Humans ; Herpesvirus 4, Human ; Epstein-Barr Virus Infections ; Carcinoma, Small Cell ; Nasopharynx/pathology* ; Carcinoma, Neuroendocrine/pathology* ; Nasopharyngeal Neoplasms/pathology*

High-risk human papillomavirus (HPV)-related cancers consist of cervical cancer, anal cancer, penile cancer, vulvar cancer, vaginal cancer, and head and neck cancer (HNC). Of these, the disease burden of HNC is second only to cervical cancer. HNC mostly originates from malignant lesions of squamous epithelial cells and mainly includes oral cavity cancer, pharyngeal cancer (including nasopharyngeal cancer, oropharyngeal cancer, and hypopharyngeal cancer), and laryngeal cancer. Tobacco use, alcohol abuse, and HPV infection are three primary risk factors. Recently, there is an upward trend of HNC incidence globally, especially in high-income countries. In China, the disease burden and trends of HPV-related HNC are still not clear. A few small sample size and single-center studies suggest a high HPV prevalence and increasing trend in HNC. Methodological differences in HPV testing and regional variabilities still exist among these studies. Among the anatomic sites, oropharyngeal cancer has been shown to be caused by HPV infection, but the association of HPV with other sites is still under debate. In addition, there is a paucity of relevant studies. Here, this review narrates the association between HPV infection and HNC, compares the differences between global and Chinese studies, and then explores the importance of HPV infection in various anatomical sites. The main objective is to highlight the research on HPV-related HNC and promote relevant prevention and treatment programs.
Female ; Humans ; Human Papillomavirus Viruses ; Papillomavirus Infections/prevention & control* ; Uterine Cervical Neoplasms/complications* ; Nasopharyngeal Neoplasms/complications* ; Head and Neck Neoplasms/epidemiology* ; Oropharyngeal Neoplasms/epidemiology* ; Papillomaviridae

To investigate the γ pass rate limit of plan verification equipment for volumetric modulated arc therapy (VMAT) plan verification and its sensitivity on the opening and closing errors of multi-leaf collimator (MLC), 50 cases of nasopharyngeal carcinoma VMAT plan with clockwise and counterclockwise full arcs were randomly selected. Eight kinds of MLC opening and closing errors were introduced in 10 cases of them, and 80 plans with errors were generated. Firstly, the plan verification was conducted in the form of field-by-field measurement and true composite measurement. The γ analysis with the criteria of 3% dose difference, distance to agreement of 2 mm, 10% dose threshold, and absolute dose global normalized conditions were performed for these fields. Then gradient analysis was used to investigate the sensitivity of field-by-field measurement and true composite measurement on MLC opening and closing errors, and the receiver operating characteristic curve (ROC) was used to investigate the optimal threshold of γ pass rate for identifying errors. Tolerance limits and action limits for γ pass rates were calculated using statistical process control (SPC) method for another 40 cases. The error identification ability using the tolerance limit calculated by SPC method and the universal tolerance limit (95%) were compared with using the optimal threshold of ROC. The results show that for the true composite measurement, the clockwise arc and the counterclockwise arc, the descent gradients of the γ passing rate with per millimeter MLC opening error are 10.61%, 7.62% and 6.66%, respectively, and the descent gradients with per millimeter MLC closing error are 9.75%, 7.36% and 6.37%, respectively. The optimal thresholds obtained by the ROC method are 99.35%, 97.95% and 98.25%, respectively, and the tolerance limits obtained by the SPC method are 98.98%, 97.74% and 98.62%, respectively. The tolerance limit calculated by SPC method is close to the optimal threshold of ROC, both of which could identify all errors of ±2 mm, while the universal tolerance limit can only partially identify them, indicating that the universal tolerance limit is not sensitive on some large errors. Therefore, considering the factors such as ease of use and accuracy, it is suggested to use the true composite measurement in clinical practice, and to formulate tolerance limits and action limits suitable for the actual process of the institution based on the SPC method. In conclusion, it is expected that the results of this study can provide some references for institutions to optimize the radiotherapy plan verification process, set appropriate pass rate limit, and promote the standardization of plan verification.
Humans ; Radiotherapy, Intensity-Modulated ; Immune Tolerance ; Nasopharyngeal Carcinoma ; ROC Curve ; Nasopharyngeal Neoplasms/radiotherapy*

