Surgical Treatment for Advanced Oropharyngeal Cancer: A Narrative Review.

Background and Objectives: to describe current scientific knowledge regarding the treatment options in advanced oropharyngeal cancer. The standard care for advanced oropharyngeal cancer (OPSCC) has been chemoradiotherapy, although surgical approaches followed by adjuvant treatment have been proposed. The best therapy for each patient should be decided by an interdisciplinary tumour-board. Different strategies should be considered for the specific patient's treatment: surgery, chemotherapy and radiation therapy or combinations of them. The treatment choice is influenced by tumour variability and prognostic factors, but it also depends on cancer extension, extranodal extension, nervous invasion, human papilloma virus (HPV) presence, making the decisional algorithm not always clear. HPV-related OPSCC is strongly associated with a favourable overall survival (OS) and disease-free survival rate (DSS); by contrast, HPV-negative OPSCC often flags a worse prognosis. Consequently, the American Joint Committee on Cancer (AJCC) differentiates OPSCC treatment and prognosis based on HPV status. Methods: we carried out a review of current scientific literature to analyze the different indications and limitations of surgical treatment options in OPSCC stage III and IV. Conclusion: robotic surgery or open approaches with reconstructive flaps can be considered in advanced stages, resulting in the de-intensification of subsequent systemic therapy and fewer related side effects. Furthermore, in the event of the primary failure of systemic therapy or disease recurrence, the surgical approach constitutes an additional therapeutic option which lengthens patient survival functions.

International recommendations for plasma Epstein-Barr virus DNA measurement in nasopharyngeal carcinoma in resource-constrained settings: lessons from the COVID-19 pandemic.

The effects of the COVID-19 pandemic continue to constrain health-care staff and resources worldwide, despite the availability of effective vaccines. Aerosol-generating procedures such as endoscopy, a common investigation tool for nasopharyngeal carcinoma, are recognised as a likely cause of SARS-CoV-2 spread in hospitals. Plasma Epstein-Barr virus (EBV) DNA is considered the most accurate biomarker for the routine management of nasopharyngeal carcinoma. A consensus statement on whether plasma EBV DNA can minimise the need for or replace aerosol-generating procedures, imaging methods, and face-to-face consultations in managing nasopharyngeal carcinoma is urgently needed amid the current pandemic and potentially for future highly contagious airborne diseases or natural disasters. We completed a modified Delphi consensus process of three rounds with 33 international experts in otorhinolaryngology or head and neck surgery, radiation oncology, medical oncology, and clinical oncology with vast experience in managing nasopharyngeal carcinoma, representing 51 international professional societies and national clinical trial groups. These consensus recommendations aim to enhance consistency in clinical practice, reduce ambiguity in delivering care, and offer advice for clinicians worldwide who work in endemic and non-endemic regions of nasopharyngeal carcinoma, in the context of COVID-19 and other airborne pandemics, and in future unexpected settings of severe resource constraints and insufficiency of personal protective equipment.

Treatment Options in Early Stage (Stage I and II) of Oropharyngeal Cancer: A Narrative Review.

OBJECTIVE: to show an overview on the treatments' options for stage I and II oropharyngeal carcinomasquamous cell carcinoma (OPSCC). BACKGROUND: The traditional primary treatment modality of OPSCC at early stages is intensity modulated radiation therapy (IMRT). Trans-oral robotic surgery (TORS) has offered as an alternative, less invasive surgical option. Patients with human papilloma virus (HPV)-positive OPSCC have distinct staging with better overall survival in comparison with HPV-negative OPSCC patients. METHODS: a comprehensive review of the English language literature was performed using PubMed, EMBASE, the Cochrane Library, and CENTRAL electronic databases. CONCLUSIONS: Many trials started examining the role of TORS in de-escalating treatment to optimize functional consequences while maintaining oncologic outcome. The head-neck surgeon has to know the current role of TORS in HPV-positive and negative OPSCC and the ongoing trials that will influence its future implementation. The feasibility of this treatment, the outcomes ensured, and the side effects are key factors to consider for each patient. The variables reported in this narrative review are pieces of a bigger puzzle called tailored, evidence-based driven medicine. Future evidence will help in the construction of robust and adaptive algorithms in order to ensure the adequate treatment for the OPSCC at early stages.

