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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]

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]

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]

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

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

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

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

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

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

Simple Summary: Currently, many researchers are focusing their study on the search for new, non-invasive biomarkers with high diagnostic and prognostic usefulness in head and neck cancers (HNCs). Most of them concern nasopharyngeal cancer (NPC). However, our research team focused on the most common form in our region, i.e., cancer located in the oropharynx. This was the premise for undertaking research assessing the diagnostic usefulness of measuring nuclear factor kappa B (NF-κB) in oropharyngeal squamous cell carcinoma (OPSCC) linked to EBV. Therefore, we assessed the frequency and level of NF-κB in the serum of patients with this cancer, taking into account clinicopathological features, i.e., grading (G1–G3) and TN classification. The obtained results indicate a significantly higher NF-κB level in the advanced clinical stage of cancer. In turn, ROC analysis confirmed the diagnostic accuracy of this protein. It has been shown that the determination of NF-κB may be a useful diagnostic and prognostic marker of OPSCC linked to EBV. Early diagnosis and effective therapy are the fundamental challenge for modern oncology. Hence, many researchers focus on the search for new or improved biomarkers. Due to the great importance of nuclear factor kappa B (NF-κB) in physiological and pathological processes, we focused on assessing its usefulness as a biomarker in OPSCC. The purpose of the research presented here was to evaluate the prevalence and the level of NF-κB in the serum of OPSCC patients (ELISA). Serum NF-κB levels were also assessed depending on the degree of histological differentiation of the tumor and TN classification. Additionally, we considered the existence of a correlation between the concentration of NF-κB and EBV antibody titers, viral load and selected MMPs—MMP3 and MMP9. Taken together, the obtained results demonstrated that NF-κB level was significantly higher among patients with EBV-related OPSCC than among those without EBV. In addition, the level of NF-κB was significantly higher in more advanced clinical stages. Moreover, a positive correlation was found between the concentration of NF-κB and the level of selected EBV antibodies, viral load and both tested MMPs. The diagnostic accuracy of NF-κB was confirmed by ROC analysis. [ABSTRACT FROM AUTHOR]

Head and neck cancers rank as the sixth most prevalent cancers globally. In addition to traditional risk factors such as smoking and alcohol use, human papillomavirus (HPV) infections are becoming a significant causative agent of head and neck cancers, particularly among Western populations. Although HPV offers a significant survival benefit, the search for better biomarkers is still ongoing. In the current study, our objective was to investigate whether the expression levels of three PDZ-domain-containing proteins (SCRIB, NHERF2, and DLG1), known HPV E6 cellular substrates, influence the survival of HNSCC patients treated by primary surgery (n = 48). Samples were derived from oropharyngeal and oral cancers, and HPV presence was confirmed by PCR and p16 staining. Clinical and follow-up information was obtained from the hospital database and the Croatian Cancer registry up to November 2023. Survival was evaluated using the Kaplan–Meier method and Cox proportional hazard regression. The results were corroborated through the reanalysis of a comparable subset of TCGA cancer patients (n = 391). In conclusion, of the three targets studied, only SCRIB levels were found to be an independent predictor of survival in the Cox regression analysis, along with tumor stage. Further studies in a more typical Western population setting are needed since smoking and alcohol consumption are still prominent in the Croatian population, while the strongest association between survival and SCRIB levels was seen in HPV-negative cases. [ABSTRACT FROM AUTHOR]

Background: To investigate the perception of young European otolaryngologists (OTOs), i.e., head and neck surgeons, toward transoral robotic surgery (TORS). Methods: Members of the Young Confederation of European Otorhinolaryngology-Head and Neck Surgery and Young Otolaryngologists of International Federation of Otorhinolaryngological Societies were surveyed about TORS perception and practice. Results: The survey was completed by 120 young OTOS (26%). The most important barriers to TORS were robot availability (73%), cost (69%), and lack of training (37%). The participants believed that the main benefits include better surgical filed view (64%), shorter hospital stay (62%), and better postoperative outcomes (61%) than the conventional approach. Head and neck surgeons considered cT1-T2 oropharyngeal cancers (94%), resection of base of tongue for sleep apnea (86%), or primary unknown cancer (76%) as the most appropriate indications. A total of 67% of TORS surgeons assessed themselves as adequately trained in TORS. Conclusions: Young European OTOs report positive perception, adoption, and knowledge of TORS. The cost-related unavailability and the lack of training or access are reported to be the most important barriers for the spread of TORS. [ABSTRACT FROM AUTHOR]

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

Simple Summary: Proton therapy allows for more effective organs at risk avoidance than photon radiotherapy, thus reducing both radiation-induced toxicity and second cancer risk. The aim of the present paper is to compare protons and photons outcomes in the context of oropharyngeal and nasopharyngeal cancer and provide an updated comprehensive overview of the most promising new approaches and methodologies for treating head and neck cancer with protons. The growing interest in proton therapy (PT) in recent decades is justified by the evidence that protons dose distribution allows maximal dose release at the tumor depth followed by sharp distal dose fall-off. But, in the holistic management of head and neck cancer (HNC), limiting the potential of PT to a mere dosimetric advantage appears reductive. Indeed, the precise targeting of PT may help evaluate the effectiveness of de-escalation strategies, especially for patients with human papillomavirus associated-oropharyngeal cancer (OPC) and nasopharyngeal cancer (NPC). Furthermore, PT could have potentially greater immunogenic effects than conventional photon therapy, possibly enhancing both the radiotherapy (RT) capability to activate anti-tumor immune response and the effectiveness of immunotherapy drugs. Based on these premises, the aim of the present paper is to conduct a narrative review reporting the safety and efficacy of PT compared to photon RT focusing on NPC and OPC. We also provide a snapshot of ongoing clinical trials comparing PT with photon RT for these two clinical scenarios. Finally, we discuss new insights that may further develop clinical research on PT for HNC. [ABSTRACT FROM AUTHOR]

Simple Summary: The United States is suffering from an epidemic associated with infections with the Human Papilloma Virus (HPV) that are responsible for the development of head and neck squamous cell carcinoma (HNSCC). Our study aims to characterize immune profiles, and the oral microbiota in oropharyngeal tumors associated with anti-PD-1 treatment response in a preclinical murine model for HPV+ oropharyngeal cancer. We confirmed 16 immune markers and specific bacteria in the oral cavity that differentiate between treatment responders and non-responders, which may be used as potential biomarkers for PD-1 blockade response. The United States is suffering from an epidemic associated with high-risk strains of the Human Papillomavirus (HPV) predominantly responsible for the development of head and neck squamous cell carcinoma (HNSCC). Treatment with immune checkpoint inhibitors targeting programmed death 1 (PD-1) or its ligand PD-L1 has shown poor efficacy in HNSCC patients, observing only a 20–30% response. Therefore, biological marker identification associated with PD-1 blockade response is important to improve prognosis and define novel therapeutics for HNSCC patients. Therapy response was associated with increased frequencies of activated CD27+T cells, activated CD79a+ B cells, antigen-presenting CD74+ dendritic and B cells, and PD-L1+ and PD-L2+ myeloid-derived suppressor cells (MDSCs). The oral microbiota composition differed significantly in mice bearing tongue tumors and treated with anti-PD-1. A higher abundance of Allobaculum, Blautia, Faecalibacterium, Dorea, or Roseburia was associated with response to the therapy. However, an increase in Enterococcus was attributed to tongue tumor-bearing non-responding mice. Our findings indicate that differences in immune phenotypes, protein expression, and bacterial abundance occur as mice develop tongue tumors and are treated with anti-PD-1. These results may have a clinical impact as specific bacteria and immune phenotype could serve as biomarkers for treatment response in HNSCC. [ABSTRACT FROM AUTHOR]

