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Background: To date, no targeted therapy has been approved for nasopharyngeal carcinoma (NPC), suggesting that comprehensive understanding of genomic changes turns out to be an urgent need to break through the calm of currently known therapies of NPC., Methods: Whole exome sequencing (WES) was performed for 14 NPC patients, including 6 NPC-IIA cases, 8 NPC-IIB cases. The cancer chip expression data named GSE12452 was downloaded from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) of each subtype were obtained using the Lima R package. Then gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed. Protein-protein interaction (PPI) network and Gene Set Enrichment Analysis (GSEA) were performed. Finally 7 potentially subtype relevant genes (PSRGs) 1 were obtained., Results: In total, 37 clinically relevant mutations (CRMs) 2 were obtained from WES. The 2 NPC subtypes exhibited different mutational landscapes, indicating that different NPC subtypes harbor different CRMs. Notably, we discovered that mutations of CCND1 and FGF family appeared simultaneously in 3 NPC-IIB cases, but 0 in NPC-IIA. In addition, 1395 DEGs were identified from GSE12452. PI3K-Akt signaling pathway showed significant enrichment in both the pathway distribution of CRMs and KEGG analysis of DEGs, suggesting that it is a key pathway in the development of NPC. Through PPI analysis of genes involved in the PI3K-Akt pathways and expression significance analysis of DEGs co-expressed by the 2 subtypes, 54 genes finally were screened for expression significance analysis. The GSEA analysis between patients with high and low expression of 11 candidate genes were performed. As a result, 7 PSRGs were selected, including COL4A1, ASB9, RDH10, TNFRSF21, BACE2, EVA1C and LHX2., Conclusions: These results indicate that different NPC subtypes have different genetic changes, suggesting that they may be potential targets for the diagnosis and treatment of NPC, and ultimately point to new strategies for intelligence., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Background: While nasopharyngeal carcinoma (NPC) is rare in non-endemic regions such as the North America, endemic countries, such as Thailand, continue to struggle with high incidence and mortality rates. NPC has a complex etiology that varies by histological subtype., Methods: NPC cases (1990-2014) were identified using the International Classification of Diseases for Oncology (ICD-O) code C11 from the Chiang Mai, Khon Kaen, Lampang, and Songkhla cancer registries and compared to Asian/Pacific Islanders (A/PI) from the US SEER program. Age-standardized incidence rates and changes in annual percent change (APC) for overall and subtype specific NPC were assessed using R and Joinpoint. Kaplan Meier curves were generated in SAS to evaluate differences in survival by sex, year of diagnosis and histological subtype. Five-year relative survival estimates were calculated between 2000-2014., Results: Non-keratinizing NPC predominated across all registries except Songkhla, where the keretinizing subtype made up ~60% of all reported cases. Incidence of keratinizing NPC significantly decreased among Chiang Mai males between 1996 and 2014 (APC:-13.0 [95%CI:-16.2, -9.6]), Songkhla females (APC:-4.0 [95%CI: -7.4, -0.5]) and males between 2006 and 2014 (APC:-15.5 [95%CI:-25.0, -4.7]), as well as A/PI females (APC:-5.1 [95%CI:-6,7, -3.4]) and males (APC: -4.8 [95%CI:-5.9, -3.7]). Non-keratinizing NPC increased among Songkhla males (APC:4.3 [95%CI:1.8, 6.9]). The keratinizing subtype exhibited the worst survival, while the non-keratinizing undifferentiated subtype had the best survival. Although US A/PI had the highest 5-year relative survival estimates, among the Thai registries Chiang Mai had the best and Lampang the worst survival., Conclusion: Although US A/PIs exhibited similar rates of NPC as seen in the endemic Thai population, improved tobacco control has led to a decrease in keratinizing NPC incidence irrespective of geography. Additionally, while challenges associate with access to care may still exist among rural Thais, chemoradiation was shown to confer a survival benefit in non-keratinizing NPC treatment.

Objectives: This study aimed to evaluate the value of nodal grouping (NG), defined as the presence of at least three contiguous lymph nodes (LNs) within one LN region, in staging and management of patients with non-metastatic nasopharyngeal carcinoma (NPC)., Methods: MR images were reviewed to evaluate LN variables, including NG. The Kaplan-Meier method and multivariate Cox regression models evaluated the association between the variables and survival. Harrell's concordance index (C-index) was used to measure the performance of prognostic models. The outcome of induction chemotherapy (IC) in patients with and without NG was compared using matched-pair analysis., Results: In 1224 patients enrolled, NG was found to be an independent prognostic factor for overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and regional recurrence-free survival. The hazard ratio and 95% confidence interval (CI) of NG for OS (3.86, 2.09-7.12) were higher than those of stage N2 (3.54, 1.89-6.70). On upgrading patients with NG from stages N1 to N2, the revised N staging yielded a higher C-index compared to the American Joint Committee on Cancer system in predicting PFS (0.664 vs. 0.658, p = 0.022) and DMFS (0.699 vs. 0.690, p = 0.005). Results of the matched-pair analysis revealed that for patients with NG in stages N1 and N2, IC was correlated with improved OS (p = 0.022), PFS (p = 0.007), and DMFS (p = 0.021)., Conclusions: NG is a significant prognostic factor for patients with NPC. Patients with NG may be upgraded from stages N1 to N2. NG was also a marker for identifying patients who would benefit from IC., Key Points: • Nodal grouping, defined as the presence of at least three contiguous LNs within one LN region on MRI, was identified as a significant prognostic factor. • In patients with nasopharyngeal carcinoma, nodal grouping may influence lymph node staging. • Nodal grouping was a marker for identifying patients who may benefit from induction chemotherapy.

Background: Tumor-nodal-metastasis (TNM) is the most important survival predictor in nasopharyngeal carcinoma (NPC). Distant metastasis (DM) is the predominant failure pattern of NPC in the intensity-modulated radiotherapy (IMRT) era. The DM risk appears to be different for T-N subsets within the same clinical stage. Appropriately depicting DM risk has emerged as an important issue in tailoring individualized treatment and underpins the reason for this study., Methods: A total of 1616 non-metastatic (M0) NPC patients treated with IMRT were included. All were re-staged according to the 8th edition AJCC/UICC TNM (TNM-8). DM-free survival (DMFS) was calculated and compared among T-N subsets within each stage and DM risk groups were derived by Recursive-partitioning analysis (RPA) based on ordinal T and N categories., Results: Significant heterogeneity in DM risk was evident among T-N subsets within cTNM-8 stages II-IV. The RPA algorithm classified patients into four DM risk groups: RPA-I (T1N0-1 and T2-3N0), RPA-II (T2-3N1), RPA-III (T4N0-1 and T1-3N2) and RPA-IV (T4N2 and T1-4N3), with 5-year DMFS of 93.4% (95% CI: 91.3-96.1), 84.3% (80.8-87.8), 78.9% (75.4-82.4) and 63.6% (56.3-70.9), respectively (p < 0.001). Compared to cTNM-8 stage grouping, RPA grouping had a lower Akaike information criterion (AIC) and higher Harrell's concordance index (c-index) for DMFS., Conclusions: Significant heterogeneity in DM risk exists among T-N subsets within cTNM-8 stages. The RPA groups demonstrated improved intra-group hazard consistency compared to cTNM-8 stage groups. While further validation is warranted, these RPA prognostic groupings provide a strong anatomic foundation to augment DM prediction for optimal targeting in future clinical trials., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Backgrounds: With the aim to validate the applicability of the eighth T classifications of AJCC/UICC staging system for nasopharyngeal carcinoma patients., Materials and Methods: We compare the seventh and eighth T classifications of the UICC/AJCC staging system in 382 newly diagnosed nasopharyngeal carcinoma patients without cervical lymph node metastasis who were staged with magnetic resonance imaging and treated by intensity-modulated radiotherapy. Univariate analysis was performed using the log-rank test and multivariate analyses with the Cox proportional hazards model were used to evaluate the prognostic values between adjacent stage categories. The Akaike information criterion and Harrell's concordance index were applied to compare the two systems., Results: The median follow-up time was 61.1 months. For local relapse-free survival and distant metastasis failure-free survival, the eighth editions had superior prognostic value to the seventh edition. The Akaike information criterion value was smaller and Harrell's concordance index value was larger for the eighth edition compared with the seventh edition staging system. Our research also found that the difference in overall survival, local relapse-free survival and distant metastasis failure-free survival rates between T1 and T2 patients was not significant according to the eighth edition of the UICC/AJCC staging system, indicating that the discrimination among T1-2 patients was diminished., Conclusions: Intensity-modulated radiotherapy with elective neck irradiation provides excellent local-regional control for nasopharyngeal carcinoma patients and the eighth T classification seems to be superior to the seventh T classification. Since local control has improved in the modern era, the study considered that the staging system could be further improved and simplified by downstaging the current T2 classification patients to T1 with modern treatment. Researchers are attempting to incorporate individualized prognostic factors, such as Epstein-Barr virus DNA, into nomogram.

