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Concurrent chemoradiotherapy is the established treatment for locally advanced nasopharyngeal carcinoma (NPC). However, there is no evidence supporting routine adjuvant chemotherapy. We aimed to demonstrate the effect of adjuvant chemotherapy on survival and distant metastasis in high-risk N3 NPC patients. We linked the Taiwan Cancer Registry and Cause of Death database to obtain data. Clinical N3 NPC patients were divided as those receiving definitive concurrent chemoradiotherapy (CCRT) with adjuvant 5-fluorouracil and platinum (PF) chemotherapy and those receiving no chemotherapy after CCRT. Patients receiving neoadjuvant chemotherapy were excluded. We compared overall survival, disease-free survival, local control, and distant metastasis in both groups using Cox proportional hazards regression analysis. Propensity-score matching was also performed to evaluate the independent effect of adjuvant PF in a matched cohort with similar baseline characteristics. We included 431 patients (152 and 279 patients in the adjuvant PF and observation groups, respectively). Median follow-up was 4.3 years. The 5-year overall survival were 69.1% and 57.4% in the adjuvant PF chemotherapy and observation groups, respectively (p = 0.02). Adjuvant PF chemotherapy was associated with a lower risk of death (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.43-0.84; p = 0.003), even after adjusting for baseline prognostic factors (HR 0.61, 95% CI 0.43-0.86; p = 0.005). Distant metastasis-free survival at 12 months was higher in the adjuvant PF chemotherapy group than in the observation group (98% vs 84.8%; p < 0.001). After adjusting for baseline prognostic factors, adjuvant PF chemotherapy was associated with freedom from distant metastasis (HR 0.11, 95% CI 0.02-0.46; p = 0.003). Adjuvant chemotherapy was also associated with a decreased risk of death (HR 0.59, 95% CI 0.41-0.85, p = 0.004) in a propensity score-matched cohort. Prospective evaluation of adjuvant PF chemotherapy in N3 NPC patients treated with definitive CCRT is warranted because adjuvant PF chemotherapy was associated with improved overall survival and decreased risk of distant metastasis., (© 2022. The Author(s).)

Background: Combined radiotherapy and chemotherapy is considered the standard of care for locally advanced nasopharyngeal carcinoma (LA-NPC) in Epstein-Barr virus infection endemic area. This study compared the long-term outcomes between LA-NPC patients treated with neoadjuvant chemotherapy followed by radiotherapy (NACT) and those treated with concurrent chemoradiotherapy (CCRT)., Methods: From 2003 to 2007, a total of 128 histopathologically proven LA-NPC patients receiving either NACT or CCRT were consecutively enrolled at the National Cheng Kung University Hospital in Taiwan. NACT consisted of 3-week cycles of mitomycin, epirubicin, and cisplatin on day 1 and fluorouracil and leucovorin on day 8 (MEPFL) or weekly alternated cisplatin on day 1 and fluorouracil and leucovorin on day 8 (P-FL). CCRT comprised 3-week cycles of cisplatin (Cis 100) or 4-week cycles of cisplatin and fluorouracil (PF4). The first failure site, disease free survival (DFS), overall survival (OS), and other prognostic factors were analyzed., Results: Thirty-eight patients (30%) received NACT. Median follow-up duration was 53 months. More patients with advanced nodal disease (N2-N3) (86.8% vs 67.8%, p =0.029) and advanced clinical stage (stage IVA-IVB) enrolled in the NACT group (55.2% vs 26.7%, p =0.002). For NACT, both MEPFL and P-FL had similar 5-year DFS and OS (52.9% vs 50%, p =0.860 and 73.5% vs 62.5%, p =0.342, respectively). For CCRT, both PF4 and Cis 100 had similar 5-year DFS and OS (62.8% vs 69.6%, p =0.49 and 72.9% vs 73.9%, p =0.72, respectively). Compared to CCRT, NACT had similar 5-year DFS and OS (51.5% vs 65.1%, p =0.28 and 71.7% vs 74.3%, p =0.91, respectively). Among patients who were recurrence-free in the first 2 years after treatment, those treated with NACT experienced poorer locoregional control compared to those treated with CCRT (Hazard ratio =2.57, 95% confidence interval: 1.02 to 6.47, p =0.046)., Conclusions: For LA-NPC, both CCRT and NACT were similarly efficacious treatment strategies in terms of long-term disease control and survival probability. Close locoregional follow-up is recommended for patients receiving NACT, because these patients are more prone to develop locoregional failure than patients receiving CCRT.

