Can dysphagia aspiration related structures (DARS) be spared in patients with oropharyngeal cancers? Dosimetric evaluation in a prospective study of DARS optimized intensity modulated radiation therapy.

PURPOSE: To evaluate the feasibility of sparing the dysphagia-aspiration-related structures (DARS) in various head and neck cancer sites treated with definitive DARS-optimized intensity modulated radiation therapy (IMRT) and concurrent chemotherapy. MATERIALS AND METHODS: Target volumes, organs at risk, and in addition, individual DARS were delineated, including the superior, middle, and inferior pharyngeal constrictor muscles, supraglottic and glottic larynx, the base of the tongue, esophageal inlet muscles and cervical esophagus in 35 patients with head and neck squamous cell carcinoma. Volume-based dose constraints were applied to the DARS outside the planning target volume (PTV). An IMRT plan was then generated to limit doses to DARS without compromising PTV dose coverage. RESULTS: Twelve (34.3%) patients had an oropharyngeal primary (OPX), 18 (51.4%) had a laryngeal, and 5 (14.3%) patients had hypopharyngeal primary. The mean dose to the DARS was 47.93 Gy for the entire group, while it was 54.6 Gy in oropharyngeal primaries and 44.4 Gy in laryngopharyngeal primaries. DARS mean dose of ≤45 Gy could be achieved in a significantly lesser number of patients with oropharyngeal primaries (P < 0.02). Similarly, DARS mean dose was 42.25 Gy in patients with N0 disease, 49.6 Gy with ipsilateral involved nodes, and 55 Gy with bilateral disease. Sparing of DARS was feasible when the volume of PTV was ≤150 cc (P < 0.025). CONCLUSION: Sparing of DARS structures appears to be challenging in patients with oropharyngeal cancers without compromising the dose to the PTVs while it is feasible in laryngopharyngeal cancers. DARS sparing is feasible when the PTV volume is < 150 cc and in patients with negative or unilateral nodal disease.

PD-L1 immunohistochemical expression considering HPV status in oropharyngeal squamous cell carcinoma.

This systematic review aims to determine whether the presence of human papillomavirus (HPV) influences the immunohistochemical expression of programmed cell death-1 ligand (PD-L1) in oropharyngeal squamous cell carcinoma (OPSCC). PD-L1 immunohistochemical expression varies in OPSCC, and the presence of HPV is a plausible explanation for this variability. Comprehending these findings is crucial, as high PD-L1 expression in the tumor microenvironment of OPSCC can help identify patient subgroups that could be suitable for immunotherapy. Therefore, a systematic review was conducted following PRISMA guidelines (CRD42023437800). An electronic literature search was performed without time or language restrictions. The search included PubMed/MEDLINE, Embase, Scopus, Web of Science, https://clinictrials.gov, and relevant journals. A meta-analysis was performed using RStudio. Fourteen studies involving 1,629 participants were included. The sample consisted predominantly of males (81.26%) with a mean age of 58.3 years. Concerning clinical and pathological characteristics, the most frequently described anatomical location was the tonsils (68.54%), and most participants were either current or former smokers (78%) and alcohol users (79%). Advanced TNM IV was the most common stage. Regarding histopathological characteristics, HPV 16 was the only type mentioned, and half of the cases were detected through immunohistochemistry. The SP142 clone (35.7%) and the pattern of membrane immunostaining in tumor cells (71%) were the most commonly employed methods. The most prevalent findings were positive expression of PD-L1 (64.28%) and negative HPV status (57.14%). The association between PD-L1 positivity and HPV positivity (78.57%) was confirmed by meta-analysis. The conclusion was that HPV-positive status has an impact on immunohistochemical expression of PD-L1 in OPSCC.

[Surgical Treatment of Hypopharyngeal Carcinoma, Neck Dissection and Adjuvant Postoperative Therapy of Oropharyngeal and Hypopharyngeal Cancer: Recommendations of the current S3 Guideline - Part II]. / Neck Dissection und adjuvante postoperative Therapie beim Oro- und Hypopharynxkarzinom: Empfehlungen der aktuellen S3-Leitlinie ­ Teil II.

