Objective:By combining static and dynamic methods of obtaining natural head position, this study examined whether compensatory head tilt in patients with non-syndromic asymmetric facial deformities contributes to of pseudo-"vertical eye canting". Methodology:Patients with non-syndromic asymmetric facial deformities patients and symmetric dento-maxillofacial deformity who met the inclusion and exclusion criteria were divided into observation and control groups. Static photographs were measured to analyze the static head position of the subjects in each follow-up period; dynamic natural head positions of the subjects in different states in each period were recorded by posture sensors for dynamic analysis. Intergroup and intragroup changes were analyzed with Mann-Whitney U-test and one way ANOVA. Results:The static natural head position of the observation group at 1 year after surgery was significantly different from that of the pre-surgery period, whereas each dynamic natural head position at all follow-up periods after surgery was significantly different from dynamic natural head position of the pre-surgery period. The range of dynamic head position in the rolling direction was smaller in the observation group than in the preoperative period at 6 months and 1 year after surgery, but the dynamic head position range in the rolling direction was not significantly different in the control group at the different follow-up stages. Conclusions:Changes in natural head position (NHP) following orthognathic surgery were associated with improved stabilization of head posture in roll orientation and reduced pseudo-eye canting in non-syndromic asymmetric facial deformities (NSAFD) patients. Clinical Trial Number KQEC-2021-58-01.

A 41-year-old male presented with a 3-month history of recurrent sore throat, intermittent fever, and yellow, purulent sputum. Laryngoscopy revealed congestion and mild swelling of the mucosa in the bilateral arytenoid and postcricoid regions. What is your diagnosis?

BACKGROUND:To compare outcomes of the combined transcervical-submandibular and transoral endoscopic approach versus the open transcervical parotid approach and transoral endoscopic surgery alone, and to clarify the indications and advantages of the combined technique. METHODS:This retrospective observational study was conducted at a tertiary academic hospital in China between January 2013 and December 2024. A total of 114 consecutive patients with histologically confirmed benign parapharyngeal space tumors underwent the open transcervical parotid approach (n = 48), transoral endoscopic surgery alone (n = 42), or the combined transcervical-submandibular and transoral endoscopic approach (n = 24). Tumor size, intraoperative blood loss, hospitalization duration, tracheotomy rates, en-bloc resection rates, and surgery-related complications were compared among the three groups. RESULTS:The combined surgery group had significantly larger tumors and a lower incidence of surgery-related complications. No statistically significant differences were observed among the three approaches in tracheostomy rates, intraoperative blood loss, operative duration, or hospitalization duration. CONCLUSIONS:The combined approach appears effective in reducing complications associated with resection of large, anatomically complex benign parapharyngeal tumors, particularly those involving critical neurovascular structures. This technique shows clinical value and warrants broader application.

ABSTRACT Background The optimal therapeutic strategy for patients with T2‐3N0‐3 M0 or T1N1‐3 M0 hypopharyngeal squamous cell carcinoma (HPSCC) and the use of postoperative radiotherapy with or without systemic therapy for patients with T1‐2N1M0 HPSCC remain controversial. We aimed to determine whether these additional treatments improve the prognosis in HPSCC. Methods We retrospectively analyzed the databases held by the SEER (surveillance, epidemiology, and end results) program and a tertiary referral center in China to evaluate the survival outcomes of surgical intervention for T2‐3N0‐3 M0 and T1N1‐3 M0 HPSCC and of postoperative radiotherapy for T1‐2N1M0 disease. Results The SEER contained data for 1235 patients with T2‐3N0‐3 M0 or T1N1‐3 M0 HPSCC, of whom 220 underwent surgery as their first treatment and 737 received non‐surgical treatment. There was no statistically significant difference in overall survival (OS) between these two groups. Data were also available for 30 patients in the SEER who were treated by surgery alone (n = 11), surgery plus postoperative radiotherapy (n = 7), or surgery plus postoperative radiotherapy with systemic therapy (n = 12). Similarly, 23 patients at our hospital were identified to have been treated by surgery alone (n = 7), surgery plus postoperative radiotherapy (n = 10), or surgery plus postoperative radiotherapy with systemic therapy (n = 6). The SEER data indicated that postoperative radiotherapy improved OS (hazard ratio 0.281, 95% confidence interval 0.079–0.998; p = 0.036). This finding was supported by the data from our hospital, although the improvement in OS was not statistically significant (hazard ratio 0.360, 95% confidence interval 0.057–2.261; p = 0.224). Postoperative radiotherapy with systemic therapy seemed not to improve OS beyond that achieved by postoperative radiotherapy alone. Conclusions There was no significant difference in OS in patients with T2‐3N0‐3 M0 or T1N1‐3 M0 HPSCC according to whether or not they underwent surgery as first‐line treatment. Surgery plus postoperative radiotherapy was associated with a more favorable prognosis than surgery alone in patients with T1‐2N1M0 HPSCC.

