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

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

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

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

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

The MD Anderson Dysphagia Inventory (MDADI), a measure of swallowing-related quality of life, has become the preferred patient-reported outcome measure (PROM) in contemporary clinical trials evaluating the experience of human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPVOPSCC) survivors. With many potentially practice-changing studies using the MDADI composite score as either a primary or coprimary endpoint, or as a key secondary endpoint, it is important to understand its psychometric properties as judged by contemporary PROM standards, with a particular focus on its application to contemporary HPVOPSCC populations. In this critical review, we evaluate contemporary HPVOPSCC studies reporting MDADI outcomes, followed by a detailed evaluation of the psychometric properties of the MDADI. Although the focus of this review was the MDADI, the issues discussed are not unique to the MDADI and have broader applicability to the evaluation and assessment of other PROMs currently in use. First, it may be possible to improve administration of the instrument, as related to missing items, scoring, and the number of items required. Second, although in many instances, the MDADI has been intended as a direct or surrogate measure of swallowing physiology, the MDADI composite score captures a broader health-related quality of life construct affected by both swallowing and eating, the latter of which may be affected by a range of nonswallowing treatment-related toxicities. Finally, a clinically meaningful change of 10 in the MDADI composite score, widely accepted and applied to the clinical trial setting, represents an undoubtably clinically relevant difference in unselected head and neck cancer survivors. However, the smallest difference that might be clinically important to a highly functional HPVOPSCC cohort remains uncertain. Understanding the purpose and properties of the MDADI instrument and furthering the sophistication with which we apply it in this population would improve its interpretation in clinical trials. [ABSTRACT FROM AUTHOR]

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

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

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

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

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

Certain human papillomaviruses (HPVs) are etiological agents for several anogenital and oropharyngeal cancers. During initial infection, HPV16, the most prevalent cancer-causing type, specifically interacts with heparan sulfates (HSs), not only enabling initial cell attachment but also triggering a crucial conformational change in viral capsids termed structural activation. It is unknown, whether these HPV16-HS interactions depend on HS sulfation patterns. Thus, we probed potential roles of HS sulfations using cell-based functional and physicochemical assays, including single-molecule force spectroscopy. Our results demonstrate that N-sulfation of HS is crucial for virus binding and structural activation by providing high-affinity sites, and that additional 6O-sulfation is required to mechanically stabilize the interaction, whereas 2O-sulfation and 3O-sulfation are mostly dispensable. Together, our findings identify the contribution of HS sulfation patterns to HPV16 binding and structural activation and reveal how distinct sulfation groups of HS synergize to facilitate HPV16 entry, which, in turn, likely influences the tropism of HPVs. [ABSTRACT FROM AUTHOR]

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

Currently, there are no specific antiviral therapeutic approaches targeting Human papillomaviruses (HPVs), which cause around 5% of all human cancers. Specific antiviral reagents are particularly needed for HPV-related oropharyngeal cancers (HPV+OPCs) whose incidence is increasing and for which there are no early diagnostic tools available. We and others have demonstrated that the estrogen receptor alpha (ERα) is overexpressed in HPV+OPCs, compared to HPV-negative cancers in this region, and that these elevated levels are associated with an improved disease outcome. Utilizing this HPV+-specific overexpression profile, we previously demonstrated that estrogen attenuates the growth and cell viability of HPV+ keratinocytes and HPV+ cancer cells in vitro. Expansion of this work in vivo failed to replicate this sensitization. The role of stromal support from the tumor microenvironment (TME) has previously been tied to both the HPV lifecycle and in vivo therapeutic responses. Our investigations revealed that in vitro co-culture with fibroblasts attenuated HPV+-specific estrogen growth responses. Continuing to monopolize on the HPV+-specific overexpression of ERα, our co-culture models then assessed the suitability of the selective estrogen receptor modulators (SERMs), raloxifene and tamoxifen, and showed growth attenuation in a variety of our models to one or both of these drugs in vitro. Utilization of these SERMs in vivo closely resembled the sensitization predicted by our co-culture models. Therefore, the in vitro fibroblast co-culture model better predicts in vivo responses. We propose that utilization of our co-culture in vitro model can accelerate cancer therapeutic drug discovery. [ABSTRACT FROM AUTHOR]