Part II of the S3 guideline report deals with the surgical treatment of hypopharyngeal carcinoma, neck dissection for oropharyngeal and hypopharyngeal carcinomas and adjuvant therapy options. Primary surgical therapy ± adjuvant radio- or radiochemotherapy and primary radio- or radiochemotherapy are established as primary therapies for local-regional hypopharyngeal carcinomas. Direct randomized comparisons of both basic therapeutic procedures were never conducted. Available registry data show a worse prognosis of hypopharyngeal carcinoma compared to oropharyngeal carcinomas in all locoregional tumor stages, regardless of the treatment method. For T1N0-T2N0 squamous cell carcinoma of the hypopharynx, there are no relevant differences in overall survival and locoregional relapse rate between primary surgical and primary non-surgical treatment. Primary surgical therapy ± adjuvant radiotherapy or radiochemotherapy and primary radiotherapy or radiochemotherapy are established as primary therapies for advanced but locoregionally limited hypopharyngeal carcinomas. Neck dissection is an integral part of the primary surgical treatment of oropharyngeal and hypopharyngeal cancer. There are only a few randomized studies on non-surgical organ preservation for advanced hypopharyngeal cancer as an alternative to pharyngolaryngectomy, but these have led to the recommendation of alternative concepts in the new guideline. The indication and implementation of postoperative adjuvant radiotherapy and radiochemotherapy for hypopharyngeal carcinoma do not differ from those for HPV/p16-negative and -positive oropharyngeal carcinoma.

Differential molecular characterization of human papillomavirus-associated oropharyngeal squamous cell carcinoma and its prognostic value.

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

Knowledge, attitude and perception of Italian dental students toward HPV-related oropharyngeal cancer and vaccination: a cross-sectional study.

BACKGROUND: Human papillomavirus (HPV) infection is a leading cause of oropharyngeal squamous cell cancer (OPSCC). This study aimed to carry out a Knowledge, Attitude and Perception survey on HPV infection, HPV+ OPSCC, and HPV vaccination among Italian dental students. METHODS: Through an online self-administered questionnaire consisting of 82 questions, data on dental students' sociodemographic characteristics, knowledge, attitudes and perceptions concerning HPV+ OPSCC, infection and vaccination were acquired. A statistical analysis, based on their year of attendance (early career, from 1st to 3rd year vs. late career, from 4th to 6th year) was also conducted. RESULTS: A total of 412 dental students completed the questionnaire. Knowledge of HPV+ OPSCC was reported by 61% of early-career students and 73% of late-career students, with high awareness of the HPV-OPSCC correlation in both groups (85% vs. 89%, respectively). The percentage of correct responses regarding HPV infection knowledge was 61% for early-career and 73% for late-career students, while vaccine knowledge was 70% and 78%, respectively. Over 90% of students acknowledged the dentist's role in educating patients about HPV and OPSCC, and attitudes toward discussing HPV and vaccination were positive. However, only about half would recommend the vaccine to either gender. Statistically significant differences were found between early- and late-career groups across all knowledge sections (p < 0.001), while no significant differences emerged for perception (p = 0.076) or attitude (p = 0.147). CONCLUSIONS: The study reveals encouraging results but highlights significant gaps in dental students' knowledge, perceptions, and attitudes toward HPV+ OPSCC, infection, and vaccination. Addressing these gaps through targeted education and training in dental curricula could improve HPV prevention awareness and patient education, ultimately enhancing public health outcomes.

A Case of Labile BP in a Patient With Oropharyngeal Carcinoma.

CASE PRESENTATION: A 71-year-old man with a history of recurrent tonsillar squamous cell carcinoma was admitted to the hospital with oropharyngeal bleeding. He received high-dose radiation therapy with curative intent. On day 4 of hospitalization, he demonstrated hypoxia resulting from an airway mucus plug and was brought to the medical ICU.