Objectives: For intraoperative bleeding control in patients with juvenile nasopharyngeal angiofibroma (JNA), we developed a novel surgical strategy system. This system is focused on feeding artery management, based on the spatial relationship between the tumor entity and feeding artery as determined by three-dimensional reconstruction. Methods: This historical controlled study was conducted at a tertiary medical institution from October 2013 to September 2022. The retrospective group comprised of previous JNA patients received traditional nasoendoscopic sursery. Three-dimensional CT reconstruction based on their preoperative contrast-enhanced CT and CTA was used for segmentation of spatial relationship between dominant feeding artery (DFA) and tumor entity. The prospective group comprised JNA patients undergoing endoscopic/endoscopic-assisted surgery reinforced DFA management by intraoperative ligation. Efficacy evaluation between two groups focused on intraoperative bleeding, complete resection rate and Postoperative hospitalized duration. Results: Twelve patients were included in the retrospective group. The three-dimensional reconstruction models were successfully performed, and the DFA was located in all patients. According to the segmentation of the DFA, we established a novel surgical strategy system focused on feeding artery management. All 11 patients in the prospective group underwent successful management of the DFA by intraoperative ligation with less intraoperative bleeding. Conclusions: In this study, we introduced a novel surgical strategy system for JNA. The system focuses on feeding artery management, ensuring bleeding control based on the location of DFA on three-dimensional image reconstruction. As a result of clear and straightforward image classification, intraoperative bleeding was decreased. This system may become a meaningful reference for JNA preoperative planning.

OBJECTIVE:To explore the treatment options and prognostic factors of vocal fold leukoplakia. METHODS:The study examined conservative and surgical treatment approaches, and analysed prognostic factors influencing vocal fold leukoplakia outcomes. RESULTS:In the conservative treatment group, lesion size (p = 0.035) and smoking (p < 0.001) were identified as independent factors influencing treatment outcomes. In the surgical treatment group, lesion size (p = 0.018) was identified as an independent factor affecting recurrence. There was no statistically significant difference in the effectiveness of conservative versus surgical treatment for patients with hyperplasia (p = 0.223), mild dysplasia (p = 0.634) and moderate dysplasia (p = 0.758). CONCLUSION:Smoking and lesion size are key factors influencing the outcome of conservative treatment, while lesion size is a significant factor affecting recurrence in surgically treated patients. More importantly, conservative treatment should be prioritised for patients with moderate dysplasia and milder vocal fold leukoplakia.

