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Our aim was to compare risk of synchronous and metachronous hepatobiliary second primary malignancies (SPMs) in survivors of human papillomavirus (HPV)-related [i.e., p16(+)] and HPV-unrelated [i.e., p16(-)] oropharyngeal cancer (OPC). A retrospective study was conducted for cases with OPC diagnosis during years 2018–2021 who had known p16 status using data of USA from Surveillance, Epidemiology, and End Results (SEER) Program [Incidence - SEER Research Limited-Field Data, 22 Registries (excl IL and MA), Nov 2023 Sub (2000–2021)]. In the statistical analyses, death was considered as a competing event for the development of a hepatobiliary SPM. Bias due to unbalanced baseline characteristics was eliminated by adjustments using propensity score and inverse probability of treatment weighting (IPTW). Risk of development of a hepatobiliary SPM was assessed using propensity-score-adjusted time-varying Cox proportional hazard regression [adjusted hazard ratio (aHR) with 95 % confidence interval (95 % CI)]. Overall, 25759 cases with tumor status of p16(-) (6353) and p16(+) (19406) with median (interquartile range) follow-up times of 14 (6, 26) and 20 (9, 32) months, respectively, were included. From these, 48 had a hepatobiliary SPM. Compared to HPV-related OPC, HPV-unrelated OPC had significantly elevated risk of synchronous all hepatobiliary SPMs [aHR= 2.39 (95 % CI, 1.11–5.15); P = 0.026] and synchronous hepatocellular carcinoma (HCC) SPM [aHR= 2.86 (95 % CI, 1.18–6.92); P = 0.020], but not metachronous ones. Curves of cumulative incidence of a hepatobiliary (or HCC) SPM and cumulative survival probability for those with a hepatobiliary SPM, both stratified by p16 status and adjusted by IPTW, were generated. The median survival time among patients with a hepatobiliary SPM was shorter for HPV-unrelated OPC (0.8 years) compared to HPV-related OPC (2.6 years). The observed elevated risk was likely due to heavy alcohol and tobacco use and the protective role of HPV infection against HCC development in carriers of hepatitis C virus. •HPV-unrelated [p16(-)] and HPV-related [p16(+)] subgroups show different biology.•Hepatobiliary second primary malignancies (SPMs) significantly reduce survival.•Using inverse probability of treatment weighting (IPTW) to eliminate baseline bias.•IPTW-weighted Kaplan-Meier estimates of survival curves stratified by p16 status.•IPTW-adjusted cumulative incidence curves of hepatobiliary SPMs by p16 status.

Background Human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) is increasing in prevalence, but the drivers of metastasis remain poorly understood, which impacts the ability to personalise management decisions. Much of the genomic research to date focuses on the HPV-negative population. Here, we utilise single-cell and spatial single-cell techniques to understand the drivers of metastasis. Methods Patients with HPV-positive OPC and cervical lymph node metastases treated with curative surgery had matched samples from the primary and lymph nodes collected for research. Single-cell RNA sequencing, single-cell spatial sequencing (Visium) and in-situ spatial platforms were performed. Cancer clones were delineated using inferred copy number variation. Expression phenotypes and interactions with the tumour microenvironment were compared between the metastasising and non-metastasising cancer clones. Results Individual cancer clones have varied abilities to metastasise and undergo clonal expansion in the lymph node, with only a subset of clones present in the primary expanding in the lymph node. Four mechanisms were identified as defining the metastatic phenotype, including protein translation adaptation, immunoproteasome dysfunction and immune evasion, suppression of the IFN immune response and cap-independent protein translation. Conclusions This research elucidates multiple mechanisms driving the expansion of cancer clones in HPV-positive oropharyngeal cancer. By detailing the roles of translational adaptation, immunoproteasome dysfunction, suppression of the interferon immune response and cap-independent protein translation, we provide insights into how these processes contribute to immune evasion and tumour survival.

PurposeCompromised swallowing, speaking, and local complications are the major disadvantages of established approaches to the posterior tongue and oropharynx. The mandibular split involves an esthetically unpleasant bipartition of the lower lip and is prone to bony non-union or sequestration. The conventional pull-through technique on the other hand lacks the secure reattachment of the lingually released soft tissues.MethodsThe feasibility of a new modified pull-through approach was tested on three anatomical specimens. CAD/CAM cutting guides were used to design a retentive bone flap to properly refixate the genioglossus and geniohyoid muscles after the procedure. The radiographic assessment and treatment planning was performed on 12 cadavers. The entire procedure was tested surgically via dissection in three of those cases. This procedure was then applied in a clinical case.ResultsPrecise repositioning and dynamic compression of bony segments was possible reproducibly and without injury to adjacent structures. In all dissected cases, a median lingual foramen was found and in two cases vessels entering it could be dissected Radiologic anatomical landmarks were sufficient in all 12 cases to perform the clinical planning procedure. Clinically, the osteotomized segment demonstrated good blood supply and plateless repositioning was verified postoperatively via cone beam scan.ConclusionThe method presented is safe and easy to perform. Individual cutting guides improve the safety and accuracy of the procedure, potentially eliminating the need for osteosynthesis. We provide the anatomical and radiologic basis for clinical evaluation of this pedicled bone flap procedure and present the clinical application of this modified pull-through approach.