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

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]

The incidence of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) is increasing worldwide. HPV vaccines have shown efficacy in preventing diseases in both males and females. Therefore, there is a need to develop cost-effective strategies for HPV vaccines to prevent HPV-related OPC. This meta-analysis aimed to evaluate cost-effectiveness using the global mean of incremental cost-effectiveness ratios compared to the willingness-to-pay threshold and incremental net benefits (INBs) of HPV vaccination strategies between boys' extension vaccine and girls only. These recommendations will be useful for countries that have not implemented universal HPV vaccines in national programs, such as Taiwan. Studies evaluating the cost-effectiveness of HPV vaccination strategies in the prevention of OPC that included both sexes versus girls only were identified through the Cochrane Library, EMBASE, PubMed, ScienceDirect, and Web of Science databases on February 05, 2024, and a meta-analysis of pooled INBs was performed using a random-effects model. The outcome was an effective measurement of the OPC burden. The results are represented in USD (2024). Fifteen model analyses were included. All the studies were conducted in high-income countries. The global mean of incremental cost-effectiveness ratio was $39,553 (95% CI, $27,008–66,641) per quality-adjusted life years gained, which was below the global mean of the willingness-to-pay threshold of $65,473 (95% CI, $52,138–83,755). Pooled INBs of $9370 (95% CI, $5046–13,695; P < 0.001) favored the extended HPV in boys. HPV vaccination strategies that include boys are cost-effective compared to those with girls only in preventing OPC burden. By implementing a universal HPV vaccination program, countries can receive $9370 in additional monetary benefits per patient. Given its relevance to high-income countries, this study offers key insights that can aid policymakers in Taiwan. [ABSTRACT FROM AUTHOR]

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

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

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

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

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

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

Simple Summary: When we consider nutrition in patients with head and neck cancer (HNC), we mostly focus on the type of nutrition; studies on the type of nutrition at different time points are sparse. This retrospective study analyzed patients with HNC according to their nutritional status and association with percutaneous endoscopic gastrostomy (PEG) from admission to six months after treatment at a tertiary hospital in Germany from 2017 to 2019. Results showed that 14.9% required PEG before starting therapy. The need for PEG increased to 22.7% at six weeks after therapy and remained stable at 23% six months later. PEG placement was more frequently required for alcohol or nicotine use, oropharyngeal and hypopharyngeal carcinoma, squamous cell carcinoma, cancer stage III/IV, chemotherapy and impaired feeding. There has been an increase in the percentage of PEG over the observation period. This retrospective monocentric cohort study analyzed patients with head and neck cancer according their nutritional status and association of percutaneous endoscopic gastrostomy (PEG) from admission to six months after treatment at a tertiary hospital in Germany from 2017 to 2019. A total of 289 patients (76.5% men; median age 62 years; 63.3% stage IV) were included. Univariate analyses and ANOVAs with repeated measures were performed to analyze differences over time. The percentage of patients requiring PEG was 14.9% (43 of 289 patients) before start of treatment (Z0), 14% (40 of 286 patients alive) after one week (Z1), 22.7% (58 of 255 patients) after six weeks (Z2) and 23% (53 of 230 patients) after six months (Z3) from the end of treatment. PEG placement was associated with alcohol or nicotine consumption, in oropharyngeal and hypopharyngeal carcinoma, squamous cell carcinoma, cancer stage III/IV, chemotherapy and impairment of food intake (all p < 0.05). Weight loss between Z1 and Z3 with PEG did not differ from patients without PEG at Z0 (p = 0.074), although patients with PEG at Z0 had a lower mean weight at the beginning. PEG was important for a quarter of the patients alive at Z3 and helped to prevent weight loss. [ABSTRACT FROM AUTHOR]