The publication of the new WHO classification of head and neck tumours in 2017 brought major modifications. Especially, a new chapter is dedicated to the oropharynx, focusing on the description of squamous cell carcinoma induced by the virus Human Papilloma Virus (HPV), and new entities of tumors are described in nasal cavities and sinuses. In this article are presented the novelties and main changes of this new classification, as well as the updates of the diagnostic methods (immunohistochemistry, cytogenetics or molecular biology)., (Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background and Purpose: In 2017, the 8th edition of the nasopharyngeal carcinoma (NPC) staging manual published by the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) defined new rules regarding the involvement of anatomical masticatory muscles (MM). The purpose of this study is to evaluate the validity of the current T-staging system after the addition of revisions regarding MM involvement., Methods: We performed a retrospective review of 608 patients, who were newly diagnosed with NPC and treated with intensity-modulated radiotherapy (IMRT) between January 2008 and March 2010., Results: We found MM involvement in 398 NPC cases (65.4%). We observed a significant difference in overall survival (OS; 75.6% vs. 86.7%, P = .043) and in local relapse-free survival (LRFS; 81.5% vs. 88.6%, P = .048) between patients with and without MM involvement, but no difference in distant metastasis-free survival (DMFS; 80.3% vs. 85.0%, P = .147) or disease-free survival (DFS; 77.9% vs. 81.6%, P = .081). Significant differences in OS and LRFS were also found among different types of MM involvement. Compared with patients who had concurrent involvement of the lateral pterygoid muscle (LP), patients with tumors invading only the medial pterygoid muscle (MP) had a higher OS and LRFS rates, according to univariate and multivariate analysis (P < .05)., Conclusions: MM involvement is an independent prognostic factor for OS and LRFS. We conclude that the decision to down-stage MP as T2 in the 8th edition staging system is valid. However, tumors with LP involvement were more rational classified into a higher T-staging category than tumors with only-MP involvement., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: This paper is intend to observe the feasibility of surgical approach with which communicating neoplasm outside cerebral dura mater and orbital fasciae was removed by transnasal endoscopic surgery. Method: Nine patients suffered from communicating neoplasm in the area of naso-orbital-cranio complex were treated with transnasal endoscopic surgery. The size of skull base bone defect was from 1.25 cm×1.13 cm to 3.25 cm×2.69 cm. No eye enucleation was done. No reconstructions of skull base and medial wall of orbital cavity were done. Iodoform gauze was packed in paranasal sinuses fourteen days. Patients with malignant tumor were treated radiation therapy and chemical therapy after surgical treatment. The degree of resection, complications of intracranial and orbital cavities, survival condition were the focus of this study. Result: The tumor were completely removed and all operations were successfully completed by trasnasal endoscopic surgery. Only one patient was required blood transfusion due to seriously bleeding from tumor during the operation. There was no orbital, intracranial, and vascular complications. The defect of bone at skull base and lamina papyracea were automatic reconstructed. Three patients have showed recurrence of neoplasm, and two of them died during two years of following up time. Conclusion: Transnasal endoscopic surgery is a safe, reliable and effective approach to treat communicating neoplasm in the area of naso-orbital-cranio complex, of which main part of tumor exists in the sinunasal cavity., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Purpose: To analyze the clinical outcomes of nasopharyngeal carcinoma (NPC) patients with post-radiation nasopharyngeal necrosis (PRNN) and construct a new risk classification system for predicting survival of PRNN., Methods: A total of 276 patients with PRNN were consecutively enrolled. Complete magnetic resonance (MR) images of the nasopharynx and neck were available for all patients and were used to assess nasopharyngeal necrosis status. After 2010, patients with PRNN were initially treated by radical endoscopic necrectomy followed by reconstruction with nasal flap (ENNF)., Results: The 1-year and 2-year overall survival (OS) was 65.0% and 51.6%, respectively. Three variables affected survival: osteoradionecrosis, re-irradiation, and internal carotid artery (ICA) exposure, and only two variables were found to be independent prognostic factors: re-irradiation (hazard ratio [HR] 1.75, P=0.001) and internal carotid artery (ICA) exposure (hazard ratio [HR] 1.80, P=0.001). These two variables were combined to create a new risk classification system for PRNN. 131 (47.5%), 110 (39.9%), and 35 (12.7%) patients were classified into low-, intermediate- and high-risk group, with the 2-year OS rates of 64.8%, 45.1%, and 22.5%, respectively (P<0.001). ENNF was associated with a better OS in these three group patients compared with conservative management with statistical or marginal statistical significance (2-year OS low-risk group, 90.9% vs 61.1%, p=0.081; intermediate-risk group: 100% vs 37.8%, P=0.001; and high-risk group, 57.1% vs 20.8%, p=0.066)., Conclusion: The new risk classification system provides accurate estimates of prognosis. ENNF surgery may lead to better survival outcome than conservative management in PRNN patients., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The current WHO classification system for tumors of the head and neck has made few changes from the previous edition with regards to tumors of the nasopharynx. The classification system is discussed here with particular attention to nasopharyngeal carcinoma, nasopharyngeal papillary adenocarcinoma, salivary gland anlage tumor, hairy polyp, juvenile angiofibroma, and other tumors.

Cranial-nasal-orbital communicating tumors involving the anterior and middle skull base are among the most challenging to treat surgically, with high rates of incomplete resection and surgical complications. Currently, there is no recognized classification of tumors with regard to the choice of surgical approaches. From January 2004 to January 2014, we classified 32 cranial-nasal-orbital communicating tumors treated in our center into three types according to the tumor body location, scope of extension and direction of invasion: lateral (type I), central (type II) and extensive (type III). This classification considerably facilitated the choice of surgical routes and significantly influenced the surgical time and amount of hemorrhage during operation. In addition, we emphasized the use of transnasal endoscopy for large and extensive tumors, individualized treatment strategies drafted by a group of multidisciplinary collaborators, and careful reconstruction of the skull base defects. Our treatment strategies achieved good surgical outcomes, with a high ratio of total resection (87.5 %, 28/32, including 16 cases of benign tumors and 12 cases of malignant tumors) and a low percentage of surgical complications (18.8 %, 6/32). Original symptoms were alleviated in 29 patients. The average KPS score improved from 81.25 % preoperatively to 91.25 % at 3 months after surgery. No serious perioperative complications occurred. During the follow-up of 3 years on average, four patients with malignant tumors died, including three who had subtotal resections. The 3-year survival rate of patients with malignant tumors was 78.6 %, and the overall 3-year survival rate was 87.5 %. Our data indicate that the simple classification method has practical significance in guiding the choice of surgical approaches for cranial-nasal-orbital communicating tumors and may be extended to other types of skull base tumors.