Human Papillomaviruses 16 and 18 E6 Oncoprotein Detection Test in Primary Oropharyngeal Carcinomas and Metastatic Lymph Nodes: A Cross-Sectional Study.

PURPOSE: Accuracy in the diagnosis of HPV-associated oropharyngeal carcinoma (OPSCC) of a rapid, low-cost lateral flow immunochromatographic assay for detecting E6 oncoprotein of HPV-16 and HPV-18 was previously evaluated in a small pilot study. This cross-sectional study aimed to assess on a large case series the sensitivity and specificity of E6 oncoprotein as a diagnostic marker for HPV-associated carcinogenesis in OPSCC. METHODS: 137 consecutive patients with histologically confirmed OPSCC were enrolled in two hospitals in Northeast Italy. HPV status was determined by PCR for HPV DNA and p16INK4a immunohistochemistry on primary tumor biopsies. An OPSCC was defined as HPV-associated when double positive for high-risk HPV-DNA and p16INK4a overexpression in primary lesion. Cytological samples from primary tumors and metastatic lymph nodes were obtained and tested for HPV16/18 E6 oncoproteins using the lateral flow immunochromatographic assay, which requires between 90 and 120 min to provide a result. Diagnostic performances were calculated as percentage with confidence intervals (CI). RESULTS: Of the 137 OPSCC cases, 68 (49.6%) were HPV-associated, testing positive for both high-risk HPV-DNA and p16INK4a, with HPV16 predominating (82.4%). An average waiting time of 22 days was observed to obtain the results of p16INK4a and HPV-DNA after primary lesions biopsy. In patients with HPV16/18-associated OPSCC, the HPV16/18 E6 oncoprotein was detected in 59 out of 60 cytological samples from the primary lesion (sensitivity: 98.3%; 95% CI: 91.1-100%) and in 45 out of 51 cytological samples from lymph node metastases (sensitivity: 88.2%; 95% CI: 76.1-95.6%). The E6 oncoprotein assay showed a specificity of 100% in both primary tumors and lymph node metastases. CONCLUSION: The low-cost lateral flow immunochromatographic assay for detecting HPV16/18 E6 oncoproteins confirmed high accuracy for identifying HPV-associated OPSCC, particularly in primary tumors, suggesting its potential as a valuable diagnostic tool in clinical practice. Its rapid diagnostic capability could significantly accelerate the process of treatment decision-making, enhancing the timely management of patients.

Multinational epidemiological analysis of oral human papillomavirus incidence in 3,137 men.

Oral human papillomavirus (HPV) is associated with oropharyngeal cancer (OPC). Although OPC incidence is increasing globally, knowledge of oral HPV infection rates is limited. Here we carried out an observational epidemiological analysis of oral HPV incidence in 3,137 men enrolled from the United States, Mexico and Brazil between 2005 and 2009. Individuals were followed for new HPV infection for a median of 57 months. Cumulative incidence and factors associated with acquisition were also assessed. The incidence rate of oral oncogenic HPV was 2.4 per 1,000 person-months, did not vary with age and was constant throughout the study period. Risk of oral HPV acquisition was significantly associated with alcohol consumption, having male sexual partners, more lifetime female sexual partners, more oral sex given and higher educational attainment. These data indicate that men are at risk of acquiring oral HPV throughout their lifetime, suggesting that catch-up vaccination may reduce new infection incidence.

Predictive potential of dynamic contrast-enhanced MRI and plasma-derived angiogenic factors for response to concurrent chemoradiotherapy in human papillomavirus-negative oropharyngeal cancer.

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

Using an anti-racist research framework to design studies of oral human papillomavirus and oropharyngeal cancer in San Francisco: rationale and protocol for the Health Equity and Oral Health in People living with HIV (HEOHP) qualitative study.