Background: Human papilloma virus (HPV) has been implicated in the carcinogenesis and prognosis of certain head and neck cancers. Whether it also has a role in the pathogenesis of nasopharyngeal carcinoma (NPC) in Taiwan is unclear., Methods: Detection and genotyping of HPVs were performed in 43 primary NPCs (one WHO-I and 42 WHO-II/III) and 40 nasopharyngeal controls using PCR-based HPV genotyping arrays. Localisation of high-risk HPV and Epstein-Barr virus genomes was performed in another 46 primary NPCs (five WHO-I and 41 WHO-II/III) and seven paired metastatic WHO-II/III NPCs using in situ hybridisation., Results: In the HPV genotyping cohort, oncogenic HPVs were detected equally in WHO-II/III NPCs (31%, 13/42) and nasopharyngeal controls (35%, 14/40). Tumour high-risk HPV status did not correlate with the prognosis of patients with NPC. In the high-risk HPV in situ hybridisation cohort, 14 (88%) of the 16 oncogenic HPV-positive WHO-II/III NPCs showed a unique cytoplasmic/perinuclear staining pattern, which is distinct from the typical dot/punctate nuclear staining pattern indicating HPV genome integration. In addition, oncogenic HPVs were not always retained in NPC cells during the process of metastasis., Conclusions: This study does not support an association between oncogenic HPV and the carcinogenesis or prognosis of WHO-II/III NPCs in Taiwan.

In the present study, the authors compared the long-term risk of nasopharyngeal carcinoma (NPC) of male participants in an NPC multiplex family cohort with that of controls in a community cohort in Taiwan after adjustment for anti-Epstein-Barr virus (EBV) seromarkers and cigarette smoking. A total of 43 incident NPC cases were identified from the 1,019 males in the NPC multiplex family cohort and the 9,622 males in the community cohort, for a total of 8,061 person-years and 185,587 person-years, respectively. The adjusted hazard ratio was 6.8 (95% confidence interval (CI): 2.3, 20.1) for the multiplex family cohort compared with the community cohort. In the evaluation of anti-EBV viral capsid antigen immunoglobulin A and anti-EBV deoxyribonuclease, the adjusted hazard ratios were 2.8 (95% CI: 1.3, 6.0) and 15.1 (95% CI: 4.2, 54.1) for those positive for 1 EBV seromarker and positive for both seromarkers, respectively, compared with those negative for both EBV seromarkers. The adjusted hazard ratio was 31.0 (95% CI: 9.7, 98.7) for participants who reported a family history of NPC and who were anti-EBV-seropositive compared with individuals without such a history who were anti-EBV-seronegative. The findings suggest that both family history of NPC and anti-EBV seropositivity are important determinants of subsequent NPC risk and that the effect of family history on NPC risk cannot be fully explained by mediation through EBV serologic responses.

Endoplasmic reticulum (ER) stress-activated unfolded protein response (UPR) plays multiple roles in cancer development, but its specific roles for virus-associated cancers have not been fully understood. It is still unknown whether ER stress/UPR occurs in and contributes to nasopharyngeal carcinoma (NPC), an epithelial malignancy closely associated with EBV. Here, we report that UPR proteins are frequently detected in NPC biopsies. In addition, we reveal that, in EBV-infected NPC cells, ER stress inducers up-regulate a potent EBV oncoprotein latent membrane protein 1 (LMP1), and the ER stress-induced LMP1 enhances production of interleukin-8. ER stress triggers LMP1 expression at a transcriptional level, activating a distal LMP1 promoter TR-L1. TR-L1 contains an ER stress-responsive element, which is targeted by an UPR protein XBP-1. Ectopic expression of XBP-1 induces LMP1 expression, and knockdown of XBP-1 blocks ER stress-triggered up-regulation of LMP1 in NPC cells. Furthermore, XBP-1 significantly correlates with LMP1 expression in NPC tumor biopsies. Therefore, this study not only provides a novel clue linking ER stress/UPR to EBV-associated NPC but also suggests that ER stress/UPR can promote virus-associated cancer in a unique way by driving expression of a viral oncogene.