This study investigates the therapeutic potential of bone marrow macrophages-derived dendritic cells (BMΦDCs) in enhancing antitumor immunity against head and neck squamous cell carcinoma (HNSCC), focusing on their effects in inhibiting tumor growth, reducing metastasis, and modulating the tumor microenvironment. BMΦDCs were generated by culturing bone marrow cells with macrophage colony-stimulating factor (M-CSF) followed by granulocyte–macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). MTCQ-1 tumor lysates were used for antigen loading. The phenotypic characteristics of BMΦDCs were analyzed using flow cytometry. In vivo antitumor efficacy was assessed in subcutaneous and lung metastasis models in immunocompetent C57BL/6 mice. Tumor growth was monitored, and tumor tissues were collected for histological analysis using hematoxylin and eosin (H E), Masson’s trichrome, and anti-CD8 staining. BMΦDCs displayed higher maturation marker expression (CD40, CD86) compared to traditional BMDCs. In the subcutaneous tumor model, BMΦDCs significantly inhibited tumor growth and enhanced cytotoxic T lymphocyte (CTL) activity. In the lung metastasis model, BMΦDCs effectively reduced metastatic burden. Histological analysis revealed increased CD8+ T cell infiltration and reduced tumor fibrosis in BMΦDC-treated mice. No significant toxicity or organ damage was observed. BMΦDCs are a promising immunotherapeutic approach for HNSCC, demonstrating superior antitumor efficacy, enhanced immune responses, and excellent biosafety. These findings highlight the potential of BMΦDCs in advancing cancer immunotherapy.

Importance The necessity of adjuvant radiotherapy in patients with pT1-2N1-2b oropharyngeal squamous cell carcinoma (OPSCC) remains unclear. Objective To examine the prognostic role of adjuvant radiotherapy in patients with either p16-positive or p16-negative pT1-2N1-2b OPSCC. Design Retrospective study. Setting Surveillance, Epidemiology, and End Results database. Participants Patients diagnosed between 2010 and 2015 with either p16-positive or p16-negative T1-2N1-2bM0 OPSCC who received primary surgery with neck dissection with or without adjuvant radiotherapy were screened for inclusion. Intervention Primary surgery with neck dissection with or without adjuvant radiotherapy. Main Outcomes and Measures Overall survival (OS) and disease-specific survival (DSS) were main outcomes. The overlap propensity score weighting method was applied to account for known confounding. Cox regression analysis and weighted cox regression analysis were used to calculate the hazard ratio (HR) and 95% confidence interval (CI). Results A total of 247 patients with p16-negative OPSCC (median follow-up duration: 39 months; 3-year OS: 84.9%; 3-year DSS: 89.5%) and 1175 patients with p16-positive OPSCC (median follow-up duration: 35 months; 3-year OS: 95.3%; 3-year DSS: 96.7%) were included. Adjuvant radiotherapy was associated with improved OS [weighted HR (95% CI): 0.37 (0.17-0.79)] and DSS [weighted HR (95% CI): 0.34 (0.13-0.88)] in pT1-2N1-2b p16-negative OPSCC. No prognostic role of adjuvant radiotherapy was observed in pN1 subgroup of p16-negative OPSCC [weighted HR (95% CI) for OS: 0.89 (0.20-4.06); weighted HR (95% CI) for DSS: 1.12 (0.19-6.71)]. Adjuvant radiotherapy was associated with improved OS [weighted HR (95% CI): 0.34 (0.18-0.62)] and DSS [weighted HR (95% CI): 0.30 (0.14-0.64)] in pT1-2N1-2b p16-positive OPSCC. Subgroup analyses of p16-positive OPSCC, including pN1, pN2a-2b, and positive lymph nodes ≤4 subgroups, supported that adjuvant radiotherapy had positive prognostic role. Conclusions and Relevance Consistent with the National Comprehensive Cancer Network guidelines, patients with pT1-2N2a-2b OPSCC should receive adjuvant radiotherapy (regardless of p16 status), while patients with pT1-2N1 p16-negative OPSCC could consider omitting adjuvant radiotherapy. Patients with pT1-2N1 p16-positive OPSCC may benefit from adjuvant radiotherapy.