The hidden curve behind COVID-19 outbreak: the impact of delay in treatment initiation in cancer patients and how to mitigate the additional risk of dying-the head and neck cancer model.

PURPOSE: The rapid spread of the SARS-CoV-2 pandemic around the world caused most healthcare services to turn substantial attention to treatment of these patients and also to alter the structure of healthcare systems to address an infectious disease. As a result, many cancer patients had their treatment deferred during the pandemic, increasing the time-to-treatment initiation, the number of untreated patients (which will alter the dynamics of healthcare delivery in the post-pandemic era) and increasing their risk of death. Hence, we analyzed the impact on global cancer mortality considering the decline in oncology care during the COVID-19 outbreak using head and neck cancer, a known time-dependent disease, as a model. METHODS: An online practical tool capable of predicting the risk of cancer patients dying due to the COVID-19 outbreak and also useful for mitigation strategies after the peak of the pandemic has been developed, based on a mathematical model. The scenarios were estimated by information of 15 oncological services worldwide, given a perspective from the five continents and also some simulations were conducted at world demographic data. RESULTS: The model demonstrates that the more that cancer care was maintained during the outbreak and also the more it is increased during the mitigation period, the shorter will be the recovery, lessening the additional risk of dying due to time-to-treatment initiation. CONCLUSIONS: This impact of COVID-19 pandemic on cancer patients is inevitable, but it is possible to minimize it with an effort measured by the proposed model.

The Management of rNPC: Salvage Surgery vs. Re-irradiation.

PURPOSE OF REVIEW: Treatment failure, in the form of either persistence or local recurrence, occurs in 10 to 30% of nasopharyngeal carcinoma patients after initial radiotherapy (RT). Early detection of persistent or recurrent disease aids in the recognition of tumors that can be candidates for salvage nasophayngectomy or re-irradiation. There is no consensus till now on the indications or selection of the above two salvage treatment. RECENT FINDINGS: In recent years, there has been a paradigm shift from open to endoscopic approach for nasopharyngectomy, which carries nearly no complications. For salvage re-irradiation, intensity-modulated radiotherapy (IMRT) is the most commonly indicated modality. Compared to IMRT, salvage endoscopic nasopharyngectomy may be more beneficial in terms of prolonging survival, improving quality of life, and minimizing treatment-related complications and medical costs in a selected subset of recurrent nasopharyngeal carcinoma (rNPC) patients. Salvage nasopharyngectomy should be the mainstay of treatment for rNPC.

Modified Design of Anterolateral Thigh Flap for Total Pharyngolaryngectomy Reconstruction: A Single-Center Experience.

BACKGROUND: Defects after total pharyngolaryngectomy for hypopharyngeal cancer often require reconstruction via free tissue transfer. Recently, anterolateral thigh (ALT) flap has become the gold standard in many centers because of its advantages with respect to versatility, minimal donor-site morbidity, good speech quality, and relatively low fistula and anastomotic leakage rates. Moreover, ALT allows 2 surgical teams to work simultaneously. However, the height of the parallelogram in the ALT design for neoesophagus reconstruction is usually set at a minimum of 9.4 cm (circumference, 2πr) for smooth food passage. Because this height exceeds 8 cm, the donor site may not be closed primarily, which highly depends on the patient's body habitus and the skin tone or quality and requires other methods, such as local flap or skin graft for wound closure, which subsequently increase operating time and donor-site complication rate. OBJECTIVES: Thus, we aimed to construct a simple and modified ALT design that will not only include the advantages described earlier but also provide adequate donor-site primary closure without jeopardizing complication rates. METHODS: Ten patients with hypopharyngeal cancer underwent reconstructive surgery using our modified ALT design after total pharyngolaryngectomy between 2010 and 2017. Our modified ALT design converts this "classical" shape into a parallelogram so that the height of the modified design is always less than 8 cm, thus allowing for easy primary closure of the wound. RESULTS: The donor-site defects of all 10 patients were closed primarily. No donor-site complications and partial or total flap loss were observed. One patient experienced persistent wound infection with dehiscence, for which debridement was performed. The stricture and fistula rates were 10% (n = 1) and 20% (n = 2), respectively. The mean follow-up time is approximately 1 year. CONCLUSIONS: Minimizing donor-site morbidity is an important goal in reconstructive surgery. Our modified ALT flap design is simple, enabling easy primary closure of the donor-site defect, with improved results for the patient and operators. Furthermore, this design is also suitable for ALT flaps with widths larger than 8 cm.

