariable‐adjusted logistic regression. Secondary outcomes included TORS versus open surgical approach, and overall survival evaluated with Cox proportional hazards analysis. Results: Of the 19,810 patients with cT1‐4, N0‐3, M0 HPV‐positive OPSCC included in this study, 4921 (24.8%) were treated at LBH, 12,201 (61.6%) were treated at MBH, and 2688 (13.6%) were treated at HBH. In multivariable‐adjusted analysis, compared with treatment at LBH, treatment at HBH was associated with more frequent radiation over surgical treatment (OR: 1.26, 95% CI: 1.12–1.40, p < 0.001). For patients undergoing surgery, patients at HBH had less frequent transoral robotic surgery (OR: 0.30, 95% CI 0.24–0.38, p < 0.001) compared with patients treated at LBH. Overall survival of patients treated at HBH was worse than that of patients treated at LBH (HR: 1.27, 95% CI 1.13–1.43, p < 0.001). Conclusion: These findings highlight underlying disparities at higher safety‐net burden facilities that impact patterns of care and outcomes for patients with OPSCC. Level of Evidence: 3 Laryngoscope, 134:1733–1740, 2024 [ABSTRACT FROM AUTHOR]

This study protocol for a prospective, multicenter, diagnostic, clinical trial describes the integration of transoral and transcervical ultrasonography (US) in the initial clinical work-up of patients referred to tertiary head and neck cancer centers with suspected oropharyngeal cancer. The study evaluates the blinded detection rate of oropharyngeal tumors and their US-estimated size and T-stage before histopathology and cross-sectional imaging are available. Magnetic resonance imaging (MRI) scans will be prospectively rated while blinded to T-site histopathology and US. The primary outcome measures of diagnostic accuracy, including sensitivity, specificity, positive and negative predictive values, and overall accuracy, will be reported for both US and MRI. A sub-analysis of prospectively rated 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computerized tomography (PET/CT) scans in patients with clinically suspected unknown primary tumors will also be compared to US and MRI. Secondary outcome measures, including a comparison of tumor size estimation between US, MRI, and CT, will also be reported. This prospective multicenter study will provide clinically impactful information regarding the use of transoral and transcervical US for the diagnostic work-up of oropharyngeal cancer. [ABSTRACT FROM AUTHOR]

Background: Apparent diffusion coefficient is not specifically sensitive to tumor microstructure and therapy‐induced cellular changes. Purpose: To investigate time‐dependent diffusion imaging with the short‐time‐limit random walk with barriers model (STL‐RWBM) for quantifying microstructure parameters and early cancer cellular response to therapy. Study Type: Prospective. Population: Twenty‐seven patients (median age of 58 years and 7.4% of females) with p16+/p16− oropharyngeal/oral cavity squamous cell carcinomas (OPSCC/OCSCC) underwent MRI scans before therapy, of which 16 patients had second scans at 2 weeks of the 7‐weeks chemoradiation therapy (CRT). Field Strength/Sequence: 3‐T, diffusion sequence with oscillating gradient spine echo (OGSE) and pulse gradient spin echo (PGSE). Assessment: Diffusion weighted images were acquired using OGSE and PGSE. Effective diffusion times were derived for the STL‐RWBM to estimate free diffusion coefficient D0, volume‐to‐surface area ratio of cellular membranes V/S, and cell membrane permeability κ. Mean values of these parameters were calculated in tumor volumes. Statistical Tests: Tumor microstructure parameters were compared with clinical stages of p16+ I‐II OPSCC, p16+ III OPSCC, and p16− IV OCSCC by Spearman's rank correlation and with digital pathological analysis of a resected tissue sample. Tumor microstructure parameter responses during CRT in the 16 patients were assessed by paired t‐tests. A P‐value of <0.05 was considered statistically significant. Results: The derived effective diffusion times affected estimated values of V/S and κ by 40%. The tumor V/S values were significantly correlated with clinical stages (r = 0.47) as an increase from low to high clinical stages. The in vivo estimated cell size agreed with one from pathological analysis of a tissue sample. Early tumor cellular responses showed a significant increase in D0 (14%, P = 0.03) and non‐significant increases in κ (56%, P = 0.6) and V/S (10%, P = 0.1). Data Conclusion: Effective diffusion time estimation might impact microstructure parameter estimation. The tumor V/S was correlated with OPSCC/OCSCC clinical stages. Level of Evidence: 1 Technical Efficacy Stage: 1 [ABSTRACT FROM AUTHOR]