Objective: Risk assessment of second head/neck and Epstein Barr Virus (EBV)-related malignancies in patients with different nasopharyngeal carcinoma (NPC) subtypes., Methods: This is a cross-sectional study. Pathology records were retrieved from PALGA (a Dutch pathology registry database) between 1995 and 2013. Second primary malignancy (SPM) data was extracted from PALGA. Odds ratios (OR) for SPM in the head/neck, and the upper/lower airways were calculated using logistic regression. Pearson X(2)-test and Fisher's exact test were used to assess the relationship between NPC (and EBV-status) with SPM. Standardized incidence rates (SIR) were calculated., Results: Histologically diagnosed NPC (keratinizing and undifferentiated and differentiated non-keratinizing subtypes) (n=1175) were identified. NPC patients have an increased risk of second head/neck malignancies (SIR 4.7 95% CI 3.3-6.5). Keratinizing NPCs have an OR of 1.947 (95% CI 1.362-2.782) for SPM, an OR of 4.026 (95% CI 2.308-7.023) for carcinomas of the upper/lower airways, an OR of 4.306 (95% CI 2.299-8.066) for head/neck malignancies, an OR of 5.289 (95% CI 2.740-10.211) for HNSCC with a SIR of 4.7 (95CI 3.3-6.5). Non-keratinizing NPCs also have an increased risk of head/neck malignancies with a SIR of 3.2 (95% CI 1.8-5.1), but less than keratinizing NPCs (p=<0.001). Positive EBV-status is not associated with (EBV-related) SPM., Conclusion: NPCs have a higher risk of SPM regardless of EBV status. SPM (especially HNSCC and malignancies of the upper aerodigestive tract) are more prevalent in keratinizing NPC compared to non-keratinizing NPC. Close clinical follow-up of NPC patients, with specific attention on SPM, is justified., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The aim of this study was to develop a prognostic classifier and subdivided the M1 stage for nasopharyngeal carcinoma patients with synchronous metastases (mNPC). A retrospective cohort of 347 mNPC patients was recruited between January 2000 and December 2010. Thirty hematological markers and 11 clinical characteristics were collected, and the association of these factors with overall survival (OS) was evaluated. Advanced machine learning schemes of a support vector machine (SVM) were used to select a subset of highly informative factors and to construct a prognostic model (mNPC-SVM). The mNPC-SVM classifier identified ten informative variables, including three clinical indexes and seven hematological markers. The median survival time for low-risk patients (M1a) as identified by the mNPC-SVM classifier was 38.0 months, and survival time was dramatically reduced to 13.8 months for high-risk patients (M1b) (P < 0.001). Multivariate adjustment using prognostic factors revealed that the mNPC-SVM classifier remained a powerful predictor of OS (M1a vs. M1b, hazard ratio, 3.45; 95% CI, 2.59 to 4.60, P < 0.001). Moreover, combination treatment of systemic chemotherapy and loco-regional radiotherapy was associated with significantly better survival outcomes than chemotherapy alone (the 5-year OS, 47.0% vs. 10.0%, P < 0.001) in the M1a subgroup but not in the M1b subgroup (12.0% vs. 3.0%, P = 0.101). These findings were validated by a separate cohort. In conclusion, the newly developed mNPC-SVM classifier led to more precise risk definitions that offer a promising subdivision of the M1 stage and individualized selection for future therapeutic regimens in mNPC patients.

Purpose: To define the role of neoadjuvant and concurrent chemotherapy in stage II nasopharyngeal carcinoma, we compared the treatment outcomes of patients treated with curative radiotherapy with or without chemotherapy., Materials and Methods: From 2004 to 2011, 138 patients with American Joint Committee on Cancer (AJCC) 2002 stage II nasopharyngeal carcinoma were treated with curative radiotherapy in 12 hospitals in South Korea. Treatment methods included radiotherapy alone in 34 patients, neoadjuvant chemotherapy followed by radiotherapy alone in seven, concurrent chemoradiotherapy in 80, and neoadjuvant chemotherapy followed by concurrent chemoradiotherapy in 17. Adjuvant chemotherapy was used in 42 patients. Total radiation dose ranged from 64 Gy to 74.2 Gy (median, 70 Gy)., Results: Median follow-up was 48 months (range, 7 to 97 months) for all patients. At the last follow-up, 13 patients had died and 32 had experienced treatment failure; locoregional failure occurred in 14, distant failure in 16, and both in two. Five-year locoregional relapse-free survival, distant metastasis-free survival, progression-free survival, and overall survival were 86.2%, 85.5%, 74.4%, and 88.2%, respectively. Multivariate analyses showed that the significant prognostic factors were concurrent chemotherapy and N stage for locoregional relapse-free survival, concurrent chemotherapy for progression-free survival, and age and N stage for overall survival. Neither neoadjuvant nor concurrent chemotherapy improved distant metastasis-free survival., Conclusion: Concurrent chemotherapy significantly improved 5-year locoregional relapse-free survival and progression-free survival in stage II nasopharyngeal carcinoma. However, neoadjuvant chemotherapy failed to improve either.

Staging of tumors is very important in treatment and surgical decision making, as well as in predicting disease recurrence and prognosis. This review focuses on the different available classifications of juvenile nasopharyngeal angiofibroma (JNA) and their impact on the evaluation, management, and prognosis of JNA. The literature was reviewed, and publications on JNA staging were examined. Our MEDLINE search of the entire English-language literature found no review article on the current available staging systems for JNA. In this article, we review the common JNA classification systems that have been published, and we discuss some of their advantages and disadvantages. The most commonly used staging systems for JNA are the Radkowski and the Andrews-Fisch staging systems. However, some newer staging systems that are based on advances in technology and surgical approaches-the Onerci, INCan, and UPMC systems-have shown promising utility, and they will probably gain popularity in the future.

Objective: To evaluate concurrent chemotherapy for T4 classification nasopharyngeal carcinoma (NPC) treated by intensity-modulated radiotherapy (IMRT)., Methods: From July 2004 to June 2011, 180 non-metastatic T4 classification NPC patients were retrospectively analyzed. Of these patients, 117 patients were treated by concurrent chemoradiotherapy (CCRT) using IMRT and 63 cases were treated by IMRT alone., Results: The median follow-up time was 58.97 months (range, 2.79-114.92) months. For all the patients, the 1, 3 and 5-year local failure-free survival (LFFS) rates were 97.7%, 89.2% and 85.9%, regional failure free survival (RFFS) rates were 98.9%, 94.4% and 94.4%, distant failure-free survival (DFFS) rates were 89.7%, 79.9% and 76.2%, and overall survival (OS) rates were 92.7%, 78.9% and 65.3%, respectively. No statistically significant difference was observed in LFFS, RFFS, DFFS and OS between the CCRT group and the IMRT alone group. No statistically significant difference was observed in acute toxicity except leukopenia (p = 0.000) during IMRT between the CCRT group and the IMRT alone group., Conclusion: IMRT alone for T4 classification NPC achieved similar treatment outcomes in terms of disease local control and overall survival as compared to concurrent chemotherapy plus IMRT. However, this is a retrospective study with a limited number of patients, such results need further investigation in a prospective randomized clinical trial.