Repair of oronasal fistula with silicone button in patients with head and neck cancer.

UNLABELLED: Until now, there is no optimal technique for repairing oronasal fistula in patients with prior head and neck radiotherapy and trismus. Use of the silicone button is a safe, office-based, and validated method in this situation. The indications of this procedure are also clarified in this study. This is a retrospective study of four patients who underwent a newly designed endoscopic repair of oronasal fistula with silicone button under local anesthesia from July 2012 to August 2012. Data on the size of the defect, length of operation, symptom relief, and post-operative complications were collected. Four patients underwent endoscopic repair of oronasal fistula with silicone button under local anesthesia. The diagnoses were benign palate lesion s/p operation, oral cancer s/p operation and radiotherapy. The defect diameter varied from 1 to 1.5 cm. The operation durations were between 20 and 30 min. In all cases, nasal regurgitation symptoms were relieved. The hypernasality of one case improved, while another had decreased nasal crusting and foul odors. No major complications were noted. There was a minor complication in one case, which exhibited frequent crusting around the silicone button. Silicon button can act as a temporary obturator to improve quality of life of patients. The indications for this procedure include patient undergone head and neck radiotherapy with (1) chronic fistula (>6 months); (2) small defect (1-2 cm); and (3) trismus. LEVEL OF EVIDENCE: 4.

Prognostic utility of the geriatric nutritional risk index for head and neck cancer: Systematic review and meta-analysis.

We conducted a systematic review of the literature to assess the potential prognostic utility of geriatric nutritional risk index (GNRI) for head and neck cancer (HNC). We selected studies and extracted data after searching the Cochrane Library, EMBASE, and PubMed databases. The associations between GNRI and survival outcomes were explored by calculating hazard ratios (HRs) and 95% confidence intervals (CIs) through a random-effects meta-analysis. We included 11 studies that involved 2887 patients with HNC. The combined HR demonstrated significant associations of low GNRI with unfavorable progression-free survival (HR = 1.87, 95% CI = 1.32-2.65, p < 0.001) and overall survival (HR = 3.04, 95% CI = 2.30-4.03, p < 0.001). The association between the GNRI and overall survival persisted across various subgroups. The GNRI could serve as a valuable prognostic biomarker for patients with HNC. Low GNRI scores are significantly associated with unfavorable survival outcomes.

A gender-specific association of CNV at 6p21.3 with NPC susceptibility.

Copy number variations (CNVs), a major source of human genetic polymorphism, have been suggested to have an important role in genetic susceptibility to common diseases such as cancer, immune diseases and neurological disorders. Nasopharyngeal carcinoma (NPC) is a multifactorial tumor closely associated with genetic background and with a male preponderance over female (3:1). Previous genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) that are associated with NPC susceptibility. Here, we sought to explore the possible association of CNVs with NPC predisposition. Utilizing genome-wide SNP-based arrays and five CNV-prediction algorithms, we identified eight regions with CNV that were significantly overrepresented in NPC patients compared with healthy controls. These CNVs included six deletions (on chromosomes 3, 6, 7, 8 and 19), and two duplications (on chromosomes 7 and 12). Among them, the CNV located at chromosome 6p21.3, with single-copy deletion of the MICA and HCP5 genes, showed the highest association with NPC. Interestingly, it was more specifically associated with an increased NPC risk among males. This gender-specific association was replicated in an independent case-control sample using a self-established deletion-specific polymerase chain reaction strategy. To the best of our knowledge, this is the first study to explore the role of constitutional CNVs in NPC, using a genome-wide platform. Moreover, we identified eight novel candidate regions with CNV that merit future investigation, and our results suggest that similar to neuroblastoma and prostate cancer, genetic structural variations might contribute to NPC predisposition.