Background: Inflammation has long been a key tenet in the diagnosis and management of malignancies, likely contributing to cancer incidence, staging, and progression. Systemic inflammation, in particular, is often elevated prior to and during cancer development. Systemic inflammation in the context of cancer diagnosis and monitoring is measured by various inflammatory indexes such as the systemic inflammatory response index (SIRI), plasma-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), and neutrophil-to-lymphocyte ratio (NLR). We set out to determine the relationship between pre- and post-treatment levels of these inflammatory indexes and the prognosis and outcomes of oropharyngeal cancer (OPC). Methods: A retrospective chart review was performed of 172 patients with OPC who underwent treatment for oropharyngeal cancer at University Medical Center in Lubbock, TX between May 2013 to May 2023. Sites of primary cancer were obtained through chart review. HPV infection status and differentiation of the tumor were noted for each patient. Treatment modalities were classified as surgery, radiation, chemotherapy, or concurrent chemotherapy and radiation. Treatment outcomes were classified based on recurrence and death secondary to disease. The relationships between treatment outcome and the described inflammatory indexes were evaluated. Appropriate parametric tests were selected based on the large number of variables. Results: Pre-treatment SIRI and Albumin levels were positively predictive in determining locoregional recurrence (p = 0.031 and p = 0.039). NLR, SII, and SIRI levels taken at three months post-treatment were also found to be positively predictive of locoregional recurrence (p = 0.005, p < 0.0005, and p = 0.007). SIRI taken at six months post-treatment was also found to be positively predictive of locoregional recurrence (p = 0.008). SII at six months post-treatment was found to be positively predictive of survival (p = 0.027). Conclusion: This study suggested that post-treatment levels of several inflammatory indexes, particularly SIRI, NLR, and SII, may be useful in determining the long-term outlook and recurrence of head and neck cancer following treatment. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) presents unique challenges and opportunities for treatment, particularly regarding de-escalation strategies to reduce treatment morbidity without compromising oncological outcomes. This paper examines the role of Transoral Robotic Surgery (TORS) as a de-escalation strategy in managing HPV-related OPSCC. We conducted a comprehensive literature review from January 2010 to June 2023, focusing on studies exploring TORS outcomes in patients with HPV-positive OPSCC. These findings highlight TORS's potential to reduce the need for adjuvant therapy, thereby minimizing treatment-related side effects while maintaining high rates of oncological control. TORS offers advantages such as precise tumor resection and the ability to obtain accurate pathological staging, which can guide the tailoring of adjuvant treatments. Some clinical trials provide evidence supporting the use of TORS in specific patient populations. The MC1273 trial demonstrated promising outcomes with lower doses of adjuvant radiotherapy (RT) following TORS, showing high locoregional tumor control rates and favorable survival outcomes with minimal side effects. ECOG 3311 evaluated upfront TORS followed by histopathologically directed adjuvant therapy, revealing good oncological and functional outcomes, particularly in intermediate-risk patients. The SIRS trial emphasized the benefits of upfront surgery with neck dissection followed by de-escalated RT in patients with favorable survival and excellent functional outcomes. At the same time, the PATHOS trial examined the impact of risk-adapted adjuvant treatment on functional outcomes and survival. The ongoing ADEPT trial investigates reduced-dose adjuvant RT, and the DART-HPV study aims to compare standard adjuvant chemoradiotherapy (CRT) with a reduced dose of adjuvant RT in HPV-positive OPSCC patients. These trials collectively underscore the potential of TORS in facilitating treatment de-escalation while maintaining favorable oncological and functional outcomes in selected patients with HPV-related OPSCC. The aim of this scoping review is to discuss the challenges of risk stratification, the importance of HPV status determination, and the implications of smoking on treatment outcomes. It also explores the evolving criteria for adjuvant therapy following TORS, focusing on reducing radiation dosage and volume without compromising treatment efficacy. In conclusion, TORS emerges as a viable upfront treatment option for carefully selected patients with HPV-positive OPSCC, offering a pathway toward treatment de-escalation. However, selecting the optimal candidate for TORS-based de-escalation strategies is crucial to fully leverage the benefits of treatment de-intensification. [ABSTRACT FROM AUTHOR]

Simple Summary: Human papillomavirus (HPV) causes 5% of cancers and is the main cause of oropharyngeal cancer in the United States and of cervical cancer worldwide. HPV proteins induce DNA damage and exploit and hijack the host DNA damage response. The HPV oncoproteins E6 and E7 induce chromosomal instability (CIN), or chromosome missegregation during mitosis, which also causes DNA damage and can lead to profound genetic alterations in the host cell. Though these features are known to contribute to HPV-induced carcinogenesis, how this affects tumor cell response to DNA damaging treatments is not well understood. Here, we review how HPV induces DNA damage and activates the DNA damage response and how the HPV-induced CIN likely exacerbates this. We then discuss how this viral protein-mediated DNA damage may affect the efficacy of chemoradiation therapy. High-risk human papillomaviruses (HPVs) are the main cause of cervical, oropharyngeal, and anogenital cancers, which are all treated with definitive chemoradiation therapy when locally advanced. HPV proteins are known to exploit the host DNA damage response to enable viral replication and the epithelial differentiation protocol. This has far-reaching consequences for the host genome, as the DNA damage response is critical for the maintenance of genomic stability. HPV+ cells therefore have increased DNA damage, leading to widespread genomic instability, a hallmark of cancer, which can contribute to tumorigenesis. Following transformation, high-risk HPV oncoproteins induce chromosomal instability, or chromosome missegregation during mitosis, which is associated with a further increase in DNA damage, particularly due to micronuclei and double-strand break formation. Thus, HPV induces significant DNA damage and activation of the DNA damage response in multiple contexts, which likely affects radiation sensitivity and efficacy. Here, we review how HPV activates the DNA damage response, how it induces chromosome missegregation and micronuclei formation, and discuss how these factors may affect radiation response. Understanding how HPV affects the DNA damage response in the context of radiation therapy may help determine potential mechanisms to improve therapeutic response. [ABSTRACT FROM AUTHOR]

(1) Background: Human papillomavirus (HPV) infection is significantly associated with oropharyngeal squamous cell carcinoma (HPV-OPSCC), which is one of the fastest-growing cancer incidences globally. Dental practitioners play a crucial role in the primary and secondary prevention of HPV-OPSCC. There is little known about dental students' awareness regarding HPV-OPSCC and HPV vaccination, as well as their intention to promote 'primordial prevention' among their patients. HPV vaccine, and the extent of their professional responsibilities. (2) Methods: This cross-sectional study was conducted in the western region of Saudi Arabia and involved undergraduate dental students (n = 688) from six public and private dental schools. Participants were requested to complete a sequential-section anonymous online survey, with 257 successfully completing all sections of the questionnaire. The association between participant characteristics and HPV-OPSCC, HPV vaccination awareness ratings, and perceived engagement in prevention were analyzed using ANOVA and chi-squared testing. A binary logistic regression analysis was conducted to examine the variables linked to these outcomes. (3) Results: Generally, the overall level of awareness of HPV-OPSCC and HPV vaccination was acceptable, with an average score of 53.44 ± 29.3 out of 100. However, a significant knowledge gap was observed, with 53% of respondents being unaware of the common sites for HPV-OPSCC and 63.8% being uninformed of the appropriate age for HPV vaccination. Females and those with a prior history of sexually transmitted diseases (STDs) had considerably higher levels of HPV vaccination knowledge (p < 0.05). The participants showed a favorable attitude towards their responsibility of informing patients about HPV-OPSCC and advocating HPV immunization. (4) Conclusions: This study underscores the need to enhance dental students' understanding of HPV-OPSCC and HPV immunization, enabling them to effectively engage in primary and secondary preventative efforts against HPV-OPSCC. [ABSTRACT FROM AUTHOR]