Objective: To evaluate the long-term survival outcomes and toxicity of a larger series of patients with non-metastatic T4 classification nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT)., Materials and Methods: From March 2004 to June 2011, 335 non-metastatic T4 classification NPC patients treated by IMRT were analyzed retrospectively. Treatment induced toxicities were scored according to the Common Terminology Criteria for Adverse Events version 3.0., Results: With a median follow-up time of 53.6 months (range, 2.8-114.9 months), the 5-year local failure-free survival (LFFS), regional failure free survival (RFFS), distant failure-free survival (DFFS), and overall survival (OS) were 84.1%, 92.2%, 74.1%, and 63.0%, respectively. At their last follow-up visit, 118 patients (35.2%) had developed treatment failure. Distant metastasis was the major failure pattern after treatment. The most common toxicities were mainly in grade 1 or 2. Concurrent chemotherapy failed to improve survival rates for patients with T4 classification NPC., Conclusion: The results of T4 classification NPC treated by IMRT were excellent, and distant metastasis was the most commonly failure pattern. Treatment-related toxicities were well tolerable. The role of concurrent chemotherapy for T4 classification NPC needs to be further investigated in the era of IMRT., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

TNM system is a universally recognized cancer classification. It's based on the assessment of anatomical extent of tumor (T), nodal (N) and distant metastases (M). The first edition of TNM was published in 1968 and has since been updated several times. Relevant characteristics that affect prognosis prognosis, such as depth of invasion, tumor volume, surgical margin infiltration, and the number of involved nodes as well as the presence of extracapsular spread (such data should be determined by the pathologist and included in pTNM staging – ed. note) are not included in the TNM classification. Following a discussion on most recent classification updates we will discuss the factors, which in our opinion and in concordance with the most recent literature, deserve special consideration and influence management of oral carcinomas.

Purpose: To subclassify parapharyngeal extension in nasopharyngeal carcinoma (NPC) and investigate its prognostic value and staging categories based on magnetic resonance imaging (MRI)., Methods and Materials: Data from 1504 consecutive NPC patients treated with definitive-intent radiotherapy were analyzed retrospectively. Sites of parapharyngeal extension were defined by MRI. Overall survival (OS), local relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were calculated by the Kaplan-Meier method and compared with the log-rank test. Hazard consistency and hazard discrimination were determined by multivariate analysis with Cox proportional hazards models., Results: 1104 patients (73.4%) had parapharyngeal extension; 1.7-63.8% had involvement of various anatomic sites. The hazard ratio for death was significantly higher with extensive parapharyngeal extension (lateral pterygoid muscle of masticator space and beyond or parotid space) than with mild extension (medial pterygoid muscle of masticator space, or carotid, prestyloid, and prevertebral or retropharyngeal space). OS, LRFS, and DMFS with extensive parapharyngeal extension were similar to those in T4 disease; OS, LRFS, and DMFS with mild parapharyngeal extension were significantly higher than in those T3 disease (all P ≤ 0.015)., Conclusions: Parapharyngeal extension in NPC should be subclassified as mild or extensive, which should be regarded as stages T2 and T4 diseases, respectively.

This study aimed to investigate the association between Epstein-Barr virus (EBV)-related biomarkers and TNM classification according to the seventh edition of AJCC/UICC staging system for nasopharyngeal carcinoma. Serum VCA-IgA and EA-IgA titers and plasma EBV-DNA load were quantified at baseline in 779 patients; the rates of positivity and titers/load were compared by TNM classification. The VCA-IgA-positive rate was significantly associated with advanced N classification and stage; the EA-IgA-positive rate with advanced T and N classifications and stage; the EBV-DNA-positive rate with advanced T, N and M classifications and stage. The percentage of triple-positive patients was higher in patients with advanced TNM classification. The VCA-IgA titer and EA-IgA titer correlated positively with T classification, N classification and disease stage (1:117 in Stage I, 1:188.4 in Stage II, 1:231.12 in Stage III, 1:265.91 in Stage IV, and 1:18.34 in Stage I, 1:32.11 in Stage II, 1:34.77 in Stage III, 1:37.65 in Stage IV, respectively). EBV DNA load correlated positively with T, N and M classification and stage [median lg (EBV DNA): 0 (IQ range 0-1.85) in Stage I, 1.32 (0-3.51) in Stage II, 3.33 (0-4.30) in Stage III, 3.83 (2.85-4.71) in Stage IV]. Serum VCA-IgA/EA-IgA titers and plasma EBV DNA correlated strongly with TNM classification according to the seventh edition of the AJCC/UICC; however, plasma EBV DNA load could accurately predict metastatic disease. EBV serological biomarkers may enhance the accuracy of TNM staging and help to avoid excessive imaging examinations in routine evaluation.

Purpose: To propose a novel clinical typing classification focusing on the distinct progression patterns of nasopharyngeal carcinoma (NPC), to supplement our knowledge of the clinical-biological behavior, to provide useful knowledge for treatment planning, and to contribute to basic research in NPC., Methods: 632 consecutive patients were retrospectively reviewed and analyzed according to the novel typing system. We considered that NPC can be divided into 5 types as follows: limited (L), ascending (A), descending (D) ascending- descending (mixed) (AD), and distant metastasis types (M). The distribution of these clinical types, their association with Epstein-Barr virus (EBV) serology and prognostic value were explored., Results: 55 (8.70%), 59 (9.34%), 177 (28.01%), 321 (50.79%) and 20 (3.16%) patients were classified as Type L, A, D, AD and M, respectively. EBV (VCA)-IgA titers, EBV early antigen (EA)-IgA serum titers, and capsid antigen lg(EBV DNA) were positively associated with the clinical typing (p<0.05). The 3-year overall survival (OS) rates for Types L, A, D, AD and M were 100, 100, 95.10, 88.20 and 59.30%, respectively (p<0.001). A prognostic model was constructed based on pretreatment lg (EBV DNA) and clinical type, which were independent predictors of OS (multivariate Cox proportional model). The prognostic model stratified patients into 4 risk subgroups. The 3-year OS rates of the low, intermediate, high and extremely high risk groups were 99.5, 90.0, 85.5 and 53.2%, respectively (p<0.001). Compared with the low-risk group, the risk of death was 4.96, 8.75 and 35.9 in the intermediate, high and extremely high risk groups, respectively (p<0.001). The model also predicted OS independently of TNM classification., Conclusion: This novel clinical typing system and prognostic model can supplement TNM classification, and may help design novel treatment strategies, evaluate risk stratification and investigate the varied biological characteristics of NPC.

Objective: To analyze the dysregulated genes among the differentially expressed genes in 41 nasopharyngeal biopsy samples and identify their protective transcriptional factors., Methods: The differentially expressed gene profiles were obtained by analyzing both types I and II nasopharyngeal carcinoma (NPC&#95;I and NPC&#95;II, respectively) using EXCEL and Bioinformatics tools. The transcriptional factors were further studied only when (1) the difference in the binding sites of the differentially expressed genes between NPC&#95;I and NPC&#95;II groups was statistically significant, (2) the expressions of the transcription factors were correlated with the gene expressions in the samples, and (3) the transcription factors affected at least 40% of the expression of the related genes., Results: In NPC&#95;I samples, 80 transcription factors were found to be up-regulated, in which RUNX3, GATA3, NR3C1, NRF1, RXRA, SMAD7, TBP, and ZBTB6 were positive factors and HLF and MTF1 were negative factors, involved in the regulation of the genes in T cell receptor signaling pathway. No eligible transcription factors were found in association with down-regulated genes in NPC&#95;I compared to NPC&#95;II gene expression profiles., Conclusions: The over-expressed genes in NPC&#95;I are mainly related to immune responses, and we found 8 positive factors and 2 negative factors that regulate the genes in T cell receptor signaling pathway. The 10 transcription factors may serve as potential therapeutic targets for NPC&#95;I. We failed to identify any transcription factors associated with down-regulated genes in NPC&#95;I relative to NPC&#95;II possibly as a result of multiple factors that affect the differential gene expressions in NPC&#95;II including the transcription factors, DNA phosphorylation and modification, chromosome variation and environmental factors.