Benign fibrous histiocytoma of the cheek.

Benign fibrous histiocytoma (FH) is a benign neoplasm of a mixture of fibroblastic and histiocytic cells. The tumor occurs most frequently on the skin of the extremities but rarely in deep soft tissues of the head and neck. The diagnosis of benign FH may be clinically difficult, and is frequently confirmed after excision. The most important diagnostic distinction is the separation of this tumor from malignant FH. A 22-year-old male presented with a painless swelling mass on the left cheek. Detailed clinical and laboratory examinations were performed. The patient received angiography with embolization and underwent an intraoral excision of the mass under general anesthesia with primary closure. The histopathology revealed a benign FH. The complete image survey and appropriate treatment of benign FH of the cheek are emphasized.

The Global Otolaryngology-Head and Neck Surgery Workforce.

Importance: A core component of delivering care of head and neck diseases is an adequate workforce. The World Health Organization report, Multi-Country Assessment of National Capacity to Provide Hearing Care, captured primary workforce estimates from 68 member states in 2012, noting that response rates were a limitation and that updated more comprehensive data are needed. Objective: To establish comprehensive workforce metrics for global otolaryngology-head and neck surgery (OHNS) with updated data from more countries/territories. Design, Setting, and Participants: A cross-sectional electronic survey characterizing the OHNS workforce was disseminated from February 10 to June 22, 2022, to professional society leaders, medical licensing boards, public health officials, and practicing OHNS clinicians. Main Outcome: The OHNS workforce per capita, stratified by income and region. Results: Responses were collected from 121 of 195 countries/territories (62%). Survey responses specifically reported on OHNS workforce from 114 countries/territories representing 84% of the world's population. The global OHNS clinician density was 2.19 (range, 0-61.7) OHNS clinicians per 100 000 population. The OHNS clinician density varied by World Bank income group with higher-income countries associated with a higher density of clinicians. Regionally, Europe had the highest clinician density (5.70 clinicians per 100 000 population) whereas Africa (0.18 clinicians per 100 000 population) and Southeast Asia (1.12 clinicians per 100 000 population) had the lowest. The OHNS clinicians deliver most of the surgical management of ear diseases and hearing care, rhinologic and sinus diseases, laryngeal disorders, and upper aerodigestive mucosal cancer globally. Conclusion and Relevance: This cross-sectional survey study provides a comprehensive assessment of the global OHNS workforce. These results can guide focused investment in training and policy development to address disparities in the availability of OHNS clinicians.

Genome-wide association study reveals multiple nasopharyngeal carcinoma-associated loci within the HLA region at chromosome 6p21.3.

Nasopharyngeal carcinoma (NPC) is a multifactorial malignancy closely associated with genetic factors and Epstein-Barr virus infection. To identify the common genetic variants linked to NPC susceptibility, we conducted a genome-wide association study (GWAS) in 277 NPC patients and 285 healthy controls within the Taiwanese population, analyzing 480,365 single-nucleotide polymorphisms (SNPs). Twelve statistically significant SNPs were identified and mapped to chromosome 6p21.3. Associations were replicated in two independent sets of case-control samples. Two of the most significant SNPs (rs2517713 and rs2975042; p(combined) = 3.9 x 10(-20) and 1.6 x 10(-19), respectively) were located in the HLA-A gene. Moreover, we detected significant associations between NPC and two genes: specifically, gamma aminobutyric acid b receptor 1 (GABBR1) (rs29232; p(combined) = 8.97 x 10(-17)) and HLA-F (rs3129055 and rs9258122; p(combined) = 7.36 x 10(-11) and 3.33 x 10(-10), respectively). Notably, the association of rs29232 remained significant (residual p < 5 x 10(-4)) after adjustment for age, gender, and HLA-related SNPs. Furthermore, higher GABA(B) receptor 1 expression levels can be found in the tumor cells in comparison to the adjacent epithelial cells (p < 0.001) in NPC biopsies, implying a biological role of GABBR1 in NPC carcinogenesis. To our knowledge, it is the first GWAS report of NPC showing that multiple loci (HLA-A, HLA-F, and GABBR1) within chromosome 6p21.3 are associated with NPC. Although some of these relationships may be attributed to linkage disequilibrium between the loci, the findings clearly provide a fresh direction for the study of NPC development.

