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

Objectives: Large language model (LLM)-based chatbots such as ChatGPT have been publicly available and increasingly utilized by the general public since late 2022. This study sought to investigate ChatGPT responses to common patient questions regarding Human Papilloma Virus (HPV) positive oropharyngeal cancer (OPC). Methods: This was a prospective, multi-institutional study, with data collected from high volume institutions that perform >50 transoral robotic surgery cases per year. The 100 most recent discussion threads including the term "HPV" on the American Cancer Society's Cancer Survivors Network's Head and Neck Cancer public discussion board were reviewed. The 11 most common questions were serially queried to ChatGPT 3.5; answers were recorded. A survey was distributed to fellowship trained head and neck oncologic surgeons at 3 institutions to evaluate the responses. Results: A total of 8 surgeons participated in the study. For questions regarding HPV contraction and transmission, ChatGPT answers were scored as clinically accurate and aligned with consensus in the head and neck surgical oncology community 84.4% and 90.6% of the time, respectively. For questions involving treatment of HPV+ OPC, ChatGPT was clinically accurate and aligned with consensus 87.5% and 91.7% of the time, respectively. For questions regarding the HPV vaccine, ChatGPT was clinically accurate and aligned with consensus 62.5% and 75% of the time, respectively. When asked about circulating tumor DNA testing, only 12.5% of surgeons thought responses were accurate or consistent with consensus. Conclusion: ChatGPT 3.5 performed poorly with questions involving evolving therapies and diagnostics—thus, caution should be used when using a platform like ChatGPT 3.5 to assess use of advanced technology. Patients should be counseled on the importance of consulting their surgeons to receive accurate and up to date recommendations, and use LLM's to augment their understanding of these important health-related topics. [ABSTRACT FROM AUTHOR]

Introduction: Patients presenting with head and neck squamous cell carcinoma of unknown primary (HNSCCUP) remain challenging clinical scenarios as large variation exists in practices used to locate the primary. Objective: The objective of this systematic review is to review of the literature and offer recommendations for oropharyngeal biopsies in HNSCCUP. Method: Pubmed, Medline and Embase were searched to identify studies from inception to October 2021. The Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA) guidelines were followed. Results: A total of 483 articles were included and screened, 41 studies met the inclusion criteria, including over 3400 patients from the original articles (122 of these patients were reported on in two sequential articles by a single author – table 1) and 4 large metaanalyses including 1852 patients. The primary site identification rate following random biopsies or deep tissue biopsies is less than 5% in most studies. The mean detection rate following ipsilateral tonsillectomy is 34%; two pooled analyses indicate that the mean detection rate following tongue base mucosectomy is 64%, with this figure rising when the tonsils are negative. Conclusions: High level evidence is lacking, with heterogeneity in the reported studies. Published meta‐analyses are based on retrospective data. There is little evidence supporting the practice of random/non‐directed oropharyngeal biopsies. Available evidence supports palatine tonsillectomy and tongue base mucosectomy compared to deep tissue biopsies. [ABSTRACT FROM AUTHOR]

Kilovoltage computed tomography plays a crucial role in radiotherapy planning. However, the presence of high-density metallic objects can introduce streaking artifacts in CT scans, resulting in inaccurate dose calculations by the treatment planning software. Previous studies have explored manual density overrides and artifact reduction algorithms individually to enhance dose calculation accuracy, but their combined application on patient plans within a treatment planning system remains unexplored. This research aims to assess the necessity of manual density overrides when an artifact reduction algorithm is already employed to address dental artifacts in oropharyngeal cancer treatment plans. A total of 20 previously treated volumetric modulated arc therapy plans were collected, and manual density overrides were removed followed by plan recalculation. Dosimetric parameters were then compared between the original and modified plans. Statistical analysis revealed several dosimetric parameters for the planning target volume (PTV), clinical target volume (CTV), and oral cavity that exhibited statistically significant differences upon removing the manual density override. However, these differences were found to be small in absolute terms. No other organs evaluated demonstrated statistically significant differences in dose. The most significant disparity observed was an 8.26 cGy increase in mean dose to the CTV, which represents only 0.12% of the prescription dose. Based on these findings, it can be concluded that manual density overrides are likely unnecessary when an artifact reduction algorithm is employed in oropharyngeal cancer cases. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplants are associated with a greater susceptibility to secondary malignancies. The present study examines the prevalence and risk factors of developing secondary oral and oropharyngeal cancer. This was a chart review of 286 allogeneic stem cell transplant recipients treated at a large Health Center, with a mean follow-up time of 5 years. The eligibility included adults who underwent allogeneic hematopoietic stem cell transplants between October 2016 and June 2021. Two hundred eighty-six charts were reviewed of them: leukemia (65%), aplastic anemia (10%), and lymphoma (9%). 57 (20%) developed secondary cancers Five cases of the secondary cancers (8.8%) were oral squamous cell carcinoma, and three were human papillomavirus-related. Graft versus host disease occurred in 77.1% and 100% of oral/oropharyngeal cancers. About 50% across the groups had a history of smoking. graft versus host disease, immunosuppression, and smoking. The risk factors for secondary oral/oropharyngeal cancer; chronic graft versus host disease, immunosuppression, and smoking were not statistically significant. These findings support the recommendation for increased follow-up time and close monitoring of hematopoietic stem cell transplant recipients for secondary oral/oropharyngeal malignancies. The involvement of the human papillomavirus in these cases should be further investigated. [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]

