The tumor microenvironment of benign and malignant salivary gland tumors.

BACKGROUND: Treatment of salivary gland tumors (SGTs) remains challenging. Little is known about the immune landscape of SGTs. We aimed to characterize the tumor microenvironment in benign and malignant SGTs. METHODS: Eleven benign and nine malignant tumors were collected from patients undergoing curative intent surgery. Specimens were analyzed using mass cytometry by time-of-flight. Immune cell populations were manually gated, and T cells were clustered using the FlowSOM algorithm. Population frequencies were compared between high-grade and low-grade malignancies, corrected for multiple hypothesis testing. RESULTS: There were trends towards increased CD4+ and CD8+ T cells among malignant tumors. High-grade malignancies exhibited trends towards higher frequencies of CD8+ PD-1+ CD39+ CD103+ exhausted T cells, CD4+ FoxP3+ TCF-1+ CD127- Tregs, and CD69+ CD25- CD4+ T cells compared to low-grade malignancies. CONCLUSION: SGTs exhibit significant immunologic diversity. High-grade malignancies tended to have greater infiltration of exhausted CD8+ T cells and Tregs, which may guide future studies for immunotherapy strategies.

Postoperative inpatient surgical complications following head and neck microvascular free tissue transfer.

BACKGROUND: Complications following head and neck microvascular free tissue transfer (MFTT) are common. Less is known about when they occur. METHOD: Retrospective study of patients with primary or recurrent head and neck cancer undergoing MFTT reconstruction at a tertiary care institution. MFTT reconstructions with inpatient postoperative complications were included. The Kruskal-Wallis test was used to compare median postoperative day (POD) onset of complication by flap type. RESULTS: Of 1090 patients undergoing MFTT reconstruction, 126 (11.6%) patients experienced inpatient complications including fibula (n = 35), anterolateral thigh (n = 60), or radial forearm (n = 31) MFTTs. POD onset was shortest for surgical site hematoma (median = 1 [IQR 1-5]), and longest for donor site infection (median = 11.5 [IQR 8-15]). There was no significant difference between flap types and POD onset of complications (p > 0.05). CONCLUSION: Hematoma formation and flap failure occur earliest during hospitalization, while dehiscence, infection, and fistula occur later. There is no difference in complication timing between flap types.

Management of Pediatric Persistent Asymptomatic Cervical Lymphadenopathy.

OBJECTIVE: Persistent asymptomatic cervical lymphadenopathy (PACL) is a common outpatient referral diagnosis for pediatric otolaryngologists. Historically, excisional biopsy under general anesthesia has been the gold standard for diagnosis but is associated with some risks. Current literature provides little guidance on less invasive monitoring. Our hypothesis is that the majority of children who present with PACL can be safely monitored with ultrasound and avoid the risks of excisional biopsy. STUDY DESIGN: A retrospective review was performed of patients <18 years of age, referred to a tertiary care children's hospital for PACL who also underwent at least 1 neck ultrasound from 2007 to 2021. Patients with acute neck infections, congenital masses, or known rheumatologic, immunologic, or malignant conditions were excluded. A multivariate logistic regression model was used to determine patient and nodal factors associated with the decision for operative management. SETTING: University of California, San Francisco Pediatric Otolaryngology Department. RESULTS: Among the 197 patients meeting inclusion criteria, 30 (15.2%) underwent surgical biopsy. Overall, 26% underwent repeat ultrasound with a mean interval of 6.6 months, and a mean decrease in nodal size of 0.34 cm. Of the 30 surgical cases, 27 (90%) patients had benign pathology. Multivariate regression analysis revealed pain (p = .04), firmness (p < .001), and lack of a normal fatty hilum on ultrasound (p = .04) as statistically significantly correlated with decisions for surgical management. CONCLUSION: The majority of pediatric PACL is benign and does not require an excisional biopsy to rule out lymphoma. Serial clinical follow-up with neck ultrasound can be used to safely monitor patients.

The neutrophil-to-lymphocyte ratio in salivary gland cancers treated with pembrolizumab.

