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.

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.

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.

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.

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.

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.

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.

Adjuvant radiotherapy after curative surgery for oral cavity squamous cell carcinoma and treatment effect of timing and duration on outcome-A Taiwan Cancer Registry national database analysis.

Conduct an accurate risk assessment of resected oral cavity squamous cell carcinoma (OSCC) patients by accessing a nationwide systemic investigation is pivotal to improve treatment outcomes. In this article, we tried to determine the impact of different prognostic factors for OSCC patients who received adjuvant radiotherapy (RT) after curative surgery, using Taiwan's national cancer registry database (TCR). A nationwide, large population-based study was conducted using TCR with patients identified from 2007 to 2015. The study variables included age, gender, cancer subsites, stage, histology grade, margin and extra-nodal extension (ENE) status, treatment type, surgery to RT interval (ORI), total RT treatment time (RTT), and RT dose. Univariate and multivariate analysis were performed to identify predictors of the variables associated with overall survival (OS), cause-specific survival (CSS), local-regional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS). 8986 OSCC patients treated with surgery and adjuvant RT were analyzed. In multivariate analysis, worse outcomes were associated with males, older age, subsite in the oral tongue, advanced stage, higher histologic grade, involved margin, and positive ENE. ORI only showed an adverse trend in LRFS, when exceeding 7 weeks (P = .06). RTT >8 weeks was a significant poor predictor in OS, CSS and LRFS (P < .001). Extreme RT dose (>70 Gy or ≤50 Gy) also demonstrated an adverse impact on the outcomes. Prolonged RT treatment time and extreme RT doses were identified as significantly poor prognostic predictors in OSCC patients who received adjuvant RT after curative surgery.

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.

Thromboxane A2 Regulates CXCL1 and CXCL8 Chemokine Expression in the Nasal Mucosa-Derived Fibroblasts of Chronic Rhinosinusitis Patients.

BACKGROUND: Chronic rhinosinusitis without nasal polyps (CRSsNP) is a common chronic disease and the etiology remains unclear. Thromboxane A2 (TXA2) participates in platelet aggregation and tissue inflammation. In this study, the CXCL1/8 chemokine and TXA2-TP receptor expression in the CRSsNP mucosa was investigated. EXPERIMENTAL APPROACH: Immunohistochemistry, chemokine release assay by ELISA, RT-PCR, Real-time PCR, Western blotting, pharmacological and siRNA knockdown analysis were applied in the CRSsNP tissue specimen and cultured nasal mucosa-derived fibroblasts. RESULTS: The immunohistochemistry results indicated that CXCL1 and CXCL8 were highly expressed in the CRSsNP mucosa compared with the controls; however, the TP receptors were expressed in both mucosa. Therefore, U46619 and IBOP, a TXA2 analog and TP agonist, were used to explore the role of TP activation in CXCL1/8 expression; both of these induced CXCL1/8 mRNA and protein expression in CRSsNP mucosa-derived fibroblasts. U46619 phosphorylated PI-3K, cyclic AMP (cAMP)/PKA, PKC, and cAMP response element (CREB). Activation of cAMP/PKA, PKC, and CREB was the major pathway for cxcl1/8 gene transcription. Pharmacological and siRNA knockdown analyses revealed that activation of cAMP/PKA and PKCµ/PKD pathways were required for CREB phosphorylation and PKA/C crosstalked with the PI-3K pathway. CONCLUSION AND IMPLICATIONS: Our study provides the first evidence for abundant TP receptor and CXCL1/8 expression in human CRSsNP mucosa and for TXA2 stimulation inducing CXCL1/8 expression in nasal fibroblasts primarily through TP receptor, cAMP/PKA, PKCµ/PKD, and CREB-related pathways.

Involvement of B2 receptor in bradykinin-induced proliferation and proinflammatory effects in human nasal mucosa-derived fibroblasts isolated from chronic rhinosinusitis patients.

Chronic rhinosinusitis (CRS) is a chronic inflammatory disease of the sinonasal mucosa either accompanied by polyp formation (CRSwNP) or without polyps (CRSsNP). CRSsNP accounts for the majority of CRS cases and is characterized by fibrosis and neutrophilic inflammation. However, the pathogenesis of CRS, especially CRSsNP, remains unclear. Immunohistochemistry of CRSsNP specimens in the present study showed that the submucosa, perivascular areas, and the mucous glands were abundant in fibroblasts. Therefore, we investigated the effects bradykinin (BK), an autacoid known to participate in inflammation, on human CRSsNP nasal mucosa-derived fibroblasts (NMDFs). BK increased CXCL1 and -8 secretion and mRNA expression with EC50 ranging from 0.15~0.35 µM. Moreover, BK enhanced cell proliferation and upregulated the expressions of proinflammatory molecules, including cell adhesion molecules (CAMs) and cyclooxygenase (COX)-1 and -2. These functionally caused an increase in monocyte adhesion to fibroblast monolayer. Using pharmacological intervention and BKR siRNA knockdown, we demonstrated that the BK-induced CXCL chemokine release, cell proliferation and COX and CAM expressions were mainly through the B2 receptor (B2R). Accordingly, the B2R was preferentially expressed in the NMDFs than B1R. The B2R was highly expressed in the CRSsNP than the control specimens, while the B1R and kininogen (KNG)/BK expression slightly increased in the CRSsNP mucosa. Collectively, we report here for the first time that fibroblasts, KNG/BK, and BKRs are overexpressed in CRSsNP mucosa and BK upregulates chemokine expression, proliferation, and proinflammatory molecule expression in NMDFs via B2R activation, which lead to a functional increase in monocyte-fibroblast interaction. Our findings reveal a critical role of fibroblast, KNG/BK, and BKRs in the development of CRSsNP.