Background: Head and neck cancer (HNC) incidence is on the rise, often diagnosed at late stage and associated with poor prognoses. Risk prediction tools have a potential role in prevention and early detection. Methods: The IARC‐ARCAGE European case–control study was used as the model development dataset. A clinical HNC risk prediction model using behavioral and demographic predictors was developed via multivariable logistic regression analyses. The model was then externally validated in the UK Biobank cohort. Model performance was tested using discrimination and calibration metrics. Results: 1926 HNC cases and 2043 controls were used for the development of the model. The development dataset model including sociodemographic, smoking, and alcohol variables had moderate discrimination, with an area under curve (AUC) value of 0.75 (95% CI, 0.74–0.77); the calibration slope (0.75) and tests were suggestive of good calibration. 384 616 UK Biobank participants (with 1177 HNC cases) were available for external validation of the model. Upon external validation, the model had an AUC of 0.62 (95% CI, 0.61–0.64). Conclusion: We developed and externally validated a HNC risk prediction model using the ARCAGE and UK Biobank studies, respectively. This model had moderate performance in the development population and acceptable performance in the validation dataset. Demographics and risk behaviors are strong predictors of HNC, and this model may be a helpful tool in primary dental care settings to promote prevention and determine recall intervals for dental examination. Future addition of HPV serology or genetic factors could further enhance individual risk prediction. [ABSTRACT FROM AUTHOR]

Background: The Australian Burden of Disease Study has shown that cancer is the single most important entity responsible for the greatest cause of health burden in Australia. Unfortunately, Aboriginal and Torres Strait Islander peoples experience a greater burden of this disease, with cancer of the lung, breast, bowel and prostrate being the most common. Lip, oral cavity and pharyngeal cancer incidence is rapidly rising globally and is now the sixth most common cancer in Australia. This paper aims to summarize, for the first time, the incidence and prevalence trends of lip, oral cavity and pharyngeal cancers in Aboriginal and Torres Strait Islander Australians. Methods: Data were obtained from the Australian Cancer Database (ACD), which is compiled at the Australian Institute of Health and Welfare (AIHW) from 1999 to 2018 to estimate the incidence and prevalence of certain head and neck cancers (ICD‐10 codes C00–C10, C14). The other variables requested were age groups and sex. Results: Results were stratified by ICD‐10 code, sex and age group at diagnosis and time period (i.e. grouped years of diagnosis). The total incidence of lip, oral cavity and pharyngeal cancers increased by 1.3 times from 1999 to 2008 (107/100 000) to 2009–2018 (135/100 000). The overall 5‐year prevalence of lip, oral cavity and pharyngeal cancers was 0.17% (0.24% for men and 0.09% for women). Conclusions: The significantly increased incidence of lip, oral cavity and pharyngeal cancers in Aboriginal and Torres Strait Islander peoples in Australia is concerning and should be explored. A targeted, comprehensive and culturally safe model of care for Aboriginal and Torres Strait Islander peoples with lip, oral cavity and pharyngeal cancers is imperative. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer globally. Notably, human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is on the rise, accounting for 70% of all OPSCC cases. Persistent high-risk HPV infection is linked to various cancers, but HPV infection alone is not sufficient to cause cancer. Advances in next-generation sequencing have improved our understanding of changes in the human microbiome of cancerous environments. Yet, there remains a dearth of knowledge on the impact of HPV-microbiome crosstalk in HPV-positive OPSCC. In this review, we examine what is known about the oropharyngeal microbiome and the compositional shifts in this microbiome in HPV-positive OPSCC. We also review potential mechanisms of crosstalk between HPV and specific microorganisms. Additional research is needed to understand these interactions and their roles on cancer development and progression. [ABSTRACT FROM AUTHOR]

Introduction: Head and neck cancer (HNC) is a complex disease, and multiple risk factors can lead to its progression. Observational studies indicated that herpes simplex virus (HSV) may be correlated with the risk of HNC. However, the causal effects and direction between them were still unclear. Methods: This study utilized a Mendelian randomization (MR) approach for causality assessment between HSV infection and Head and neck cancer based on the latest public health data and Genome-Wide Association Study (GWAS) data. The causal effects were estimated using IVW, weighted median, and MREgger. A reverse MR analysis was subsequently performed. Cochrans Q test, MREgger intercept test, leave one out analysis, and the funnel plot were all used in sensitivity analyses. Results: Genetically predicted higher level of HSV-1 IgG was causally related to HNC (OR=1.0019, 95%CI=1.0003-1.0036, p=0.0186, IVW) and oral and oropharyngeal cancer (OR=1.0018, 95%CI=1.0004-1.0033, p=0.0105, IVW). The reverse MR analysis did not demonstrate a reverse causal relationship between HSV and HNC. However, HSV-2 infection was not causally related to HNC data and oropharyngeal cancer data. Sensitivity analysis was performed and revealed no heterogeneity and horizontal pleiotropy. Conclusion: Collectively, a significant association was noted between HSV infection and increased risk of HNC, providing valuable insights into the etiology of this malignancy. Further in-depth study is needed to validate these findings and elucidate the underpinning mechanisms. [ABSTRACT FROM AUTHOR]