Background This study aims to develop a novel predictive model for determining human papillomavirus (HPV) presence in oropharyngeal cancer using computed tomography (CT). Current image‐based HPV prediction methods are hindered by high computational demands or suboptimal performance. Methods To address these issues, we propose a methodology that employs a Siamese Neural Network architecture, integrating multi‐modality off‐the‐shelf features—handcrafted features and 3D deep features—to enhance the representation of information. We assessed the incremental benefit of combining 3D deep features from various networks and introduced manufacturer normalization. Our method was also designed for computational efficiency, utilizing transfer learning and allowing for model execution on a single‐CPU platform. A substantial dataset comprising 1453 valid samples was used as internal validation, a separate independent dataset for external validation. Results Our proposed model achieved superior performance compared to other methods, with an average area under the receiver operating characteristic curve (AUC) of 0.791 [95% (confidence interval, CI), 0.781–0.809], an average recall of 0.827 [95% CI, 0.798–0.858], and an average accuracy of 0.741 [95% CI, 0.730–0.752], indicating promise for clinical application. In the external validation, proposed method attained an AUC of 0.581 [95% CI, 0.560–0.603] and same network architecture with pure deep features achieved an AUC of 0.700 [95% CI, 0.682–0.717]. An ablation study confirmed the effectiveness of incorporating manufacturer normalization and the synergistic effect of combining different feature sets. Conclusion Overall, our proposed model not only outperforms existing counterparts for HPV status prediction but is also computationally accessible for use on a single‐CPU platform, which reduces resource requirements and enhances clinical usability.

•The incidence of oral and oropharyngeal cancers fluctuated, whereas the mortality increased from 2005 to 2013 in China.•A heavier burden from oral and oropharyngeal cancers was predicted in the next two decades in China.•This is the latest summarization of the epidemiological trends of oral and oropharyngeal cancers in China. Oral and oropharyngeal cancers are among the most common cancers globally. This study aimed to assess the incidence and mortality trends of oral and oropharyngeal cancers in China between 2005 and 2013. Estimates of national trends of oral and oropharyngeal cancers were based on the data from Chinese Cancer Registry Annual Reports. The crude incidence rates of oral and oropharyngeal cancers between 2015 and 2035 were evaluated. The age-standardized rate was based on the world standard population. It was estimated that 285,857 new cases and 132,698 deaths were related to oral and oropharyngeal cancers in China between 2005 and 2013, with mouth and tongue cancers being the most frequently diagnosed and the leading causes of death among all oral and oropharyngeal cancers. The incidence rates of oral and oropharyngeal cancer fluctuated from 1.69 to 1.89 per 100,000 person-years, and the mortality rate showed an increasing trend, ranging from 0.77 and 0.84 per 100,000 person-years. Males were more susceptible than females to oral and oropharyngeal cancers. The incidence and mortality rates of oral and oropharyngeal cancers were significantly higher in urban regions. The crude incidence rates of oral cancers are projected to increase from 2.26 to 3.21 per 100,000 person-years over the next 20 years in China. The incidence of oral and oropharyngeal cancers fluctuated, whereas the mortality rate showed an upward trend from 2005 to 2013. A heavier burden from oral and oropharyngeal cancers is predicted in the next two decades in China.

IntroductionHead 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.MethodsThis 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 MR-Egger. A reverse MR analysis was subsequently performed. Cochrans Q test, MR‐Egger intercept test, leave one out analysis, and the funnel plot were all used in sensitivity analyses.ResultsGenetically 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.ConclusionCollectively, 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.