A New Trend in the Management of Esophageal Foreign Body: Transnasal Esophagoscopy.

OBJECTIVES: (1) To analyze the outcomes of patients with esophageal foreign body managed by transnasal esophagoscopy. (2) To review the value of lateral neck X-ray. STUDY DESIGN: Case series with chart review. SETTING: Tertiary referral center, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. SUBJECTS AND METHODS: Lateral neck X-ray was used for initial screening in patients suspected of having an esophageal foreign body between 2007 and 2013. Rigid esophagoscopy was used as standard for further investigations before July 2010 and transnasal esophagoscopy after July 2010. RESULTS: From January 2007 to June 2010, 43 patients who were suspected of having an esophageal foreign body under lateral neck X-ray received rigid esophagoscopy, 31 of whom were found to have an esophageal foreign body. From July 2010 to December 2013, 302 patients underwent transnasal esophagoscopy, and an esophageal foreign body was noted in only 52 of these patients. In the 302 patients who underwent transnasal esophagoscopy, the sensitivity and specificity of having an esophageal foreign body by lateral neck X-ray were 59% and 83%, respectively. CONCLUSION: The introduction of transnasal esophagoscopy has changed the diagnosis and management for an esophageal foreign body. Transnasal esophagoscopy is a quick and safe procedure that can be performed under local anesthesia. Transnasal esophagoscopy could replace lateral neck X-ray to become the initial screening procedure and a useful treatment for patients with an esophageal foreign body.

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.

Biofilm formations in nasopharyngeal tissues of patients with nasopharyngeal osteoradionecrosis.

OBJECTIVE: Determine the presence of nasopharynx biofilms in patients with nasopharyngeal cancer (NPC) and osteoradionecrosis (ORN) and patients with NPC but no ORN. STUDY DESIGN: Cross-sectional study. SETTING: Tertiary referral medical center. SUBJECTS AND METHODS: We enrolled 27 patients with NPC from our outpatient clinic during January 2010 to June 2012. These patients were diagnosed with NPC between 1980 and 2012, and all had received radiotherapy. Of these 27 patients, 15 presented with ORN, and 12 did not. The nasopharynx biopsied specimens were processed and analyzed within 2 hours of collection with the FilmTracer LIVE_DEAD Biofilm Viability Kit (Molecular Probes, Invitrogen, Carlsbad, California). A blinded investigator determined the formation of biofilms by fluorescence microscopy. Bacterial cultures were collected. RESULTS: Eleven of 15 (73%) ORN patients had biofilm formations in nasopharynx biopsy specimens. Five of these samples (45%) yielded positive cultures, and 4 of these cultures indicated the presence of methicillin-resistant Staphylococcus aureus (MRSA). Only 1 of 12 NPC patients without ORN had nasopharynx biofilm formation, and all culture results were negative. CONCLUSION: Biofilm formations were common in nasopharynx samples of NPC patients with ORN but rare in samples of NPC patients without ORN. The presence of biofilms, especially MRSA, may have a role in the disease progression of ORN or may contribute to the chronicity and resistance to antibiotic treatment.

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 relationship between secretory leukocyte protease inhibitor expression and Epstein-Barr virus status among patients with nasopharyngeal carcinoma.

AIM: The aim was to study the expression of Secretory Leukocyte Protease Inhibitor (SLPI) and to explore its correlation with the presence of Epstein-Barr Virus (EBV) among patients with nasopharyngeal carcinoma. MATERIALS AND METHODS: The expression levels of SLPI mRNA in NPC cell lines and in ten matched-pairs of NPC and adjacent normal tissue were examined by quantitative real-time Polymerase Chain Reaction (PCR). Furthermore, protein expression of SLPI in 71 paraffin-embedded NPC biopsies was assessed by immunohistochemistry. Finally, the serum level of SLPI in 177 NPC patients and 103 healthy controls was evaluated by enzyme-linked immunosorbent assay (ELISA). RESULTS: The expression of SLPI mRNA in NPC cells was significantly lower than in the adjacent normal epithelium (p<0.001). When the expression of SLPI in EBV-positive and -negative NPC cell lines was compared, we found that both mRNA and protein expressions of SLPI were significantly higher in EBV-negative cells. Furthermore, the results of immunohistochemical analysis demonstrated that the frequency of reduced SLPI expression in EBV-positive biopsies was significantly higher than that in EBV-negative biopsies. CONCLUSION: In this study, we have confirmed that SLPI is significantly down-regulated in NPC tissues. In addition, based on our preliminary results, we propose that the reduction of SLPI in NPC cells is associated with the presence of the EBV genome and/or the expression of EBV-encoded genes. SLPI may play an important role in EBV-mediated NPC tumorigenesis.

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.