Background: While cervical cancer incidence rates (IR) in the United States have dropped in the last 20 years, non‐cervical human papillomavirus (HPV) associated cancers increased. Many people in Texas (TX) live in medically underserved areas and have higher risk of developing HPV‐associated cancers. Since previous studies of these regions focused on cervical cancer, we included other HPV‐associated cancers in our analysis of IR in East TX and the TX‐Mexico Border compared to other TX regions. Methods: Cancer data from 2006 to 2019 were obtained from the TX Cancer Registry. Cases of HPV‐associated cervical, vaginal, vulvar, penile, anal, and oropharyngeal cancers and corresponding patient‐level demographic data were included. We calculated IR per 100,000 and drew heat maps to visualize cancer IR by county. To control potential confounders, we added county‐level risk factors: rates for smoking, excessive drinking, obesity, STIs, primary care provider availability and dentist availability, from the County Health Rankings and Roadmaps program. We reported IRs by region and time and estimated unadjusted and adjusted risk ratio (RR) for association of each type of cancer and region. Lastly, we created adjusted models for each cancer by period to see time trends of regional differences. Results: Risk of anal, cervical, and oropharyngeal cancer was lower at parts of the Border than in the rest of TX in the adjusted model. We also observed increasing anal and oropharyngeal cancer risk and decreasing cervical and vaginal cancer risk over time. Conclusion: Patient sociodemographics, behavioral risk factors, and access to care may contribute to some observed differences in cancer IR across regions. This indicates that targeted prevention efforts towards these regions, especially in low socioeconomic status communities, may benefit future generations. [ABSTRACT FROM AUTHOR]

Background/Objective: The incidence of oropharyngeal cancer (OPC) remains significant, with a rising prevalence of HPV-positive (HPV+) cases, underscoring the growing importance of appropriate treatment approaches for this condition. While HPV+ OPC typically exhibits a more favorable prognosis than HPV-negative (HPV−) OPC, certain HPV+ OPC patients still face adverse outcomes. This study aimed to assess the effectiveness of TORS versus traditional surgery in treating OPC patients and investigate the prognostic implications of specific variants in the HPV genome. Methods: The clinical information, including pathological features, treatments, and outcomes (death), of 135 OPC patients treated with traditional surgery from 2008 to 2018 (the non-TORS group) and 130 OPC patients treated with TORS from 2017 to 2021 (the TORS group) were obtained from Sun Yat-sen University Cancer Center (SYSUCC). A comparative analysis of 3-year overall survival (OS) was performed between these two groups. Furthermore, we conducted next-generation sequencing for the HPV16 genome of the 68 HPV+ OPC cases to characterize single-nucleotide variations (SNVs) in the HPV16 genome and evaluate its association with HPV+ OPC patient survival. Results: The comparative analysis of 3-year OS between the two groups (TORS vs. non-TORS) revealed a significant prognostic improvement in the TORS group for OPC patients with a T1–T2 classification (89.3% vs. 72.0%; p = 1.1 × 10−2), stages I–II (92.1% vs. 82.2%; p = 4.6 × 10−2), and stages III–IV (82.8% vs. 62.2%; p = 5.7 × 10−2) and for HPV− patients (85.5% vs. 33.3%; p < 1.0 × 10−6). Furthermore, three SNVs (SNV1339A>G, SNV1950A>C, and SNV4298A>G) in the HPV16 genome were identified as being associated with worse survival. These SNVs could alter protein interactions and weaken the binding affinity for MHC-II, promoting viral amplification and immune evasion. Conclusions: TORS exhibited a superior prognosis to traditional surgery in OPC patients. Additionally, identifying specific SNVs within the HPV16 genome provided potential prognostic markers for HPV+ OPC. These significant findings hold clinical relevance for treatment decision-making and prognostic assessment in patients with OPC. [ABSTRACT FROM AUTHOR]