Nasopharyngeal carcinoma (NPC) patients may have persistent or recurrent neck masses following radiotherapy. The clinicopathological features for these two subgroups are not fully characterized, however. In this study, we reviewed our experiences in patients with neck masses underwent either local excision or neck dissection. Between 1990 and 2004, 37 NPC patients who had persistent (n=18) or recurrent (n=19) neck masses following radiotherapy were enrolled. The clinical and pathological parameters were measured. Squamous cell carcinoma was found in the resected specimens of 72.2% of the patients (13/18) with persistent neck mass and 89.5% of the analogs with the recurrent form (17/19). Extra-nodal tumor extension was noted in 53.8% (7/13) of persistent neck malignancies and 64.7% (11/17) of the recurrent variants. At the time of the neck surgery, individuals with persistent neck malignancies had fewer concomitant distant failures (23.1%, 3/13) as compared to their counterparts with the recurrent form (58.8%, 10/17) (P=0.07). At the end of the follow-up, however, the rates of local and/or distant failures were both high for the persistent (92.3%, 12/13) and recurrent groups (76.5%, 13/17). In conclusion, following radiotherapy for NPC, both persistent and recurrent neck masses were associated with a high rate of squamous cell carcinoma. Although patients with persistent neck malignancies have significantly fewer additional sites of failures at the time of their neck surgeries, they tend to develop local and/or distant recurrences later during follow-up.

Purpose: Radiotherapy is the most effective treatment for nasopharyngeal carcinoma (NPC). The aim of this study is to evaluate the efficacy and toxicity of fractionated stereotactic body radiation therapy (SBRT) boost for NPC., Methods and Materials: Sixty-four patients with newly diagnosed, nonmetastatic NPC were treated with conventional radiotherapy 64.8-68.4 Gy followed by fractionated SBRT boost 12-15 Gy between January 2002 and July 2004. Most patients (72%) presented with Stage III-IV disease. Fifty-two patients also received cisplatin-based concurrent (38) or neoadjuvant (14) chemotherapy. The major endpoints were local control, overall survival, and complications., Results: All patients finished the planned dose of radiotherapy. After a median follow-up of 31 months (range, 22-54), 15 patients developed tumor recurrences--3 in the nasopharynx, 4 in the neck, 5 in distant sites, 1 in both nasopharynx and neck, 2 in the neck and a distant site. The 3-year actuarial rate of local control was 93.1%, regional control 91.4%, freedom from distant metastasis 90.3%, and overall survival 84.9%, respectively. There were no Grade 4 acute or chronic radiation-related complications., Conclusions: Fractionated SBRT boost for NPC is technically feasible and provides good local control without any severe complications.

Background: Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine and may act as an endogenous tumor promoter. Single nucleotide polymorphisms (SNPs) of the TNF-alpha gene promoter region have been found to be associated with certain cancers. We conducted a case-control study to evaluate the association between these SNPs and nasopharyngeal carcinoma (NPC)., Methods: We used polymerase chain reaction followed by restriction fragment length polymorphism analysis to determine the -308 TNF-alpha promoter genotypes of 89 NPC patients and 360 healthy controls. In 23 NPC patients and 50 controls, we determined the sequence from -1065 to -101 nucleotides of the TNF-alpha gene promoter region to detect SNPs., Results: In comparison with the controls, the NPC patients had higher proportions of men and carriage of IgA antibodies against the capsid antigen of Epstein-Barr virus, but had a similar carrier rate of the -308A allele (odds ratio [OR], 1.2; 95% confidence interval [CI], 0.7-2.0). The carriage of the -308A allele was not associated with the occurrence of NPC in comparison with -308G homozygosity. We also found no significant differences in the distributions of allelic variants of the -1031, -863, -857, and -806 loci of the TNF-alpha promoter region, but observed a lower carrier rate of the novel -806T allele in the NPC patients (OR, 0.3; 95% Cl, 0.0-2.9)., Conclusion: Allelic variants of the TNF-alpha promoter gene may not be used as biomarkers of susceptibility to NPC. The role of the -806T allele needs to be studied further.