Simple Summary: Transoral Robotic Surgery (TORS) is increasingly used for various conditions, yet its success and failure remain underexplored. In this multicenter study, we assessed 220 TORS interventions across 211 patients. Success criteria differed by condition, including tumor identification for CUP, resection margins for malignancies, and symptom improvement for benign cases like OSA and chronic lingual tonsillitis. Predictors of success varied, with factors such as patient comorbidity, tumor characteristics, and demographics playing roles. Conversely, failure predictors encompassed postoperative complications and pain, linked to patient health and demographics. These insights into TORS outcomes may aid in patient selection and counseling across different conditions, informing clinical practice and enhancing patient care. Transoral Robotic Surgery (TORS) is utilized for treating various malignancies, such as early-stage oropharyngeal cancer and lymph node metastasis of an unknown primary tumor (CUP), and also benign conditions, like obstructive sleep apnea (OSA) and chronic lingual tonsillitis. However, the success and failure of TORS have not been analyzed to date. In this retrospective observational multicenter cohort study, we evaluated patients treated with TORS using the da Vinci surgical system. Success criteria were defined as identification of the primary tumor for CUP, >2 mm resection margin for malignant conditions, and improvement on respiratory polygraphy and tonsillitis complaints for benign conditions. A total of 220 interventions in 211 patients were included. We identified predictors of success, such as low comorbidity status ACE-27, positive P16 status, and lower age for CUP, and female gender and OSA severity for benign conditions. For other malignancies, no predictors for success were found. Predictors of failure based on postoperative complications included high comorbidity scores (ASA) and anticoagulant use, and for postoperative pain, younger age and female gender were identified. This study provides valuable insights into the outcomes and predictors of success and failure in TORS procedures across various conditions and may also help in patient selection and counseling. [ABSTRACT FROM AUTHOR]

The use of conventional chemotherapy in conjunction with targeted and immunotherapy drugs has emerged as an option to limit the severity of side effects in patients diagnosed with head and neck cancer (HNC), particularly oropharyngeal cancer (OPC). OPC prevalence has increased exponentially in the past 30 years due to the prevalence of human papillomavirus (HPV) infection. This study reports a comprehensive review of clinical trials registered in public databases and reported in the literature (PubMed/Medline, Scopus, and ISI web of science databases). Of the 55 clinical trials identified, the majority (83.3%) were conducted after 2015, of which 77.7% were performed in the United States alone. Eight drugs have been approved by the FDA for HNC, including both generic and commercial forms: bleomycin sulfate, cetuximab (Erbitux), docetaxel (Taxotere), hydroxyurea (Hydrea), pembrolizumab (Keytruda), loqtorzi (Toripalimab-tpzi), methotrexate sodium (Trexall), and nivolumab (Opdivo). The most common drugs to treat HPV-associated OPC under these clinical trials and implemented as well for HPV-negative HNC include cisplatin, nivolumab, cetuximab, paclitaxel, pembrolizumab, 5-fluorouracil, and docetaxel. Few studies have highlighted the necessity for new drugs specifically tailored to patients with HPV-associated OPC, where molecular mechanisms and clinical prognosis are distinct from HPV-negative tumors. In this context, we identified most mutated genes found in HPV-associated OPC that can represent potential targets for drug development. These include TP53, PIK3CA, PTEN, NOTCH1, RB1, FAT1, FBXW7, HRAS, KRAS, and CDKN2A. [ABSTRACT FROM AUTHOR]

The human papillomavirus (HPV) vaccine can prevent HPV-related oropharyngeal cancers. Dental practitioners are uniquely positioned to promote HPV vaccines during routine dental care but experience barriers to doing so. Qualitative interviews were conducted with dental practitioners to understand barriers and inform intervention strategies to promote HPV vaccines. Dental practitioners were invited to participate in phone interviews about knowledge, self-efficacy, and the fear of negative consequences related to HPV vaccine promotion as well as feedback on potential interventions to address these barriers. Interviews were audio recorded, transcribed, and analyzed using rapid qualitative analysis with a sort-and-sift matrix approach. Interviews were completed with 11 practitioners from six dental clinics (avg. 31 min). Though most thought HPV vaccination was important, they lacked detailed knowledge about when and to whom the vaccine should be recommended. This led to a hypothesized need for discussions of sexual history, feelings of limited self-efficacy to make the recommendation, and fear of patient concerns. Still, practitioners were supportive of additional training opportunities and provided input into specific interventions. The nuance of how these barriers were described by practitioners, as well as the possible solutions they identified, will help shape future interventions supporting HPV vaccine promotion in dental care. [ABSTRACT FROM AUTHOR]

The dental treatment of patients with oral cavity and oropharyngeal squamous cell carcinoma (OOPSCC) may be challenging for dentists. This study aimed to characterize systemic changes in patients with OOPSCC undergoing dental treatment prior to cancer therapy, with a specific focus on laboratory assessments. The primary objectives included identifying potential adverse events, such as infections or bleeding, resulting from dental procedures. Additionally, the study aimed to correlate baseline patient characteristics with treatment-related toxicities. This was a prospective cohort study that included 110 OOPSCC patients referred to the Dental Oncology Service at São Paulo State Cancer Institute, Brazil, between November/2019 and December/2020. Comorbidities, sociodemographic data, medication in use, cancer treatment-related toxicities, and altered laboratory tests results were correlated. The most common comorbidities and altered laboratory results were hypertension, dyslipidemia, diabetes, as well as elevated levels of C-reactive protein, hemoglobin, and hematocrit. Toxicities exhibited a progressive pattern over time, encompassing oral mucositis (OM), xerostomia, dysphagia, dysgeusia, trismus, and radiodermatitis. No correlation between comorbidities and cancer treatment-related toxicities, a positive correlation between medications in use and OM, and a negative correlation between medications and dysgeusia were found. OM was associated with altered thyroxine (T4) and free thyroxine (FT4), calcium, urea, creatinine, alkaline phosphatase, and syphilis. Family income and housing were OM predictors. Altered T4/FT4/urea/calcium/alkaline phosphatase/creatinine/syphilis may be useful clinical predictors of OM. Despite the elevated prevalence of comorbidities and abnormal laboratory findings, dental treatment prior to cancer treatment yielded no adverse events. [ABSTRACT FROM AUTHOR]

Osteoradionecrosis of the jaw is a morbid complication of radiotherapy in patients with oral and oropharyngeal cancers that may be precipitated by dental extractions. Pentoxifylline and tocopherol (PENTO) has been utilized in the management of osteoradionecrosis and as prophylaxis for post-radiated head and neck oncology patients requiring an invasive dental procedure. This observational study aims to report the outcome of the prophylactic use of PENTO in the prevention of osteoradionecrosis of the jaw after dental extractions in post-radiated oral and oropharyngeal cancer patients and to review the current literature on this topic. Four post-radiated oral and oropharyngeal oncology patients were referred to the dental oncology clinic of the University Dental Practice, University of Tennessee Health Sciences Center for dental extractions. All four patients were prescribed pentoxifylline 400 mg BID (twice a day) and tocopherol 400 IU BID (oral tablets) for 2 weeks before extraction(s) and for 6 weeks after extraction(s). All patients were followed up every week after the second week post-extraction if feasible until the extraction site(s) healed (covered by mucosa). The assessment endpoint was defined as 6 weeks post-extraction with the outcomes assessed as using four categories determined by the area of exposed bone: complete healing (complete mucosal coverage of extraction site); partial healing (reduction in size of extraction site); no change; and progression (increase in size of the extraction site). At the assessment endpoint, all patients had complete healing of all extraction sites. The ORN rate at the patient level (0/4) and individual tooth level (0/8) was 0%. All patients tolerated the PENTO medications and no adverse effects from the use of these medications were reported. This limited study in addition to the other reviewed studies estimates the rate of ORN at the patient level as 3.2% (14/436) for post-radiated head and neck oncology patients after dental extractions/invasive oral procedures. In conclusion, this PENTO regimen can reduce/prevent the incidence of ORN in post-radiated head and neck oncology patients. This safe and cost-effective protocol (PENTO regimen) should be further evaluated as prophylaxis for post-radiated head and neck oncology patients requiring an invasive dental procedure. We recommend large prospective studies to be carried out to further validate these findings. [ABSTRACT FROM AUTHOR]