Background: We aimed to analyze and compare the timing and patterns of treatment failure, and survival after progression between HPV‐positive (HPV+) and HPV‐negative (HPV−) patients undergoing chemoradiation for oropharyngeal squamous cell carcinomas (OPSCC). Methods: A retrospective review was performed of all patients undergoing primary chemoradiation for OPSCC between 2008 and 2021. Demographic and clinical data were collected. Kaplan–Meier estimates for overall survival (OS), and time to recurrence/metastases (TTR) were compared using the log‐rank test, with Cox regression used for multivariable modeling comparing HPV+ and HPV− patients. Results: HPV− patients developed recurrence or metastases at earlier time points than HPV+ patients (8.8 vs. 15.2 months, p < 0.05), due to earlier local/locoregional recurrence and distant metastases, but not isolated regional recurrences. HPV− distant metastases exclusively occurred in a single organ, most commonly the lungs or bone, while HPV+ metastases frequently had multi‐organ involvement in a wide variety of locations (p < 0.05). Once progression (recurrence/metastases) was diagnosed, HPV+ patients experienced superior survival to HPV− patients on univariate and multivariate analysis, largely due to improved outcomes after treatment of local/locoregional recurrences (p < 0.05). There were no differences in survival after isolated regional recurrences or distant metastases. Conclusion: HPV+ OPSCC patients relapse later compared to HPV− patients in local/locoregional and distant sites. HPV+ patients with local/locoregional recurrence experience superior survival after recurrence, which does not hold true for isolated regional recurrences or distant metastases. These data can be useful to inform prognosis and guide treatment decisions in patients with recurrent OPSCC. [ABSTRACT FROM AUTHOR]

Background: Metastatic carcinoma of unknown primary origin to the head and neck lymph nodes (HNCUP) engenders unique diagnostic considerations. In many cases, the detection of a high-risk human papillomavirus (HR-HPV) unearths an occult oropharyngeal squamous cell carcinoma (SCC). In metastatic HR-HPV-independent carcinomas, other primary sites should be considered, including cutaneous malignancies that can mimic HR-HPV-associated SCC. In this context, ultraviolet (UV) signature mutations, defined as ≥ 60% C→T substitutions with ≥ 5% CC→TT substitutions at dipyrimidine sites, identified in tumors arising on sun exposed areas, are an attractive and underused tool in the setting of metastatic HNCUP. Methods: A retrospective review of institutional records focused on cases of HR-HPV negative HNCUP was conducted. All cases were subjected to next generation sequencing analysis to assess UV signature mutations. Results: We identified 14 HR-HPV negative metastatic HNCUP to either the cervical or parotid gland lymph nodes, of which, 11 (11/14, 79%) had UV signature mutations, including 4 (4/10, 40%) p16 positive cases. All UV signature mutation positive cases had at least one significant TP53 mutation and greater than 20 unique gene mutations. Conclusion: The management of metastatic cutaneous carcinomas significantly differs from other HNCUP especially metastatic HR-HPV-associated SCC; therefore, the observation of a high percentage of C→T with CC →TT substitutions should be routinely incorporated in next generation sequencing reports of HNCUP. UV mutational signatures testing is a robust diagnostic tool that can be utilized in daily clinical practice. [ABSTRACT FROM AUTHOR]

Head and Neck Squamous Cell Carcinoma (HNSCC) is one of the most common malignancies worldwide with most of the patients presenting in advanced stage. The associated high mortality and poor prognosis of the tumour has rendered the search for better therapeutic options than the traditional modalities of surgery, radiotherapy and chemotherapy. Immunotherapy targeting Programmed Cell Death Protein 1 / Programmed Cell Death Ligand 1 (PD-1/PD-L1) has been approved in recurrent/ metastatic HNSCC cases. PD-L1 expressing HNSCCs are likely to respond to immunotherapy. PD-L1 expression has been studied in peripheral blood utilising Circulating Tumour Cells (CTC) and soluble exosomes. Despite these non invasive techniques, PD-L1 expression has been most frequently assessed by immunohistochemistry (IHC) application on the Formalin Fixed Paraffin Embedded (FFPE) tissue of the tumour. Currently, many antibody clones and various IHC platforms are available for PD-L1, but only 22c3 has been approved by the Food and Drug Administration (FDA). Although, the availability of multiple options has made PD-L1 assessment possible and affordable at many centres worldwide, but various procedural, pre-analytical, and analytic issues have to be considered prior to the interpretation of immunoexpression of PD-L1. In this review, the authors aim to highlight the problem areas, and to understand the implications of PD-L1 expression in HNSCC. The authors propose recommendations for the optimal assessment of PD-L1 expression in HNSCC on IHC. [ABSTRACT FROM AUTHOR]