Nasopharyngeal carcinoma (NPC) is an epithelial tumor uniquely prevalent in southern Chinese. HLA-A2 is associated with NPC. In a previous study, we showed that the genes associated with susceptibility to NPC are primarily located within the HLA-A locus in Taiwanese NPC patients. However, the pathogenic genes causing NPC susceptibility remain unknown. Here, 8 polymorphic microsatellite markers distributed over a 1 megabase region surrounding the HLA-A locus were subjected to genetic analysis for the NPC-susceptibility locus. Statistical studies of associated alleles detected on each microsatellite locus showed that the NPC- susceptibility genes are most likely located between the D6S510 and D6S211 markers within a 132 kb segment containing the HLA-A locus. These results undoubtedly would facilitate the further positional cloning of the NPC-susceptibility locus, which has been elusive for the past 30 years., ((c) 2005 Wiley-Liss, Inc.)

Background: In nasopharyngeal carcinoma (NPC), Fas-ligand (Fas-L)-mediated apoptosis might contribute to the immune privilege of tumors. In some cancers, dysregulation of Fas-L protein in tumors might lead to disease progression. The purpose of this study was to evaluate the correlations between Fas-L expression and the clinical outcomes in patients with NPC., Methods: We recruited 78 patients with primary NPC, classified clinical stages according to the 1997 American Joint Committee on Cancer staging system, and assessed Fas-L with immunohistochemical methods., Results: Forty-one (53%) of 78 patients were Fas-L-positive. The prevalence was 0%, 57%, 58%, and 82% from stages I to IV, respectively (p <.001). Fas-L expression was associated with the N classification (p=.05) but not the T classification. Patients with positive Fas-L expression had a lower rate of disease-free survival and overall survival (p=.01 for all log-rank tests)., Conclusion: Patients with NPC with Fas-L-positive tumors had higher clinical stages and lymph node metastasis at diagnosis and poorer disease-free survival and overall survival; therefore, Fas-L expression may be a potential biomarker of prognosis.

Loss of heterozygosity at 3p21 is common in various cancers including nasopharyngeal carcinoma (NPC). BLU is one of the candidate tumor suppressor genes (TSGs) in this region. Ectopic expression of BLU results in the inhibition of colony formation of cancer cells, suggesting that BLU is a tumor suppressor. We have identified a functional BLU promoter and found that it can be activated by environmental stresses such as heat shock, and is regulated by E2F. The promoter and first exon are located within a CpG island. BLU is highly expressed in testis and normal upper respiratory tract tissues including nasopharynx. However, in all seven NPC cell lines examined, BLU expression was downregulated and inversely correlated with promoter hypermethylation. Biallelic epigenetic inactivation of BLU was also observed in three cell lines. Hypermethylation was further detected in 19/29 (66%) of primary NPC tumors, but not in normal nasopharyngeal tissues. Treatment of NPC cell lines with 5-aza-2'-deoxycytidine activated BLU expression along with promoter demethylation. Although hypermethylation of RASSF1A, another TSG located immediately downstream of BLU, was detected in 20/27 (74%) of NPC tumors, no correlation between the hypermethylation of these two TSGs was observed (P=0.6334). In addition to methylation, homozygous deletion of BLU was found in 7/29 (24%) of tumors. Therefore, BLU is a stress-responsive gene, being disrupted in 83% (24/29) of NPC tumors by either epigenetic or genetic mechanisms. Our data are consistent with the interpretation that BLU is a TSG for NPC.

