Classification Of Nasopharyngeal Carcinoma Research Articles

Identification of novel molecular subtypes to improve the classification framework of nasopharyngeal carcinoma

BackgroundNasopharyngeal carcinoma (NPC) treatment is largely based on a ‘one-drug-fits-all’ strategy in patients with similar pathological characteristics. However, given its biological heterogeneity, patients at the same clinical stage or similar therapies exhibit significant clinical differences. Thus, novel molecular subgroups based on these characteristics may better therapeutic outcomes.MethodsHerein, 192 treatment-naïve NPC samples with corresponding clinicopathological information were obtained from Fujian Cancer Hospital between January 2015 and January 2018. The gene expression profiles of the samples were obtained by RNA sequencing. Molecular subtypes were identified by consensus clustering. External NPC cohorts were used as the validation sets.ResultsPatients with NPC were classified into immune, metabolic, and proliferative molecular subtypes with distinct clinical features. Additionally, this classification was repeatable and predictable as validated by the external NPC cohorts. Metabolomics has shown that arachidonic acid metabolites were associated with NPC malignancy. We also identified several key genes in each subtype using a weighted correlation network analysis. Furthermore, a prognostic risk model based on these key genes was developed and was significantly associated with disease-free survival (hazard ratio, 1.11; 95% CI, 1.07–1.16; P < 0.0001), which was further validated by an external NPC cohort (hazard ratio, 7.71; 95% CI, 1.39–42.73; P < 0.0001). Moreover, the 1-, 3-, and 5-year areas under the curve were 0.84 (95% CI, 0.74–0.94), 0.81 (95% CI, 0.73–0.89), and 0.82 (95% CI, 0.73–0.90), respectively, demonstrating a high predictive value.ConclusionsOverall, we defined a novel classification of nasopharyngeal carcinoma (immune, metabolism, and proliferation subtypes). Among these subtypes, metabolism and proliferation subtypes were associated with advanced stage and poor prognosis of NPC patients, whereas the immune subtype was linked to early stage and favorable prognosis.

A new prognostic histopathologic classification of nasopharyngeal carcinoma.

BackgroundThe current World Health Organization (WHO) classification of nasopharyngeal carcinoma (NPC) conveys little prognostic information. This study aimed to propose an NPC histopathologic classification that can potentially be used to predict prognosis and treatment response.MethodsWe initially developed a histopathologic classification based on the morphologic traits and cell differentiation of tumors of 2716 NPC patients who were identified at Sun Yat-sen University Cancer Center (SYSUCC) (training cohort). Then, the proposed classification was applied to 1702 patients (retrospective validation cohort) from hospitals outside SYSUCC and 1613 patients (prospective validation cohort) from SYSUCC. The efficacy of radiochemotherapy and radiotherapy modalities was compared between the proposed subtypes. We used Cox proportional hazards models to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for overall survival (OS).ResultsThe 5-year OS rates for all NPC patients who were diagnosed with epithelial carcinoma (EC; 3708 patients), mixed sarcomatoid-epithelial carcinoma (MSEC; 1247 patients), sarcomatoid carcinoma (SC; 823 patients), and squamous cell carcinoma (SCC; 253 patients) were 79.4%, 70.5%, 59.6%, and 42.6%, respectively (P < 0.001). In multivariate models, patients with MSEC had a shorter OS than patients with EC (HR = 1.44, 95% CI = 1.27–1.62), SC (HR = 2.00, 95% CI = 1.76–2.28), or SCC (HR = 4.23, 95% CI = 3.34–5.38). Radiochemotherapy significantly improved survival compared with radiotherapy alone for patients with EC (HR = 0.67, 95% CI = 0.56–0.80), MSEC (HR = 0.58, 95% CI = 0.49–0.75), and possibly for those with SCC (HR = 0.63; 95% CI = 0.40–0.98), but not for patients with SC (HR = 0.97, 95% CI = 0.74–1.28).ConclusionsThe proposed classification offers more information for the prediction of NPC prognosis compared with the WHO classification and might be a valuable tool to guide treatment decisions for subtypes that are associated with a poor prognosis.