Background The impact of societal factors on the occurrence of head and neck cancers (HNCs) remains understudied, especially in the Nordic countries. Methods To quantify the association between socio-economic status (SES) and the occurrence of HNCs, this cohort study uses data from the Nordic Occupational Cancer project that combine occupational and cancer registry data from 1961 to 2005 of 14.9 million individuals aged between 30 and 64 years. Occupational categories were combined into seven socio-economic categories. Standardized incidence ratio (SIR) analyses were conducted with the cancer incidence rates for the entire national study populations used as reference rates. Results Altogether, 83 997 HNCs—72% in men and 28% in women—were recorded. Among men, a gradient of risk associated with SES was observed for cancers of the tongue, other oral cavity subsites, pharynx, oropharynx and larynx in groups with lower SES. Managers showed decreased SIRs of 0.50 to –0.90 also for cancers of the lip, tongue, other oral cavity subsites, oropharynx, nasopharynx, nose and larynx. In contrast, excess risks of tongue, other oral cavity subsites, pharyngeal, oropharyngeal and laryngeal cancers were observed among clerical (SIRs 1.05–1.16), skilled workers (1.04–1.14), unskilled workers (1.16–1.26) and economically inactive men (1.38–1.87). Among women, no risk gradient similar to that in men was revealed. Conclusions The current study underscores the influence of SES on the incidence of HNCs and highlights the need for targeted interventions, including tobacco and alcohol control policies, and improved access to healthcare services, particularly for socio-economically disadvantaged populations. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Diabetes has been related to an increased risk of oral cancer. Nevertheless, the impact of diabetes on the outcome of individuals with oral and oropharyngeal cancer is not clear. In this study, a meta‐analysis was carried out to assess the link between diabetes and the survival of individuals with oral and oropharyngeal cancer. Materials and Methods: Relevant cohort studies for the meta‐analysis objective were obtained through searching electronic databases, such as PubMed, Web of Science and Embase. The data were combined using a random effects model that accounted for differences between studies. Results: A total of 10 cohorts involving 21,871 patients with oral and oropharyngeal cancer were included. Pooled results suggest that compared with those with normoglycemia, oral and oropharyngeal cancer patients with diabetes were associated with a poor overall survival (hazard ratio 1.69, 95% confidence interval 1.29–2.22, P < 0.001; I2 = 69%). Subgroup analysis suggested a stronger association between diabetes and poor overall survival in patients aged ≥52 years as compared with those aged <52 years (hazard ratio 2.08 vs 1.34, P = 0.03). Other study characteristics, such as study country, tumor stage or follow‐up duration, did not seem to significantly affect the association (P for subgroup difference all >0.05). In addition, diabetes was also associated with a poor progression‐free survival of patients with oral and oropharyngeal cancer (hazard ratio 1.61, 95% confidence interval 1.30–1.99, P < 0.001; I2 = 9%). Conclusions: Patients with oral and oropharyngeal cancer might have a poor survival if they have pre‐existing diabetes. [ABSTRACT FROM AUTHOR]

The purpose of this study was to assess if multicriteria optimization could limit interoperator variability in radiation therapy planning and assess if this method could contribute to target volume coverage and sparing of organ at risk for intensity-modulated curative radiation therapy of head and neck cancers. We performed a retrospective analysis on 20 patients treated for an oropharyngeal or oral cavity squamous cell carcinoma. We carried out a comparative dosimetric study of manual plans produced with Precision® software, compared with the plans proposed using the multicriteria optimization method (RayStation®). We assessed interoperator reproducibility on the first six patients, and dosimetric contribution in sparing organs at risk using the multicriteria optimization method. Median age was 69 years, most lesions were oropharyngeal carcinoma (65%), and 35% lesions were stage T3. First, we obtained a high degree of similarity between the four operator measurements for each patient at the level of each organ. Intraclass correlation coefficients were greater than 0.85. Second, we observed a significant dosimetric benefit for contralateral parotid gland, homolateral and contralateral masseter muscles, homolateral and contralateral pterygoid muscles and for the larynx (P < 0.05). For the contralateral parotid gland, the mean dose difference between the multicriteria optimization and manual plans was −2.0 Gy (P = 0.01). Regarding the larynx, the mean dose difference between the two plans was −4.6 Gy (P < 0.001). Multicriteria optimization is a reproducible technique and faster than manual optimization. It allows dosimetric advantages on organs at risk, especially for those not usually taken into consideration in manual dosimetry. This may lead to improved quality of life. [ABSTRACT FROM AUTHOR]

Background: To investigate the technical feasibility of RT–PCR and direct sequencing to quantify HPV DNA in the saliva of patients with Human-Papilloma-Virus related oropharyngeal cancer (HPV-OPC), the level of which is known to predict prognosis after treatment. Methods: Nine patients with locally advanced HPV-OPC treated with definitive radiotherapy with chemotherapy or cetuximab, or radiotherapy alone between April 2016 and September 2017, were enrolled, two of whom also received induction chemotherapy. Saliva was collected before (baseline), during (mid-RT) and after (post-RT) radiotherapy. HPV-16 DNAs (E6 and E7) in saliva were quantified by RT–PCR and sequencing, the latter using a custom cancer panel. Correlations between HPV DNA levels and clinical outcomes were assessed. Results: Compared to the baseline, the relative cycle threshold (Ct) value of E6 and E7 reduced at the point of mid-RT in the majority of the patients (100% and 75% for E6 and E7, respectively). Similarly, the relative Ct value from the baseline to post-RT reduced in 86% and 100% of the patients for E6 and E7, respectively. During the follow-up period, three patients (33%) experienced disease progression. The relative baseline Ct values of these three patients were in the top 4 of all the patients. The sequences of HPV DNA were detected in five (83%) of six samples of the baseline saliva that underwent DNA sequencing, along with several gene mutations, such as TP53,CDKN2A and PIK3CA. Conclusions: This study demonstrates that, in addition to detection and quantification of HPV DNA by RT–PCR, detection by sequencing of HPV-DNA using a customized cancer panel is technically possible. [ABSTRACT FROM AUTHOR]