Constitutively activated signal transducers and activators of transcription (STAT) factors, in particular STAT1, STAT3 and STAT5, have been demonstrated in a variety of human tumours and cancer cell lines. However, data on the expression of these STATs in nasopharyngeal carcinoma (NPC) are limited. In this study, the expression patterns of STAT1, STAT3 and STAT5 were immunohistochemically examined on the archival specimens from 61 patients with NPC. Staining results of each STATs were then correlated with the clinical parameters and prognosis of these patients. The results showed that constitutive activation of STAT3 and STAT5 was detected in the majority, 70.5 and 62.3%, respectively, of the 61 tumour specimens. Furthermore, coexpression of activated STAT3 and STAT5 was found in 54.1% of the specimens. In contrast, constitutive activated STAT1 could only be detected in 8 (13.1%) cases. Surprisingly, following radiotherapy, patients with constitutive STAT5 activation, or activation of both STAT3 and STAT5, had better disease-free survival and overall survival than those without activated STAT5. To our knowledge, this is the first report providing the overall expression patterns and prognostic significance of specific STATs in NPC.

NPC is an epithelial tumor that is highly prevalent among the southern Chinese. Numerous studies have indicated that specific HLA haplotypes and genes within the HLA complex are associated with NPC. As a first effort to localize the gene responsible for susceptibility, the HLA-A, -B, and -A2 subtypes were examined for their association to NPC. Consistent with previous reports, frequencies of HLA-A2 [OR = 2.50, pc = 0.020 (study population); OR = 3.73, pc = 0.0030 (> or =40 years old)] were significantly higher in patients with NPC than in healthy controls. Two-locus analysis indicated that A2(+)B46(+) individuals are at greater risk for NPC than A2(-)B46(-) individuals in both the population studied and the > or =40-year-old group. This, however, may be due to the close linkage of these 2 genes. Moreover, A2(+)B38(+) individuals were at higher risk than A2(-)B38(-) individuals in both the population studied and the > or =40-year-old group; A2 and B38 are not genetically linked. These findings suggest that B38 or B46 alone cannot confer a high risk of NPC but that, in conjunction with A2, B38 or B46 positivity greatly increases risk. None of 5 A2 subtypes identified from studied populations was significantly associated with NPC. Microsatellite marker D6S211, located 97 kb telomeric to HLA-A, was analyzed for its association with NPC. Allele 4 of D6S211 was significantly associated with NPC (OR = 3.97, pc = 0.0042). These results strongly support the hypothesis that genes associated with susceptibility to NPC in the HLA region are within the HLA-A locus., (Copyright 2002 Wiley-Liss, Inc.)

Background: The detection of tumor-derived DNA within the circulation of patients with malignant disease using polymerase chain reaction (PCR)-based strategies has opened a new avenue for the diagnosis and monitoring of these patients. Because of the universal association of Epstein-Barr virus (EBV) with the nonsquamous type of nasopharyngeal carcinoma (NPC; World Health Organization types II and III), the detection of cell free EBV DNA in sera from patients with NPC may be a valuable tool for monitoring the progress of tumors or to provide advanced warning of tumor recurrence., Methods: Serum samples were obtained from different patients, and cell free EBV DNA was detected with a conventional PCR approach. A total of 134 patients were sampled, including 36 patients with primary NPC, 28 control patients, 18 patients suffering from locoregional recurrence, 7 patients with distant metastasis, and 45 patients with NPC in clinical remission. A conventional PCR approach employing standard 35-cycle and 50-cycle reactions was used to detect cell free EBV genomes. Results from the two PCR cycles were compared to provide a semiquantitative picture of the relative quantity of EBV genome in each serum sample., Results: The EBV DNA detection rates, i.e., the rates of positive detection, for 35-cycle and 50-cycle PCR analyses, respectively, were 38.9% and 75% for patients with primary NPC, 3.5% and 10.7% for control patients, 27.8% and 88.9% for patients with locoregional disease recurrence, 71.4% and 100% for patients with distant metastasis, and 7.1% and 36.5% for patients with disease in clinical remission. The rates of positive detection among patients with active disease all appeared to be significantly greater compared with the rates among patients with disease in clinical remission. Longitudinal data for six patients with recurrent tumors revealed a close correlation between the relative quantity of circulating cell free EBV genomes and the disease course of these patients. The sensitivity, specificity, positive predictive value, and negative predictive value of the 50-cycle PCR analysis for detecting recurrent disease were 92%, 63.5%, 42.6%, and 96.4%, respectively., Conclusions: This study demonstrated that, by using a 50-cycle PCR-based approach, high sensitivity and high negative predictive value for detecting recurrent disease can be obtained from the detection of the cell free EBV genome in sera from patients with NPC. The 50-cycle PCR analysis, therefore, may provide a simple, clinically useful adjuvant method for monitoring patients with NPC., (Copyright 2002 American Cancer Society. DOI 10.1002/cncr.10251)