Objective: To describe a technique of endoscopic transoral approach nasopharyngectomy for petroclival and jugular foramen nasopharyngeal carcinoma, based on anatomic studies and surgeries. Methods: Three dry human skulls and five fresh human cadaver heads were used for anatomic study of a endoscopic transoral approach to expose petroclival and jugular foramen. The anatomical landmarks and the extent of exposure were recorded. Six clinical cases who were treated in Eye & ENT Hospital, Fudan University from June 2020 to April 2022 were used to illustrate the technique and feasibility of this approach and to assess its indications and advantages, including 3 males and 3 females, aged 42 to 69 years old. Descriptive analysis was used in this research. Results: On the basis of the preservation of the internal pterygoid muscle and the external pterygoid muscle, this approach could fully expose the parapharyngeal, petrosal and paraclival segment internal carotid arteries, and safely deal with the lesions of jugular foramen and petroclival region. The 6 patients in our study tolerated the procedure well. Postoperative enhanced MRI showed complete resection of the tumor and no postoperative masticatory dysfunction. Conclusion: Endoscopic transoral approach is a safe, minimally invasive and effective surgical treatment for petroclival and jugular foramen recurrent nasopharyngeal carcinoma.
Male ; Female ; Humans ; Adult ; Middle Aged ; Aged ; Nasopharyngeal Carcinoma ; Jugular Foramina ; Neoplasm Recurrence, Local ; Endoscopy/methods* ; Nasopharyngeal Neoplasms/surgery*

Objective: To investigate the efficacy of the first-day suspension method for improving the success rate of construction of nasopharyngeal carcinoma-patient derived organoids (NPC-PDO). Methods: The tumor samples of 14 nasopharyngeal carcinoma(NPC) patients, i.e.,13 males and 1 female, with a mean age of 43.0±12.0 years old, were collected from the Affiliated Tumor Hospital of Guangxi Medical University and the First Affiliated Hospital of Guangxi Medical University from January 2022 to July 2022. The tumor samples of 3 patients were digested into single cell suspension and divided into 2 groups, for comparing the efficacy of NPC-PDO construction by the direct inoculation method and the first-day suspension method. The remaining 11 patients were randomized to receive either the direct inoculation method or the first-day suspension method for NPC-PDO construction. The diameter and the number of spheres of NPC-PDO constructed by the two methods were compared by optical microscope; the 3D cell viability detection kit was used to compare the cell viability; the survival rates were compared by trypan blue staining; the success rates of the two construction methods were compared; the number of cases which could be successfully passaged for more than 5 generations and were consistent with the original tissue by pathological examination was counted; and the dynamic changes of cells in suspension overnight were observed by live cell workstation. The independent sample t-test was applied to compare the measurement data of the two groups, and the chi-square test was used to compare the classification data. Results: Compared with the direct inoculation, the diameter and the number of spheres of NPC-PDO constructed by the first-day suspension method were increased, with a higher cell activity, and the success rate of construction was obviously improved (80.0% vs 16.7%, χ²=4.41, P<0.05). In the suspension state, some of the cells aggregated and increased their ability to proliferate. Conclusion: The first-day suspension method can improve the success rate of NPC-PDO construction, especially for those whose original tumor sample size is small.
Male ; Humans ; Female ; Adult ; Middle Aged ; Nasopharyngeal Carcinoma ; China ; Microscopy ; Organoids ; Nasopharyngeal Neoplasms