Simple Summary: Convincing data have indicated that human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) is associated with much better locoregional control and survival than its HPV-unrelated counterparts. It is also worth noting that the distant metastases (DM) rate does not differ between HPV-related and HPV-unrelated OPSCC. Recently, the analysis of HPV in liquid biopsy (circulating tumor-related HPV DNA, ctHPV) has gained significant prognostic importance. Little is known about the importance of viral load (VL) levels of ctHPV16 in OPSCC on survival. Meanwhile, our results provide comprehensive data that the pretreatment ctHPV16 VL in liquid biopsy may be a biomarker of the risk of DM. Background: There are definite reasons to implement molecular diagnostics based on the measurement of human papillomavirus (HPV) DNA in liquid biopsy into clinical practice. It is a quick, repeatable, and health-safe test for cancer biomarkers in the blood. In this study, we investigated whether the circulating tumor-related HPV16 (ctHPV16) viral load (VL) in patients with oropharyngeal squamous cell carcinoma (OPSCC) was important for determining the risk of locoregional recurrence-free survival (LRFS), metastasis-free survival (MFS), and overall survival (OS). Methods: This study included 91 patients with ctHPV16-positive OPSCC who had been treated with radical radiotherapy and chemotherapy. The VL was measured using quantitative PCR (qPCR) and a probe specific for HPV16. Based on 10 years of follow-up, the 2-, 3-, 5-, and 9-year LRFS, MFS, and OS were estimated. Results: The 5-year actuarial LRFS, MFS, and OS rates of patients with ctHPV16-positive/OPSCC were 88%, 90%, and 81%, respectively. The VL was significantly higher in patients who subsequently developed distant metastases (DM) than in those who did not (VL 4.09 vs. 3.25; p = 0.009). In a Cox proportional hazards regression model for MFS, a higher ctHPV16 VL appeared to be a significant independent prognostic factor for the occurrence of DM (HR 2.22, p = 0.015). The ROC curve revealed a cutoff value of 3.556 for VL (p = 0.00001). Conclusions: A high VL before treatment indicates patients with a significant risk of DM, and should be used in OPSCC treatment stratification. [ABSTRACT FROM AUTHOR]

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

Introduction: Oropharyngeal cancer requires a comprehensive evaluation of treatment options, including surgery, radiation therapy, and chemotherapy. It is crucial to customize these treatments based on the stage of the tumor and the overall health of the patient, enabling personalized or combined approaches. Transoral surgical techniques have regained popularity due to the advancements and limitations of non-surgical strategies. The potential influence of surgical procedures on patients' quality of life highlights the need for careful intervention selection; among them, the transoral approach has proven to be especially beneficial for early-stage oropharyngeal neoplasms. Methods: To explore potential treatments for early-stage oropharyngeal malignancies, this study carefully reviews the literature, using information from papers, current research, and global databases. The review protocol commenced on November 2023. A comprehensive search of the PUBMED database was undertaken, employing pertinent terms associated with oropharyngeal, transoral surgery or radiotherapy, robotic surgery, and chemotherapy. Results: Treating early-stage oropharyngeal neoplasms is particularly intriguing due to the multitude of variables influencing treatment decisions, leading to ongoing debates in specialized literature. Regardless of the chosen approach, maintaining a high quality of life is crucial. To assess this, standardized questionnaires from the European Organization for Research and Treatment of Cancer were employed, revealing superior outcomes for patients solely undergoing surgical intervention. Additionally, in the realm of specialized literature, cases of HPV-positive oropharyngeal neoplasms are recognized for their heightened radiosensitivity and more favorable long-term prognosis. Conclusions: Surgical intervention and radiotherapy are the main treatment options for oropharyngeal cancer, and they can be used separately or together for maximum effectiveness. Amid ongoing discussions, determining the superior effectiveness between the two options continues to be a matter of debate. This study provides a comprehensive analysis, offering valuable perspectives for future discussions. Neoplasm in the oropharynx can be effectively treated using transoral microsurgery. [ABSTRACT FROM AUTHOR]

Simple Summary: The recent increase in oropharyngeal cancer cases in Western countries prompted this research, which focuses on evaluating the role of human papillomavirus (HPV) in the incidence of this cancer type in Romania. This study employed p16 overexpression as a biomarker to distinguish HPV-related oropharyngeal cancers from those attributed to other etiologies, like smoking and alcohol consumption. Comparative analysis of treatment responses revealed a markedly improved prognosis in patients with p16-positive oropharyngeal cancers, underscoring the significance of HPV in the pathogenesis and clinical outcomes of these malignancies. Background: Oropharyngeal cancer is a global health concern due to its multifaceted nature. Recent molecular studies have linked p16 overexpression, associated with the human papillomavirus, to oropharyngeal cancer and its prognostic implications. Materials and Methods: This retrospective study in Western Romania examined 60 patients, categorizing them based on p16 biomarker status: 28 were p16 positive, and 32 were p16 negative. Statistical tests, including Fisher's exact and chi2, were used for analysis. Results: Patients with p16-positive oropharyngeal cancer exhibited a better prognosis (3-year survival, p = 0.0477; midtreatment, p = 0.0349) and reported lower alcohol (p = 0.0046) and tobacco (p < 0.0001) use. Conclusions: The study highlights the importance of p16 testing in oropharyngeal carcinoma diagnosis. It suggests modifying treatment approaches based on p16 status and underscores the differing prognoses associated with p16-positive and p16-negative cases. [ABSTRACT FROM AUTHOR]

The high incidence of, and mortality from, head and neck cancers (HNCs), including those related to Epstein–Barr virus (EBV), constitute a major challenge for modern medicine, both in terms of diagnosis and treatment. Therefore, many researchers have made efforts to identify diagnostic and prognostic factors. The aim of this study was to evaluate the diagnostic usefulness of matrix metalloproteinase 3 (MMP 3) and matrix metalloproteinase 9 (MMP 9) in EBV positive oropharyngeal squamous cell carcinoma (OPSCC) patients. For this purpose, the level of these MMPs in the serum of patients with EBV-positive OPSCC was analyzed in relation to the degree of histological differentiation and TNM classification. Our research team's results indicate that the level of both MMPs is much higher in the EBV positive OPSCC patients compared to the EBV negative and control groups. Moreover, their levels were higher in more advanced clinical stages. Considering the possible correlation between the level of MMP 3, MMP 9 and anti-EBV antibodies, and also viral load, after statistical analysis using multiple linear regression, their high correlation was demonstrated. The obtained results confirm the diagnostic accuracy for MMP 3 and MMP 9. Both MMPs may be useful in the diagnosis of EBV positive OPSCC patients. [ABSTRACT FROM AUTHOR]

The Italian National Immunization Plan (NIP) states that public health today aims at immunizing adolescents of both sexes for maximum protection against all HPV-related vaccine-preventable diseases. Nowadays, the vaccination offer to primary cohorts is reaffirmed with continued free vaccination up to at least 26 years of age for females and up to at least 18 years of age for males. The Italian NIP 2023–2025 recommends HPV vaccination for at-risk categories, including individuals with HIV, men who have sex with men (MSM), women treated for intermediate- or high-grade lesions, and travelers. Catch-up vaccination is recommended for women at least up to 26 years of age, also using the appropriate occasion of the call for the first screening for the prevention of cervical cancer as an opportunity for vaccination, and for men at least up to and including 18 years of age if they have not been previously vaccinated or have not completed the vaccination cycle. In summary, the Italian vaccination offer has been extended to additional cohorts in order to reduce the burden of HPV-related diseases and to improve vaccination coverage of the Italian population. [ABSTRACT FROM AUTHOR]