To assess the exact role of high-risk HPV testing in patients of carcinoma unknown primary with secondary metastasis to the neck who underwent TORS and neck dissection for identification of the primary site. A prospective study was carried out at a tertiary care centre over one year. Patients with unilateral neck swelling, which was cytologically proven squamous cell carcinoma neck metastasis, were included in the study. After clinicopathological evaluation, they underwent TORS-assisted ipsilateral radical tonsillectomy, tongue base mucosal wedge biopsy for primary site identification, and ipsilateral neck dissection. They underwent HPV RNA ISH from the tonsil, the base of the tongue and blood. They also underwent HPV DNA testing from the blood. P16 was done in the base of tongue, tonsil, and lymph node specimens. In the study cohort of 18 patients who underwent ipsilateral radical tonsillectomy, mucosal tongue base wedge biopsy and neck dissection, p16 positivity was isolated in 5.56%, 0% and 2.78% of patients, respectively. (n = 1/18, 0/18, 5/18). Interestingly, HPV E7 mRNA expression was absent in the tonsil /base of tongue specimens, but metastatic lymph nodes displayed expression in 11.11%. HPV DNA was undetected in all analysed tissues and patients' blood. In the Indian subcontinent, it is not essential to do detailed high-risk HPV analysis in cases of carcinoma unknown primary with secondary metastasis to the neck. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with locoregional head and neck cancer often receive radiation and/or surgery with curative intent. Chemotherapy is often used as a radiation sensitizer or adjunctively to improve treatment effect. However, these modalities are often associated with significant and potentially debilitating adverse events, which negatively impacts quality of life. HPV-associated oropharyngeal head and neck cancer has been shown to be more responsive to treatment compared to HPV-negative disease. Therefore, various de-escalation strategies have been under investigation in hopes of optimizing therapeutic response while also minimizing toxicity from treatment. The incidence of HPV-related oropharyngeal cancers has increased in recent decades. While cure rates exceed those of HPV-negative head and neck cancers, both acute and long-term sequelae of chemotherapy, radiation and surgery have led to clinical investigation into de-escalation of treatment. De-escalation trials have sought to reduce long-term treatment-related morbidity by altering or omitting chemotherapy, reducing radiation, or incorporating less invasive surgical resection through transoral surgery. More recent approaches include the use of novel agents such as immunotherapy in place of cisplatin. With the advent of tumor-tissue-modified HPV DNA detection and monitoring in blood, new strategies incorporating this biomarker are being developed. [ABSTRACT FROM AUTHOR]

Simple Summary: Oropharyngeal carcinoma (OPC) and its treatments can negatively affect patient quality of life (QoL). This study focused on assessing the impact on QoL in OPC survivors using the EORTC QLQ-C30 and EORTC QLQ-H&N35 scales before treatment and in the first and third years after treatment. Of 72 patients treated for OPC, 51 completed all questionnaires over 3 years. A variable deterioration of the QoL scores was detected prior to treatment. Most items of QoL worsened significantly after treatment and during the first year and improved in the third year. Advanced-stage cancer and definitive chemoradiotherapy treatment showed the worst scores. Patients treated with an open surgical approach exhibited significant deterioration compared to transoral surgery. This prospective long-term study in a homogeneous group of OPC survivors showed that although QoL was generally good, patients needed a long period of time to recover from both cancer and treatment effects. (1) Background: This prospective study aimed to assess the impact on quality of life (QoL) from pretreatment to 3 years after treatment in oropharyngeal carcinoma (OPC) survivors. (2) Methods: QoL was measured with the EORTC QLQ-C30 and EORTC QLQ-H&N35 scales before treatment and in the first and third years. (3) Results: Of 72 patients, 51 completed all questionnaires over 3 years. A variable deterioration of QoL scores was detected before treatment. Most items worsened significantly after treatment and during the first year and improved in the third year. Advanced-stage cancer and definitive chemoradiotherapy treatment showed the worst scores. At 3 years, patients who underwent surgery with adjuvant radiation therapy/chemotherapy had significantly better scores on global QoL and emotional functioning compared to those treated with definitive chemoradiotherapy, who also reported problems with sticky salivation and dry mouth. Patients treated with an open surgical approach showed significantly greater deterioration in physical and role functioning compared to transoral surgery. (4) Conclusions: This long-term prospective study is the first in Spain to use EORCT scales in a homogeneous group of OPC survivors. QoL was generally good, although patients needed a long period of time to recover from both cancer and side effects of treatment. Advanced-stage cancer and definitive chemoradiotherapy showed the worst scores. [ABSTRACT FROM AUTHOR]