Anti-PD-1/PD-L1 has made breakthrough progress in the treatment of recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, the Asian population in KEYNOTE-048 only accounts for 13.2 % of the total population, and there is a lack of data on the mainland Chinese population. This multi-center trial (ChiCTR2400090060) evaluated the efficacy and safety of pembrolizumab in patients with R/M HNSCC. Between July 2020 and January 2024, 291 patients who received pembrolizumab-based therapy were enrolled from 20 hospitals across China. All patients were divided into two cohort: cohort 1 included patients unable surgery or radiotherapy (RT), who received first-line treatment of pembolizumab-based, and cohort 2 included patients eligible for surgery or RT, who received pembrolizumab-based treatment with or without local therapy. The primary endpoint was overall survival (OS), while secondary endpoints included time of pembrolizumab treatment (TOPT), immune-related adverse events (irAEs), and best overall response (BOR). With a median follow-up of 18.5 months, the mOS was not reached, with a 18mo-OS rate was 63.2 %. The mOS for cohort 1 was 21.2 months. Interestingly, mOS for cohort 2 was not reached. Patients who received local therapy had a significantly improvement on 18mo-OS rate compared to those who did not (86.1 % vs. 65.8 %, p = 0.021). A total of 24.7 % of patients experienced irAEs. The study was the first report that the patient who was eligible for local treatment had a benefit from pembrolizumab, especially the OS was significantly improved for pembrolizumab followed by surgery or RT.

Head and neck squamous cell carcinoma (HNSCC) demonstrates suboptimal responses to current immune checkpoint inhibitors (ICIs), with objective response rates (ORRs) of merely 15–20%. The molecular mechanisms underlying these low ORRs remain incompletely defined. Here, two functionally distinct CD8⁺ T cell subsets are identified within the tumor microenvironment: precursor exhausted T (Tex prog ) cells and terminally exhausted T (Tex term ) cells. Notably, although anti‐PD‐1 therapy reduced Tex prog cell frequencies, it failed to reverse Tex term cells. Elevated Tex term cell infiltration correlated with advanced tumor–node–metastasis (TNM) staging and poor prognosis. Furthermore, non‐responders exhibited significantly higher baseline Tex term proportions than responders before immunotherapy. Multivariate analysis established stromal Tex term cell density as both an independent prognostic factor and predictor of ICIs resistance. Mechanistically, Tex term cell infiltration strongly correlated with PD‐L1 on tumor‐derived extracellular vesicles (PD‐L1 + EVs). Most importantly, it is demonstrated that PD‐L1 + EVs drive Tex term cell differentiation by upregulating the basic leucine zipper transcription factor, ATF‐like (BATF) in CD8⁺ T cells. Knocking out PD‐L1 on EVs reduced Tex term cell infiltration and BATF expression. These findings elucidate an EV‐mediated immune evasion axis and reveal actionable targets to overcome immunotherapy resistance.

The optimal treatment strategy for oropharyngeal cancer (OPC) is undetermined. We aim to compare the survival outcomes of OPC patients treated with upfront surgery versus definitive radiotherapy (RT). A total of 8057 cases were retrieved from the Surveillance, Epidemiology, and End Results database. Primary endpoints were cancer-specific and noncancer mortalities, which were estimated using cumulative incidence function and compared by Gray’s test. Univariate and multivariate Fine–Gray subdistribution hazard models were used to estimate the effects of treatment modality on mortality. Subgroup analyses were performed in propensity-score-matched cohorts. All the analyses were conducted separately in human papillomavirus (HPV)-negative and HPV-positive cohorts. In the HPV-negative cohort, definitive RT was independently associated with increased risk of cancer-specific mortality (adjusted subdistribution hazard ratio [SHR], 1.31; 95