Background: The correlation between primary tumor volume and nasopharyngeal carcinoma (NPC) UICC 2002 T classification, N classification and distant metastasis after radiation therapy was discussed to provide further evidence for the inclusion of tumor volume into the TNM classification staging system., Methods: Between February 2001 and December 2008, 666 patients with NPC treated with intensity-modulated radiation therapy (IMRT) were analyzed retrospectively. Primary gross tumor volume was calculated from treatment planning computed tomography scans. The Kruskal-Wallis and Mann-Whitney tests were used for comparison of continuous variables and the chi-square test was used for categorical variables. A logistic regression model was used for multivariate analysis., Results: Median primary tumor volume of the 666 patients was 20.35 ml (range, 0.44 - 192.63 ml), and it gradually increased with T classification. Statistically significant differences in tumor volume were observed between patients with different T classifications (p < 0.001). The cervical lymph node metastasis rate was 64.7% (430/666); the differences in primary tumor volume between patients with or without lymph node metastasis were statistically significant (p < 0.001). Posttreatment distant metastasis occurred in 100 NPC patients, and the five-year distant metastasis-free survival was 84.2%. Univariate and multivariate analyses showed that N classification (p < 0.001) and tumor volume (p = 0.007) were the main factors influencing distant metastasis., Conclusion: Tumor volume was correlated with T classification, cervical lymph node mestastasis and distant metastasis after radiation therapy in nasopharyngeal carcinoma, suggesting that tumor volume should be included into the TNM staging system.

Objectives: To describe a clear and simplified classification system for juvenile nasopharyngeal angiofibroma (JNA), and to describe suitable management options., Study Design: Retrospective medical record review., Methods: The clinical and imaging materials of 51 cases of JNA diagnosed at our hospital between 1981 and 2011 were collected and studied. Based on our experiences, we prefer to divide JNAs into three types. Type I includes JNAs fundamentally localized to the nasal cavity, paranasal sinus, nasopharynx, or pterygopalatine fossa. Type II is a JNA extending into the infratemporal fossa, cheek region, or orbital cavity, with anterior and/or minimal middle cranial fossa extension but intact dura mater. Type III is a calabash-like massive tumor lobe in the middle cranial fossa. The management and prognosis for the three types of JNA were compared and evaluated., Results: Among cases of type I JNA (n=16), the entire mass was removed by the initial operation in 15 cases and by a repeat operation in 1 case. Among cases of type II JNA (n=29), the entire mass was removed by the first operation in 24 cases and by repeat operation in 5 cases. In cases of type III JNA (n=6), the huge calabash-like lobe in the middle cranial fossa could not be completely excised; 4 cases underwent radiotherapy and 2 cases were lost to follow-up., Conclusions: 1) The transnasal cavity approach with endoscopic guidance is suitable for type I JNA resection. 2) The transantral-infratemporal fossa-nasal cavity combined approach is reliable for resection of a type II JNA, which extends into the deep anterior cranial fossa and/or minimally into the middle cranial fossa, with intact dura mater. 3) The complete removal of a type III JNA is difficult, even through a combined extracranial and intracranial approach. Radiotherapy is useful for treating the residual intracranial tumor. The successful or failed experiences of 6 typical cases prove that this revised classification system is reasonable and reliable., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Conclusion: Advanced parapharyngeal space (PPS) involvement showed stronger prognostic value than PPS involvement. The classification of PPS involvement proposed by Min or Sham was the most appropriate classification for parapharyngeal extension in nasopharyngeal carcinoma (NPC). The degree of tumor extension into the PPS should be considered in future TNM staging revisions., Objectives: This study was conducted to evaluate the prognostic significance of the various classifications for PPS involvement in patients with NPC., Methods: From January to July 2000, a total of 176 patients with pathologically diagnosed NPC were prospectively enrolled in this study. The extent of PPS involvement was examined by contrast-enhanced computed tomography (CT) scan and graded according to the four previously reported classifications (Min, Sham, Xiao, and Heng)., Results: The incidence of PPS involvement was 81.8%. The 5-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and local relapse-free survival rates (LRFS) of the patients with and without PPS involvement were 68.1% and 90.2% (p = 0.010), 66.1% and 87.2% (p = 0.013), 76.7% and 93.6% (p = 0.032), and 84.9% and 93.1% (p = 0.220), respectively. Multivariate analysis showed that PPS involvement (yes vs no) was not an independent prognostic factor. However, graded PPS involvement was an independent factor affecting the prognosis of NPC. When the four classifications were included in a Cox model, it was shown that PPS involvement based on Min's classification was an independent factor for OS (p = 0.001). PPS involvement based on Sham's classification was an independent factor for PFS (p = 0.010) and DMFS (p = 0.009).

Purpose: To subclassify patients with the T4 classification nasopharyngeal carcinoma (NPC), according to the seventh edition of the American Joint Committee on Cancer staging system, using magnetic resonance imaging (MRI), and to evaluate the prognostic value of subclassification after intensity-modulated radiotherapy (IMRT)., Methods and Materials: A total of 140 patients who underwent MRI and were subsequently histologically diagnosed with nondisseminated classification T4 NPC received IMRT as their primary treatment and were included in this retrospective study. T4 patients were subclassified into two grades: T4a was defined as a primary nasopharyngeal tumor with involvement of the masticator space only; and T4b was defined as involvement of the intracranial region, cranial nerves, and/or orbit., Results: The 5-year overall survival (OS) rate and distant metastasis-free survival (DMFS) rate for T4a patients (82.5% and 87.0%, respectively), were significantly higher than for T4b patients (62.6% and 66.8%; p = 0.033 and p = 0.036, respectively). The T4a/b subclassification was an independent prognostic factor for OS (hazard ratio = 2.331, p = 0.032) and DMFS (hazard ratio = 2.602, p = 0.034), and had no significant effect on local relapse-free survival., Conclusions: Subclassification of T4 patients, as T4a or T4b, using MRI according to the site of invasion, has prognostic value for the outcomes of IMRT treatment in NPC., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: The mainstay treatment for Juvenile Nasopharyngeal Angiofibroma (JNA) is complete excision. Surgical approach should allow maximal exposure of the tumour with minimum morbidity. One such possible approach is Lefort I maxillary osteotomy., Objective: To review our experience on feasibility of Lefort I osteotomy approach to achieve the best result and to look at the outcome in our series of patients at a tertiary centre in India., Method: This prospective study involves 22 patients with JNA who have been treated by Lefort I approach between August 2006 and December 2007 at the Department of Neurosurgery, National Institute of Mental Health And Neurosciences, Bangalore, India., Results: All patients underwent primary surgical resection through Lefort I approach. No major intra-operative and post-operative complications were noted except in one patient where loss of vision in one eye due to prior pre-operative orbital involvement. The mean follow-up period was 2.8 years. To date, there has been no cases of residual tumour or recurrence that can be attributed to the procedure except in one case., Conclusion: Our experience suggests that the Lefort I osteotomy approach is a useful technique for the removal of extensive JNA which has distinct advantages over traditional approaches, providing a more direct vision, improved exposure, and cosmesis., (Copyright © 2011 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objective: To explore the effective treatment regimen for osteoradionecrosis of temporal bone., Method: Twenty-seven patients with massive osteoradionecrosis in temporal bone were included and retrospectively analyzed, in which, 15 cases received surgery and the other 12 cases adopted non-surgical treatment., Result: In the surgery group, three cases died one year postoperatively and died of massive hemorrhage due to internal carotid blowout. One case died four years after surgery without clear cause of death, and two cases were lost to follow up. Out of the nine survivors, the follow up period ranged from four months to eight years (one was followed up eight years, one was followed up over four years, four were followed up two-three years, one was followed up over one year, one was followed up nine months, and one was followed up four months, respectively). Patients classified as the type III received best outcome, and patients of type V and IV without invasion of the internal carotid artery received good surgical effects, while patients classified as the type IV with internal carotid artery invasion presented low survival rate. Two cases in the non-surgical group died of internal carotid rupture, and the other ten cases presented with repeated infection and expansion of the osteoradionecrosis lesion., Conclusion: The new classification criteria is helpful in diagnosis of location of lesions,and can serve as a guide for clinical therapy. Massive osteoradionecrosis in temporal bone responded unfavorably to conservative treatment, compared to that, surgery can effectively control the expansion of the lesion and markedly improve patient quality of life. Long-term follow up is necessary because of the slow development of osteoradionecrosis after surgery.