The role of induction chemotherapy (IC) in locally advanced oropharyngeal cancer (OPC) remains debatable, and suitable candidates for de-escalation treatment in these patients have not been fully identified. Therefore, the present study aimed to identify high-risk candidates for human papillomavirus (HPV)-positive OPC by analyzing patients who underwent IC followed by chemoradiotherapy (CRT) to guide optimal treatment strategies. Patients diagnosed with stage III-IVA OPC and treated with a minimum of two cycles of IC followed by CRT, between 2004 and 2020, were retrospectively reviewed. All the patients were restaged according to the American Joint Committee on Cancer, 8th edition. The overall response rate and survival outcomes associated with clinical factors based on HPV status were analyzed using univariate and multivariate analyses. The present study analyzed 105 patients with a median age of 60 years (range, 40-76 years). Among 105 patients, 40 (38.1%) were HPV-negative and 65 (61.9%) HPV-positive. In all patients, survival outcomes were notably poorer in patients aged ≥60 years (P=0.006) and those who did not achieve complete response post-CRT (P<0.001), irrespective of the HPV status. The median relative dose intensity of IC was ≥80%, indicating adequate treatment, regardless of age. In contrast to patients with HPV-negative OPC, age ≥60 years (P=0.011) and T4 stage (P=0.019) emerged as substantial poor prognostic factors for survival outcomes in patients with HPV-positive OPC. Patients with HPV-positive OPC were categorized into three groups based on the number of clinical factors at diagnosis (such as age and T4 stage). The progression-free and overall survival showed significant stratification across each group as the number of high-risk factors increased despite IC and CRT. The findings indicated that patients with these high-risk factors require a cautious therapeutic strategy even when they are diagnosed with HPV-positive OPC, and the role of combined modality, including IC, will need to be investigated in a randomized trial to be routinely incorporated into clinical practice.

► We estimated the annual direct medical costs attributable to HPV in the USA. ► The overall annual direct medical cost burden was estimated to be $8.0 billion. ► Most of this cost was for cervical cancer screening and follow-up ($6.6 billion). Estimates of the direct medical costs attributable to human papillomavirus (HPV) can help to quantify the economic burden of HPV and to illustrate the potential benefits of HPV vaccination. The purpose of this report was to update the estimated annual direct medical costs of the prevention and treatment of HPV-associated disease in the United States, for all HPV types. We included the costs of cervical cancer screening and follow-up and the treatment costs of the following HPV-associated health outcomes: cervical cancer, other anogenital cancers (anal, vaginal, vulvar and penile), oropharyngeal cancer, genital warts, and recurrent respiratory papillomatosis (RRP). We obtained updated incidence and cost estimates from the literature. The overall annual direct medical cost burden of preventing and treating HPV-associated disease was estimated to be $8.0 billion (2010 U.S. dollars). Of this total cost, about $6.6 billion (82.3%) was for routine cervical cancer screening and follow-up, $1.0 billion (12.0%) was for cancer (including $0.4 billion for cervical cancer and $0.3 billion for oropharyngeal cancer), $0.3 billion (3.6%) was for genital warts, and $0.2 billion (2.1%) was for RRP.

Background and Objectives: Anatomical variations in the head, neck and chest are common, and are observed as occasional findings on computed tomography (CT). Although anatomical variations are mostly asymptomatic and do not cause any negative influence on the body function, they may jeopardize diagnosis and may be confused with pathological conditions. The presence of variations may also limit surgical access during tumor removal. The aim of this study was to investigate the prevalence of six anatomical variations—os acromiale, episternal ossicles, cervical rib, Stafne bone cavity, azygos lobe and tracheal bronchus—in an open-access computed tomography dataset obtained from oropharyngeal cancer patients. Materials and Methods: A total of 606 upper-chest and neck computed-tomography scans (79.4% male and 20.6% female) were retrospectively investigated. Sex difference was evaluated using the z-test for two proportions. Results: Os acromiale, episternal ossicles, cervical rib, Stafne bone cavity, azygos lobe, and tracheal bronchus were present in 3.1%, 2.2%, 0.2%, 0%, 0.3% and 0.5%, respectively, of all patients. Os acromiale was identified as meso-acromion in 86.6%, and as pre-acromion in 17.4%, of all acromia. Episternal ossicles were present unilaterally in 58.3%, and bilaterally in 41.7%, of all sterna. Only the cervical rib showed a sex difference in prevalence. Conclusions: awareness of these variations is important for radiologists interpreting head, neck and chest CTs; for example, those of oropharyngeal cancer patients. This study also illustrates the applicability of publicly available datasets in prevalence-based anatomical research. While most of the variations investigated in the present study are well-known, the episternal ossicles are not well explored, and need further investigation.

Oropharyngeal cancer (OPC), which is a common type of head and neck squamous cell carcinoma (HNSCC), is associated with tobacco and alcohol use, and human papillomavirus (HPV) infection. Underlying mechanisms and as a result prognosis of the HPV-positive and HPV-negative OPC patients are different. Like stem cells, the ability of self-renewal and differentiate, cancer stem cells (CSCs) have roles in tumor invasion, metastasis, drug resistance, and recurrence after therapy. Research revealed their roles to some extent in all of these processes but there are still many unresolved points to connect to CSC-targeted therapy. In this review, we will focus on what we currently know about CSCs of OPC and limitations of our current knowledge. We will present perspectives that will broaden our understanding and recent literature which may connect to therapy.