Simple Summary: In this retrospective study conducted at Taichung Veterans General Hospital, 54,692 participants were examined, including 385 with esophageal, oropharyngeal, or hypopharyngeal squamous cell carcinoma (SCC). Researchers investigated the correlation between cancer incidence and prognosis and a polygenic risk score (PRS) derived from 8353 single-nucleotide polymorphisms. Those with a high PRS (Q4) exhibited a 1.83-fold higher risk of SCCs compared to the low-PRS group (Q1), particularly notable in esophageal and hypopharyngeal cancers. Notably, PGS001087 displayed discernible associations with SCC risk, especially in specific subtypes and advanced stages, although not significantly linked to clinical staging. The study underscores the significance of genetic factors in upper aerodigestive tract cancers, notably esophageal SCC, offering insights for future research and risk assessment strategies. These findings highlight the importance of PRS in understanding cancer susceptibility, guiding targeted interventions, and informing personalized treatment approaches. Esophageal cancer shares strong associations with oropharyngeal and hypopharyngeal cancers, primarily due to shared risk factors like excessive tobacco and alcohol use. This retrospective study at Taichung Veterans General Hospital involved 54,692 participants, including 385 with squamous cell carcinoma (SCC) of the esophagus, oropharynx, or hypopharynx. Using a polygenic risk score (PRS) derived from 8353 single-nucleotide polymorphisms, researchers aimed to assess its correlation with cancer incidence and prognosis. The study found a 1.83-fold higher risk of esophageal, oropharyngeal, and hypopharyngeal SCCs in participants with a high PRS (Q4) compared to the low-PRS group (Q1). Esophageal cancer risk demonstrated a significant positive association with the PRS, as did hypopharyngeal cancer. Clinical parameters and staging showed limited associations with PRS quartiles, and the PRS did not significantly impact recurrence or mortality rates. The research highlighted that a higher PRS is linked to increased susceptibility to esophageal and hypopharyngeal cancer. Notably, a specific polygenic risk score, PGS001087, exhibited a discernible association with SCC risk, particularly in specific subtypes and advanced disease stages. However, it was not significantly linked to clinical cancer staging, emphasizing the multifactorial nature of cancer development. This hospital study reveals that a higher PRS correlates with increased susceptibility to esophageal and hypopharyngeal cancers. Notably, PGS001087 shows a discernible association with SCC risk in specific subtypes and advanced stages, although not significantly linked to clinical cancer staging. These findings enhance our understanding of genetic factors in upper aerodigestive tract cancers, particularly esophageal SCC, guiding future research and risk assessment strategies. [ABSTRACT FROM AUTHOR]

Evidence is emerging about the value of textural features as powerful outcome predictors in cancer lesions. The aim of this study is to evaluate the potential of [18F]FDG PET/CT conventional and textural parameters as survival predictors in patients with stage III and IV oropharyngeal cancer. The database includes 39 patients. Segmentation of the primary lesions was performed. A total of 48 features were extracted, comprising conventional parameters and textural features. A 2-year follow-up period to analyze the Overall Survival (OS) and Relapse-Free Survival (RFS) rates was defined. Kaplan–Meier and Cox proportional hazards regression analyses were computed. Higher TLG (p = 0.001) and Surface (p = 0.001) are significantly related to better OS in Cox regression analysis after multiple-testing correction. Higher GLZLM_ZLNU (p = 0.001) is significantly related to greater relapse rates in RFS Kaplan–Meier analysis after multiple-testing correction. Quantitative [18F]FDG PET/CT image features, especially the TLG, have been confirmed as predictors of OS and RFS. Textural features, such as GLZLM_ZLNU, demonstrated a potential predictive value for the OS and RFS of the patients. RFS analysis suggest stabilization of patients adhering to the treatment, showing no relapse events after 20 months of follow-up. [18F]FDG PET/CT is a useful tool for predicting prognosis after chemoradiation therapy of oropharyngeal cancer patients. [ABSTRACT FROM AUTHOR]

The prognostic significance of tumor-infiltrating neutrophils in head and neck squamous cell carcinoma (HNSCC) is poorly understood. It is unclear how the presence of neutrophils affects prognosis due to their polarization into cytotoxic N1 or immunosuppressive N2. Therefore, we determined the number of CD66b+ neutrophil granulocytes separately in the stromal and epithelial compartments in cancer tissues from 397 patients with HNSCC. Tumor samples from six historical patient groups were processed into tissue microarrays and stained immunohistochemically. In total, 21.9% were HPV positive (p16+). Neutrophil counts were much lower in the stromal compartment (372 ± 812) than in the epithelial cancer compartment (1040 ± 1477) (p < 0.001), with large differences between groups. In three groups with high neutrophil infiltration, high rates were associated with a favorable prognosis, whereas in two groups, high rates were a negative prognostic factor. In p16- oropharyngeal and hypopharyngeal cancer high infiltration was associated with a favorable prognosis. Cancers with an exclusion of neutrophils in the epithelial compartment were associated with improved prognosis. In oropharyngeal and hypopharyngeal HPV-negative cancer high neutrophil infiltration rates were clearly associated with prolonged survival. Neutrophil granulocytes in HNSCC may contribute to a favorable or unfavorable prognosis. [ABSTRACT FROM AUTHOR]

Head and neck cancer (HNC) is a prevalent and aggressive form of cancer with high mortality rates and significant implications for nutritional status. Accurate assessment of malnutrition in patients with HNC is crucial for optimizing treatment outcomes and improving survival rates. This study aimed to evaluate the use of ultrasound techniques for predicting nutritional status, malnutrition, and cancer outcomes in patients with HNC. A total of 494 patients with HNC were included in this cross-sectional observational study. Various tools and body composition measurements, including muscle mass and adipose tissue ultrasound evaluations, were implemented. Using regression models, we mainly found that high levels of RF-CSA (rectus femoris cross-sectional area) were associated with a decreased risk of malnutrition (as defined with GLIM criteria (OR = 0.81, 95% CI: 0.68–0.98); as defined with PG-SGA (OR = 0.78, 95% CI: 0.62–0.98)) and sarcopenia (OR = 0.64, 95% CI: 0.49–0.82) after being adjusted for age, sex, and BMI. To predict the importance of muscle mass ultrasound variables on the risk of mortality, a nomogram, a random forest, and decision tree models were conducted. RF-CSA was the most important variable under the random forest model. The obtained C-index for the nomogram was 0.704, and the Brier score was 16.8. With an RF-CSA < 2.7 (AUC of 0.653 (0.59–0.77)) as a split, the decision tree model classified up to 68% of patients as possessing a high probability of survival. According to the cut-off value of 2.7 cm2, patients with a low RF-CSA value lower than 2.7 cm2 had worse survival rates (p < 0.001). The findings of this study highlight the importance of implementing ultrasound tools, for accurate diagnoses and monitoring of malnutrition in patients with HNC. Adipose tissue ultrasound measurements were only weakly associated with malnutrition and not with sarcopenia, indicating that muscle mass is a more important indicator of overall health and nutritional status. These results have the potential to improve survival rates and quality of life by enabling early intervention and personalized nutritional management. [ABSTRACT FROM AUTHOR]