Recently, microRNAs (miR) were identified to have potential links with oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC) oncogenesis, specifically miR-21. Since HPV is a major risk factor for the development of these diseases, we aimed to search the literature regarding miR-21 expression in both HPV-positive and HPV-negative OSCC/OPSCC. The search was performed in the PubMed (MEDLINE), Scopus, Web of Science, and Cochrane electronic databases. The research question was as follows: Is there a difference in the tissue expression of miR-21 between patients with HPV-positive and those with HPV-negative OSCC/OPSCC? After conducting a meticulous search strategy, four studies were included, and they had a pooled sample size of 621 subjects with OSCC and/or OPSCC. Three studies did not find any significant difference in miR-21 expression between HPV-positive and HPV-negative OSCC/OPSCC. The findings of this systematic review showed that there are no differences in miR-21 expression between HPV-positive and HPV-negative OSCC/OPSCC. Nevertheless, it is worth noting that there are still insufficient studies regarding this important subject, because understanding how HPV influences miR-21 expression and its downstream effects can provide insights into the molecular mechanisms underlying OSCC/OPSCC development and progression. [ABSTRACT FROM AUTHOR]

Background: The buccinator myomucosal island flaps are an excellent option for "like with like" oropharyngeal reconstruction in selected cases. We report a series of 15 patients and discuss the functional outcomes. Methods: From January 1, 2020 to February 31, 2023, 15 patients underwent oropharyngeal tumor resection and reconstruction with myomucosal island flaps. Buccal artery myomucosal island flap and tunnelized facial artery myomucosal island flap were used in 10 and 5 patients, respectively. In four cases, a total soft palate reconstruction was performed. Before removing the nasogastric tube, a videoendoscopy was performed in all cases to assess postoperative swallowing. Functional assessment was evaluated after a follow‐up of at least 12 months. Speech intelligibility and patient speech perception were assessed using the Hirose's 10‐point scoring system and the Voice Handicap Index. Dysphagia was assessed using the Dysphagia Outcome and Severity Scale and the Dysphagia Handicap Index. Finally, donor site morbidity was analyzed, and quality of life was assessed using the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ‐C30). Results: The median length of hospital stay was 10.5 days. Nasal feeding tube was removed on average in 8.6 days after surgery, and all patients were able to tolerate an oral soft diet. Intelligibility was very good in all cases. No major complications were detected, and donor site morbidity was low. Global quality of life was acceptable in all cases. Conclusions: Buccinator myomucosal island flaps represent a very interesting and versatile option for the functional reconstruction of oropharyngeal defects up to 7–8 cm. Level of Evidence: IV [ABSTRACT FROM AUTHOR]

Few reports have analyzed the fusion genes involved in carcinogenesis in the oropharynx, where the incidence of human papillomavirus-associated tumors is relatively low. The aim of this study was to identify novel driver fusion genes in patients with oropharyngeal cancer. The study enrolled fifty-seven patients who were diagnosed with oropharyngeal carcinoma. RNA sequencing data from fresh-frozen specimens were used to identify candidate fusion genes via the JAFFA, arriba, and STAR-Fusion pipelines. Candidate fusion genes were confirmed by direct sequencing. The expression level of a candidate fusion gene was compared to that of tumors without fusion genes. Finally, filtering was performed for driver genes using the annoFuse pipeline. In addition, the VIRTUS pipeline was used to analyze the presence of human papillomavirus in the tumors. We identified 5 (8.8 %) novel potential driver in-frame fusion genes, MKNK2 :: MOB3A, ICMT :: RPS6KA3, ATP1B3 :: GRK7, CSNK2A1 :: KIF16B , and FGFR3 :: MAEA , and 1 (1.8 %) known in-frame fusion gene, FGFR3 :: TACC3 , in 57 patients with pharyngeal carcinoma. Our results suggest that sporadic fusion genes may contribute to tumorigenesis in oropharyngeal carcinomas. [ABSTRACT FROM AUTHOR]

The oropharynx represents one of the most challenging areas to reconstruct for the head and neck surgeon. The buccinator myomucosal island flaps pedicled on the facial artery [tunnelized facial artery myomucosal island flap (t-FAMMIF)] or the buccal artery [buccal artery myomucosal island flap (BAMMIF)] are an ideal reconstructive option for moderate size defects measuring up to 8–9 cm. Two fresh specimens have been used to show the step-by-step surgical technique of both island flaps. Design and flap extension, dissection plane, identification of the vascular pedicle, flap rotation and insetting are described. Reconstructive indications and the pros and cons of each one are discussed in this article. Myomucosal island flaps represent a very useful and versatile option for the functional reconstruction of the oropharynx. A detailed knowledge of the vascular anatomy of the cheek is key to obtain a large flap while minimizing the risk of complications. [ABSTRACT FROM AUTHOR]