Objective To evaluate the efficacy and safety of cetuximab instead of cisplatin in combination with downstaging radiotherapy for papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma (HPV+ OPSCC). Design Meta-analysis and systematic evaluation. Data sources The PubMed, Embase, Web of Science, and Cochrane library databases were searched up to June 8, 2023, as well as Clinicaltrials.gov Clinical Trials Registry, China Knowledge Network, Wanfang Data Knowledge Service Platform, and Wiprojournal.com. Eligibility criteria for selecting studies Randomized controlled trials reporting results of standard regimens of cetuximab + radiotherapy vs cisplatin + radiotherapy in treating HPV+ OPSCC were included. The primary outcomes of interest were overall survival (OS), progression-free survival (PFS), local regional failure rate (LRF), distant metastasis rate (DM), and adverse events (AE). Data extraction and synthesis Two reviewers independently extracted data and assessed the risk of bias of the included studies. The HR and its 95% CI were used as the effect analysis statistic for survival analysis, while the OR and its 95% CI were used as the effect analysis statistic for dichotomous variables. These statistics were extracted by the reviewers and aggregated using a fixed-effects model to synthesise the data. Results A total of 874 relevant papers were obtained from the initial search, and five papers that met the inclusion criteria were included; a total of 1,617 patients with HPV+ OPSCC were enrolled in these studies. Meta-analysis showed that OS and PFS were significantly shorter in the cetuximab + radiotherapy group of patients with HPV+ OPSCC compared with those in the conventional cisplatin + radiotherapy group (HR = 2.10, 95% CI [1.39–3.15], P = 0.0004; HR = 1.79, 95% CI [1.40–2.29], P < 0.0001); LRF and DM were significantly increased (HR = 2.22, 95% CI [1.58–3.11], P < 0.0001; HR = 1.66, 95% CI [1.07–2.58], P = 0.02), but there was no significant difference in overall grade 3 to 4, acute and late AE overall (OR = 0.86, 95% CI [0.65–1.13], P = 0.28). Conclusions Cisplatin + radiotherapy remains the standard treatment for HPV+ OPSCC. According to the 7th edition AJCC/UICC criteria, low-risk HPV+ OPSCC patients with a smoking history of ≤ 10 packs/year and non-pharyngeal tumors not involved in lymphatic metastasis had similar survival outcomes with cetuximab/cisplatin + radiotherapy. However, further clinical trials are necessary to determine whether cetuximab + radiotherapy can replace cisplatin + radiotherapy for degraded treatment in individuals who meet the aforementioned characteristics, particularly those with platinum drug allergies. Prospero registration number CRD42023445619.

Abstract Protein glycosylation responds sensitively to disease states. It is implicated in every hallmark of cancer and has recently started to be considered as a hallmark itself. Changes in N‐glycosylation microheterogeneity are more dramatic than those of protein expression due to the non‐template nature of protein glycosylation. This enables their potential use in serum‐based diagnostics. Here, we perform glycopeptidomics on serum from patients with oropharyngeal squamous cell carcinoma (OPSCC), compared to controls and comparing between cancers based on etiology (human papilloma virus‐ positive or negative). Using MS2, we then targeted glycoforms, significantly different between the groups, to identify their glycopeptide compositions. Simultaneously we investigate the same serum proteins, comparing whether N‐glycosylation changes reflect protein‐level changes. Significant glycoforms were identified from proteins such as alpha‐1‐antitrypsin (SERPINA1), haptoglobin, and different immunoglobulins. SERPINA1 had glycovariance at 2 N‐glycosylation sites, that were up to 35 times more abundant in even early‐stage OPSCCs, despite minimal differences between SERPINA1 protein levels between groups. Some identified glycoforms' fold changes (FCs) were in line with serum protein level FCs, others were less abundant in early‐stage cancers but with great variance in higher‐stage cancers, such as on immunoglobulin heavy constant gamma 2, despite no change in protein levels. Such findings indicate that glycovariant analysis might be more beneficial than proteomic analysis, which is yet to be fruitful in the search for biomarkers. Highly sensitive glycopeptide changes could potentially be used in the future for cancer screening. Additionally, characterizing the glycopeptide changes in OPSCC is valuable in the search for potential therapeutic targets.