Management of oral feeding following total laryngectomy around the world: YO-IFOS international study.

BACKGROUND: To analyze worldwide practices regarding the initiation of oral feeding after total laryngectomy (TL). METHODS: Online survey. RESULTS: Among the 332 responses received, 278 from 59 countries were analyzed. Our results showed that 45.6% of respondents started water and 45.1% started liquid diet between postoperative days 7 and 10. Semi-solid feeds were initiated between days 10 and 14 for 44.9% of respondents and a free diet was allowed after day 15 for 60.8% of respondents. This timing was significantly delayed in cases of laryngo-pharyngectomy and after prior radiotherapy (p < 0.001). A greater proportion of respondents in Africa and Oceania allowed early oral feeding before day 6 as compared with the rest of the world (p < 0.001). CONCLUSION: Despite increasing number of publications, there is still a lack of evidence to support early oral feeding. The majority of respondents preferred to delay its initiation until at least 7 days after surgery.

Enhanced interferon signaling pathway in oral cancer revealed by quantitative proteome analysis of microdissected specimens using 16O/18O labeling and integrated two-dimensional LC-ESI-MALDI tandem MS.

Oral squamous cell carcinoma (OSCC) remains one of the most common cancers worldwide, and the mortality rate of this disease has increased in recent years. No molecular markers are available to assist with the early detection and therapeutic evaluation of OSCC; thus, identification of differentially expressed proteins may assist with the detection of potential disease markers and shed light on the molecular mechanisms of OSCC pathogenesis. We performed a multidimensional (16)O/(18)O proteomics analysis using an integrated ESI-ion trap and MALDI-TOF/TOF MS system and a computational data analysis pipeline to identify proteins that are differentially expressed in microdissected OSCC tumor cells relative to adjacent non-tumor epithelia. We identified 1233 unique proteins in microdissected oral squamous epithelia obtained from three pairs of OSCC specimens with a false discovery rate of <3%. Among these, 977 proteins were quantified between tumor and non-tumor cells. Our data revealed 80 dysregulated proteins (53 up-regulated and 27 down-regulated) when a 2.5-fold change was used as the threshold. Immunohistochemical staining and Western blot analyses were performed to confirm the overexpression of 12 up-regulated proteins in OSCC tissues. When the biological roles of 80 differentially expressed proteins were assessed via MetaCore analysis, the interferon (IFN) signaling pathway emerged as one of the most significantly altered pathways in OSCC. As many as 20% (10 of 53) of the up-regulated proteins belonged to the IFN-stimulated gene (ISG) family, including ubiquitin cross-reactive protein (UCRP)/ISG15. Using head-and-neck cancer tissue microarrays, we determined that UCRP is overexpressed in the majority of cheek and tongue cancers and in several cases of larynx cancer. In addition, we found that IFN-beta stimulates UCRP expression in oral cancer cells and enhances their motility in vitro. Our findings shed new light on OSCC pathogenesis and provide a basis for the future development of novel biomarkers.

Tracheostomy During the COVID-19 Pandemic: Comparison of International Perioperative Care Protocols and Practices in 26 Countries.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has led to a global surge in critically ill patients requiring invasive mechanical ventilation, some of whom may benefit from tracheostomy. Decisions on if, when, and how to perform tracheostomy in patients with COVID-19 have major implications for patients, clinicians, and hospitals. We investigated the tracheostomy protocols and practices that institutions around the world have put into place in response to the COVID-19 pandemic. DATA SOURCES: Protocols for tracheostomy in patients with severe acute respiratory syndrome coronavirus 2 infection from individual institutions (n = 59) were obtained from the United States and 25 other countries, including data from several low- and middle-income countries, 23 published or society-endorsed protocols, and 36 institutional protocols. REVIEW METHODS: The comparative document analysis involved cross-sectional review of institutional protocols and practices. Data sources were analyzed for timing of tracheostomy, contraindications, preoperative testing, personal protective equipment (PPE), surgical technique, and postoperative management. CONCLUSIONS: Timing of tracheostomy varied from 3 to >21 days, with over 90% of protocols recommending 14 days of intubation prior to tracheostomy. Most protocols advocate delaying tracheostomy until COVID-19 testing was negative. All protocols involved use of N95 or higher PPE. Both open and percutaneous techniques were reported. Timing of tracheostomy changes ranged from 5 to >30 days postoperatively, sometimes contingent on negative COVID-19 test results. IMPLICATIONS FOR PRACTICE: Wide variation exists in tracheostomy protocols, reflecting geographical variation, different resource constraints, and limited data to drive evidence-based care standards. Findings presented herein may provide reference points and a framework for evolving care standards.