BackgroundWhether eye canting in patients with asymmetric dento-maxillofacial deformities is the result of anatomical asymmetry or a compensatory head position remains controversial.ObjectiveThis cross-sectional study aims to verify whether eye canting is correlated with craniofacial skeletal asymmetry.Methods & materialsThis study was performed by measuring the computed tomographic scans of 223 patients with dento-maxillofacial deformities in Mimics 21.0 software. First grouping was determined based on the intersection angle between the line passing through bilateral lateral canthus point and Frankfurt horizontal plane, and final grouping was based on measurements of the pregroups.ResultsThe patients were finally categorized into three groups: symmetry group (n = 163), asymmetry subgroups 1 (n = 33) and asymmetry subgroups 2 (n = 27). The results of multiple linear regression and comparisons among groups suggests the presence of orbital skeletal asymmetry in patients with eye canting and the eye canting is partly increment dependent of orbital skeletal asymmetry when using bilateral ears as the reference. The result also reveals that there is a greater angle between the line through bilateral ocular landmarks and the line through the bilateral ear landmarks in patients with ocular canting compared to patient without eye canting.ConclusionPatients with asymmetric dento-maxillofacial deformities and with eye canting have vertical asymmetry of the orbital and cranial skeletal landmarks. These symmetry differences between the eyes and ears may affect the overall craniofacial symmetry after orthognathic surgery

Purpose: Flattening filter-free (FFF)-based volumetric modulated arc therapy (VMAT) has been shown to be feasible and significantly improves treatment efficiency and lung protection for synchronous bilateral breast irradiation (SBBI). This research compared the commonly used VMAT field arrangements using FFF beams. Methods: Twenty-eight patients underwent SBBI were retrospectively enrolled to design irradiation plans using tangential arc VMAT (taVMAT), half arc VMAT (haVMAT), and large arc VMAT (laVMAT). Dosimetric and delivery parameters of all designed plans were recorded and compared. Results: Comparable target volume coverage was observed for all field arrangements. taVMAT significantly reduced the dose to spinal cord and the volume covered by 5 Gy (V5 Gy) and V7 Gy of the lungs while decreasing the conformity index of the target volume. It also increased the volume covered by 105% of the prescription dose (V105%) and V107% of the target volume. haVMAT considerably decreased V20 Gy and V30 Gy of the lungs, mean dose (Dmean) and V30 Gy of the heart and the liver. It also notably reduced Dmean and V40 Gy of the left anterior descending coronary artery while increasing the beam-on time. laVMAT significantly reduced the mean treatment time (range, 113-117 seconds) compared with the other field arrangements. Conclusions: There were distinct differences in various dosimetric and delivery parameters for different field arrangements, highlighting the importance of selecting the appropriate field arrangement based on specific treatment goals and considerations. This study contributes valuable insights into the use of FFF-based VMAT techniques in SBBI. (c) 2023 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

BACKGROUND: Kidney renal clear cell carcinoma (KIRC) is one of the most common types of renal cell carcinoma, and there is often a poor prognosis for advanced KIRC patients. C1QTNF1 plays a key role in inflammatory signaling. However the prognostic value of C1QTNF1 in KIRC remains unknown. METHODS: Our study investigated the potential function of C1QTNF1 in KIRC comprehensively. RESULTS: The expression of C1QTNF1 was upregulated significantly in KIRC. Moreover, a higher level of expression of C1QTNF1 was associated with a poor prognosis and an advanced stage of cancer. In addition, KIRC showed a significant association between C1QTNF1 expression and the numbers of NK cells, DC, Tam, and Th1/Th2 cells infiltrating the tumor. It has been shown that a nomogram model based on C1QTNF1, and several clinical factors is effective at predicting overall survival. CONCLUSIONS: C1QTNF1 may participate in carcinogenesis of KIRC and contribute to immune cell infiltration, as evidenced by these observations.

Background: Induction chemotherapy (ICT) has become an initial treatment for head and neck squamous cell carcinoma (HNSCC). However, myelosuppression, an unavoidable side effect of ICT, significantly impacts follow-up treatment and prognosis. The main objective of this study is to identify the risk factors and predictors of myelosuppression and its different severity after ICT for ICT. Methods: We retrospectively reviewed medical records of 102 patients with hypopharyngeal cancer or oropharyngeal cancer who received initial ICT from 2013 to 2022. Univariate and multivariate logistic regression analyses were performed to identify risk factors for myelosuppression. Receiver-operating characteristic (ROC) curves were generated using the results of multiple logistic regression analysis to identify data with the highest sensitivity and lowest false-negative rate. Results: Pretreatment lymphocyte count (PLC) and the pretreatment platelet count (PPC) were identified as independent risk factors of myelosuppression ( P < .05). Pretreatment hemoglobin count (PHC) was an independent risk factor for predicting myelosuppression in patients with grades III to IV disease. Patients with myelosuppression after ICT are more sensitive to chemotherapy. Conclusions: The PLC and PPC predicted myelosuppression in patients with HNSCC-administered ICT, and the PHC predicted grades III to IV myelosuppression. Myelosuppressed patients were more chemosensitive after ICT.