Abstract Objectives Margin status interpretation following transoral robotic surgery (TORS) for oropharyngeal squamous cell carcinoma (OPSCC) is challenging. This study aims to assess the discrepancy between status of margins as reported by the pathologist versus as determined by multi‐disciplinary team review (MDTB). Methods A retrospective study of 57 patients with OPSCC who underwent TORS from January 2010 to December 2016 was conducted. Our primary outcome measure was the discrepancy between the surgical specimen margins as described in the pathology report versus final margin status that was determined after the multi‐disciplinary team discussion. Fisher's exact test was used. Results Based on the pathologist‐report, 29 subjects (51%) had positive margins, compared to 2 (4%) after multi‐disciplinary team discussion. Receipt of chemotherapy correlated with final margin status as determined by MDTB, not with initial main specimen margins (p = .02 and p = .08, respectively). With a median follow up of 28.4 months, two subjects (4%) had loco‐regional recurrence. Conclusion Following TORS, there was a significant discrepancy between status of margins as reported by the pathologist versus as determined by MDTB review. Chemotherapy was avoided in 93.1% of cases that were originally reported as positive margins by the pathologist with an acceptably low recurrence rate. Level of evidence 4.

Abstract Background In addition to the conventional aetiologic agents of oropharyngeal squamous cell carcinoma (OPSCC) such as tobacco usage, alcohol consumption and betel quid usage, it has been established that a proportion of OPSCC are driven by persistent oncogenic human papillomavirus (HPV) infections. Currently, there is a lack of data on the burden of HPV- associated OPSCC in Asian countries including Malaysia. Methods A cross-sectional multicentre study with tissue analysis of Malaysian patients diagnosed with primary OPSCC within a five-year period, from 2015 to 2019 between 01/01/2015 to 31/12/2019 was undertaken. Determination of HPV status was carried out using p16INK4a immunohistochemistry on tissue microarrays constructed from archived formalin-fixed paraffin-embedded tissue. Results From the cases identified, 184 cases had sufficient tissue material for analysis. Overall, median age at diagnosis was 63.0 years (IQR = 15) and 76.1% of patients were males. In our cohort, 35.3% of patients were Indian, 34.2% were Chinese, 21.2% were Malay and 9.2% were from other ethnicities. The estimated prevalence of HPV-associated OPSCC in our cohort was 31.0% (CI 24.4–38.2%). The median age for the HPV-associated OPSCC sub-group of patients was not significantly lower than the median age of patients with HPV-independent OPSCC. More than half of HPV-associated OPSCC was seen in patients of Chinese ethnicity (54.4%). Patients with HPV-associated OPSCC had a much better overall survival than patients with HPV-independent OPSCC (Log rank test; p

Objective　 To observe the expression changes of Notch4 mRNA in tissues and cells of oropharyngeal squamous cell carcinoma, and to explore the effect of knocking down Notch4 mRNA expression on the proliferation, migration, and invasion abilities of oropharyngeal squamous cell carcinoma cells. Methods　 We collected 12 pairs of oropharyngeal squamous cell carcinoma tissues and adjacent tissues, and detected Notch4 mRNA expression levels in the cancer tissues and adjacent tissues by RT-qPCR. We cultivated oropharyngeal squamous cell carcinoma cell lines Detroit 562 and WSU-HN-30, and control cells HaCaT, 2BS to detect Notch4 mRNA. The cell lines Detroit 562 and WSU-HN-30 were randomly divided into the si-NC group (transfected with si-NC double stranded nucleotide), si-Notch4-1 group (transfected with si-Notch4-1 double stranded nucleotide), and si-Notch4-2 group（transfected with si-Notch4-2 double stranded nucleotide). Notch4 mRNA was detected in cells of each group, and the proliferation ability (CI value) of cells in each group was observed using RTCA method. The invasion and migration abilities of cells in each group were observed by Transwell experiment. Results　 Compared with the adjacent tissues, the relative expression level of Notch4 mRNA in oropharyngeal squamous cell carcinoma tissues was higher (P<0. 01). There was no difference in the relative expression level of Notch4 mRNA between HaCaT and 2BS cells in the control group. Compared with HaCaT cells in the control group, the relative expression levels of Notch4 mRNA were higher in the Detroit 562 and WSU-HN-30 cells (both P<0.01) . In the Detroit 562 and WSU-HN-30 cells, compared with the si-NC group, the cell proliferation, migration, and invasion abilities of the si-Notch4-1 and si-Notch4-2 groups decreased (all P<0.001). Conclusion　 Notch4 was highly expressed in oropharyngeal squamous carcinoma tissues and cells, and knockdown of Notch4 expression significantly inhibited the proliferation, migration and invasion of oropharyngeal squamous carcinoma cells. [ABSTRACT FROM AUTHOR]