Simple Summary: Unlike NPC, there is little research concerned with the role of EBV in the development of OPSCC. Therefore, it is necessary to search for new markers enabling the early diagnosis and prognosis of this disease. The aim of this study was to evaluate the diagnostic utility of anti-Zta and anti-LMP1 antibodies in EBV positive OPSCC patients. For this purpose, experiments were carried out to determine both the prevalence and level of anti-Zta and anti-LMP1 antibodies in serum patients with OPSCC in relation to grading and TNM classification. The highest level of tested antibodies was observed in more advanced clinical stages. The diagnostic accuracy of anti-Zta antibodies was confirmed using ROC analysis. We showed that the determination of both types of antibodies may be useful in the diagnosis of OPSCC. Moreover, anti-LMP1 antibody may be a diagnostic as well as prognostic biomarker. Background: The role of the Epstein–Barr virus (EBV), the first known human oncogenic virus, in the development of nasopharyngeal cancer (NPC) is already well documented. There are few studies in the available scientific literature on oropharyngeal cancer associated with EBV infection. Due to the lack of an effective vaccine against EBV, it is necessary to search for new markers for the early diagnosis and prognosis of this disease. The aim of current study was to determine the usefulness of anti-Zta and anti-LMP1 antibodies as diagnostic and prognostic markers in EBV positive OPSCC patients. Methods: For this purpose, experiments were carried out to determine both the prevalence and level of EBVCA, EBNA1, EA, Zta, and LMP1 antibodies in serum patients depending on histological differentiation-grading and TNM classification (ELISA assay). Results: Based on the obtained results, we showed that OPSCC EBV positive patients are characterized by a higher level of anti-Zta antibodies than in the EBV negative group. Their level depended on the clinical stage. Moreover, a ROC analysis confirmed the diagnostic accuracy of anti-Zta antibodies. Conclusions: Anti-Zta and anti-LMP1 antibodies may be useful in the diagnosis of OPSCC. It seems that combined antibody testing should be performed to increase diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Notably, the incidence of lung cancer among never-smokers, predominantly women, has been rising in recent years. Among the various implicated risk factors, human papilloma virus (HPV) may play a role in the development of NSCLC in a certain subset of patients. The prevalence of high-risk HPV-DNA within human neoplastic lung cells varies across the world; however, the carcinogenetic role of HPV in NSCLC has not been completely understood. Bloodstream could be one of the routes of transmission from infected sites to the lungs, along with oral (through unprotected oral sex) and airborne transmission. Previous studies reported an elevated risk of NSCLC in patients with prior HPV-related tumors, such as cervical, laryngeal, or oropharyngeal cancer, with better prognosis for HPV-positive lung cancers compared to negative forms. On the other hand, 16% of NSCLC patients present circulating HPV-DNA in peripheral blood along with miRNAs expression. Typically, these patients have a poorly differentiated NSCLC, often diagnosed at an advanced stage. However, HPV-positive lung cancers seem to have a better response to target therapies (EGFR) and immune checkpoint inhibitors and show an increased sensitivity to platinum-based treatments. This review summarizes the current evidence regarding the role of HPV in NSCLC development, especially among patients with a history of HPV-related cancers. It also examines the diagnostic and prognostic significance of HPV, investigating new future perspectives to enhance cancer screening, diagnostic protocols, and the development of more targeted therapies tailored to specific cohorts of NSCLC patients with confirmed HPV infection. [ABSTRACT FROM AUTHOR]

Human papilloma virus (HPV) is known as the main cause of cervical cancer. Data also indicate its role in head–neck cancer, especially oropharyngeal cancer. The correlation between high-risk HPV and oral cancer is still controversial. HPV-related lesions of the oral cavity are frequent and, in most cases, benign. The primary aim of this study was to establish if there is a different follow-up necessity between HPV-positive compared to HPV-negative oral lesions. The secondary aim was to evaluate the recurrence of HPV-related lesions. All patients who underwent a surgical procedure of oral biopsy between 2018 and 2022, with ulterior histopathological examination and HPV typing, were examined. A total of 230 patients were included: 75 received traumatic fibroma as diagnosis, 131 HPV-related lesions, 9 proliferative verrucous leukoplakia, and 15 leukoplakia. The frequency and period of follow-up varied in relation to HPV positivity and diagnosis. This study confirms what has already been reported by other authors regarding the absence of recommendations of follow-up necessity in patients with oral mucosal lesions. However, the data demonstrate that there was a statistically significant difference in the sample analyzed regarding the follow-up of HPV-positive vs. HPV-negative patients. It also confirms the low recurrence frequency of HPV-related oral lesions. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral infection with high-risk human papillomaviruses is one of the known risk factors for oropharyngeal cancer. Human papillomavirus-related oropharyngeal cancer is a rising trend in many Western countries. Hong Kong is a vibrant Chinese cosmopolitan city in East Asia where data on the trend of change in human papillomavirus-related oropharyngeal cancer are not available. This study found that oropharyngeal cancer cases have increased persistently over the last three decades in Hong Kong, despite a notable decrease in other head and neck cancers such as the laryngeal cancer. By testing a series of cancer samples collected over the past several years, this study found that the proportion of oropharyngeal cancer infected with high-risk human papillomaviruses has increased substantially over the last decade. Strategies to prevent oral human papillomavirus infection and its associated diseases including oropharyngeal cancer are urgently needed. Research on the early detection of oropharyngeal cancer is a priority. The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is rising in the West, but little is known in Asia. This study elucidated changes in the incidence and HPV-positive portion of OPSCC in Hong Kong. Data from population-based cancer registry were used to analyze the incidence of OPSCC in association with other head and neck cancers. Archived tumor tissues were tested for HPV. From 1986 to 2020, there was a marked decrease in the incidence of nasopharyngeal and laryngeal cancers, but a persistent increase in OPSCC from 36 cases in 1986 to 116 cases in 2020. The average positive rate for high-risk HPV was 36.1% (112/310) among OPSCC diagnosed in 2010–2020. The HPV-positive rate in recent years was significantly higher than earlier cases (tonsil SCC: 64.7% (55/85) in 2016–2020 vs. 40.4% (19/47) in 2010–2015, p = 0.007). Patients with HPV-positive tonsil cancers were significantly younger than those negative (mean [SD]: 58.9 [9.9] vs. 64.3 [13.3] years, p = 0.006), but no significant difference was observed between genders. A persistent increase in the incidence of oropharyngeal cancer over the last few decades was observed in Hong Kong, which can be explained by the remarkable increase in HPV-positive tonsil cancers. [ABSTRACT FROM AUTHOR]

Simple Summary: Tumor-associated neutrophils (TANs) participate in the initiation and development of cancer by exerting either anti-tumorigenic or pro-tumorigenic roles, depending on their functional state. Oropharyngeal cancer associated with human papillomavirus (HPV) infection is related to a better prognosis, and, interestingly, it has a lower infiltration of TANs. However, the impact of HPV's presence on neutrophil polarization remains unknown. In this work, the effect of supernatants from oral cancer cell lines on the functional phenotype of neutrophils was evaluated. It was observed that the modulation of neutrophil polarization by tumor cells varied depending on the HPV status, with HPV− cells inducing a highly activated functional state in neutrophils, which could be associated with a pro-tumorigenic effect. High-risk human papillomavirus (HPV) infection is one of the leading causes of oropharyngeal squamous cell carcinoma (OPSCC), while the correlation between HPV and oral squamous cell carcinoma (OSCC) remains controversial. The inflammatory infiltrate involved in these epithelial neoplasms differs based on their association with HPV. HPV− tumors show higher tumor-associated neutrophil (TAN) infiltration. It is believed that TANs can play a dual role in cancer by exerting either anti-tumorigenic or pro-tumorigenic effects. However, the impact of HPV status on neutrophil polarization remains unknown. Therefore, this study aimed to investigate the effect of OSCC cells, both HPV− and HPV16+, on the functional phenotype of neutrophils. Peripheral blood neutrophils were stimulated with supernatants from OSCC cell lines and non-tumorigenic HaCaT keratinocytes transduced with HPV16 E6/E7 oncogenes. Subsequently, cytokine production, cell viability, metabolism, expression of degranulation markers, and PD-L1 expression were evaluated. Our findings demonstrate that in contrast to UPCI:SCC154 (HPV+ OSCC) cells, the SCC-9 (HPV− OSCC) cell line induced a highly activated functional state in neutrophils, which is potentially associated with a pro-tumorigenic effect. The HaCaT 16-E7 supernatant only stimulated the activation of some neutrophil functions. Understanding the complex interplay between neutrophils and their microenvironment has the potential to identify TANs as viable therapeutic targets. [ABSTRACT FROM AUTHOR]