Background Oral human papillomavirus (HPV) infection and the oral microbiome are associated with oropharyngeal cancer. However, population-based data on the association of oral microbiome with oral HPV infection are limited. Method A cross-sectional analysis of 5496 20–59-year-old participants in the 2009–2012 National Health and Nutrition Examination Survey was performed. Associations with oral HPV infection were assessed using multivariable logistic regression for oral microbiome α-diversity (within-sample diversity), and using principal coordinate analysis and permutational multivariate analysis of variance for β-diversity (between-sample heterogeneity). Results Overall, for α-diversity, a lower number of observed amplicon sequence variants (adjusted odds ratio [aOR] = 0.996; 95% confidence interval [CI] =.992–.999) and reduced Faith's phylogenetic diversity (aOR = 0.95; 95% CI =.90–.99) were associated with high-risk oral HPV infection. β-diversity showed differentiation of oral microbiome community by high-risk oral HPV infection as measured by Bray-Curtis dissimilarity (R 2 = 0.054%; P =.029) and unweighted UniFrac distance (R 2 = 0.046%; P =.045). There were differential associations when stratified by sex. Conclusions Both oral microbiome α-diversity and β-diversity were marginally associated with oral HPV infection. Longitudinal studies are needed to characterize the role of the microbiome in the natural history of oral HPV infection. [ABSTRACT FROM AUTHOR]

The impact of computed tomography-defined sarcopenia on outcomes in head and neck cancer has been well described. Sarcopenic obesity (SO) (depleted muscle mass combined with obesity) may pose a more serious risk than either condition alone. We investigated SO and its impact on survival and critical weight loss (≥ 5 %) in patients with head and neck cancer who received curative radiotherapy (± other modalities). Retrospective analysis of computed tomography cross-sectional muscle at cervical (C3), thoracic (T2) and lumbar (L3) regions was conducted. Patients were grouped by BMI and sarcopenia status based on established thresholds. A total of 413 patients were included for analysis, the majority having oropharyngeal carcinoma (52 %), and 56 % received primary concurrent chemoradiotherapy. The majority of the cohort (65 %) was overweight or obese (BMI ≥ 25 kg/m2). Sarcopenia was found in 43 %, with 65 % having SO (n 116), equating to 28 % of the whole cohort. Critical weight loss was experienced by 58 % (n 238). A significantly higher proportion of patients with SO experienced critical weight loss (n 70 v. 19, P < 0·001) and were four times more likely to do so during treatment (OR 4·1; 95 % CI 1·5, 7·1; P = 0·002). SO was not found to impact on overall or cancer-specific survival; however, in patients with sarcopenia, those with SO had better overall survival (median 9·1 v. 7·0 years; 95 % CI 5·2, 16·8; P = 0·021). SO at the time of presentation in patients with head and neck cancer is predictive of critical weight loss during treatment, and muscle evaluation can be useful in identifying patients at nutritional risk regardless of BMI and obvious signs of wasting. [ABSTRACT FROM AUTHOR]

Objective: To analyse the rate of contralateral nodal metastasis in human papillomavirus (HPV)-associated oropharyngeal carcinoma and identify the patient cohorts that would benefit from bilateral neck treatment. Methods: A retrospective cohort review was performed on 110 HPV-positive oropharyngeal carcinoma patients who underwent transoral robotic surgery and bilateral neck dissections from 2012 to 2022. The primary outcome was to investigate the pathological incidence and location of contralateral neck node metastasis. Results: The contralateral nodal disease rate was 12.7 per cent (n = 14), of which 2 patients (2 per cent) were occult findings, with comparable results between tongue base and tonsil sub-groups. The most commonly involved contralateral nodal station was level II (11 of 110 patients, 10 per cent). The presence of extra-nodal extension and multiple ipsilateral positive nodes was associated with increased risk of contralateral nodal disease. Conclusion: The incidence of contralateral nodal and occult disease in the studied cohort is low. The characteristics of patients who may benefit from bilateral neck treatment were demonstrated. [ABSTRACT FROM AUTHOR]

Branchial cleft cyst (BCC) most frequently arises from the second branchial cleft and is located anterior to the sternocleidomastoid muscle at the mandibular angle. However, very rarely, this may occur in the parapharyngeal space. Interestingly, the parapharyngeal BCC is frequently misdiagnosed as a peritonsillar abscess. In this study, we reported 2 cases of parapharyngeal BCC misdiagnosed as peritonsillar abscess. [ABSTRACT FROM AUTHOR]