Identification of candidate nasopharyngeal carcinoma serum biomarkers by cancer cell secretome and tissue transcriptome analysis: potential usage of cystatin A for predicting nodal stage and poor prognosis.

Nasopharyngeal carcinoma (NPC) is usually diagnosed at advanced clinical stages, resulting in poor outcomes. To discover serum biomarkers for improved NPC diagnosis and/or management, we simultaneously analyzed the NPC cell secretome and tissue transcriptome to identify candidate genes/proteins that are highly upregulated in NPC tissues and also secreted/released from NPC cells. Among the 30 candidates identified, 11 proteins were chosen for further validation using the serum samples from NPC patients and healthy controls, including cystatin A, cathepsin B, manganese superoxide dismutase and matrix metalloproteinase 2. The results showed that serum levels of all the four proteins were indeed higher in NPC patients versus healthy controls and that the use of a three-marker panel (cystatin A, manganese superoxide dismutase and matrix metalloproteinase 2) can contribute to a better NPC detection than each marker alone. In addition, a higher pretreated serum level of cystatin A was found to be associated with a higher nodal stage and poorer prognosis of NPC patients and cystatin A could modulate the migration and invasion of NPC cells in vitro. Altogether, our results indicate that analysis of both the cancer cell secretome and tissue transcriptome is a feasible strategy for efficient identification of novel NPC serum marker panel.

Overexpression of activin A in oral squamous cell carcinoma: association with poor prognosis and tumor progression.

BACKGROUND: Both activin A, a member of transforming growth factor beta superfamily, and its inhibitor follistatin have been shown to be overexpressed in various cancers. We examined the potential role of activin A and follistatin in tissue and blood samples from patients with oral squamous cell carcinoma. METHODS: For activin A and follistatin, the expression of tissue samples from 92 patients was examined by immunohistochemical study, and the serum levels of blood samples from 111 patients and 91 healthy controls were measured by enzyme-linked immunosorbent assay. RESULTS: We found that overexpression of immunohistochemically detected activin A was correlated with positive N stage, poor histological differentiation, and perineural invasion (P = 0.029, 0.002, and 0.014, respectively). In survival analyses, patients with oral squamous cell carcinoma, whose tumors overexpressed activin A, had a worse prognosis for overall survival and disease-free survival (P = 0.009 and 0.007). However, expression of follistatin in tumor was not correlated with overall survival or disease-free survival. Serum activin A and follistatin levels in 111 untreated patients were neither significantly different from those of 91 control samples nor associated with any clinicopathological manifestations. In vitro suppression of activin A expression in OC3 cells using specific interfering RNA-attenuated cell proliferation, migration, and invasiveness. CONCLUSIONS: These findings suggest that activin A overexpression in oral squamous cell carcinomas is associated with patients' survival and may contribute to tumor progression and metastasis.

Cardiac tamponade: a rare presentation from a rare metastatic site in oral squamous cell carcinoma.

Metastatic head and neck squamous cell carcinoma (HNSCC) is a rare cause of cardiac tamponade. We report on a 62-year-old male who presented with metastatic squamous cell carcinoma (SCC) that caused cardiac tamponade secondary to a primary SCC originating from the retromolar trigone of the oral cavity. The clinical diagnosis was confirmed by physical examination, echocardiography and complete resolution of symptoms after pericardial fluid drainage. Cytologic examination of the pericardial fluid was the only investigational tool able to render a definitive evidence of malignant pericardial effusion. However, evidence of a hemorrhagic pericardial effusion must raise the suspicion of a malignant etiology regardless of the result of the cytologic examination. Metastatic HNSCC may involve multiple organ systems including the heart. We report this rare clinical presentation of cardiac tamponade as the initial location of distant metastasis. Otolaryngologists should keep a high index of suspicion and pay special attention to the symptoms arising on the non-head and neck sites to establish an early diagnosis and prompt management of the disease process.