Nasopharyngeal carcinoma (NPC) is a human malignant tumor with a high incidence and a poor prognosis in Southern China and South-eastern Asia. In this study, we comprehensively analyzed the gene expression profiles in 24 samples of primary differentiated-type nonkeratining NPC (DNK-NPC) tissues, 24 samples of normal nasopharyngeal tissues and 4 DNK-NPC cell lines using cDNA microarray technology and bioinformatics methods. We found expression level of some genes was wildly alerted in the DNK-NPC samples. In addition, our hierarchical clustering analysis revealed 2 distinctive subtypes of gene expression patterns in DNK-NPC tissue samples. The discriminator genes were identified using a signal-to-noise (S(2)N) algorithm by permuting of the data set 10,000 times. To further characterize the clinical relevance of the tumor subtypes, we evaluated a surrogate marker, CCND2, differentially expressed between the 2 tumor subgroups by using immunohistochemistry in an independent set of 137 DNK-NPC samples. CCND2 was highly expressed in the subgroups with "aggressive" features and was associated with T classification (p = 0.006) and clinical stage (p = 0.013). Patients with high level of CCND2 expression had poorer overall survival than those with low level (p = 0.034). Our results suggest that DNK-NPC can be classified into 2 subtypes based on gene expression patterns, which can be used in determining prognosis and treatment of the tumor., (Copyright © 2010 UICC.)

Background: Adoptive immunotherapy with EBV-specific CTLs (EBV-CTL) has been used to treat EBV-associated nasopharyngeal carcinoma (NPC) but only a fraction of the patients shows noticeable clinical response., Patients and Methods: Sixty-seven newly diagnosed NPC patients from 2005 to 2007 and 21 healthy donors were collected. Immunological parameters and immune function of PBMCs and EBV-CTL were analyzed by flow cytometer analysis (FACS) and ⁵¹Cr releasing experiment; Molecular characteristics on NPC tumor cells were investigated by immunochemical staining and statistic analysis., Results: NPC patients can be classified into two groups based on the percentage of CD3+ T cells in peripheral blood before accepted any treatment, (>52.6%, mean-2SE from healthy controls, NPC Group 1; <52.6%, NPC Group 2). The patients in Group 2 showed a significant decrease of CD3+CD8+ T-cells, CD3+CD4+ T-cells and CD3+CD45RO+ memory T cells, and increase of CD3⁻CD16+ NK cells compared to Group 1 patients and healthy controls (P<0.001). EBV-specific T cell responses, were weaker in this group of patients and their tumor cells expressed lower levels of the EBV encoded latent membrane protein (LMP)-1 and HLA class II protein compared with the patients of NPC Group 1 (P<0.05)., Conclusion: These findings demonstrate that NPC patients could be distinguished on the basis of their immune status which will affect the efficacy of EBV-CTL immunotherapy.

This article reviews all related research and reports on nasopharyngeal cancer (NPC) histopathological classifications worldwide. Despite continuous advance of Chinese and international NPC histopathological classification research, it was difficult to unify previous with current China classifications, and the China with World Health Organization (WHO) classifications. For example, non-keratinizing and undifferentiated carcinoma of the WHO NPC classification does not coincide with poorly-differentiated squamous cell carcinoma of the previous China classification. In addition, the incidence rates of different NPC pathological types show obvious regional discrepancies. It suggested that for facilitating Chinese and international NPC research and exchange, NPC histopathological classifications worldwide should be effectively unified.

Background: Nasopharyngeal carcinoma is an uncommon tumour in Nigeria but the burden of the disease in terms of morbidity and mortality is very high., Aim: The aim of the study was to document the clinic-pathological characteristics of nasopharyngeal carcinoma in Ilorin, North central Nigeria., Materials and Methods: This was a retrospective review of all patients seen in ENT department, University of Ilorin Teaching Hospital with the diagnosis of nasopharyngeal carcinoma between January 1 st 1999 and December 31st,2008. The patient's biodata, clinical presentation and histopathological findings are presented. The histopathological diagnosis was in accordance with the 1991 WHO classification., Results: A total of 30 patients with histologically confirmed nasopharyngeal carcinoma seen during the study period accounted for 2% of the total cancers recorded in Ilorin cancer registry. There were 20 males and 10 females with a mean age of 48.7 ± 15.9 years. The commonest presenting complaint was cervical lymphadenopathy in 96.7% of patients followed by epistaxis (66.7%) and hearing loss (66.7%). Identifiable risk factors included regular intake of ungutted salted smoked fish (76.7%) and tobacco use (23.3%) with some having both risk factors. Histologically, undifferentiated carcinoma was the commonest (70%) followed by well-differentiated keratinizing squamous cell carcinoma (20%) and differentiated nonkeratinizing squamous cell carcinoma (10%)., Conclusion: Undifferentiated carcinoma was the commonest type of nasopharyngeal carcinoma reported from this study especially among males in the 4th and 5th decades of life. Identifiable risk factors included consumption of ungutted salted smoked fish with tobaccon usage. diagnosis with effective referral system and easy access to radiotherapy would improve the survival outcome in patients with the disease.

Background and Objective: Traditional Chinese medicine (TCM) is a well established and time-honored practice in China, employing syndrome differentiation as a basis for the treatment of disease. According to different TCM syndrome typing findings, combining modern medical methods with TCM approaches can improve the quality of life and comprehensive effect on patients with nasopharyngeal carcinoma (NPC). This study investigated the relationship between TCM syndrome typing and imaging characterization to radiosensitivity as to provide objective evidence for the integration of Chinese and modern medical approaches in the treatment of NPC., Methods: Prior to treatment, TCM syndrome typing, computed tomography (CT) and magnetic resonance imaging (MRI) were performed on 147 patients pathologically classified with NPC. The status of tumor remission was radiologically evaluated at accumulated doses of 20 Gy, 40 Gy and 60 Gy, and at 3 months after completion of radiotherapy. Statistical results were analyzed by the Friedman and K-W test procedures., Results: Prior to treatment, TCM syndrome typing of NPC included Lung Heat, Blood Stasis, Phlegm Congealment and Blood Stasis-Phlegm Congealment. Lung Heat typing accounted for the highest proportion at 34.7% (51/147), followed by Phlegm Congealment at 32.7% (48/147), Blood Stasis at 17.0% (25/147) and Blood Stasis-Phlegm Congealment at 15.7% (23/147). Radiological imaging demonstrated a higher incidence of cervical lymph node metastases in Phlegm Congealment and Blood Stasis-Phlegm Congealment types (P<0.05), while Blood Stasis and Blood Stasis-Phlegm Congealment types were more prone to skull base invasion (P<0.05). Residual tumor size was larger in Blood Stasis and Blood Stasis-Phlegm Congealment types than in Lung Heat and Phlegm Congealment types after 3 months of treatment (P<0.05)., Conclusions: Different radiological manifestations were observed in TCM syndrome typed NPC patients, with lesser radiosensitivity demonstrated in the Blood Stasis and the Blood Stasis-Phlegm Congealment types relative to the Lung Heat and Phlegm Congealment types.