BACKGROUND: A minority of patients with recurrent/metastatic (R/M) salivary gland cancers (SGCs) benefit from immune checkpoint inhibitors (ICIs), necessitating reliable biomarkers for ICI response prediction. METHODS: Retrospective observational study of R/M SGC patients treated with pembrolizumab between 2016 and 2022, with a primary outcome of 6-month progression-free survival (PFS) and secondary outcome of 2-year overall survival (OS). Univariate and multivariable Cox proportional hazards models were employed. RESULTS: Twenty R/M SGC patients were included. After adjustment, NLR as a continuous variable was independently associated with 6-month PFS (HR 1.30, 95% CI 1.10-1.54, p = 0.002) and 2-year OS (HR 1.33, 95% CI 1.07-1.66, p = 0.010). Similarly, NLR ≥ 5 was associated with higher hazards of progression at 6 months (HR 12.85, 95% CI 2.17-76.16, p = 0.005) and death at 2 years (HR 11.25, 95% CI 1.67-75.77, p = 0.013). CONCLUSIONS: Higher pretreatment NLR was independently associated with inferior 6-month PFS and 2-year OS in pembrolizumab-treated R/M SGC patients.

Is the clinical head impulse test helpful in cochlear implantation candidacy evaluation?

Objective: Vestibular dysfunction is a known risk of cochlear implantation (CI). However, the utility of the physical exam to screen CI candidates for vestibular dysfunction is not well-studied. The objective of this study is to evaluate the preoperative role of the clinical head impulse test (cHIT) in subjects undergoing CI surgery evaluation. Study Design Setting and Subjects: We conducted a retrospective review of 64 adult CI candidacy cases between 2017 and 2020 at a tertiary health care center. Methods: All patients underwent audiometric testing and evaluation by the senior author. Patients with an abnormal catch-up saccade contralateral to their worse hearing ear during cHIT were referred for formal vestibular testing. Outcomes included clinical and formal vestibular results, operated ear with regard to audiometric and vestibular results, and postoperative vertigo. Results: Among all CI candidates, 44% (n = 28) reported preoperative disequilibrium symptoms. Overall, 62% (n = 40) of the cHITs were normal, 33% (n = 21) were abnormal, and 5% (n = 3) were inconclusive. There was one patient who presented with a false positive cHIT. Among the patients who endorsed disequilibrium, 43% had a positive preoperative cHIT. Fourteen percent of the subjects (n = 9) without disequilibrium had an abnormal cHIT. In this cohort, bilateral vestibular impairment (71%) was more common than unilateral vestibular impairment (29%). In 3% of the cases (n = 2), surgical management was revisited or altered due to cHIT findings. Conclusion: There is a high prevalence of vestibular hypofunction in the CI candidate population. Self-reported assessments of vestibular function are often not congruent with cHIT results. Clinicians should consider incorporating cHITs as part of the preoperative physical exam to potentially avoid bilateral vestibular dysfunction in a minority of patients.

Dynamic CD8+ T cell responses to cancer immunotherapy in human regional lymph nodes are disrupted in metastatic lymph nodes.

CD8+ T cell responses are critical for anti-tumor immunity. While extensively profiled in the tumor microenvironment, recent studies in mice identified responses in lymph nodes (LNs) as essential; however, the role of LNs in human cancer patients remains unknown. We examined CD8+ T cells in human head and neck squamous cell carcinomas, regional LNs, and blood using mass cytometry, single-cell genomics, and multiplexed ion beam imaging. We identified progenitor exhausted CD8+ T cells (Tpex) that were abundant in uninvolved LN and clonally related to terminally exhausted cells in the tumor. After anti-PD-L1 immunotherapy, Tpex in uninvolved LNs reduced in frequency but localized near dendritic cells and proliferating intermediate-exhausted CD8+ T cells (Tex-int), consistent with activation and differentiation. LN responses coincided with increased circulating Tex-int. In metastatic LNs, these response hallmarks were impaired, with immunosuppressive cellular niches. Our results identify important roles for LNs in anti-tumor immune responses in humans.

Patterns of Postoperative Trismus Following Mandibulectomy and Fibula Free Flap Reconstruction.