Background: Oropharyngeal cancer (OPC) survivorship is a nursing priority because patients are living longer while significant short-term and long-term treatment complications that require nursing care are increasing. Hospital readmission is costly and reflects the quality of care patients receive. Objectives: This secondary analysis aimed to determine the prevalence of treatment complications resulting in hospital admissions among persons with OPC and examine the relationship between treatment complications resulting in hospital admission among persons with OPC and all other persons with head and neck cancer. Methods: Using the National Inpatient Survey 2008-2019 database, we identified persons with relevant head and neck cancer diagnoses using specific International Classification of Disease ICD-9 and ICD-10 codes. Complications were operationalized by diagnosis-related codes; persons with codes for major elective surgery were excluded as our focus was posttreatment symptoms requiring hospitalization. Descriptive statistics were used to characterize persons with OPC hospitalized between 2008 and 2019. Binary logistic regression was used to assess complications using crude comparisons. The Elixhauser Comorbidity Index was used for controlling for comorbidities. Results: The final analysis samples included 751,533: 164,770 persons with OPC and 586,763 with other head and cancers. Themost prevalent diagnoses observed in those with OPC were esophagitis, nutrition disorder, hematological disorder, and renal failure; the least common diagnoses were sepsis, respiratory tract infection, and pneumonia. Binary regression revealed that persons with OPC experienced significantly more esophagitis, nutrition disorders, hematological disorders, and renal failure compared to persons with other head and neck cancers. Discussion: Treatment of survivors of OPC requires more intensive monitoring for early symptoms associated with treatment, including esophagitis, nutrition disorders, bleeding disorders, and renal failure, than persons with other head and neck cancers. Monitoring laboratory values and clinical manifestations of these conditions is imperative. Nurses may encounter persons with OPC in emergency departments, outpatient radiology, or inpatient general medicine floors to manage swallowing difficulties, dehydration, malnutrition, and bleeding. Delayed or ineffective treatment of these conditions contributes to readmission, financial burden, and impairment of patient's quality of life. Future research should investigate the relationship between targeted treatment for expected complications and readmission rates in persons with OPC. [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]

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: 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]

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]

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can assess tumour vascularity, which depends on the process of angiogenesis and affects tumour response to treatment. Our study explored the associations between DCE-MRI parameters and the expression of plasma angiogenic factors in human papilloma virus (HPV)-negative oropharyngeal cancer, as well as their predictive value for response to concurrent chemoradiotherapy (cCRT). Twenty-five patients with locally advanced HPV-negative oropharyngeal carcinoma were prospectively enrolled in the study. DCE-MRI and blood plasma sampling were conducted before cCRT, after receiving a radiation dose of 20 Gy, and after the completion of cCRT. Perfusion parameters ktrans, kep, Ve, initial area under the curve (iAUC) and plasma expression levels of angiogenic factors (vascular endothelial growth factor [VEGF], connective tissue growth factor [CTGF], platelet-derived growth factor [PDGF]-AB, angiogenin [ANG], endostatin [END] and thrombospondin-1 [THBS1]) were measured at each time-point. Patients were stratified into responders and non-responders based on clinical evaluation. Differences and correlations between measures were used to generate prognostic models for response prediction. Higher perfusion parameter ktrans and higher plasma VEGF levels successfully discriminated responders from non-responders across all measured time-points, whereas higher iAUC and higher plasma PDGF-AB levels were also discriminative at selected time points. Using early intra-treatment measurements of ktrans and VEGF, a predictive model was created with cut-off values of 0.259 min−1 for ktrans and 62.5 pg/mL for plasma VEGF. Early intra-treatment DCE-MRI parameter ktrans and plasma VEGF levels may be valuable early predictors of response to cCRT in HPV-negative oropharyngeal cancer. [ABSTRACT FROM AUTHOR]

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

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

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

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

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

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

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

Abstract 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%),

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]

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]

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/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]