Objectives: To investigate the clinical manifestations and treatment outcomes of non-metastatic T4N0 nasopharyngeal cancer patients, and to compare them with other stage IVA subgroups of patients., Patients and Methods: A retrospective analysis of 775 non-metastatic nasopharyngeal cancer patients, treated in four radiotherapy centers between 1990 and 2005, was undertaken. Among 197 stage IVA patients, 90 (11.6%) patients were staged as T4N0, 32 (4.1%) as T4N1, and 75 (9.7%) as T4N2. T4N0 patients constituted 40.8% of all T4 cases (median age 53 years; range 15 to 76 years). Cranial nerve involvement was detected in 59 (65.5%) of these cases., Results: The median follow-up period was 38 months. There were only nine (10%) patients younger than 30 years of age with T4N0 tumors, for patients with diseases other than T4N0, 27.1% of the patients were under 30. Survival rates for five-year loco-regional progression free survival, distant failure free survival, and disease specific survival were 65.9%, 94%, and 71.4%, respectively. Distant failure free survival of T4N0 patients was more probable than for stage T4N1 (p=0.06) and T4N2 (p=0.008) patients., Conclusion: Non-metastatic T4N0 tumors have some distinct features, including a unimodal age distribution and a better distant failure free survival than the other subgroups of stage IVA. Therefore, it may be better to include T4N0 patients in stage III instead of stage IVA.

Objectives: Nasopharyngeal carcinoma (NPC) is a rare cancer in the U.S. that has a well-established association with Epstein-Barr virus(EBV) for WHO types II/III but less so for WHO type I. Given the rise in oropharyngeal tumors positive for high risk human papillomavirus (HPV) and the unique biology of WHO type INPC, we chose to examine the relationship between HPV and WHO type I NPC., Study Design: Retrospective case comparison study., Methods: A search of a large multidisciplinary cancer center tumor registry identified 183 patients seen from January 1999 to December 2008 with incident NPC and no history of prior cancer. Available paraffin embedded tumor specimens (N=30) were analyzed for HPV status by in situ hybridization (ISH) and polymerase chain reaction (PCR) for HPV 16 and 18, EBV status by ISH, and p16 expression by immunohistochemistry. Demographic parameters, including race, smoking, and alcohol exposure were obtained from the medical records., Results: Patients with incident WHO-I NPC (N=18) tended to be smokers (66%) and only 17% were Asian, while for patients with incident WHO-II/III NPC (N=165), 44% were smokers and 24% were Asian. For WHO-I NPC patients with available paraffin blocks (N=8), 5 of 6 were HPV 16+ by PCR and 4 of 8 had HPV identified by ISH, while only 2 of 8 were EBV+. Of patients with WHO II/III NPC and available archival tissue (N=22), 60% were EBV+ and only one was HPV positive by ISH., Conclusions: These results suggest that WHO type I NPC may be associated with oncogenic HPV, though larger studies are needed to verify these findings.

Background: Retropharyngeal lymph node (RLN) metastasis was not included in the current American Joint Committee on Cancer (AJCC) staging system (6th edition) for nasopharyngeal carcinoma (NPC). The object of the current study was to investigate the prognostic value and staging categories of RLN metastasis in NPC detected by magnetic resonance imaging (MRI)., Methods: All 924 consecutive patients with newly diagnosed NPC were examined with MRI before treatment with definitive intent radiotherapy., Results: The incidence of RLN metastasis was 73.5%. On multivariate analysis, RLN metastasis was found to be an independent prognostic factor for distant metastasis-free survival (DMFS) in all patients (P = .040). In patients with N0 disease, significant differences were observed between patients with and those without RLN metastasis after adjusting for T classification (P = .046). With regard to laterality, no significant differences were observed in DMFS between patients with unilateral and bilateral RLN metastasis in N0 disease (P = .734). No significant difference in the hazards ratios for either DMFS or disease-free survival (DFS) was found between patients with N0 disease with RLN metastasis and patients with N1 disease (P = .092 and P = .149, respectively). When RLN was classified as N1 disease, there was a better segregation of different N classifications in terms of DFS and DMFS curves, whereas the difference in hazards ratios for N0 and N1 disease was more obvious in DMFS (from 0.461 vs 0.785 to 0.317 vs 0.690)., Conclusions: The results of the current MRI-based study demonstrate that RLN metastasis affects the DMFS rates of NPC. The authors propose that RLN metastasis be classified as N1 disease, regardless of its laterality.

Conclusions: Advanced parapharyngeal tumor involvement in nasopharyngeal carcinoma (NPC) had significant predictive value associated with poorer treatment outcome. Further subclassification of parapharyngeal invasion may be considered in the TNM staging system., Objectives: We conducted a retrospective study to elucidate the effect of parapharyngeal extension on treatment outcomes in patients with NPC who were treated with radiotherapy or concurrent chemoradiotherapy (CCRT)., Patients and Methods: A total of 99 patients with newly diagnosed NPC were enrolled in this study. The parapharyngeal space invasion examined by CT scan was identified and graded according to Sham and Choy's classification. Potentially significant parameters were analyzed by both univariate and multivariate methods using SPSS software., Results: The overall survival, recurrence-free survival, locoregional control survival and distant metastasis-free survival rates were affected by the presence of parapharyngeal space involvement (p<0.0001, p<0.0001, p<0.0001, p=0.002, respectively). In multivariate analysis accounting for all previously known prognostic factors, parapharyngeal invasion was associated with increased risk for any recurrence, locoregional recurrence, distant metastasis, and overall survival. After adjusting with TNM classification, parapharyngeal invasion was still an independent prognostic factor in NPC.

Background & Objective: Upward (local growth and invasion of the base of skull), downward (distant metastasis) and mixed progressing types of nasopharygeal carcinoma (NPC) have been observed when the disease progress to middle-late stage. The upward and downward progressing types are evidently different in clinical symptom, therapy strategy and prognosis. Identification of the molecular differences between them is very important for molecular classification, prognostic prediction and research on neoplasia and development of NPC. This study was to discover the genes differentially expressed in upward and downward progressing types of NPC., Methods: An oligo gene chip containing 21 300 genes was used to detect the genes differentially expressed between upward and downward progressing types of NPC. One of the differentially expressed genes detected was analyzed by reverse transcription-polymerase chain reaction (RT-PCR)., Results: Seventeen genes were differentially expressed between upward and downward progressing types of NPC. The expression of SELB, Clorf29, GLE1L and FLJ20989 genes were up-regulated and the expression of 1D12A, ASPN, DCN, PRO2219, LRDD, DIO2, ULBP2, PRO3073, IGVH3, IGVH4, IGLJ3, PRO0943 and AK057247 genes were down-regulated in the upward progressing type as compared with those in the downward progressing type. The difference of gene expression was ranged from 2.30 to 4.23 folds. The high expression rate of DIO2 gene was significantly higher in downward progressing type than in upward progressing type (90.0% vs. 33.3%, P = 0.020)., Conclusions: The gene expression patterns are significantly different between upward and downward progressing types of NPC. The expression of DIO2 gene is higher in the downward progressing type than in upward progressing type, which may be closely related to the metastasis potential of NPC.