Abstract Background The impact of prior cancer history on survival of hypopharyngeal cancer patients remains unknown. The present study assessed the impact of prior cancer history on survival of patients with hypopharyngeal cancer. Methods Patients with primary hypopharyngeal cancer diagnosed between 2004 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was conducted to balance baseline characteristics. One‐to‐one PSM, Kaplan–Meier method, and log‐rank test were performed for survival analysis. Results We included 5017 patients with hypopharyngeal cancer. Prior cancer history had no significant impact on overall survival of hypopharyngeal cancer patients in comparison with those without prior cancer history (p = 0.845, after PSM). Subgroup analysis showed that prior cancer history had no significant effect on overall survival of hypopharyngeal cancer patients. Conclusion More hypopharyngeal cancer patients with prior cancer history should be considered for clinical trials. However, further prospective studies are needed.

Background To investigate the optimal radiotherapy plans for synchronous bilateral breast cancer (SBBC) patients receiving postmastectomy radiotherapy (PMRT), including regional lymph node irradiation (RNI). Methods For 10 SBBC patients who underwent bilateral mastectomy and received bilateral PMRT with RNI, 3 integrally optimized plans with a single isocenter were designed for each patient in this retrospective study: intensity-modulated radiation therapy (IMRT) with 9 fixed beams (9F-IMRT), volumetric-modulated arc therapy (VMAT) with 2 pairs of half arcs (2F-VMAT), VMAT with 2 pairs of outer tangential arcs and 1 pair of 200-degree arcs (3F-VMAT). The paired t -test (in the case of normal variables) and Friedman's test (in the case of nonnormal variables) were applied to compare the planning target volumes (PTVs) and organs at risk (OARs) values of the 3 techniques. Results The 3 techniques provided adequate target dose coverage and comparable results for PTVs. For OARs, 3F-VMAT yielded the lowest mean or median values of the left lung (15.02 ± 1.57 Gy) and right lung (14.91 ± 1.14 Gy), heart (6.19 (1.96) Gy), coronary artery (15.96 ± 5.76 Gy) and liver (8.10 ± 2.70 Gy) which were significantly different from those of 9F-IMRT and 2F-VMAT. The percentages of volume at various doses ( V 5 , V 10 , V 20 , and V 30 ) of 3F-VMAT plans were also lower than or comparable with those of 9F-IMRT and 2F-VMAT. The monitor units (MUs) of 3F-VMAT were 31% higher than those of 9F-IMRT and comparable with those of 2F-VMAT; however, there were time savings and halved beam-on times (BOTs) compared to 9F-IMRT. Conclusions The 3F-VMAT plan yielded comparable target coverage compared with 9F-IMRT and 2F-VMAT, was superior in dose sparing of normal tissues and enabled shorter BOTs, improving treatment efficiency. In our research, 3F-VMAT was the optimal radiotherapy technique for SBBC patients receiving PMRT including RNI.