The factors that contribute to postoperative trismus after mandibulectomy and fibula free flap reconstruction (FFFR) are undefined. We retrospectively assessed postoperative trismus (defined as a maximum interincisal opening ≤35 mm) in 106 patients undergoing mandibulectomy with FFFR, employing logistic regression to identify risk factors associated with this sequela. The surgical indication was primary ablation in 64%, salvage for recurrence in 24%, and osteonecrosis in 12%. Forty-five percent of patients had existing preoperative trismus, and 58% of patients received adjuvant radiation/chemoradiation following surgery. The overall rates of postoperative trismus were 76% in the early postoperative period (≤3 months after surgery) and 67% in the late postoperative period (>6 months after surgery). Late postoperative trismus occurred more frequently in patients with ramus-involving vs. ramus-preserving posterior mandibulotomies (82% vs. 46%, p = 0.004). A ramus-involving mandibulotomy was the only variable significantly associated with trismus >6 months postoperatively on multivariable logistic regression (OR, 7.94; 95% CI, 1.85−33.97; p = 0.005). This work demonstrates that trismus is common after mandibulectomy and FFFR, and suggests that posterior mandibulotomies that involve or remove the ramus may predispose to a higher risk of persistent postoperative trismus.

Approaches to the Management of Metastatic Adenoid Cystic Carcinoma.

High rates of recurrence and distant metastasis are a foremost challenge in the management of adenoid cystic carcinoma (ACC), occurring in approximately 40% of all ACC patients. Despite the morbidity and mortality resulting from recurrent/metastatic (R/M) disease, there are no FDA-approved systemic agents for these patients. In this review, we summarize pertinent ACC pathophysiology and its implications for different systemic treatment regimens in R/M ACC. We review the evidence for the most widely used systemic agents - cytotoxic chemotherapy and tyrosine kinase inhibitors (TKIs) targeting VEGFR - in addition to immune checkpoint inhibitors and non-TKI biologic agents. Exciting emerging targets for R/M ACC, including inhibitors of Notch signaling, stemness, PRMT5, and Axl, are also discussed. Lastly, we review local therapies for small-volume lung disease in patients with oligometastatic ACC, specifically pulmonary metastasectomy and stereotactic body radiation therapy (SBRT). Future development of targeted molecular agents which exploit the underlying biology of this disease may yield novel therapeutic options to improve clinical outcomes in patients with R/M ACC.

Development of a Community-Based Network to Promote Anti-Drug Messaging and Identify Hidden Drug Abusers in Hong Kong.

Developing a community-based network by training peers as anti-drug ambassadors (ADAs) is a feasible strategy to identify hidden drug abusers. The Ask, Warn, Advise, Refer and Do-it-again (AWARD) model of smoking cessation is useful for enhancing people's confidence in making referrals to anti-drug services. This study evaluated the effectiveness of such a network by examining the change in knowledge, attitudes and practices (KAP) of 198 ADAs aged 13-18 before and after six months of our training. A one-group pre-test and repeated post-test design was used. One-way repeated-measures analysis of variance was applied to assess the changes in KAP, with p-values adjusted by Bonferroni correction. The results showed that the ADAs statistically significantly improved their KAP regarding drug abuse at the six-month follow-up compared to baseline. All ADAs who knew drug abusers (n = 3) had referred them to services based on the AWARD model. A total of 154 anti-drug abuse activities were conducted, reaching 4561 people. Based on the results, we concluded that the community-based network was effective in improving the KAP of ADAs regarding drug abuse, as well as referring hidden drug abusers. Future studies should consider implementing the network on a larger scale, thus maximizing its anti-drug capacity.

The Role of ECM Remodeling, EMT, and Adhesion Molecules in Cancerous Neural Invasion: Changing Perspectives.