Recent findings show that tumor volume is a significant prognostic factor for the treatment of nasopharyngeal carcinoma (NPC). The inclusion of tumor volume as an additional prognostic factor in the UICC TNM classification system was suggested; however, how tumor volume could possibly be incorporated is still unexplored. In this paper, we report a quantitative analysis on the relationship between NPC tumor volume and T-classification, using the data from 206 NPC patients. By T-classification and semi-automatic tumor volume measurement, the difference in tumor volumes among the various TNM T-classification groups was examined. In addition, a statistics-based analysis scheme, which used the T-classification as the "gold standard", was proposed to classify NPC tumors into volume-based groups to explore the possible links. The results show that NPC tumor volume has positive correlation with advancing T-classification groups and significant difference existed in the distribution of T-classification among various volume-based groups (P < 0.001). By the proposed statistical scheme, tumor volume could be included as an additional prognostic factor in the TNM framework, following validation studies.

Nonkeratinizing nasopharyngeal carcinoma (NPC) is 100% associated with Epstein-Barr Virus (EBV) and divided into two subtypes (WHO types II and III) based on histology. We tested whether these subtypes can be distinguished at the molecular genetic level using an algorithm that analyzes sets of related genes (gene set enrichment analysis). We found that a class of IFN-stimulated genes (ISG), frequently associated with the antiviral response, was significantly activated in type III versus type II NPC. Consistent with this, replication of the endogenous EBV was suppressed in type III. A strong association was also seen with a subset of ISGs previously identified in systemic lupus erythematosus, another disease in which 'normal' EBV biology is deregulated, suggesting that this pattern of ISG expression may be linked to the increased EBV activity in both diseases. In contrast, unsupervised hierarchical clustering of the complete expression profiles failed to distinguish the two subsets. These results suggest that type II and III NPC have not originated from obviously distinct epithelial precursors; rather, the histologic differences may be a consequence of a differential antiviral response, involving IFNs, to chronic EBV infection.

The overall decline in incidence rate of nasopharyngeal carcinoma in Hong Kong during 1988-2002 was limited primarily to a decrease in keratinising carcinoma, which could be explained by the decline in cigarette smoking. Genetic and Epstein-Barr virus interactions may explain the relatively stable incidence rate of non-keratinising carcinoma.

Background: Diagnosis of nasopharyngeal carcinoma (NPC) at an early disease stage is important for successful treatment and improving the outcome of patients. The use of serum protein profiles and a classification tree algorithm were explored to distinguish NPC from noncancer., Methods: Serum samples were applied to metal affinity protein chips to generate mass spectra by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Protein peak identification and clustering were performed using the Biomarker Wizard software. Proteomic spectra of serum samples from 50 NPC patients and 54 noncancer controls were used as a training set and a classification tree with 6 distinct protein masses was generated by using Biomarker Pattern software. The validity of the classification tree was then challenged with a blind test set including another 20 NPC patients and 25 noncancer controls., Results: The software identified an average of 93 mass peaks/spectrum and 6 of the identified peaks were used to construct the classification tree. The classification tree correctly determined 83% (123 of 149) of the test samples with 83% (58 of 70) of the NPC samples and 82% (65 of 79) of the noncancer samples. In a combination of the serum protein profiles with Epstein-Barr (EBV) nuclear antigen 1 (EBNA1 IgA) test, the diagnostic sensitivity and specificity were increased to 99% and 96%, respectively., Conclusions: The results suggest that SELDI-TOF-MS serum protein profiles could discriminate NPC from noncancer. The combination of serum protein profiles with an EBV antibody serology test could further improve the accuracy of NPC screening., (Copyright 2006 American Cancer Society.)

Patients with metastatic nasopharyngeal carcinoma have variable survival outcomes. We previously designed a scoring system to better prognosticate these patients. Here, we report results on validation of this new prognostic index score in a separate cohort of patients. Clinical features and laboratory parameters were examined in 172 patients with univariate and multivariate analyses and a numerical score was derived for each independent prognostic variable. Significant independent prognostic variables and their scores assigned included poor performance status (score 5), haemoglobin < 12 g dl(-1) (score 4) and disease-free interval (DFI) (DFI < or = 6 months (score 10) or metastases at initial diagnosis (score 1)). Maximum score was 19 and patients stratified into three prognostic groups: good, 0-3; intermediate, 4-8; poor, > or = 9. When applied to a separate cohort of 120 patients, 59 patients were good, 43 intermediate and 18 poor prognosis, with median survivals of 19.6 (95% CI 16.1, 23.1), 14.3 (95% CI 12.3, 16.2) and 7.9 (95% CI 6.6, 9.2) months, respectively. (logrank test: P = 0.003). We have validated a new prognostic score with factors readily available in the clinics. This simple score will prove useful as a method to prognosticate and stratify patients as well as to promote consistent reporting among clinical trials.

Malignant tumors of nasopharyngeal epithelium differ clinically depending on the course of disease and applied therapy. They are presented in regard to the sex, age, smoking habits, alcohol usage and nutrition factors. Various studies already showed various etiological-causal links with Epstein-Barr virus (EBV). This leads to diversity of various morphological and histological types of diseases belonging to various classifications. In this work we presented 60 diagnosed and treated cases with malignant tumor of nasopharyngeal epithelium in the Institute for Otorynolaringology and maxillofacial surgery of Clinical Center of Serbia. All of them were pato-histologicaly examined and 24 of them received serological examination in regard to the concept of association between malignant epithelial tumour and EBV. An important correlation between histopathology and serology was found. Finally, the terminology used by WHO classification is not optimal for further histological determination of nasopharyngeal malignancy; therefore we recommend the French classification of C. Micheaua.

Background: Only two reports on nasopharyngeal cancer (NPC) are available from this large centre and both covered the years 1961--1966 and 1966--1980., Objective: This study describes the update of nasopharyngeal cancer at the Ibadan Cancer Registry from 1981 to 2000., Method: This is a retrospective review of all histologically confirmed cases of nasopharyngeal cancer accumulated in the Ibadan Cancer Registry from 1981--2000., Results: Two hundred and twenty three cases were analysed consisting of 156 (70%) males and 67 (30%) females with a male: female of 2.3:1. There is a steady increase in the incidence of nasopharyngeal cancer over the last two decades. Overall, the mean age was 41.1years (age range 10 to 81 years). The females had a mean age of 36.1years (age range 11 to 80 years) and males 43.2 years (age range 10 to 81 years). The peak age group of incidence for the females was 20-29 and 50-59 for the males with an almost equal incidence in the preceding three (3) decades. The ratio of Regaud to Schmincke type cancer reversed with increasing age amongst the females with the Schmincke type more common in the first decade but this was not reproduced in the males., Conclusion: There is a steady increase in the incidence of nasopharyngeal cancer over the last two decades. The two main histological types showed differential variation between the sexes suggesting a possible biological effect in the manifestation of this disease.

An algorithm based on support vector machines (SVM), the most recent advance in pattern recognition, is presented for use in classifying light-induced autofluorescence collected from cancerous and normal tissues. The in vivo autofluorescence spectra used for development and evaluation of SVM diagnostic algorithms were measured from 85 nasopharyngeal carcinoma (NPC) lesions and 131 normal tissue sites from 59 subjects during routine nasal endoscopy. Leave-one-out cross-validation was used to evaluate the performance of the algorithms. An overall diagnostic accuracy of 96%, a sensitivity of 94%, and a specificity of 97% for discriminating nasopharyngeal carcinomas from normal tissues were achieved using a linear SVM algorithm. A diagnostic accuracy of 98%, a sensitivity of 95%, and a specificity of 99% for detecting NPC were achieved with a nonlinear SVM algorithm. In a comparison with previously developed algorithms using the same dataset and the principal component analysis (PCA) technique, the SVM algorithms produced better diagnostic accuracy in all instances. In addition, we investigated a method combining PCA and SVM techniques for reducing the complexity of the SVM algorithms., ((c) 2004 Society of Photo-Optical Instrumentation Engineers.)