Development and validation of a staging system for HPV-related oropharyngeal cancer by the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S): a multicentre cohort study

Human papillomavirus-related (HPV+) oropharyngeal cancer is a rapidly emerging disease with generally good prognosis. Many prognostic algorithms for oropharyngeal cancer incorporate HPV status as a stratification factor, rather than recognising the uniqueness of HPV+ disease. The International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S) aimed to develop a TNM classification specific to HPV+ oropharyngeal cancer. The ICON-S study included patients with non-metastatic oropharyngeal cancer from seven cancer centres located across Europe and North America; one centre comprised the training cohort and six formed the validation cohorts. We ascertained patients' HPV status with p16 staining or in-situ hybridisation. We compared overall survival at 5 years between training and validation cohorts according to 7th edition TNM classifications and HPV status. We used recursive partitioning analysis (RPA) and adjusted hazard ratio (AHR) modelling methods to derive new staging classifications for HPV+ oropharyngeal cancer. Recent hypotheses concerning the effect of lower neck lymph nodes and number of lymph nodes were also investigated in an exploratory training cohort to assess relevance within the ICON-S classification. Of 1907 patients with HPV+ oropharyngeal cancer, 661 (35%) were recruited at the training centre and 1246 (65%) were enrolled at the validation centres. 5-year overall survival was similar for 7th edition TNM stage I, II, III, and IVA (respectively; 88% [95% CI 74-100]; 82% [71-95]; 84% [79-89]; and 81% [79-83]; global p=0·25) but was lower for stage IVB (60% [53-68]; p<0·0001). 5-year overall survival did not differ among N0 (80% [95% CI 73-87]), N1-N2a (87% [83-90]), and N2b (83% [80-86]) subsets, but was significantly lower for those with N3 disease (59% [51-69]; p<0·0001). Stage classifications derived by RPA and AHR models were ranked according to survival performance, and AHR-New was ranked first, followed by AHR-Orig, RPA, and 7th edition TNM. AHR-New was selected as the proposed ICON-S stage classification. Because 5-year overall survival was similar for patients classed as T4a and T4b, T4 is no longer subdivided in the re-termed ICON-S T categories. Since 5-year overall survival was similar among N1, N2a, and N2b, we re-termed the 7th edition N categories as follows: ICON-S N0, no lymph nodes; ICON-S N1, ipsilateral lymph nodes; ICON-S N2, bilateral or contralateral lymph nodes; and ICON-S N3, lymph nodes larger than 6 cm. This resembles the N classification of nasopharyngeal carcinoma but without a lower neck lymph node variable. The proposed ICON-S classification is stage I (T1-T2N0-N1), stage II (T1-T2N2 or T3N0-N2), and stage III (T4 or N3). Metastatic disease (M1) is classified as ICON-S stage IV. In an exploratory training cohort (n=702), lower lymph node neck involvement had a significant effect on survival in ICON-S stage III but had no effect in ICON-S stage I and II and was not significant as an independent factor. Overall survival was similar for patients with fewer than five lymph nodes and those with five or more lymph nodes, within all ICON-S stages. Our proposed ICON-S staging system for HPV+ oropharyngeal cancer is suitable for the 8th edition of the Union for International Cancer Control/American Joint Committee on Cancer TNM classification. Future work is needed to ascertain whether T and N categories should be further refined and whether non-anatomical factors might augment the full classification. None.

Nasopharyngeal carcinoma, an analysis of histological subtypes and their association with EBV, a study of 100 cases of Pakistani population