OBJECTIVE: To screen the risk factors for death in patients with nasopharyngeal carcinoma (NPC) using artificial intelligence (AI) technology and establish a risk prediction model. METHODS: The clinical data of NPC patients obtained from SEER database (1973-2015). The patients were randomly divided into model building and verification group at a 7∶3 ratio. Based on the data in the model building group, R software was used to identify the risk factors for death in NPC patients using 4 AI algorithms, namely eXtreme Gradient Boosting (XGBoost), Decision Tree (DT), Least absolute shrinkage and selection operator (LASSO) and random forest (RF), and a risk prediction model was constructed based on the risk factor identified. The C-Index, decision curve analysis (DCA), receiver operating characteristic (ROC) curve and calibration curve (CC) were used for internal validation of the model; the data in the validation group and clinical data of 96 NPC patients (collected from First Affiliated Hospital of Bengbu Medical College) were used for internal and external validation of the model. RESULTS: The clinical data of a total of 2116 NPC patients were included (1484 in model building group and 632 in verification group). Risk factor screening showed that age, race, gender, stage M, stage T, and stage N were all risk factors of death in NPC patients. The risk prediction model for NPC-related death constructed based on these factors had a C-index of 0.76 for internal evaluation, an AUC of 0.74 and a net benefit rate of DCA of 9%-93%. The C-index of the model in internal verification was 0.740 with an AUC of 0.749 and a net benefit rate of DCA of 3%-89%, suggesting a high consistency of the two calibration curves. In external verification, the C-index of this model was 0.943 with a net benefit rate of DCA of 3%-97% and an AUC of 0.851, and the predicted value was consistent with the actual value. CONCLUSIONS Gender, age, race and TNM stage are risk factors of death of NPC patients, and the risk prediction model based on these factors can accurately predict the risks of death in NPC patients.
Humans ; Nasopharyngeal Neoplasms ; Nasopharyngeal Carcinoma ; Artificial Intelligence ; Algorithms ; Software

Humans ; Carcinogenesis/genetics* ; Gene Expression Regulation, Neoplastic ; Genes, cdc ; Nasopharyngeal Carcinoma/genetics* ; Nasopharyngeal Neoplasms/genetics* ; RNA Helicases/metabolism*

Nasopharyngeal carcinoma (NPC) is a malignant tumor that mainly occurs in East and Southeast Asia. Although patients benefit from the main NPC treatments (e.g., radiotherapy and concurrent chemotherapy), persistent and recurrent diseases still occur in some NPC patients. Therefore, investigating the pathogenesis of NPC is of great clinical significance. In the present study, replication factor c subunit 4 (RFC4) is a key potential target involved in NPC progression via bioinformatics analysis. Furthermore, the expression and mechanism of RFC4 in NPC were investigated in vitro and in vivo. Our results revealed that RFC4 was more elevated in NPC tumor tissues than in normal tissues. RFC4 knockdown induced G2/M cell cycle arrest and inhibited NPC cell proliferation in vitro and in vivo. Interestingly, HOXA10 was confirmed as a downstream target of RFC4, and the overexpression of HOXA10 attenuated the silencing of RFC4-induced cell proliferation, colony formation inhibition, and cell cycle arrest. For the first time, this study reveals that RFC4 is required for NPC cell proliferation and may play a pivotal role in NPC tumorigenesis.
Humans ; Nasopharyngeal Carcinoma/pathology* ; Carcinoma/pathology* ; Replication Protein C/metabolism* ; Nasopharyngeal Neoplasms/pathology* ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Cell Movement