Nasopharyngeal carcinoma (NPC) is an epithelial cancer with a high incidence in Southeast Asia. How it escapes attack from the host immune system is not fully understood. Recently, pieces of evidence show that Fas-ligand (Fas-L)-mediated apoptosis may be involved in immune privilege of tumours. To determine whether a similar mechanism may exist in NPC, the expression of Fas-L was analysed. Biopsy specimens of the nasopharynx were taken from 27 NPC patients. Histologically, they were either non-keratinizing or undifferentiated carcinomas. Nasopharyngeal biopsies of 11 other patients that proved to have no tumour served as control. The transcripts of Fas-L were detected by reverse transcription-polymerase chain reaction. Localization of Fas-L protein was performed with immunohistostaining using an antibody recognizing human Fas-L. All nasopharyngeal tissues have a similar amount of transcripts of Fas-L. However, the Fas-L protein was detected exclusively on the cell surface of malignant epithelial cells of NPC. The present findings suggest that Fas-L protein may be involved in evading immune attack of NPC.

Background: Previous studies have reported the abundant expression of EBER1 in primary nasopharyngeal carcinoma (NPC) metastatic to lymph nodes and bone marrow (BM). This study was done to research the use of EBER1 in situ hybridization to detect micrometastasis in the marrow of NPC patients., Patients and Methods: A total of 41 patients who underwent BM biopsy either for routine pretherapeutic evaluation or suspected bone marrow metastasis were enrolled for study. Thirty-two patients underwent BM biopsy for routine staging examination (Group I) and 10 were examined for unexplained cytopenia, leukoerythroblastosis, disseminated intravascular coagulation, or extensive bone metastasis (Group II). The authors applied EBER1 in situ hybridization to investigate the expression of EBER1 in 42 BM specimens. Examinations were performed on paraffin embedded tissues using polymerase chain reaction-derived, digoxigenin-labeled EBER1 DNA probes., Results: Eight of 42 specimens (19%) were positive for BM metastasis. Just one (3%) had bone marrow involvement in Group I. However, seven (70%) were positive in Group II. All but one of them with bone marrow metastasis showed positive EBER1 in situ hybridization in the BM. Another patient suspected of having BM metastasis was negative for cytokeratin, but was positive for EBER1 in situ hybridization., Conclusion: Routine bone marrow study is not recommended in the staging of NPC, since only 3% of patients had BM metastasis. EBER1 in situ hybridization of marrow specimens cannot detect malignant cells earlier in NPC, but can be usefully applied to cases of equivocal marrow metastasis.

Epstein-Barr virus (EBV) has a well-established association with nasopharyngeal carcinoma (NPC), while its association with sinonasal carcinoma is still controversial. The role of EBV in sinonasal carcinoma and the potential value of EBER is situ hybridization in differentiating carcinomas originating from these anatomically neighboring regions were investigated. EBER in situ hybridization was applied to detect EBV in the specimens of surgically proved sinonasal carcinoma and the biopsies of carcinoma of the nasopharynx. EBER in situ hybridization was performed on paraffin embedded tissues by using PCR-derived, digoxigenin-labeled EBER-1 DNA probes. EBV was detected in 2 of 31 (6.5%) surgical specimens of sinonasal carcinoma, including 1 keratinizing squamous cell carcinoma and 1 adenocarcinoma. EBV was detected in all of 31 (100%) biopsies of carcinomas of the nasopharynx, including 1 keratining squamous cell carcinoma, 15 nonkeratinizing carcinomas, 14 undifferentiated carcinomas, and 1 adenocarcinoma. The present study does not support the role of EBV in the development of sinonasal carcinoma as does in carcinoma of the nasopharynx. EBER in situ hybridization is a useful adjunct for differentiating carcinomas originating from the sinonasal region and the nasopharynx.

