Objective: To investigate the association between the time intervals of key clinical time points and tumor progression (increase in clinical staging) in head and neck cancer patients before and during the pandemic. Methods: Design: Retrospective Cohort Study. Setting: Tertiary Government Training Hospital. Participants: A total of 81 head and neck cancer patients who consulted at the OPD and underwent elective surgery between January 1, 2018, and December 31, 2022, under the Department of Otorhinolaryngology – Head and Neck Surgery of East Avenue Medical Center were included in the study; 40 patients comprised the pre-pandemic group and 41 patients-the pandemic group. Results: Majority of patients were men (61.73%), and the mean age was 54 years. The most prevalent tumor site was the oral cavity (37.04%). Most patients were Clinical Stage IV at the time of diagnosis (32.10%) and at the time of surgery (58.02%). In the pre-pandemic period, median time-to-consult was 180 days, time-to-diagnosis was 14 days, and time-to-treatment was 57 days. During the pandemic, median time-to-consult significantly increased to 365 days (Mann-Whitney test, U = 589, p = .028), but time-to-diagnosis decreased to 10 days, and time to-treatment decreased to 43 days, although these were not significant (U = 775, p = .667; U = 809, p = .917). Among the 81 patients in the study, 14 (17.28%) showed tumor progression (pre-pandemic: 6; 15%; pandemic: 8; 19.51%), but there was no significant association between time-to-consult and increase in clinical staging for both pre-pandemic (χ2(38) = 34.2, p = .646) and pandemic groups (χ2(16) = 23.1, p = .110) or between time-to-diagnosis and increase in clinical staging for pre-pandemic (χ2(56) = 36.8, p = .978) and pandemic groups (χ2(23) = 28.3, p = .267). Overall, there was no significant association between time-to-treatment and increase in clinical staging for both pre-pandemic (χ2(62) = 80.00, p = .062) and pandemic groups (χ2(32) = 30.4, p = .548), but a subset of patients with larynx primary tumor site had a statistically significant association between time-to-treatment and tumor progression (χ2(5) = 12.00, p = .035). Conclusion This study revealed that there was an increase in time to-consult for head and neck cancer patients during the pandemic. However, there was no significant difference in time-to-diagnosis and time-to-treatment. This shows that the Department of ORL-HNS, East Avenue Medical Center has provided pandemic head and neck cancer care similar to before the pandemic. No significant associations were found between tumor progression and time intervals of the key clinical time points but patients who had an increase in clinical stage were noted with longer time-to treatment. It was also observed that more patients were in advanced clinical stages during the pandemic.
Head and Neck Neoplasms ; Time-to-Treatment ; COVID-19

Existing studies have underscored the pivotal role of N-acetyltransferase 10 (NAT10) in various cancers. However, the outcomes of protein-protein interactions between NAT10 and its protein partners in head and neck squamous cell carcinoma (HNSCC) remain unexplored. In this study, we identified a significant upregulation of RNA-binding protein with serine-rich domain 1 (RNPS1) in HNSCC, where RNPS1 inhibits the ubiquitination degradation of NAT10 by E3 ubiquitin ligase, zinc finger SWIM domain-containing protein 6 (ZSWIM6), through direct protein interaction, thereby promoting high NAT10 expression in HNSCC. This upregulated NAT10 stability mediates the enhancement of specific tRNA ac⁴C modifications, subsequently boosting the translation process of genes involved in pathways such as IL-6 signaling, IL-8 signaling, and PTEN signaling that play roles in regulating HNSCC malignant progression, ultimately influencing the survival and prognosis of HNSCC patients. Additionally, we pioneered the development of TRMC-seq, leading to the discovery of novel tRNA-ac⁴C modification sites, thereby providing a potent sequencing tool for tRNA-ac⁴C research. Our findings expand the repertoire of tRNA ac⁴C modifications and identify a role of tRNA ac⁴C in the regulation of mRNA translation in HNSCC.
Humans ; DNA-Binding Proteins ; Head and Neck Neoplasms/genetics* ; N-Terminal Acetyltransferases ; RNA, Transfer ; Serine ; Signal Transduction ; Squamous Cell Carcinoma of Head and Neck