Heterogeneous ribonucleoprotein k and thymidine phosphorylase are independent prognostic and therapeutic markers for nasopharyngeal carcinoma.

PURPOSE: Heterogeneous ribonucleoprotein K (hnRNP K) regulates thymidine phosphorylase (TP) mRNA stability. The aim of the present study was to analyze hnRNP K and TP expression in nasopharyngeal carcinoma (NPC) and to evaluate the prognostic and therapeutic potential of these two markers. EXPERIMENTAL DESIGN: We analyzed hnRNP K and TP expression immunohistochemically in 121 clinically proven NPC cases. Statistical analyses were applied to correlate cytoplasmic hnRNP K with elevated TP expression and determine the prognostic significance of these parameters. The therapeutic implication of elevated TP expression was determined by measuring sensitivity of NPC cells to the TP-targeting drug, 5-fluoro-5'-deoxyuridine (5'-DFUR). RESULTS: There was a high correlation between cytoplasmic hnRNP K and high TP (P < 0.001). Both cytoplasmic hnRNP K and high TP were associated with poor overall survival (OS; P = 0.007 and P < 0.001, respectively) and distant metastasis-free survival (P = 0.003 and 0.001, respectively) of NPC patients. A multivariate analysis confirmed that both cytoplasmic hnRNP K and high TP are independent prognostic predictors for OS (P = 0.020 and 0.010, respectively). NPC cells expressing high TP were more sensitive to treatment with the TP-targeting drug, 5'-DFUR. CONCLUSIONS: Cytoplasmic hnRNP K and high TP are associated with shorter OS and distant metastasis-free survival in NPC patients. In vitro experiments suggest that NPC tumors with high TP expression may be sensitive to 5'-DFUR treatment. Cytoplasmic hnRNP K and high TP may be potential prognostic and therapeutic markers for NPC, but additional validation studies are warranted.

Macrophage inflammatory protein-3alpha is a novel serum marker for nasopharyngeal carcinoma detection and prediction of treatment outcomes.

PURPOSE: We herein examine whether macrophage inflammatory protein-3alpha (MIP-3alpha) is a biomarker for nasopharyngeal carcinoma (NPC) and whether it is involved in modulating NPC cell functions. EXPERIMENTAL DESIGN: The study population comprises 275 NPC patients and 250 controls. MIP-3alpha levels in tissues and sera were examined by immunohistochemistry and ELISA, respectively. EBV DNA load and EBV viral capsid antigen IgA were measured by quantitative real-time PCR and immunofluorescence assay, respectively. Effects of MIP-3alpha on NPC cell motility were investigated by Transwell migration/invasion assays and RNA interference. RESULTS: MIP-3alpha was overexpressed in NPC tumor cells. Serum MIP-3alpha levels were significantly higher in untreated patients, recurrent patients and patients with distant metastases versus non-NPC controls, patients with complete remission, and long-term disease-free patients. In the prospective cohort, serum MIP-3alpha levels were significantly higher in untreated NPC patients with advanced tumor-node-metastasis stage versus early stage and also correlated with EBV DNA load. Measurement of MIP-3alpha, EBV DNA, and viral capsid antigen IgA levels in serial serum/plasma samples from treated patients at 6-month intervals revealed a high association between MIP-3alpha level, EBV DNA load, and disease status. Among 155 consecutive NPC patients, subjects with pretreated MIP-3alpha serum levels over 65 pg/mL had worse prognoses for overall survival and distant metastasis-free survival in univariate and multivariate analysis. Additionally, cell functional assays showed that MIP-3alpha contributed to migration and invasion of NPC cells, which could be effectively inhibited by MIP-3alpha knockdown. CONCLUSIONS: MIP-3alpha may be a novel biomarker and prognosticator for NPC and is involved in migration and invasion of NPC cells.