Perineural invasion (PNI) refers to the cancerous invasion of nerves. It provides an alternative route for metastatic invasion and can exist independently in the absence of lymphatic or vascular invasion. It is a prominent characteristic of specific aggressive malignancies where it correlates with poor prognosis. The clinical significance of PNI is widely recognized despite a lack of understanding of the molecular mechanisms underlying its pathogenesis. The interaction between the nerve and the cancer cells is the most pivotal PNI step which is mediated by the activation or inhibition of multiple signaling pathways that include chemokines, interleukins, nerve growth factors, and matrix metalloproteinases, to name a few. The nerve-cancer cell interaction brings about specific changes in the perineural niche, which not only affects the regular nerve functions, but also enhances the migratory, invasive, and adherent properties of the tumor cells. This review aims to elucidate the vital role of adhesion molecules, extracellular matrix, and epithelial-mesenchymal proteins that promote PNI, which may serve as therapeutic targets in the future.

Feasibility of accelerated image-guided high-dose-rate interstitial brachytherapy with inverse planning simulated annealing (IPSA-HDRBT) for post-operative treatment of pathologically node-negative squamous cell carcinomas of the oral tongue.

PURPOSE: Inverse planning simulated annealing (IPSA) produces highly conformal dose distributions and quick optimizations for high-dose-rate interstitial brachytherapy (HDRBT). We report our dosimetry and overall outcomes using this approach for the accelerated post-operative treatment of pathologically node-negative squamous cell carcinomas of the oral tongue (OTSCC) with high risk of local recurrence. METHODS: Patients with newly diagnosed pN0 OTSCC treated with partial glossectomy, neck dissection, and post-operative HDRBT alone from 2007 to 2021 were retrospectively reviewed. Patients received 30 Gy in 5 fractions over 2.5 days. Target volume and mandible dosimetry are reported. Actuarial rates of local control, regional control, disease-specific survival, and overall survival were estimated using the Kaplan-Meier method. Toxicity was categorized using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. RESULTS: 19 consecutive patients were reviewed. Median follow-up was 3.2 years (IQR 1.4-8.2 years) with a 3-year estimated local control rate of 81%. Target volumes were generally small, as the median volume was 12.66 cc. Median V150% and V200% were 52% and 24%, respectively. D1cc and D2cc to the mandible were 17.31 Gy and 14.42 Gy, respectively. CONCLUSIONS: IPSA-HDRBT is feasible and highly efficient for post-operative treatment of the primary tumor bed in patients with pathologically node-negative squamous cell carcinomas of the oral tongue. Further technical optimization and prospective clinical evaluation in a larger patient cohort are planned.

Risk of Pathologic Extranodal Extension and Other Adverse Features After Transoral Robotic Surgery in Patients With HPV-Positive Oropharynx Cancer.

Importance: Understanding patient-specific risk of adverse histopathologic findings after primary surgery for human papillomavirus (HPV)-positive oropharynx squamous cell carcinoma (OPSCC) may help guide patient consultations. Objective: To determine the likelihood of adverse histopathologic features that may indicate adjuvant radiotherapy or chemoradiotherapy after primary surgery for HPV-positive OPSCC according to 2021 National Comprehensive Cancer Network guidelines. Design, Setting, and Participants: This retrospective cohort study was performed at a single academic tertiary care center. Of 258 patients who underwent transoral robotic surgery (TORS) from March 1, 2012, to March 1, 2021, 136 consecutive, treatment-naive patients with HPV-positive OPSCC without obvious clinical extranodal extension (ENE) who underwent definitive TORS and neck dissection were included in the analysis. Indications for surgical treatment included non-deeply infiltrative oropharynx tumors, minimal soft palate involvement, and low suspicion for pathologic ENE. Exposures: Primary site TORS with neck dissection. Main Outcomes and Measures: The primary outcomes were the adverse histopathologic features of pathologic ENE and positive surgical margins (PSM) that are indications for possible adjuvant chemoradiotherapy. Outcomes were compared among varying American Joint Committee on Cancer 7th edition (AJCC-7) T and N categories and patient clinical characteristics. Results: Of the 136 patients included in the analysis (113 men [83.1%]; median age, 63 [interquartile range, 55-70] years), 109 (80.1%) had at least 1 indication for possible adjuvant radiotherapy. Twenty-seven patients (19.9%) had pathologic ENE and 10 (7.3%) had PSM. Thirty-four patients (25.0%) had pathologic ENE and/or PSM, whereas 3 (2.2%) had both. Age, smoking history, history of alcohol consumption, and clinical T category were not associated with pathologic ENE, PSM, lymphovascular invasion, perineural invasion, or pN2 category or greater. The proportion of pathologic ENE varied by clinical N category: 0 of 16 for cN0, 8 of 48 (16.7%) for cN1, 3 of 23 (13.0%) for cN2a, and 16 of 45 (35.6%) for cN2b. Compared with patients with cN1-cN2a disease, patients with cN2b disease had higher odds of pathologic ENE (odds ratio, 3.01; 95% CI, 1.14-8.10). Clinical and pathologic N category were concordant in 77 patients (56.6%), whereas 42 (30.9%) were upstaged and 17 (12.5%) were downstaged. Conclusions and Relevance: In this cohort study, approximately one-quarter of carefully selected patients with HPV-positive OPSCC without obvious clinical ENE undergoing primary surgery had pathologic ENE and/or PSM. Patients with AJCC-7 cT0-cT2 cN0-cN2b disease, especially cN0-cN2a, without signs of clinical ENE may represent appropriate candidates for primary surgery when avoidance of adjuvant chemotherapy and/or reduction of adjuvant radiotherapy dose/extent are the goals.