Wnt signaling are critical pathway involved in organ development, tumorigenesis, and cancer progression. WNT7A, a member of the Wnt family, remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma (HNSCC). According to the Cancer Genome Atlas (TCGA), transcriptome sequencing data of HNSCC, the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues, which was validated using Real-time RT-PCR and immunohistochemistry. Unexpectedly, overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC. Instead, our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway, leading to enhanced cell proliferation, self-renewal, and resistance to apoptosis. Furthermore, in a patient-derived xenograft (PDX) tumor model, high expression of WNT7A and phosphorylated STAT3 was observed, which positively correlated with tumor progression. These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.
Animals ; Humans ; Squamous Cell Carcinoma of Head and Neck ; Carcinogenesis/genetics* ; Cell Transformation, Neoplastic ; Wnt Signaling Pathway ; Disease Models, Animal ; Head and Neck Neoplasms/genetics* ; Wnt Proteins ; Frizzled Receptors/genetics* ; Janus Kinase 1 ; STAT3 Transcription Factor

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. Oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic environment. To clarify the relationship between different metabolic regions and the tumor immune microenvironment (TME) in OSCC, Single cell (SC) and spatial transcriptomics (ST) sequencing of OSCC tissues were performed. The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data. The metabolic activity of each spot was calculated using scMetabolism, and k-means clustering was used to classify all spots into hyper-, normal-, or hypometabolic regions. CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others. Through CellPhoneDB and NicheNet cell-cell communication analysis, it was found that in the hypermetabolic region, fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts (iCAFs), and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12. The secretion of CXCL12 recruits regulatory T cells (Tregs), leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment. This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC, ST and TCGA bulk data, and highlights potential targets for therapy.
Humans ; Carcinoma, Squamous Cell/metabolism* ; Squamous Cell Carcinoma of Head and Neck ; Mouth Neoplasms/metabolism* ; Immunosuppression Therapy ; Transforming Growth Factor beta ; Head and Neck Neoplasms ; Gene Expression Profiling ; Tumor Microenvironment

OBJECTIVE: To compare the effectiveness of O-arm navigation and C-arm navigation for guiding percutaneous long sacroiliac screws in treatment of Denis type Ⅱ sacral fractures. METHODS: A retrospective study was conducted on clinical data of the 46 patients with Denis type Ⅱ sacral fractures between April 2021 and October 2022. Among them, 19 patients underwent O-arm navigation assisted percutaneous long sacroiliac screw fixation (O-arm navigation group), and 27 patients underwent C-arm navigation assisted percutaneous long sacroiliac screw fixation (C-arm navigation group). There was no significant difference in gender, age, causes of injuries, Tile classification of pelvic fractures, combined injury, the interval from injury to operation between the two groups ( P>0.05). The intraoperative preparation time, the placement time of each screw, the fluoroscopy time of each screw during placement, screw position accuracy, the quality of fracture reduction, and fracture healing time were recorded and compared, postoperative complications were observed. Pelvic function was evaluated by Majeed score at last follow-up. RESULTS: All operations were completed successfully, and all incisions healed by first intention. Compared to the C-arm navigation group, the O-arm navigation group had shorter intraoperative preparation time, placement time of each screw, and fluoroscopy time, with significant differences ( P<0.05). There was no significant difference in screw position accuracy and the quality of fracture reduction ( P>0.05). There was no nerve or vascular injury during screw placed in the two groups. All patients in both groups were followed up, with the follow-up time of 6-21 months (mean, 12.0 months). Imaging re-examination showed that both groups achieved bony healing, and there was no significant difference in fracture healing time between the two groups ( P>0.05). During follow-up, there was no postoperative complications, such as screw loosening and breaking or loss of fracture reduction. At last follow-up, there was no significant difference in pelvic function between the two groups ( P>0.05). CONCLUSION Compared with the C-arm navigation, the O-arm navigation assisted percutaneous long sacroiliac screws for the treatment of Denis typeⅡsacral fractures can significantly shorten the intraoperative preparation time, screw placement time, and fluoroscopy time, improve the accuracy of screw placement, and obtain clearer navigation images.
Humans ; Fracture Fixation, Internal/methods* ; Retrospective Studies ; Imaging, Three-Dimensional ; Bone Screws ; Surgery, Computer-Assisted ; Tomography, X-Ray Computed ; Spinal Fractures/surgery* ; Fractures, Bone/surgery* ; Pelvic Bones/injuries* ; Postoperative Complications ; Neck Injuries

Humans ; Osteoblastoma/surgery* ; Neck/surgery* ; Spinal Neoplasms ; Cervical Vertebrae