Protein glycosylation responds sensitively to disease states. It is implicated in every hallmark of cancer and has recently started to be considered as a hallmark itself. Changes in N‐glycosylation microheterogeneity are more dramatic than those of protein expression due to the non‐template nature of protein glycosylation. This enables their potential use in serum‐based diagnostics. Here, we perform glycopeptidomics on serum from patients with oropharyngeal squamous cell carcinoma (OPSCC), compared to controls and comparing between cancers based on etiology (human papilloma virus‐ positive or negative). Using MS2, we then targeted glycoforms, significantly different between the groups, to identify their glycopeptide compositions. Simultaneously we investigate the same serum proteins, comparing whether N‐glycosylation changes reflect protein‐level changes. Significant glycoforms were identified from proteins such as alpha‐1‐antitrypsin (SERPINA1), haptoglobin, and different immunoglobulins. SERPINA1 had glycovariance at 2 N‐glycosylation sites, that were up to 35 times more abundant in even early‐stage OPSCCs, despite minimal differences between SERPINA1 protein levels between groups. Some identified glycoforms' fold changes (FCs) were in line with serum protein level FCs, others were less abundant in early‐stage cancers but with great variance in higher‐stage cancers, such as on immunoglobulin heavy constant gamma 2, despite no change in protein levels. Such findings indicate that glycovariant analysis might be more beneficial than proteomic analysis, which is yet to be fruitful in the search for biomarkers. Highly sensitive glycopeptide changes could potentially be used in the future for cancer screening. Additionally, characterizing the glycopeptide changes in OPSCC is valuable in the search for potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Introduction Human papillomavirus-related (HPV +) oropharyngeal squamous cell carcinoma (OPSCC) is increasing in incidence and presents diagnostic challenges given its unique clinical presentation. Objective The purpose of the present study is to characterize the impact of the unique clinical presentation of HPV-related OPSCC on delays in diagnosis. Methods Retrospective review of presenting symptoms and clinical characteristics of 284 patients with OPSCC treated from 2002–2014. Delay in diagnosis was defined as the presence of any of the following: multiple non-diagnostic fine needle aspirate (FNA) biopsies; two or more courses of antibiotic therapy; surgery with incorrect preoperative diagnosis; evaluation by an otolaryngologist without further workup; or surgery without definitive postoperative diagnosis. Results p16+ tumors demonstrated a distinct clinical presentation that more commonly involved a neck mass (85.1% versus 57.3% of p16-; p < 0.001) and less frequently included odynophagia (24.6% versus 51.7% of p16-; p < 0.001). Patients who experienced diagnostic delay were more likely to have p16+ tumors (77.7% delayed versus 62.8% not delayed; p = 0.006). p16+ primary tumors were more likely to be undetectable by physical examination of the head and neck including flexible laryngoscopy (19.0% versus 6.7% of p16-; p = 0.007) and more frequently associated with nondiagnostic FNA biopsies of a cervical nodal mass (11.8% versus 3.4% of p16-, p = 0.03). Conclusions Compared with non-HPV related OPSCC, the unique clinical presentation and characteristics of HPV+ OPSCC are associated with an increased incidence of diagnostic delay. Targeted education of appropriate care providers may improve time to diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) is a common infection believed to cause 70% of oropharyngeal cancers, with incidence rising globally. Nurses play a critical role in providing care and education to patients with HPV-induced oropharyngeal squamous cell carcinoma (OPSCC). The etiology, diagnosis, and treatment of HPV-induced OPSCC are addressed. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV) integration into the host genome is an important factor in HPV(+)OPSCC carcinogenesis, in conjunction with HPV oncoproteins E6/E7. However, a well‐studied investigation about virus–host interaction still needs to be completed. Our objective is to characterise HPV integration to investigate potential mechanisms of tumourigenesis independent of E6/E7 oncoproteins. Materials and methods: High‐throughput viral integration detection was performed on 109 HPV(+)OPSCC tumours with relevant clinicopathological information. Of these tumours, 38 tumours underwent targeted gene sequencing, 29 underwent whole exome sequencing and 26 underwent RNA sequencing. Results: HPV integration was detected in 94% of tumours (with a mean integration count of 337). Tumours occurring at the tonsil/oropharyngeal wall that exhibit higher PD‐L1 expression demonstrated increased integration sites (p =.024). HPV exhibited a propensity for integration at genomic sites located within specific fragile sites (FRA19A) or genes associated with functional roles such as cell proliferation and differentiation (PTEN, AR), immune evasion (CD274) and glycoprotein biosynthesis process (FUT8). The viral oncogenes E2, E4, E6 and E7 tended to remain intact. HPV fragments displayed enrichment within host copy number variation (CNV) regions. However, insertions into genes related to altered homologous recombination repair were infrequent. Genes with integration had distinct expression levels. Fifty‐nine genes whose expression level was affected by viral integration were identified, for example, EPHB1, which was reported to be involved in cellular protein metabolic process. Conclusions: HPV can promote oncogenesis through recurrent integration into functional host genome regions, leading to subsequent genomic aberrations and gene expression disruption. This study characterises viral integrations and virus–host interactions, enhancing our understanding of HPV‐related carcinogenesis mechanisms. [ABSTRACT FROM AUTHOR]