Molecular Markers that Matter in Salivary Malignancy.

Despite aggressive initial interventions, recurrent/metastatic salivary gland cancer is not uncommon. Standard chemotherapy has not been shown to have durable clinical benefits. Several potential molecular markers have been identified in different histologic subtypes of salivary cancers. The objective of this review is to highlight the molecular markers that have been targeted in clinical trials for salivary gland cancers.

Head and neck surgery during the coronavirus-19 pandemic: The University of California San Francisco experience.

BACKGROUND: Guidelines regarding head and neck surgical care have evolved during the coronavirus-19 (COVID-19) pandemic. Data on operative management have been limited. METHODS: We compared two cohorts of patients undergoing head and neck or reconstructive surgery between March 16, 2019 and April 16, 2019 (pre-COVID-19) and March 16, 2020 and April 16, 2020 (COVID-19) at an academic center. Perioperative, intraoperative, and postoperative outcomes were recorded. RESULTS: There were 63 operations during COVID-19 and 84 operations during pre-COVID-19. During COVID-19, a smaller proportion of patients had benign pathology (12% vs 20%, respectively) and underwent thyroid procedures (2% vs 23%) while a greater proportion of patients underwent microvascular reconstruction±ablation (24% vs 12%,). Operative times increased, especially among patients undergoing microvascular reconstruction±ablation (687 ± 112 vs 596 ± 91 minutes, P = .04). Complication rates and length of stay were similar. CONCLUSIONS: During COVID-19, perioperative outcomes were similar, operative time increased, and there were no recorded transmissions to staff or patients. Continued surgical management of head and neck cancer patients can be provided safely.

Evolving Otolaryngology Resident Roles and Concerns at the Peak of the US COVID-19 Pandemic.

BACKGROUND: The roles of US otolaryngology residents have changed in response to the coronavirus disease 2019 (COVID-19) pandemic. As the pandemic peaked in the United States, we characterized resident activities and concerns. METHODS: A cross-sectional study of US otolaryngology residents between April 20, 2020 and May 2, 2020. RESULTS: A total of 219 residents at 65/118 (55%) institutions responded. Thirty (14%) residents had been redeployed. Residents reported greatest concerns regarding education (P < .00001). Assuming adequate protective equipment, 55% desired active participation in high-risk procedures on COVID-19-positive patients. Redeployed residents had greater concern for burnout and reduced in-hospital well-being (P < .05). Resident satisfaction correlated with comfort communicating concerns to their department (odds ratio [OR] = 4.9, 95% confidence interval [CI] 1.4-17.3, P = .01) and inversely correlated with low perceived meaning in work (OR = 3.1, CI 1.1-9.1, P = .03). CONCLUSION: Otolaryngology resident concerns have evolved as the pandemic progressed. Residency programs should prioritize resident education, well-being in redeployed residents, and open communication as they transition toward recovery.

Effectiveness of a video-based smoking cessation intervention focusing on maternal and child health in promoting quitting among expectant fathers in China: A randomized controlled trial.