Nasopharyngeal carcinoma (NPC) is the third most common malignancy with a high recurrence and metastasis rate in South China. Natural compounds extracted from traditional Chinese herbal medicines have been developed and utilized for the treatment of a variety of cancers with modest properties and slight side effects. Maackiain (MA) is a type of flavonoid that was first isolated from leguminous plants, and it has been reported to relieve various nervous system disorders and exert anti-allergic as well as anti-inflammatory effects. In this study, we demonstrated that MA inhibited proliferation, arrested cell cycle and induced apoptosis in nasopharyngeal carcinoma CNE1 and CNE2 cells in vitro and in vivo. The expression of the related proteins associated with these processes were consistent with the above effects. Moreover, transcriptome sequencing and subsequent Western blot experiments revealed that inhibition of the MAPK/Ras pathway may be responsible to the anti-tumor effect of MA on NPC cells. Therefore, the effects of MA and an activator of this pathway, tertiary butylhydroquinone (TBHQ), alone or combination, were investigated. The results showed TBHQ neutralized the inhibitory effects of MA. These data suggest that MA exerts its anti-tumor effect by inhibiting the MAPK/Ras signaling pathway and it has the potential to become a treatment for patients with NPC.
Humans ; Nasopharyngeal Carcinoma/pathology* ; Cell Line, Tumor ; Cell Proliferation ; Apoptosis ; Signal Transduction ; Nasopharyngeal Neoplasms/pathology*

OBJECTIVES: Nasopharyngeal cracinoma is a kind of head and neck malignant tumor with high incidence and high mortality. Due to the characteristics of local recurrence, distant metastasis, and drug resistance, the survival rate of patients after treatment is not high. Paclitaxel (PTX) is used as a chemotherapy drug in treating nasopharyngeal carcinoma, but nasopharyngeal carcinoma cells are easy to develop resistance to PTX. Inhibition of heat shock protein 90 (Hsp90) can overcome common signal redundancy and resistance in many cancers. This study aims to investigate the anti-tumor effect of ginkgolic acids C15꞉1 (C15:1) combined with PTX on nasopharyngeal carcinoma CNE-2Z cells and the mechanisms. METHODS: This experiment was divided into a control group (without drug), a C15:1 group (10, 30, 50, 70 μmol/L), a PTX group (5, 10, 20, 40 nmol/L), and a combination group. CNE-2Z cells were treated with the corresponding drugs in each group. The proliferation of CNE-2Z cells was evaluated by methyl thiazolyl tetrazolium (MTT). Wound-healing assay and transwell chamber assay were used to determine the migration of CNE-2Z cells. Transwell chamber was applied to the impact of CNE-2Z cell invasion. Annexin V-FITC/PI staining was used to observe the effect on apoptosis of CNE-2Z cells. The changes of proteins involved in cell invasion, migration, and apoptosis after the combination of C15꞉1 and PTX treatment were analyzed by Western blotting. RESULTS: Compared with the control group, the C15꞉1 group and the PTX group could inhibit the proliferation of CNE-2Z cells (all P<0.05). The cell survival rates of the C15꞉1 50 μmol/L combined with 5, 10, 20, or 40 nmol/L PTX group were lower than those of the single PTX group (all P<0.05), the combination index (CI) value was less than 1, suggesting that the combined treatment group had a synergistic effect. Compared with the 50 μmol/L C15꞉1 group and the 10 nmol/L PTX group, the combination group significantly inhibited the invasion and migration of CNE-2Z cells (all P<0.05). The results of Western blotting demonstrated that the combination group could significantly down-regulate Hsp90 client protein matrix metalloproteinase (MMP)-2 and MMP-9. The results of double staining showed that compared with the 50 μmol/L C15꞉1 group and the 10 nmol/L PTX group, the apoptosis ratio of CNE-2Z cells in the combination group was higher (both P<0.05). The results of Western blotting suggested that the combination group could decrease the Hsp90 client proteins [Akt and B-cell lymphoma-2 (Bcl-2)] and increase the Bcl-2-associated X protein (Bax). CONCLUSIONS The combination of C15꞉1 and PTX has a synergistic effect which can inhibit cell proliferation, invasion, and migration, and induce cell apoptosis. This effect may be related to the inhibition of Hsp90 activity by C15꞉1.
Humans ; Nasopharyngeal Carcinoma ; Paclitaxel/therapeutic use* ; Nasopharyngeal Neoplasms/metabolism* ; Antineoplastic Agents/therapeutic use* ; Apoptosis ; Cell Proliferation ; Cell Line, Tumor