The mainstay treatment of nasopharyngeal carcinoma (NPC) is radiotherapy. Although NPC is a radiosensitive tumor, 25% of NPC patients still suffered from local relapse in Taiwan. Whether the pathologic changes induced by radiation have impact on the interpretation of suspicious recurrent NPC specimens is seldom mentioned. We retrospectively analyzed 20 irradiated NPC patients who were suspected to have local recurrence and received serial nasopharyngeal biopsies. A total of 31 nasopharyngeal tissues including 15 local recurrent specimens and 16 negative specimens were entered into this study. Compared with non-irradiated nasopharyngeal tissue, the irradiated nasopharynx showed fibrosis and areas of necrosis mixed with acute or chronic inflammation. Stroma cells were enlarged, with prominent nuclei and cytoplasm, and some bizarre cells might be confused with tumor cells. These post-irradiation effects did have an impact on histological interpretation. In this study, 2 out of 16 nasopharyngeal tissues were misdiagnosed as having no recurrent tumor by using H and E stain only. However, scattered cancer cells can be clearly visualized by using EBER1 in situ hybridization. Therefore, it is recommended that EBER1 in situ hybridization is routinely used in irradiated nasopharyngeal tissues in helping the diagnosis of recurrent NPC.

Since radiotherapy is the treatment of choice for nasopharyngeal carcinoma, the influence of irradiation on the temporal bone is of great concern for these patients. In this study, the caloric test and posturography were used to investigate vestibular function in 41 irradiated patients with nasopharyngeal carcinoma. Caloric testing showed a high incidence of canal paresis; five unilateral and 10 bilateral. Factors such as middle ear effusion had no significant effect on the occurrence of canal paresis. Posturography showed no difference from the control group. The authors conclude that the influence of irradiation on the vestibular apparatus of patients with nasopharyngeal carcinoma might result in a canal paresis, while postural control is preserved. Central compensation may play an important role in the postural control of these patients.

Many anticancer treatments, including radiation therapy, have been demonstrated to work through apoptosis. The treatment of choice on nasopharyngeal carcinoma (NPC), a radiosensitive tumor, is radiotherapy. Apoptosis therefore provides a good model to predict or re-evaluate the therapeutic response in NPC. Cellular genes such as p53 and bcl-2 have been shown to be involved in apoptosis. Proliferating cell nuclear antigen (PCNA) is a useful marker for proliferating cells. This study was designed to investigate whether the expression of p53, bcl-2 and PCNA, evaluated on tumor specimens obtained at diagnosis, is indicative of the subsequent local recurrence and distant metastasis following radiation therapy. We analyzed the expression of p53, bcl-2 and PCNA by immunohistochemical methods from NPC specimens prior to radiation therapy. A total of 63 T3/T4 NPC patients including 10 patients with local relapse (Group I), 19 patients with distant metastasis (Group II), and 34 disease-free patients (Group III) were assessed. Six of the 10 (60%) group I NPC, 4 of the 19 (21.1%) group II NPC, and 13 of the 34 (38.2%) group III NPC exhibited positive p53 expression. For bcl-2 immunostaining, 8 of the 10 (80%) group I NPC, 10 of the 19 (52.6%) group II NPC, and 10 of the 34 (29.4%) group III NPC were positive. High PCNA labelling index was shown in 6 of the 10 (60%) group I NPC, 7 of the 19 (36.8%) group II NPC, and 5 of the 34 (14.7%) group III NPC. The bcl-2 and PCNA reactivity in NPC developing local recurrence after radiation therapy was significantly higher than that in the disease-free NPC (p < 0.05). These findings show that the overexpression of bcl-2 and high PCNA labelling index are probably related to local relapse in NPC patients receiving radiation therapy alone as primary treatment.