Background: Transoral videolaryngoscopic surgery (TOVS) is widely used in Japan, and conventional two‐dimensional (2D) endoscopic methods have been established. Three‐dimensional (3D) endoscopic surgery offers superior distance perception because it provides stereoscopic views. Recently, we have developed 3D endoscopy for TOVS (3D TOVS). Methods: This study included 46 patients with pharyngeal cancer who underwent 3D TOVS. The perioperative complications and survival curves were retrospectively analyzed. Results: One patient with oropharyngeal cancer who underwent neck dissection and transoral resection simultaneously experienced postoperative hemorrhage of the neck. Another patient with oropharyngeal cancer underwent hemostasis for postoperative pharyngeal hemorrhage. There was one case of aspiration pneumonia. One patient developed cervical lymph node recurrence; however, there was no local recurrence or primary mortality. The 2‐year overall survival, disease‐specific survival, local control rates, locoregional control rate, and invasive disease‐free survival were 90.9%, 100%, 100%, 97.4%, and 79.9%, respectively. Conclusions: Three‐dimensional endoscopy can be safely applied to TOVS. [ABSTRACT FROM AUTHOR]

Background: Differences in pretreatment body mass index (BMI) have been associated with survival in squamous cell carcinoma of head and neck (SCCHN). We examined effects of BMI on survival in SCCHN patients after stratifying patients by tumor human papillomavirus (HPV) status and subsite. Methods: Totally 2204 SCCHN patients in a prospective study were included in this secondary analysis. Multivariable Cox models were used to evaluate associations between pretreatment BMI and overall survival, disease‐specific survival, and disease‐free survival. Results: BMI was significantly higher among patients with HPV‐positive tumors than HPV‐negative tumors. BMI >25 kg/m2 was associated with improved survival, while BMI <18.5 kg/m2 was associated with reduced survival, particularly in patients with HPV‐positive oropharyngeal cancer tumors. Conclusions: This exploratory analysis suggests that pretreatment BMI could be an independent prognostic factor of survival outcomes in SCCHN patients, particularly in patients with HPV‐positive oropharyngeal cancer tumors. Further prospective investigations are warranted. [ABSTRACT FROM AUTHOR]

There is limited understanding of epidemiology and time trends of human papilloma virus (HPV)‐driven head and neck cancers (HNC) in Japan, especially outside of the oropharynx. To assess HPV‐driven HNC, a non‐interventional study (BROADEN) of HNC patients diagnosed in 2008–2009 and 2018–2019 was conducted in Japan. Adult patients with oropharyngeal, nasopharyngeal, laryngeal, hypopharyngeal or oral cavity cancers were included in this study. HPV was centrally tested using p16INK4a immunohistochemistry, HPV‐DNA PCR and HPV E6*I mRNA. HPV attributability required positivity in at least two tests (p16INK4a immunohistochemistry, HPV‐DNA PCR, HPV E6*I mRNA) in the oropharynx, and HPV‐DNA and HPV E6*I mRNA positivity for non‐oropharynx sites. Nineteen hospitals included a total of 1108 patients, of whom 981 had valid samples. Men accounted for 82% of HNC diagnoses. Patients in the earlier cohort were younger and included a higher percentage of smokers. There was an increasing trend of HPV‐driven oropharyngeal cancer over the last decade, from 44.2% to 51.7%. HPV attribution in nasopharyngeal cancers was 3.2% in 2008–2009 and 7.5% in 2018–2019; and 4.4% and 0% for larynx respectively. In total, 95.2% of HPV‐driven HNC were attributed to HPV genotypes included in the 9‐valent HPV vaccine being HPV16 the most prominent genotype. These results suggest that an epidemiologic shift is happening in Japan, with a decrease in smoking and alcohol use and an increase in HPV‐driven HNC. The increasing trend of HPV‐driven HNC in Japan highlights the need for preventive strategies to mitigate the rise of HPV‐driven HNC. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) infections are an increasing cause of oropharyngeal squamous cell carcinomas (OPSCC). Integration of the viral genome into the host genome is suggested to affect carcinogenesis, however, the correlation with OPSCC patient prognosis is still unclear. Research on HPV integration is hampered by current integration detection technologies and their unsuitability for formalin‐fixed paraffin‐embedded (FFPE) tissues. This study aims to develop and validate a novel targeted proximity‐ligation based sequencing method (targeted locus amplification/capture [TLA/TLC]) for HPV integration detection in cell lines and FFPE OPSCCs. For the identification of HPV integrations, TLA/TLC was applied to 7 cell lines and 27 FFPE OPSCCs. Following preprocessing steps, a polymerase chain reaction (PCR)‐based HPV enrichment was performed on the cell lines and a capture‐based HPV enrichment was performed on the FFPE tissues before paired‐end sequencing. TLA was able to sequence up to hundreds of kb around the target, detecting exact HPV integration loci, structural variants, and chromosomal rearrangements. In all cell lines, one or more integration sites were identified, in accordance with detection of integrated papillomavirus sequences PCR data and the literature. TLC detected integrated HPV in 15/27 FFPE OPSCCs and identified simple and complex integration patterns. In general, TLA/TLC confirmed PCR data and detected additional integration sites. In conclusion TLA/TLC reliably and robustly detects HPV integration in cell lines and FFPE OPSCCs, enabling large, population‐based studies on the clinical relevance of HPV integration. Furthermore, this approach might be valuable for clonality assessment of HPV‐related tumors in clinical diagnostics. [ABSTRACT FROM AUTHOR]