Introduction: Nasopharyngeal carcinoma is the most common nasopharyngeal malignancy. In recent decades, it has attracted world-wide attention because of complex interactions of genetic, viral, environmental and dietary risk factors, with an etiological association with the malignancy. Nasopharyngeal carcinoma (NPC) is a rare cancer throughout the world, with the exception of Southeast Asia, Southern China and North Africa. The Epstein-Barr virus (EBV) was discovered 38 years ago by electron microscopy of cells cultured from Burkitt’s lymphoma tissue by Epstein, Achong, and Barr. EBV infection is a common infection in Pakistan due to poor socioeconomic conditions but its association with Nasopharyngeal Carcinoma is yet to be firmly established in Pakistani population and there is scarce local data available. Methods: A total of 100 consecutive cases of Nasopharyngeal Carcinoma, over a period of three years (2009-2011) were retrieved and reviewed from the pathology files at the Section of Histopathology, Aga khan University Hospital. Morphological sub classification of Nasopharyngeal carcinoma was done according to WHO. For the detection of EBV, LMP1 immunostain was used. Results: Among total of 100 cases, the male to female ratio was 3:1, with an age range of 13-78 yrs and an average age of 42 yrs. Similar to other regions of world, Non-keratinizing Carcinoma (92%) is the commonest sub-type with a distinct bimodal age distribution, followed by Keratinizing Squamous Cell Carcinoma (8%) but there were no cases of Basaloid Squamous Cell Cacinoma. EBV-LMP 1 staining was demonstrated in 75/92 cases (81%), while all cases of Keratinizing Squamous Cell Carcinoma were negative for EBV-LMP 1 staining. Conclusion: Prognostic impact of LMP-1 on Nasopharyngeal carcinoma is still unclear and also there are controversial studies regarding the prognostic effect of EBV on chemotherapy and radiotherapy, it is paramount that EBV positive and EBV negative patients be investigated for response to therapy to establish the importance of EBV association in nasopharyngeal carcinoma patients. The association with EBV is also very important because with ongoing research in the etiological basis of the tumors (associated with EBV) patients may also benefit from emerging immunotherapy used in these tumors. DOI: http://dx.doi.org/10.3126/ajms.v5i4.9592 Asian Journal of Medical Sciences 2014 Vol.5(4); 16-20

Review of the histological classification of nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is a tumor arising from the epithelial cells that cover the surface and line the nasopharynx. Regardless of geographic distribution, racial background and enigmatic etiology of NPC, A major problem has been the lack of a universally accepted system for histopathologic classification of NPC. To alleviate this problem, the World Health Organization (WHO) advocated a classification using the diagnostic designation of keratinizing squamous cell carcinoma and nonkeratinizing carcinoma since 1978, although this classification system has not been accepted worldwide. During the past 50 years, several NPC histological classifications have been published and adopted in clinic. As a high-incidence area of NPC, until new classification published in 2001, Chinese NPC classifications can not be very well to link with the international classifications of NPC, which makes great misunderstandings in international communication. Actually there is still a long way to go to reach the consensus on histological classification of NPC. This review will retrospectively link the difference of these systems.

Pitfalls in the Staging of Cancer of Nasopharyngeal Carcinoma

Although nasopharyngeal carcinoma (NPC) is the most common primary malignancy of the nasopharynx, it is an uncommon malignancy in much of the Western world. Over the last several years, there have been important changes in the terminology used for histologic classification of NPC and important changes to the American Joint Committee on Cancer TNM staging of NPC. Accurate imaging assessment is critical for diagnose, to stage and plan radiation treatment, and for ongoing follow-up and surveillance. This article emphasizes important nasopharyngeal anatomy landmarks and the imaging appearances and pitfalls of NPC, its patterns of spread, and posttreatment appearances.

Automatic detection and classification of nasopharyngeal carcinoma on PET/CT with support vector machine

Positron emission tomography/computed tomography (PET/CT) has established values for imaging of head and neck cancers, including the nasopharyngeal carcinoma (NPC), utilizing both morphologic and functional information. In this paper, we introduce a computerized system for automatic detection of NPC, targeting both the primary tumor and regional nodal metastasis, on PET/CT. Candidate lesions were extracted based on the features from both PET and CT images and a priori knowledge of anatomical features and subsequently classified by a support vector machine algorithm. The system was validated with 25 PET/CT examinations from 10 patients suffering from NPC. Lesions manually contoured by experienced radiologists were used as the gold standard. Results showed that the system successfully identified all 53 hypermetabolic lesions larger than 1cm in size and excluded normal physiological uptake in brown fat, muscles, bone marrow, brain, and salivary glands. The system combined both imaging features and a priori clinical knowledge for classification between pathological and physiological uptake. Preliminary results showed that the system was highly accurate and promising for adoption in clinical use.