INTRODUCTION: The goal of our research programme is to develop culturally appropriate patient-specific interventions for primary and secondary prevention of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) among people living with HIV (PLWH); PLWH are at a higher risk for OPC than the general population and, as with many cancers, there are disparities in OPC health outcomes by race and ethnicity. Our study incorporates an anti-racist research framework that proposes considering racism as a foundational sociocultural system that causes ill health. We expand the framework to include biases due to gender, sexual orientation, HIV status and membership in other non-dominant groups. Our research programme focuses on HPV-related OPC among people living with PLWH, and on how intersecting identities may impact an individual's experience with oral health, obtaining regular and appropriate oral healthcare, knowledge and perceptions of oral HPV infection, risk factors for OPC and HPV vaccination. METHODS AND ANALYSIS: We will follow a grounded theory (GT) qualitative research methodology using focus group discussions (FGDs) to collect data. We will invite PLWH with intersecting identities to participate in one of 12-18 FGDs with 5-8 participants per group. Focus groups will be formed based on self-reported domains, including race, ethnicity, gender identity, sexual orientation and other identities that could impact oral health, such as smoking status, experience with homelessness or experience with drug use disorders. We do not know which aspects of intersecting identities are most salient to accessing oral healthcare. Using FGDs will allow us to gain this knowledge in a setting where participants can build on and reinforce shared understandings about oral healthcare. Following our GT methodology, analysis will occur concurrently with data collection, and emerging concepts or theories may result in changes to focus group guide questions. Initial focus group questions will be organised around our main objectives: (1) to identify individual, interpersonal and structural health equity factors that serve as barriers or facilitators to oral health status and care; (2) to explore knowledge and perceptions about causes, risk factors, prevention and screening for oral or OPC and (3) to elicit recommendations for improving access to regular and appropriate oral healthcare and suggestions on engaging PLWH from diverse identity groups in prevention interventions. ETHICS AND DISSEMINATION: All methods and procedures were approved by the University of California, San Francisco, Institutional Review Board (approval number: 23-39307) and are in accordance with the Declaration of Helsinki of 1975, as revised in 2000. Participants are required to provide informed consent. The results of this study will be presented at scholarly meetings and published in peer-reviewed journals. In addition, a lay summary of results will be created and distributed to our participants and community through our website and social media. TRIAL REGISTRATION NUMBER: NCT06055868.

Clinical implementation of deep learning robust IMPT planning in oropharyngeal cancer patients: A blinded clinical study.

BACKGROUND AND PURPOSE: This study aimed to evaluate the plan quality of our deep learning-based automated treatment planning method for robustly optimized intensity-modulated proton therapy (IMPT) plans in patients with oropharyngeal carcinoma (OPC). The assessment was conducted through a retrospective and prospective study, blindly comparing manual plans with deep learning plans. MATERIALS AND METHODS: A set of 95 OPC patients was split into training (n = 60), configuration (n = 10), test retrospective study (n = 10), and test prospective study (n = 15). Our deep learning optimization (DLO) method combines IMPT dose prediction using a deep learning model with a robust mimicking optimization algorithm. Dosimetrists manually adjusted the DLO plan for individual patients. In both studies, manual plans and manually adjusted deep learning (mDLO) plans were blindly assessed by a radiation oncologist, a dosimetrist, and a physicist, through visual inspection, clinical goal evaluation, and comparison of normal tissue complication probability values. mDLO plans were completed within an average time of 2.5 h. In comparison, the manual planning process typically took around 2 days. RESULTS: In the retrospective study, in 10/10 (100%) patients, the mDLO plans were preferred, while in the prospective study, 9 out of 15 (60%) mDLO plans were preferred. In 4 out of the remaining 6 cases, the manual and mDLO plans were considered comparable in quality. Differences between manual and mDLO plans were limited. CONCLUSION: This study showed a high preference for mDLO plans over manual IMPT plans, with 92% of cases considering mDLO plans comparable or superior in quality for OPC patients.

Development of 18F-Fluoromisonidazole Hypoxia PET/CT Diagnostic Interpretation Criteria and Validation of Interreader Reliability, Reproducibility, and Performance.