Background: Still, little is known about microbial dysbiosis in oropharyngeal and laryngeal tissue as risk factor for development of local squamous cell carcinoma. The site‐specific microbiota at these regions in healthy and cancer tissue and their modulation by environmental factors need to be defined. Methods: The local microbiota of cancer tissue and healthy controls was profiled by 16S rRNA gene amplicon sequencing and statistical analysis using 111 oropharyngeal and 72 laryngeal intraoperative swabs. Results: Oropharynx and larynx harbor distinct microbial communities. Clear effects of both smoking and cancer were seen in the oropharynx whereas effects in the larynx were minor. Conclusion: The distinct microbial communities at larynx and oropharynx partially explain why the effects of cancer and smoking were distinct at those sites. Thus, the use of microbiota supposed to mirror community changes in another target location should be avoided and more studies on the actual cancerous environment are necessary. [ABSTRACT FROM AUTHOR]

Objectives: This study examines oncologic outcomes in patients with HPV‐related oropharyngeal squamous cell carcinoma (HPV(+)OPSCC) who had evidence of gross cranial nerve invasion (CNI) identified at the time of surgery. Study Design: Retrospective cohort study comparing demographics, clinical features, and outcomes of HPV(+)OPSCC patients with and without gross CNI. Methods: Patients with biopsy proven HPV(+)OPSCC involving the base of tongue, tonsil, or unknown primary site, who underwent surgery as a part of their treatment between 1/1/2006–12/31/2020 (n = 874), were included in this study. Gross CNI was identified during operative intervention (n = 36). Statistical analyses were performed using SAS version 9.4 and R version 3.6.2. P‐values <0.05 were considered statistically significant. Results: HPV(+)OPSCC patients with gross CNI were nearly 5 times as likely to suffer death by cancer (HR = 5.41, 95% CI 2.51 to 11.67, p < 0.0001), over 4 times as likely to see disease progression (HR = 4.25, 95% CI 2.31 to 7.84, p < 0.0001), and nearly 5 times as likely to experience metastasis (HR = 4.46, 95% CI 2.20 to 9.06, p < 0.0001) when compared to patients without CNI. Patients with gross CNI had significantly lower overall survival, cancer‐specific survival, progression‐free survival, and distant‐metastasis free survival (p < 0.0001). Patients with gross CNI were significantly more likely to present with higher clinical N stage, higher pathological N stage and extracapsular spread than patients without gross CNI. Conclusions: Our findings indicate that the presence of CNI is associated with significantly poorer oncologic outcomes in HPV(+)OPSCC patients. Level of Evidence: 3 Laryngoscope, 134:170–177, 2024 [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC) are the most common types of cancers in the head and neck region (HNSCC). Despite very aggressive treatment modalities, the five-year survival rate has not changed for decades and is still around 60%. The search for potential specific biomarkers of aggressiveness or outcome indicators could be of great benefit in improving the treatment of these patients. One of the potential biomarkers is survivin, the protein product of the BIRC5 gene. In this study, we investigated the occurrence of BIRC5 gene polymorphisms in 48 patients with OSCC and OPSCC compared with healthy controls. A total of 18 polymorphisms were found, 11 of which occurred in HNSCC with a minor allele frequency (MAF) of more than 5%. Five polymorphisms (rs3764383, rs9904341, rs2071214, rs2239680, rs2661694) were significantly associated with tumor size, tumor stage, and advanced regional disease, but had no impact on survival. [ABSTRACT FROM AUTHOR]