Establishment of VCA and EBNA1 IgA‐based combination by enzyme‐linked immunosorbent assay as preferred screening method for nasopharyngeal carcinoma: a two‐stage design with a preliminary performance study and a mass screening in southern China

A two-stage study was conducted in southern China to determine and validate an optimal combination of Epstein-Barr virus (EBV)-related seromarkers for nasopharyngeal carcinoma (NPC) screening. In the first stage, six seromarkers [VCA-IgA, EA-IgA, Epstein-Barr virus nuclear antigen 1 (EBNA1-IgA), EBNA1-IgG, Zta-IgA and Rta-IgG] were detected by enzyme-linked immunosorbent assay (ELISA) and two traditional NPC screening seromarkers (VCA-IgA and EA-IgA) were detected by immunofluorescence assay (IFA) in serum samples from 191 NPC patients and 337 controls. An optimal combination of seromarkers for NPC diagnosis was selected using logistic regression models. Results showed that the diagnostic performances of VCA-IgA and EA-IgA tested by ELISA were superior to the performances of the same seromarkers by IFA. VCA-IgA combined with EBNA1-IgA by ELISA was identified as the optimal combination, with an area under the receiver operating characteristic (ROC) curve (AUC) up to 0.97, a sensitivity of 95.3% and a specificity of 94.1% for classification of NPCs vs. controls. In the second stage, 5,481 participants aged 30-59 years and without clinical evidence of NPC were recruited into a population-based NPC screening program from May 2008 to February 2009 in Sihui City, China. Their sera were tested simultaneously by both the new and the traditional screening schemes and eight early stage NPC patients were subsequently histopathologically confirmed. The traditional and the new screening schemes had comparable specificity (estimated as 98.5%), but the sensitivity of the new scheme (75.0%) was significantly higher than that of the traditional one (25.0%). The combination of VCA-IgA and EBNA1-IgA by ELISA outperforms the traditional NPC screening scheme and could become the preferred serodiagnostic strategy for NPC screening in high-incidence areas.

Raman spectral statistical classification of nasopharyngeal carcinoma and nasopharyngeal normal cell lines based on support vector classification

Raman spectroscopy (RS) has been used in the discrimination of normal and tumor cells for years. It is very important to validate an existing classification model using different algorithms. In this work, two algorithms of support vector classification (SVC) are utilized to validate our previous work about a LDA classification model of nasopharyngeal carcinoma (NPC) cell lines C666-1, CNE2 and nasopharyngeal normal cell line NP69. All of these two SVC algorithms use the same data set as the previous LDA model and, achieve great sensitivity and specificity. The final results show that our previous LDA classification model could be supported by different SVC algorithms and this demonstrates our classification model is reliable and may be helpful to the realization of RS to be one of diagnostic techniques of NPC.

Prevertebral muscle involvement in nasopharyngeal carcinoma

The purpose of this study is to evaluate the prevalence and prognostic significance of prevertebral muscle involvement in patients with nasopharyngeal carcinoma (NPC). Between July 1990 and December 2001, 521 newly diagnosed patients with NPC treated at Koo Foundation Sun Yat-Sen Cancer Center (KF-SYSCC) were examined with magnetic resonance imaging (MRI) for evidence of prevertebral muscle involvement before treatment. Patients were staged according to the 1997 American Joint Committee on Cancer staging classification of NPC based on the physical exams and MRI findings. All patients received radiotherapy with or without chemotherapy. The association between clinical prevertebral muscle involvement and posttreatment outcomes (overall survival, locoregional recurrence, and distant metastasis) were evaluated using Cox regression model to adjust for other prognostic factors. Of 521 patients treated at KF-SYSCC, 181 (35%) patients were found to have prevertebral muscle involvement, one-third in those with Stage II/III tumors and two-thirds in those with Stage IV tumor. In multivariate analysis accounting for all previously known prognostic factors, prevertebral muscle invasion was associated with an increased risk for any recurrence (adjusted relative risk, 2.01; p<0.001), locoregional recurrence (adjusted relative risk, 2.69; p<0.001), and distant metastasis (adjusted relative risk, 2.25; p<0.001), and with a borderline significant increased risk for overall survival (adjusted relative risk, 1.44; p=0.10). Prevertebral muscle involvement is an independent prognostic factor for NPC recurrence.