Oropharyngeal cancers (OPCa) caused by HPV have emerged as one of the leading causes of malignancies caused by HPV infection. They are also significantly more likely to occur in males and in people with a history of oral sex with multiple partners. Gay and bisexual men are disproportionately affected by HPV-positive oropharyngeal cancers. We studied 1699 gay and bisexual men on 2 major dating sites in the US to assess their knowledge about HPV-related OPCa, attitudes toward screening for it, beliefs about oropharyngeal cancer screening based on the Health Belief Model, and attitudes toward possible screening approaches for OPCa. Knowledge on a 12-item scale was low, with a median of 5 items correct: 72% knew of the benefits of HPV vaccination. Significant predictors of needing OPCa screening included perception of risk for OPCa, seeing it as severe, having lower barriers, fewer reasons to avoid screening, higher knowledge, and being HPV vaccinated were significant predictors, explaining half the total variance. Most participants would accept routine, virtual/online doctor or dental appointments, and over half would accept an in-person screening. Nearly two-thirds stated that they would accept getting checked for OPCa if they could do self-screening at home, and half were prepared to use an online screening tool or app, where they could take an "oral selfie" and send it to a healthcare provider for examination. One-third stated that they would trust the results of a home screening completed by themselves and posted to a website equally as cancer screening completed online by a healthcare provider. Data indicate that despite low OPCA knowledge levels, the risk of HPV-associated OPCa was known. Being at personal risk and having knowledge of disease severity had 70% of the sample thinking about, or preparing to get, screening. Self-screening by a smartphone "oral selfie" transmitted to a screening website was acceptable to many gay and bisexual men, and online screening by a doctor or dentist was acceptable to most. OPCa screening in this population using electronic technology, together with the increasing incidence of HPV-associated OPCa in gay and bisexual men, brings together an opportunity to detect OPCa early. [ABSTRACT FROM AUTHOR]

There is a need to develop user-friendly imaging tools estimating robust quantitative biomarkers (QIBs) from multiparametric (mp)MRI for clinical applications in oncology. Quantitative metrics derived from (mp)MRI can monitor and predict early responses to treatment, often prior to anatomical changes. We have developed a vendor-agnostic, flexible, and user-friendly MATLAB-based toolkit, MRI-Quantitative Analysis and Multiparametric Evaluation Routines ("MRI-QAMPER", current release v3.0), for the estimation of quantitative metrics from dynamic contrast-enhanced (DCE) and multi-b value diffusion-weighted (DW) MR and MR relaxometry. MRI-QAMPER's functionality includes generating numerical parametric maps from these methods reflecting tumor permeability, cellularity, and tissue morphology. MRI-QAMPER routines were validated using digital reference objects (DROs) for DCE and DW MRI, serving as initial approval stages in the National Cancer Institute Quantitative Imaging Network (NCI/QIN) software benchmark. MRI-QAMPER has participated in DCE and DW MRI Collaborative Challenge Projects (CCPs), which are key technical stages in the NCI/QIN benchmark. In a DCE CCP, QAMPER presented the best repeatability coefficient (RC = 0.56) across test–retest brain metastasis data, out of ten participating DCE software packages. In a DW CCP, QAMPER ranked among the top five (out of fourteen) tools with the highest area under the curve (AUC) for prostate cancer detection. This platform can seamlessly process mpMRI data from brain, head and neck, thyroid, prostate, pancreas, and bladder cancer. MRI-QAMPER prospectively analyzes dose de-escalation trial data for oropharyngeal cancer, which has earned it advanced NCI/QIN approval for expanded usage and applications in wider clinical trials. [ABSTRACT FROM AUTHOR]

Simple Summary: The human papillomavirus (HPV) is an important prognostic marker in oropharyngeal squamous cell carcinoma (OPSCC) due to its involvement in carcinogenesis. The presence of the virus itself or markers of a past infection are usually determined by tissue specimen. This work applies predictive machine learning models to objectified imaging features extracted from routine imaging of patients newly diagnosed with OPSCC to classify cases of HPV-positive and negative tumors. In addition to results and classification performance being in line with existing literature on imaging-based HPV classification, imaging features of the parotid gland could be shown to yield relevant information. Parotid gland imaging offers potential as a screening tool and may aid clinical decision making in cases of cancer with unknown primary in the future. Background: In treatment of oropharyngeal squamous cell carcinoma (OPSCC), human papillomavirus status (HPV) plays a crucial role. The HPV-positive subtype tends to affect younger patients and is associated with a more favorable prognosis. HPV-associated lesions have been described in the parotid gland, which is included in routine imaging for OPSCC. This work aims to explore the ability of an ML system to classify HPV status based on imaging of the parotid gland, which is routinely depicted on staging imaging. Methods: Using a radiomics approach, we investigate the ability of five contemporary machine learning (ML) models to distinguish between HPV-positive and HPV-negative OPSCC based on non-contrast computed tomography (CT) data of tumor volume (TM), locoregional lymph node metastasis (LNM), and the parotid gland (Parotid). After exclusion of cases affected by streak artefacts, 53 patients (training set: 39; evaluation set: 14) were retrospectively evaluated. Classification performances were tested for significance against random optimistic results. Results: The best results are AUC 0.71 by XGBoost (XGB) for TM, AUC 0.82 by multi-layer perceptron (MLP) for LNM, AUC 0.76 by random forest (RF) for Parotid, and AUC 0.86 by XGB for a combination of all three regions of interest (ROIs). Conclusions: The results suggest involvement of the parotid gland in HPV infections of the oropharyngeal region. While the role of HPV in parotid lesions is under active discussion, the migration of the virus from the oral cavity to the parotid gland seems plausible. The imaging of the parotid gland offers the benefit of fewer streak artifacts due to teeth and dental implants and the potential to screen for HPV in cases of an absent or unlocatable tumor. Future investigation can be directed to validation of the results in independent datasets and to the potential of improvement of current classification models by addition of information based on the parotid gland. [ABSTRACT FROM AUTHOR]

Human papillomaviruses (HPVs) represent a diverse group of DNA viruses that infect epithelial cells of mucosal and cutaneous tissues, leading to a wide spectrum of clinical outcomes. Among various HPVs, alpha (α) and beta (β) types have garnered significant attention due to their associations with human health. α-HPVs are primarily linked to infections of the mucosa, with high-risk subtypes, such as HPV16 and HPV18, being the major etiological agents of cervical and oropharyngeal cancers. In contrast, β-HPVs are predominantly associated with cutaneous infections and are commonly found on healthy skin. However, certain β-types, notably HPV5 and HPV8, have been implicated in the development of non-melanoma skin cancers in immunocompromised individuals, highlighting their potential role in pathogenicity. In this review, we comprehensively analyze the similarities and differences between α- and β-HPV E6 oncoproteins, one of the major drivers of viral replication and cellular transformation, and how these impact viral fitness and the capacity to induce malignancy. In particular, we compare the mechanisms these oncoproteins use to modulate common cellular processes—apoptosis, DNA damage repair, cell differentiation, and the immune response—further shedding light on their shared and distinct features, which enable them to replicate at divergent locations of the human body and cause different types of cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Oropharyngeal cancers may be difficult to detect with current clinical and radiographic examinations. This study explores whether a new transoral ultrasound technique using high-resolution, small-footprint ultrasound transducers can improve the detection and staging of oropharyngeal cancers in an outpatient setting. We found that clinicians can use transoral ultrasound to improve the diagnostic workup of oropharyngeal cancers with an accuracy comparable to magnetic resonance imaging. Magnetic resonance imaging (MRI) is the preferred imaging modality for oropharyngeal cancers (OPCs), but it has difficulties distinguishing between small OPCs and unilateral tonsil hypertrophy. We hypothesized that surgeon-performed transoral ultrasound (US) could be used to accurately detect T-stage OPCs. We performed a single-center prospective diagnostic accuracy study including patients with suspected or biopsy-verified OPCs during outpatient appointments. All patients were offered transoral US and MRI. If transoral US could not be tolerated by the patient, transcervical US was performed. The primary outcome was the diagnostic accuracy of detecting OPCs with US compared to MRI, using histopathology as the reference standard. The secondary outcome was comparing the primary tumor diameters between US and MRI blinded to each other. Out of the 26 patients included in the study, 21 (81%) had OPCs. Transoral US could be performed in 21/21 and 1/5 patients with suspected palatine and lingual tonsil OPCs, respectively. Overall, US diagnostic accuracy was 92%, compared to 81% with MRI (p = 0.37). US and MRI had a high correlation between tumor diameters in the anteroposterior diameter (R = 0.80, p < 0.001), corresponding to the depth axis on US. In conclusion, this small study showed the promise and feasibility of transoral US to improve the initial clinical evaluations of patients with suspected OPCs. [ABSTRACT FROM AUTHOR]