Background: A growing number of clinical studies have confirmed that mRNA vaccines are effective in the treatment of malignant tumors; however, their efficacy in head and neck squamous cell carcinoma (HNSCC) has not been determined. This study aimed to identify the potential antigens of HNSCC for mRNA vaccine development and further distinguish the immune subtypes of HNSCC to select suitable patients for vaccination. Methods: We obtained gene expression profiles and corresponding clinical information of HNSCC from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). We visualized the genetic alterations of potential antitumor antigens using cBioPortal and obtained the immune gene set from Immport. The correlation between the expression of the identified antigens and the infiltration of antigen-presenting cells was visualized by Tumor Immune Estimation Resource (TIMER). We evaluated the potential biological functions of different samples and described the immune landscape. Results: Increased expression of three potential tumor antigens, CCR4, TMCO1, and SPACA4, associated with superior prognoses and infiltration of antigen-presenting cells, was identified in HNSCC. Three immune subtypes (C1–C3) with different molecular, cellular, and clinical characteristics were defined. Patients with C3 tumor had a better prognosis, representing an immune “cold” phenotype, which may be more suitable for mRNA vaccination. In addition, different immune characteristics were observed among the three immune subtypes, including markers of immune cells, mutation burden, expression of immune checkpoints, and immune modulators. Finally, the immune landscape of HNSCC showed a high degree of heterogeneity between individual patients. Conclusion: CCR4, TMCO1, and SPACA4 may be potential antigens for developing mRNA vaccines against HNSCC, especially for patients with C3 tumor. This study could provide a theoretical basis for the development of an mRNA vaccine against HNSCC.

OBJECTIVE:To compare the survival outcomes of early-stage oropharyngeal cancer (OPC) patients treated with upfront surgery versus definitive radiotherapy (RT).STUDY DESIGN:Retrospective observational study.SETTING:Publicly available database.METHODS:A total of 1877 patients with T1-2N0-1M0 OPC were retrieved from the Surveillance, Epidemiology, and End Results database. Primary endpoints were cancer-specific and noncancer mortalities, which were estimated using cumulative incidence function and compared by Gray's test. Univariate and multivariate Fine-Gray subdistribution hazard models were used to estimate the effects of treatment modality on mortality. Subgroup analyses were performed in propensity-score-matched cohorts. All the analyses were conducted separately in human papillomavirus (HPV)-negative and HPV-positive cohorts.RESULTS:In the HPV-negative cohort, definitive RT was independently associated with increased risk of cancer-specific mortality (adjusted subdistribution hazard ratio [SHR], 2.29; 95% confidence interval [CI], 1.42-3.68; p = .001) and noncancer mortality (adjusted SHR, 2.74; 95% CI, 1.50-5.02; p = .001). In the HPV-positive cohort, definitive RT and upfront surgery could achieve similar cancer-specific and noncancer survival outcomes.CONCLUSION:Upfront surgery is associated with lower cancer-specific and noncancer mortality in HPV-negative early-stage OPC patients. However, in the setting of HPV-positive early-stage OPC with better prognosis, the 2 treatment modalities have similar efficacy in terms of cancer-specific and noncancer survival outcomes. In the future, carefully designed prospective clinical trials are needed to confirm our findings.

The positive feedback loop of activated regulatory T cells (aTregs) and M2 macrophages (M2) play a vital role in promoting the tumor immunosuppressive microenvironment of head and neck squamous cell carcinoma (HNSCC). However, the key factors regulating the positive feedback loop remain unclear. Herein, we investigated the effect of PD-L1 carried on exosomes derived from tumor cells (TEXs) on the aTreg-M2 positive feedback loop, as well as their role in mediating immunosuppression. In our study, TEXs with or without PD-L1 (TEX-PD-L1 or TEX-PD-L1KO) were treated with CD4+CD25- T cells and M0 macrophages, and the effect on the differentiation of aTregs, M2 and the aTreg-M2 positive feedback loop was assessed. TEXs carried more PD-L1 than tumor cells and not only promoted the differentiation of aTregs and M2, but also, most importantly, enhanced the positive feedback loop of aTreg-M2, which inhibited the proliferation of CD4+CD25- T cells and in turn led to tumor immune escape. Moreover, in vivo study showed that TEX-PD-L1KO could inhibit tumor growth and significantly improve the antitumor efficacy in both the peripheral and tumor microenvironments. Collectively this study revealed the role and mechanism of TEX-PD-L1 in negative immune regulation, and targeting TEX-PD-L1 may be a new idea and strategy for immunotherapy of HNSCC.