BACKGROUND: Secondhand smoke can cause adverse pregnancy outcomes, yet there is a lack of effective smoking cessation interventions targeted at expectant fathers. We examined the effectiveness of a video-based smoking cessation intervention focusing on maternal and child health in promoting quitting among expectant fathers. METHODS AND FINDINGS: A single-blind, 3-arm, randomized controlled trial was conducted at the obstetrics registration centers of 3 tertiary public hospitals in 3 major cities (Guangzhou, Shenzhen, and Foshan) in China. Smoking expectant fathers who registered with their pregnant partners were invited to participate in this study. Between 14 August 2017 to 28 February 2018, 1,023 participants were randomized to a video (n = 333), text (n = 322), or control (n = 368) group. The video and text groups received videos or text messages on the risks of smoking for maternal and child health via instant messaging. The control group received a leaflet with information on smoking cessation. Follow-up visits were conducted at 1 week and at 1, 3, and 6 months. The primary outcome, by intention to treat (ITT), was validated abstinence from smoking at the 6-month follow-up. The secondary outcomes included 7-day point prevalence of abstinence (PPA) and level of readiness to quit at each follow-up. The mean age of participants was 32 years, and about half of them were first-time expectant fathers. About two-thirds of participants had completed tertiary education. The response rate was 79.7% (815 of 1,023) at 6 months. The video and text groups had higher rates of validated abstinence than the control group (video group: 22.5% [75 of 333], P < 0.001; text group: 14.9% [48 of 322], P = 0.02; control group: 9.2% [34 of 368]) with adjusted odds ratios (ORs) of 2.80 (95% confidence interval [CI]: 1.79-4.37, P < 0.001) in the video group and 1.70 (95% CI: 1.06-2.74, P = 0.03) in the text group. The video and text groups differed in the rates of validated abstinence (22.5% versus 14.9%, P = 0.008; adjusted OR: 1.64, 95% CI: 1.10-2.46, P = 0.02). The video and text groups had higher rates of 7-day PPA than the control group at 6 months (video group: 24.6% [82 of 333] versus 11.4% [42 of 368], P < 0.001; text group: 17.4% [56 of 333] versus 11.4% [42 of 368], P = 0.02). The video and text groups also differed in the rates of 7-day PPA (24.6% versus 17.4%, P = 0.02). Excluding the quitters, the video and text groups had higher levels of readiness to quit than the control group at 6 months (video group: 43.5% [109 of 251] versus 31.6% [103 of 326], P = 0.002; text group: 40.6% [108 of 266] versus 31.6% [103 of 326], P = 0.01), No such difference was detected between the video and text groups (43.5% versus 40.6%, P = 0.29). The study was limited in that the long-term effectiveness of the intervention is uncertain. CONCLUSIONS: This smoking cessation intervention for expectant fathers that focused on explaining the ramifications of smoking on maternal and child health was effective and feasible in promoting quitting, and video messages were more effective than texts in delivering the information. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03236025.

Otolaryngology Resident Practices and Perceptions in the Initial Phase of the U.S. COVID-19 Pandemic.

OBJECTIVE: The coronavirus 2019 (COVID-19) pandemic has had widespread implications on clinical practice at U.S. hospitals. These changes are particularly relevant to otolaryngology-head and neck surgery (OHNS) residents because reports suggest an increased risk of contracting COVID-19 for otolaryngologists. The objectives of this study were to evaluate OHNS residency program practice changes and characterize resident perceptions during the initial phase of the pandemic. STUDY DESIGN: A cross-sectional survey of U.S. OHNS residents at 81 programs was conducted between March 23, 2020, and March 29, 2020. RESULTS: Eighty-two residents from 51 institutions (63% of invited programs) responded. At the time of survey, 98% of programs had enacted policy changes to minimize COVID-19 spread. These included filtered respirator use for aerosol-generating procedures even in COVID-19-negative patients (85%), decreased resident staffing of surgeries (70%), and reduced frequency of tracheotomy care (61%). The majority of residents (66%) perceived that residents were at higher risk of contracting COVID-19 compared to attendings. Residents were most concerned about protective equipment shortage (93%) and transmitting COVID-19 to patients (90%). The majority of residents (73%) were satisfied with their department's COVID-19 response. Resident satisfaction correlated with comfort level in discussing concerns with attendings (r = 0.72, P < .00001) and inversely correlated with perceptions of increased risk compared to attendings (r = -0.52, P < .00001). CONCLUSION: U.S. OHNS residency programs implemented policy changes quickly in response to the COVID-19 pandemic. Sources of resident anxieties demonstrate the importance of open communication and an integrated team approach to facilitate optimal patient and provider care during this unprecedented crisis. LEVEL OF EVIDENCE: 4. Laryngoscope, 130:2550-2557, 2020.