Tumor hypoxia, an integral biomarker to guide radiotherapy, can be imaged with 18F-fluoromisonidazole (18F-FMISO) hypoxia PET. One major obstacle to its broader application is the lack of standardized interpretation criteria. We sought to develop and validate practical interpretation criteria and a dedicated training protocol for nuclear medicine physicians to interpret 18F-FMISO hypoxia PET. Methods: We randomly selected 123 patients with human papillomavirus-positive oropharyngeal cancer enrolled in a phase II trial who underwent 123 18F-FDG PET/CT and 134 18F-FMISO PET/CT scans. Four independent nuclear medicine physicians with no 18F-FMISO experience read the scans. Interpretation by a fifth nuclear medicine physician with over 2 decades of 18F-FMISO experience was the reference standard. Performance was evaluated after initial instruction and subsequent dedicated training. Scans were considered positive for hypoxia by visual assessment if 18F-FMISO uptake was greater than floor-of-mouth uptake. Additionally, SUVmax was determined to evaluate whether quantitative assessment using tumor-to-background ratios could be helpful to define hypoxia positivity. Results: Visual assessment produced a mean sensitivity and specificity of 77.3% and 80.9%, with fair interreader agreement (κ = 0.34), after initial instruction. After dedicated training, mean sensitivity and specificity improved to 97.6% and 86.9%, with almost perfect agreement (κ = 0.86). Quantitative assessment with an estimated best SUVmax ratio threshold of more than 1.2 to define hypoxia positivity produced a mean sensitivity and specificity of 56.8% and 95.9%, respectively, with substantial interreader agreement (κ = 0.66), after initial instruction. After dedicated training, mean sensitivity improved to 89.6% whereas mean specificity remained high at 95.3%, with near-perfect interreader agreement (κ = 0.86). Conclusion: Nuclear medicine physicians without 18F-FMISO hypoxia PET reading experience demonstrate much improved interreader agreement with dedicated training using specific interpretation criteria.

Treatment De-escalation in Oropharyngeal Carcinoma and the Role of Robotic Surgery.

Oropharyngeal squamous cell carcinoma (OPSCC) related to human papillomavirus (HPV) infection has better survival outcomes compared to non-HPV-related OPSCC, leading to efforts to de-escalate the intensity of treatment to reduce associated morbidity. This article reviews recent clinical efforts to explore different de-escalation frameworks with a particular emphasis on the emergence of transoral robotic surgery and surgically driven de-escalation approaches. It discusses the current evidence for incorporating surgery into an evolving treatment paradigm for HPV-related OPSCC.

[Indications and early experience with transoral robotic surgery]. / Transzorális robotsebészeti beavatkozások indikációi és eddigi tapasztalataink.

Recently, organ preservation has gained importance for head and neck malignancies. The negative consequences of the therapies can be reduced without compromising the survival and the quality of life. Accordingly, transoral robotic surgery (TORS) is gaining ground internationally. We have been performing TORS procedures at the University of Pécs since January 2023. We operated on 27 patients until July 2024, including fifteen p16-positive tumors. Neck dissections were performed in 19 cases. The use of TORS is helpful in oropharyngeal cases, where inaccessible structures can be reached minimally invasively, compared to other transoral approaches. This is important for young patients with human papillomavirus-associated tumors, which have a better prognosis and longer life expectancy. TORS also has advantages over the previously used approaches for cancer of unknown primary (CUP). Compared to the standardly used FDG-PET/CT and "blindly" taken biopsies, TORS offers a higher detection rate of the primary tumor, by performing tonsillectomy and complete mucosectomy of the tongue base.

Effectiveness of treatment of oropharyngeal carcinoma patients.