OBJECTIVE: To obtain detailed understanding on the gene regulation of natural compounds in altering prognosis of head and neck squamous cell carcinomas (HNSC). METHODS: Gene expression data of HNSC samples and peripheral blood mononuclear cells (PBMCs) of HNSC patients were collected from Gene Expression Omnibus (GEO). Differential gene expression analysis of GEO datasets were achieved by the GEO2R tool. Common differentially expressed gerres (DEGs) were screened by comparing DEGs of HNSC with those of PBMCs. The combination was further analyzed for regulating pathways and biological processes that were affected. RESULTS: Totally 110 DEGs were retrieved and identified to be involved in biological processes related to tumor regulation. Then 102 natural compounds were screened for a combination such that the expression of all 110 commonly DEGs was altered. A combination of salidroside, ginsenoside Rd, oridonin, britanin, and scutellarein was chosen. A multifaceted, multi-dimensional tumor regression was showed by altering autophagy, apoptosis, inhibiting cell proliferation, angiogenesis, metastasis and inflammatory cytokines production. CONCLUSIONS This study has helped develop a unique combination of natural compounds that will markedly reduce the propensity of development of drug resistance in tumors and immune evasion by tumors. The result is crucial to developing a combinatorial natural therapeutic cocktail with accentuated immunotherapeutic potential.
Humans ; Leukocytes, Mononuclear ; Head and Neck Neoplasms/drug therapy* ; Squamous Cell Carcinoma of Head and Neck/drug therapy* ; Immunotherapy ; Prognosis

Objective: To identify in what phases in the treatment of head and neck cancer do delays happen at a tertiary hospital and to determine the association between the length of treatment delays and the oncologic outcomes (disease-free survival and overall survival) for patients with head and neck cancer. : Methods Design: Retrospective Cohort Study Setting: Tertiary National University Hospital Participants: Sixty-eight (68) patients who had surgery and adjuvant radiotherapy for invasive head and neck cancer at the Philippine General Hospital during the 5-year period of January 2014 to December 2019 were included in the initial consideration. Only 15 had survival data and were thus eligible for inclusion in this study. Results: The median treatment package time for head and neck cancers in our institution was 27.6 weeks or 193 days. The treatment package time statistically correlated with both overall survival, F(1,13)=12.952, p <0.005, R2=0.499, and disease-free survival, F(1-13)=12.823, p <0.005, R2= 0.497. However, the independent effects of other predictors such as time interval between first consult to histopathologic diagnosis, diagnosis to surgery, and surgery to post-operative radiotherapy, showed no statistically significant association with overall survival and disease free survival. Conclusion All study patients experienced treatment delays from diagnosis to surgery, and surgery to adjuvant radiation therapy, and in their total treatment package time. The positive correlation among treatment package time, and disease-free and overall survival in this study must be further investigated in order to elucidate the true effect of delays across time intervals in the treatment of head and neck cancer in the Philippine General Hospital. Every effort should be made towards timely management of these patients.
Head and Neck Neoplasms ; Radiotherapy ; Survival Rate ; Treatment Outcome ; Time-to-Treatment ; Surgery ; Disease-Free Survival ; Delayed Diagnosis ; Retrospective Studies ; Postoperative Care

Objective: To determine the sensitivity, specificity, positive predictive value, negative predictive value and safety of endoscopic guided office-based biopsies (OBB) in diagnosing laryngeal and pharyngeal neoplasms at the St. Luke’s Medical Center in Quezon City and Global City. : Methods Design: Diagnostic Accuracy Study Setting: Two Tertiary Private Training Hospitals Participants: Records of patients with pharyngeal and laryngeal lesions who underwent endoscopic-guided OBB were included in the study describing safety. Only patients with subsequent operative biopsies were included in assessing diagnostic accuracy. Results: Thirty-six (36) patients were included: 28 (77.78%) males and 8 (22.22%) females, with median age of 61.5 (IQR 52-73 years). Nearly half (16/36; 44.44%) of the office-based biopsies yielded malignant histopathology results, 19.44% had high grade dysplasia while 36.11% had benign findings. Of 10 patients with operative biopsy for definitive diagnosis, 8 were correctly diagnosed with carcinoma while one had a change in diagnosis from benign to malignant. Office based biopsy was well tolerated and had no complications reported. Overall, the sensitivity of OBB in predicting malignancy was 88.89%, specificity was 100%, positive predictive value was 100%, and negative predictive value was 50%. Conclusion Office-based biopsy is an accurate, reliable and safe modality for screening suspicious pharyngeal and laryngeal neoplasms, and may be part of routine screening during initial endoscopy among selected patients with suspicious pharyngeal and laryngeal neoplasms. Further investigation and larger population studies may provide more robust insights on effectiveness and safety of office-based biopsy in diagnosis of pharyngeal and laryngeal neoplasms.
Head and Neck Neoplasms ; Malignancy ; Neoplasms