Molecular Diagnostics in Human Papillomavirus-Related Head and Neck Squamous Cell Carcinoma.

The incidence of human papillomavirus (HPV)-related head and neck squamous cell carcinoma continues to increase. Accurate diagnosis of the HPV status of a tumor is vital, as HPV+ versus HPV- tumors represent two unique biological and clinical entities with different treatment strategies. High-risk HPV subtypes encode oncoproteins E6 and E7 that disrupt cellular senescence and ultimately drive tumorigenesis. Current methods for detection of HPV take advantage of this established oncogenic pathway and detect HPV at various biological stages. This review article provides an overview of the existing technologies employed for the detection of HPV and their current or potential future role in management and prognostication.

De-intensification strategies in HPV-related oropharyngeal squamous cell carcinoma-a narrative review.

Human papillomavirus-related (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) is a relatively new clinical entity that is dramatically on the rise globally. HPV+ OPSCC is thought to be a separate clinical entity compared to HPV- OPSCC with a distinct tumor biology. Patients with HPV associated disease have been shown to have a substantially better prognosis and overall survival than those patients with the HPV negative (HPV-) counterpart. The standard of care for OPSCC is definitive radiation therapy (RT) and concurrent chemoradiation therapy (CRT), for lower and higher stage disease, respectively. However, traditional CRT is also associated with severe acute and late toxicities affecting patient quality of life, such as severe mucositis, dry mouth and dysphagia. Considering that HPV+ OPSCC is on the rise in a younger, healthier patient population and the good prognosis of HPV-related disease, there has been a focus on reducing treatment toxicities and optimizing quality of life while maintaining favorable oncologic outcomes. A variety of such de-escalation regimens are currently being explored in recently completed and ongoing clinical trials. Alterations to the standard chemotherapy, radiation and surgical regimens are being explored. This review will provide an overview of the rationale for and available results of the major de-intensification strategies in the treatment of locally advanced HPV+ OPSCC.

Relationships among fatigue, physical activity, depressive symptoms, and quality of life in Chinese children and adolescents surviving cancer.

PURPOSE: Fatigue is the most common concern reported by childhood cancer survivors. Assessing its occurrence and severity is a prerequisite for planning and evaluating appropriate interventions. Nevertheless, there is a lack of large-scale surveys which examine the occurrence and severity of fatigue and its associated factors. The study aimed to shed light on this under researched area. METHODS: A cross-sectional study was used. A total of 400 childhood cancer survivors (7- to 18-year olds) were invited to participate in the study. The cancer-related fatigue, depressive symptoms, physical activity level, and quality of life of participants were assessed. RESULTS: An average of 46.4% of children and 48.4% of adolescents were found to display symptoms of cancer-related fatigue between "half the time" and "all the time" over the previous seven days. Besides, greater occurrence and severity of fatigue in childhood cancer survivors were associated with more self-reported depressive symptoms, lower level of physical activity and quality of life. In addition, the study revealed that physical activity level is a significant factor associated with cancer-related fatigue. CONCLUSION: The findings provide further support that cancer and its treatment have adverse effects on survivors' fatigue, which can manifest months or even years after the completion of treatment. Importantly, this study reveals that physical activity is a significant factor associated with fatigue in children and adolescents. It is crucial for healthcare professionals to identify strategies that can help children and adolescents surviving cancer increase their adoption and maintenance of regular activity throughout their life.