Background: Cisplatin-based chemoradiation is a standard treatment for many patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), an etiologically distinct subset of head and neck cancer. Although associated with good long-term survival, clinical risk factors for ototoxicity have been understudied in this population. This study aimed to evaluate clinical predictors associated with ototoxicity in HPV-positive OPSCC patients treated with cisplatin chemoradiation. Methods: This retrospective case-control study included 201 adult patients (>18 years) with histologically confirmed HPV-positive OPSCC who received cisplatin chemoradiation as their primary treatment from 2001 and 2019 at a single tertiary cancer center. Ototoxicity was determined using baseline and follow-up audiometry and the Common Terminology Criteria for Adverse Events v5.0 grading criteria (Grade ≥2). Multivariable logistic regression [adjusted odds ratio (aOR)] identified significant predictors that increased the odds of ototoxicity. Results: A total of 201 patients [165 males; median (IQR) age, 57 (11) years] were included in the study. The incidence of ototoxicity in the worst ear was 56.2%, with the greatest hearing loss occurring at high frequencies (4-8 kHz), resulting in a loss of 12.5 dB at 4 to 6 kHz and 20 dB at 6 to 8 kHz. High-dose cisplatin administration compared to weekly administration [aOR 4.93 (95% CI: 1.84-14.99), P =.003], a higher mean cochlear radiation dose [aOR 1.58 (95% CI: 1.12-2.30), P =.01], smoking history [aOR 2.89 (95% CI: 1.51-5.63), P =.001], and a 10 year increase in age [aOR 2.07 (95% CI: 1.25-3.52), P =.006] were each independently associated with increased odds of ototoxicity. Conclusions: Clinical predictors of ototoxicity in HPV-positive OPSCC patients treated with cisplatin-based chemoradiation include the use of a high-dose cisplatin regimen, higher cochlear radiation doses, a history of smoking, and older age. With the rising incidence of this malignancy in Western countries and overall improved survivorship, our research motivates future studies into risk stratification and earlier interventions to mitigate and reduce the risk of ototoxicity. [ABSTRACT FROM AUTHOR]

Background: There are 54,000 new cases of oral cavity and oropharyngeal cancer in the United States and more than 476,000 worldwide each year. Oral cavity and oropharyngeal squamous cell carcinoma make up most tumors with five-year survival rates of 50% due to prevalence of late-stage diagnoses. Improved methods of early detection in high-risk individuals are urgently needed. We aimed to assess the tumorigenic biomarkers soluble CD44 (solCD44) and total protein (TP) measured using oral rinses as affordable convenient screening tools for cancer detection. Methods: In this prospective cohort study, we recruited 150 healthy current or former smokers through a community screening program. Baseline and four annual visits were conducted from March 2011-January 2016 with records followed until August 2020. Participants provided oral rinses, received head and neck exams, and completed questionnaires. SolCD44 and TP levels were measured and compared across groups and time. Participants were placed in the cancer group if malignancy developed in the study period, the suspicious group if physical exams were concerning for premalignant disease or cancer in the head and neck, and the healthy group if there were no suspicious findings. This analysis used two-sample t-test for comparison of means and two-sample Wilcoxon Test for comparison of medians. For subjects with follow-ups, estimated means of biomarkers were obtained from a fitted Repeated Measures Analysis of Variance (RANOVA) model including group, visit, and their interaction. Pairwise comparisons of mean solCD44 were made, including intergroup and intragroup comparison of values at different years. Results: Most participants were males (58.7%), < 60 years of age. (90.7%), and Black (100%). Baseline mean solCD44 was elevated (2.781 ng/ml) in the cancer group compared to the suspicious group (1.849 ng/ml) and healthy group (1.779 ng/ml). Conclusion: This study supports the feasibility of a CD44-based oral rinse test as an affordable and convenient adjunctive tool for early detection of aerodigestive tract and other cancers in high-risk populations. [ABSTRACT FROM AUTHOR]

Introduction: The incidence of squamous carcinoma of the oropharynx (OPSCC) has presented an increase worldwide, a fact that occurs along with a phenomenon of epidemiological transition, whose pathogenesis is linked to human papilloma virus (HPV) in a significant part of the cases. Published evidence at the Latin American level is scarce. The present study aims to evaluate the epidemiological and clinical characteristics of patients with oropharyngeal cancer treated in a public oncology reference centre in Chile. Methodology: A cross-sectional study was carried out. Patients with histological confirmation of OPSCC aged 18 years or older, referred to the National Cancer Institute of Chile between 2012 and 2023 were included. The association with HPV was determined by immunohistochemistry for p16. Results: 178 patients were analysed, most of them in locoregionally advanced stages involving the palatine tonsil. Seventy-seven percent were male, with a median age of 60 years. Sixty-seven percent of patients were positive for p16, with a progressive increase to 85% in the last 2 years of the study. The p16(+) patients were younger and had fewer classical risk factors. Primary treatment was radiotherapy in 94% of patients. Conclusion: The epidemiological profile of patients with OPSCC treated in a Chilean public oncology referral centre reflects the epidemiological transition observed in developed countries. This change justifies the need to adapt health policies and conduct research that considers the characteristics of this new epidemiological profile. [ABSTRACT FROM AUTHOR]