Simple Summary: The impact of the relation of human papillomavirus (HPV) infection and smoking status of oropharyngeal squamous cell carcinoma (OPSCC) on overall survival (OS) was investigated in a retrospective population-based study in Thuringia, Germany. All patients with OPSCC (from 2018 to 2020) were included. OPSCC cases were 37.3% HPV-positive (+) (31.2% smokers; mean incidence: 2.91/100,000 population) and 57.8% HPV-negative (63.5% smokers; mean incidence: 4.50/100,000 population). HPV+ patients had significantly better OS than HPV-negative (−) patients. In multivariable analysis, HPV− patients had an increased 4.5-fold higher hazard of death, but the smoking status had no independent influence on risk of death. In binary logistic regression analysis, smokers showed a 4.5 increased odds ratio (OR) of being tested HPV− than for nonsmokers. HPV− smokers formed the majority in Thuringia. Optimizing OPSCC therapeutic strategies due to the dominance of HPV− is more important than discussing de-escalation strategies for HPV+ patients. The impact of the relation of human papillomavirus (HPV) and smoking status of oropharyngeal squamous cell carcinoma (OPSCC) on overall survival (OS) was investigated in a retrospective population-based study in Thuringia, Germany. A total of 498 patients with OPSCC (76.9% men; mean age 62.5 years) from 2018 to 2020 were included. OPSCC cases were 37.3% HPV-positive (+) (31.2% smokers; mean incidence: 2.91/100,000 population) and 57.8% HPV-negative (63.5% smokers; mean incidence: 4.50/100,000 population). Median follow-up was 20 months. HPV+ patients had significantly better OS than HPV-negative (−) patients (HPV+: 2-year OS: 90.9%; HPV−: 2-year OS: 73.6%; p < 0.001). In multivariable analysis, HPV− patients (hazard ratio (HR) = 4.5; 95% confidence interval (CI): 2.4–8.6), patients with higher N classification (N2: HR = 3.3; 95% CI: 1.71–6.20; N3: HR = 3.6; 95% CI: 1.75–7.31) and with a higher cancer staging (III: HR = 5.7; 95% CI: 1.8–17.6; IV: HR = 19.3; 95% CI: 6.3–57.3) had an increased hazard of death. HPV− smokers formed the majority in Thuringia. Nicotine and alcohol habits had no impact on OS. Optimizing OPSCC therapeutic strategies due to the dominance of HPV− is more important than discussing de-escalation strategies for HPV+ patients. [ABSTRACT FROM AUTHOR]

Cancer is a significant health problem worldwide; consequently, new therapeutic alternatives are being investigated, including those found in the vegetable kingdom. Eugenol (Eug) has attracted attention for its therapeutic properties, especially in stomatology. The purpose of this study was to investigate the cytotoxicity of Eug, in vitro, on osteosarcoma (SAOS-2) and oropharyngeal squamous cancer (Detroit-562) cells, as well as its potential irritant effect in ovo at the level of the chorioallantoic membrane (CAM). The data obtained following a 72 h Eug treatment highlighted the reduction in cell viability up to 41% in SAOS-2 cells and up to 37% in Detroit-562 cells, respectively. The apoptotic-like effect of Eug was indicated by the changes in cell morphology and nuclear aspect; the increase in caspase-3/7, -8 and -9 activity; the elevated expression of Bax and Bad genes; and the increase in luminescence signal (indicating phosphatidylserine externalization) that preceded the increase in fluorescence signal (indicating the compromise of membrane integrity). Regarding the vascular effects, slight signs of coagulation and vascular lysis were observed, with an irritation score of 1.69 for Eug 1 mM. Based on these results, the efficiency of Eug in cancer treatment is yet to be clarified. [ABSTRACT FROM AUTHOR]

Simple Summary: Although oropharyngeal cancers are increasing in incidence, more patients are surviving their cancer therapy. Once a patient has completed their oropharyngeal cancer treatment, they need to contend with the multiple side effects related to their cancer treatment. These factors may be acute or chronic and vary from individual to individual, depending on the cancer stage, location, and treatment modalities employed. These treatment-related side effects have an impact on their overall survival and quality of life domains such as function, taste, speech, dry mouth, dental decay, oral infection, bone necrosis, and nutrition. This review will summarize the most common oral complications from oropharyngeal cancer therapy, their causes, ways to help reduce the occurrences, and guidelines related to monitoring and treatment of the conditions. Post-oropharyngeal cancer treatment complications include a multitude of oral side effects that impact overall survival and quality of life. These include acute and chronic conditions affecting the oral cavity and head and neck, such as mucositis, infection, xerostomia, dysgeusia, radiation caries, osteonecrosis, and trismus. This review will summarize the most common oral complications from oropharyngeal cancer therapy. The authors would like to point out that the literature cited frequently combines oropharyngeal and head and neck cancer results. If recommendations are made strictly related to oropharyngeal cancers, this will be highlighted. [ABSTRACT FROM AUTHOR]

Emerging evidence indicates that intracellular calcium (Ca2+) levels and their regulatory proteins play essential roles in normal stem cell proliferation and differentiation. Cancer stem-like cells (CSCs) are subpopulations of cancer cells that retain characteristics similar to stem cells and play an essential role in cancer progression. Recent studies have reported that the Orai3 calcium channel plays an oncogenic role in human cancer. However, its role in CSCs remains underexplored. In this study, we explored the effects of Orai3 in the progression and stemness of oral/oropharyngeal squamous cell carcinoma (OSCC). During the course of OSCC progression, the expression of Orai3 exhibited a stepwise augmentation. Notably, Orai3 was highly enriched in CSC populations of OSCC. Ectopic Orai3 expression in non-tumorigenic immortalized oral epithelial cells increased the intracellular Ca2+ levels, acquiring malignant growth and CSC properties. Conversely, silencing of the endogenous Orai3 in OSCC cells suppressed the CSC phenotype, indicating a pivotal role of Orai3 in CSC regulation. Moreover, Orai3 markedly increased the expression of inhibitor of DNA binding 1 (ID1), a stemness transcription factor. Orai3 and ID1 exhibited elevated expression within CSCs compared to their non-CSC counterparts, implying the functional importance of the Orai3/ID1 axis in CSC regulation. Furthermore, suppression of ID1 abrogated the CSC phenotype in the cell with ectopic Orai3 overexpression and OSCC. Our study reveals that Orai3 is a novel functional CSC regulator in OSCC and further suggests that Orai3 plays an oncogenic role in OSCC by promoting cancer stemness via ID1 upregulation. [ABSTRACT FROM AUTHOR]

HPV has been linked to the development of precancerous and cancerous lesions. The aim of this study was to evaluate the burden of HPV-related hospitalization in Germany from 2000 to 2021 and the potential impact of the COVID-19 pandemic on it. Methods: We performed a retrospective query using data from the German Statistical Office from 2000 to 2021, including hospital admission, inpatient mortality and hospital stay length data on cervical cancer/dysplasia, female genitourinary tract, anal, penile, head and neck cancers. Results: The HPV-attributable hospitalization rate per 100,000 inhabitants in Germany has decreased over time, from 89 cases in 2000 to 60 in 2021, with an average annual percent change (AAPC) of −1.93 (CI −2.08–−1.79, p < 0.05). The same trend was observed for the average hospital stay, which declined from 9 to 7 days, with an AAPC of −1.33 (CI −1.52–−1.21, p < 0.05). An undulating but overall slightly declining pattern was observed for the inpatient mortality (AAPC −0.92, CI −1.21–−0.64, p < 0.05). We observed a reduction in the hospitalization rates for invasive and non-invasive cervical cancer, which was observed in almost all age groups and in all German federal states. Conclusion: Our study provides a comprehensive analysis of the trends in HPV-related hospitalizations over the past two decades. The decline in hospitalization rates for cervical cancer and dysplasia suggests the potential efficacy of the HPV vaccination and screening programs. [ABSTRACT FROM AUTHOR]