OBJECTIVE: Aim: To analyze the results of treatment of patients with oropharyngeal carcinoma. PATIENTS AND METHODS: Materials and Methods: 276 patients with oropharyngeal carcinoma were treated in 2008-2021. Neoadjuvant chemotherapy consisted of three to six cycles: paclitaxel 175 mg/m2 and carboplatin 350 mg/m2 (or cisplatin 100 mg/m2) on the first day. The interval between cycles was 21 days. After the cycles, all patients were prescribed a course of radiation therapy in a total focal dose (TFD) of 65 Gy. The outcome of treatment was assessed by the degree of tumor regression according to RECIST criteria one month after the end of combination treatment. Statistical processing was performed using STATISTICA 6.1 software (StatSoftInc). RESULTS: Results: The three- and five-year survival rates of the examined patients with oropharyngeal carcinoma after treatment were 40.8% respectively (95% CI 33.7 - 47.9) and 27.0%, (95% CI 20.6 - 33, 4) with a median survival of 36 months with 95% CI (35.5 - 40.2). Processing was performed using STATISTICA 6.1 software (StatSoftInc). CONCLUSION: Сonclusions: Analysis of treatment of patients with oropharyngeal carcinoma with predominance of squamous cell carcinoma (90.6%), localized primarily in the palatine tonsil (73.2%), with the most common stages T3N1M0 (30.1%) and T3N1M0 %), with regional metastases to the lymph nodes of the neck (89.9%), showed that the effectiveness of treatment of patients is quite high, because in most of the examined in the short term after combined treatment there was complete or partial regression of the tumor (91.7%), no progression of the oncological process was detected in any of them.

Trends in the treatment of human papillomavirus-associated oropharyngeal carcinoma in Slovakia.

The optimal treatment of oropharyngeal cancer (OPC) associated with human papillomavirus (HPV) is currently a subject of clinical research. This questionnaire study investigated current trends in the treatment of HPV-associated (HPV+) OPC in Slovakia with the incorporation of deintensification of oncological treatment into routine clinical practice outside of clinical trials. The Slovak Cooperative Head and Neck Cancer Group (SCHNCG) developed a questionnaire aimed at identifying trends in the oncological treatment of HPV+ OPC intended for all radiation oncology (RO) facilities in Slovakia. Specialists in the field of RO responded to general questions about the character of their individual institutions as well as to 4 theoretical clinical scenarios (case reports) regarding the treatment of HPV+ OPC, focusing primarily on the applied dose of radiotherapy (RT), the extent of target volumes, and the type of concurrent chemotherapy (CHT). The questionnaire study involved 35 RO specialists from 14 institutions in Slovakia. Regarding primary chemoradiotherapy (CRT) in T1N1M0 HPV+ OPC, 16 respondents (45.7%) would consider de-escalation of the RT dose to <70 Gy. In the case of postoperative RT in pT1pN1M0 HPV+ OPC with negative resection margins (R0) and absent extracapsular extension (ECE), 4 physicians (11.4%) would consider de-escalation of the RT dose to <60 Gy in the tumor bed area, while the majority of the treating specialists (n=19, 54.3%) would omit concurrent CHT. In the case of primary RT in elderly patient with T2N1M0 HPV+ OPC, the same number of physicians (n=16, 45.7%) would consider de-escalation of the RT dose to <70 Gy, and 14 respondents (40.0%) would completely omit CHT. In a high-risk patient with T2N3M0 HPV+ OPC with a complete response after 3 cycles of induction chemotherapy (iCHT), none of the respondents would indicate a reduction in the RT dose to the area of the original tumor and lymphadenopathy to <60 Gy. The doses and extent of irradiated volumes in the treatment of HPV+ OPC in Slovakia vary among different institutions. The tendency to de-escalate RT doses and reduce doses of concurrent systemic therapy in Slovakia is high and there was also an observed trend to reduce the extent of radiation treatment fields.

Awake Tracheostomy in a Pediatric Patient.

Awake tracheostomy is rare in the pediatric population. We describe the case of a 10-year-old male who underwent awake tracheostomy due to airway obstruction from an oropharyngeal rhabdomyosarcoma. Given the varying medical understanding and communication skills in children, advanced planning and interdisciplinary collaboration are essential to keep the patient calm and safe during awake tracheostomy.