OBJECTIVE: To compare the clinical efficacy on cervical spondylosis of nerve root type with qi stagnation and blood stasis treated with warming needle with different lengths of moxa stick. METHODS: Six hundred patients with cervical spondylosis of nerve root type with qi stagnation and blood stasis were randomly divided into 4 groups: a 4 cm length group (150 cases, 5 cases dropped off, 2 cases suspended), a 3 cm length group (150 cases, 6 cases dropped off, 2 cases suspended), a 2 cm length group (150 cases, 6 cases dropped off), and a routine acupuncture group (150 cases, 6 cases dropped off). Warming needle with moxa stick in the length of 4 cm, 3 cm and 2 cm was delivered in the 4 cm length group, the 3 cm length group and the 2 cm length group, respectively. In the routine acupuncture group, simple acupuncture was applied. The acupoints selected in the above groups included Dazhui (GV 14) and bilateral Jiaji (EX-B 2) of C₅ and C₇, Fengchi (GB 20), Jianzhen (SI 9), Quchi (LI 11), Zhongzhu (TE 3), etc. In each group, the intervention was delivered once daily and 5 times a week. One course of intervention was composed of 2 weeks and 2 courses were required. The TCM syndrome score, the score of clinical assessment scale for cervical spondylosis (CASCS), the score of the brachial plexus traction test of the affected upper limb, F wave occurrence rate and conduction velocity of the ulnar nerve, the median nerve and the radial nerve of the affected upper limb were compared before and after treatment in the patients of each group. The levels of serum inflammatory factors, i.e. interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α) and hypersensitive C-reactive protein (hs-CRP), were measured before and after treatment in the patients of each group. The clinical cfficacy was evaluated in the 4 groups. RESULTS: After treatment, the results of TCM syndrome evaluation, i.e. the scores of neck pain, activity limitation and upper limb numbness and pain, as well as the total scores; and the scores of brachial plexus traction test were reduced when compared with those before treatment in each group (P<0.01, P<0.05). The scores of subjective symptoms and adaptability, and the total scores of CASCS were elevated in comparison with those before treatment in each group (P<0.01, P<0.05). In the 4 cm length group, compared with the other 3 groups, the scores of neck pain and activity limitation for TCM syndrome evaluation, and its total score were lower (P<0.05, P<0.01); and the scores of subjective symptoms and adaptability, and the total score of CASCS were higher (P<0.05, P<0.01). The score of the brachial plexus traction test in the 4 cm length group was lower than that of the routine acupuncture group (P<0.05). After treatment, F wave occurrence rates and conduction velocity of median nerve and radial nerve were increased when compared with those before treatment in each group (P<0.05, P<0.01). F wave occurrence rate and conduction velocity of the radial nerve in the 4 cm length group were higher than those of the other 3 groups (P<0.05), and those of the median nerve were higher when compared with the routine acupuncture group (P<0.05). After treatment, the levels of serum IL-1β, IL-6 and TNF-α were all reduced when compared with those before treatment in each group (P<0.01, P<0.05); the level of serum IL-6 in the 4 cm length group was lower than those of the other 3 groups and serum level of TNF-α was lower compared with that in the routine acupuncture group (P<0.05). The total effective rate of the 4 cm length group was 78.3% (112/143), which was higher when compared with the 3 cm length group (67.6%, 96/142), the 2 cm length group (65.3%, 94/144) and the routine acupuncture group (53.5%, 77/144), respectively (P<0.05). CONCLUSION Warming needle with moxa stick of 4 cm in length effectively relieves the clinical symptoms of cervical spondylosis of nerve root type with qi stagnation and blood stasis, improves the nerve function of the upper limbs, and reduces the inflammatory responses caused by nerve compression. The clinical efficacy of this therapy with moxa stick of 4 cm in length is superior to the warming needle with moxa sticks of 3 cm and 2 cm, as well as the routine acupuncture.
Humans ; Interleukin-6 ; Neck Pain ; Qi ; Tumor Necrosis Factor-alpha ; Spondylosis/therapy*