Fibroblast stromal support model for predicting human papillomavirus-associated cancer drug responses.

Currently, there are no specific antiviral therapeutic approaches targeting Human papillomaviruses (HPVs), which cause around 5% of all human cancers. Specific antiviral reagents are particularly needed for HPV-related oropharyngeal cancers (HPV+OPCs) whose incidence is increasing and for which there are no early diagnostic tools available. We and others have demonstrated that the estrogen receptor alpha (ERα) is overexpressed in HPV+OPCs, compared to HPV-negative cancers in this region, and that these elevated levels are associated with an improved disease outcome. Utilizing this HPV+-specific overexpression profile, we previously demonstrated that estrogen attenuates the growth and cell viability of HPV+ keratinocytes and HPV+ cancer cells in vitro. Expansion of this work in vivo failed to replicate this sensitization. The role of stromal support from the tumor microenvironment (TME) has previously been tied to both the HPV lifecycle and in vivo therapeutic responses. Our investigations revealed that in vitro co-culture with fibroblasts attenuated HPV+-specific estrogen growth responses. Continuing to monopolize on the HPV+-specific overexpression of ERα, our co-culture models then assessed the suitability of the selective estrogen receptor modulators (SERMs), raloxifene and tamoxifen, and showed growth attenuation in a variety of our models to one or both of these drugs in vitro. Utilization of these SERMs in vivo closely resembled the sensitization predicted by our co-culture models. Therefore, the in vitro fibroblast co-culture model better predicts in vivo responses. We propose that utilization of our co-culture in vitro model can accelerate cancer therapeutic drug discovery. IMPORTANCE: Human papillomavirus-related cancers (HPV+ cancers) remain a significant public health concern, and specific clinical approaches are desperately needed. In translating drug response data from in vitro to in vivo, the fibroblasts of the adjacent stromal support network play a key role. Our study presents the utilization of a fibroblast 2D co-culture system to better predict translational drug assessments for HPV+ cancers. We also suggest that this co-culture system should be considered for other translational approaches. Predicting even a portion of treatment paradigms that may fail in vivo with a co-culture model will yield significant time, effort, resource, and cost efficiencies.

TNM 8 staging system beyond p16: Double HPV/p16 status is superior to p16 alone in predicting outcome in oropharyngeal squamous cell carcinoma.

PURPOSE: The assessment of p16INK4a (p16) in oropharyngeal squamous cell carcinoma (OPSCC) has been incorporated into tumor classification, as p16 has been shown to impact survival probability. However, a recent study demonstrated that human papillomavirus (HPV) status in addition to p16 may have a better discriminatory effect on survival probability. This study aims to determine the impact of combined evaluation of p16 and HPV on prognosis. METHODS: This was a multicenter, multinational analysis including retrospective and prospective cohorts of patients treated for primary OPSCC with curative intent, based on the data of the HNCIG-EPIC study. The primary outcome was to determine how the combined assessment of HPV and p16 status predicts prognosis of patients with OPSCC compared to p16 assessment alone. We employed multivariable analyses models to compute hazard ratios regarding survival. Analyses were stratified by stage, smoking status, and sub-anatomical region. RESULTS: The study included 7654 patients, with approximately half of the tumors being p16-negative (50.3 %, n = 3849). A total of 9.2 % of patients had discordant p16 and HPV status (n = 704). HPV status significantly impacted overall survival and disease-free survival regardless of p16 status and across both UICC 8th stage I-II and III-IVb cancers. p16-positive/HPV-positive OPSCC patients exhibited the best survival probability. CONCLUSION: The detection of HPV had a significant impact on survival probability for OPSCC patients with both p16-positive and p16-negative tumors. HPV testing should be integrated in cancer staging, especially in regions of low attributable fraction, alongside p16 evaluation to ensure a comprehensive assessment of prognosis.