Background: Nasopharyngeal carcinoma (NPC) is strongly associated with Epstein-Barr virus (EBV). Detection of EBV in biopsy specimens may serve as a tumor marker., Methods: To assess the sensitivity and specificity of the polymerase chain reaction (PCR) and in situ hybridization in the diagnosis of NPC, formalin fixed, paraffin embedded nasopharyngeal biopsies from patients in Taiwan suspected of having NPC were studied., Results: In specimens from 107 patients with NPC, EBV was detected by PCR in 97 cases (90.7%) and by EBER in situ hybridization in 105 cases (98.1%). In specimens from 61 patients without neoplasia, EBV was detected by PCR in 7 cases (11.5%) and by EBER in situ hybridization in 0 cases., Conclusions: These results suggest that although EBV DNA may occasionally be detected in nonneoplastic nasopharyngeal tissues, cells expressing EBER are not. EBER in situ hybridization may therefore prove to be a useful adjunct in the diagnosis of NPC.

A randomised trial was undertaken to compare the effect of three oral care protocols in delaying the onset of stomatitis and reducing oral injury in nasopharyngeal cancer patients undergoing radiotherapy, 30 eligible patients with a mean age of 56.2 years were recruited and evenly allocated to one of the three groups using a randomly permuted blocks method. Patients allocated to group E1 and group E2 were given the same instructions on oral care at 1 day, and 1 week before radiotherapy, respectively, while those allocated to the control group were given no instructions. We use the Oral Assessment Guide to assess the oral physical conditions of these patients daily. Our findings revealed that the patients in the E2 group not only had later onset of stomatitis than those in the control and the E1 groups, but also had lesser degree of oral injury measured by the overall assessment score. We thereby recommend the use of the E2 protocol for delaying the onset of stomatitis and reducing oral injury in nasopharyngeal cancer patients undergoing radiotherapy.

Background: The association of Epstein-Barr virus (EBV) with nasopharyngeal carcinoma (NPC) is well documented. Previous studies reported abundant expression of EBER1 in primary NPC and tumors metastatic to lymph nodes. However, a large series of case studies correlating World Health Organization (WHO) histologic subtypes with EBER1 is needed., Methods: The authors applied the EBER1 in situ hybridization to investigate the expression of EBER1 in 140 primary NPCs, 11 metastatic tumors to lymph nodes, 6 metastatic tumors to bone marrow, and 2 metastatic tumors to the liver. All 19 metastatic tumors had paired specimens from their primary NPCs for comparison. The in situ hybridization method was performed on paraffin embedded tissues by using polymerase chain reaction-derived, digoxigenin-labelled EBER1 DNA probes., Results: The EBER1 signal was identified in nuclei of malignant epithelial cells in 135 of 140 (96.4%) primary NPCs, including 4 of 5 (80%) WHO-I histologic subtypes, 71 of 73 (97.3%) WHO-II histologic subtypes, and 60 of 62 (96.8%) WHO-III histologic subtypes (P > 0.05). However, the positive hybridization signal in WHO-I NPC was less in proportion to malignant cells, usually limited to basal cells, than in other histologic types of NPC. In 10 of 11 specimens with metastases to the lymph nodes, hybridization was always limited to the malignant cells and not associated with lymphocytes. All 10 paired primary NPCs also demonstrated positive EBER1 hybridization. Only one paired specimen showed negative EBER1 in primary NPC and a metastases to a lymph node. Eight distant metastases, all EBER1-positive in their primary NPC, also demonstrated positive EBER1 hybridization signals in the malignant cells. The proportion of EBER1 positivity in metastatic NPC is higher than that in primary lesions as observed in paired specimens from the same patient., Conclusions: Because of abundant expression of EBER1 in primary NPC as well as in metastatic malignant cells, it is recommended that EBER1 in situ hybridization be performed on routinely processed specimens whenever NPC is suspected.

B-protein is an acidic glycoprotein that appears in the serum of cancer patients, although it is not produced by cancer cells. It is not a cell surface antigen but can serve as a biological marker for detecting malignancies and monitoring cancer therapy. From January to August 1987, serum samples were collected from 133 patients with nasopharyngeal carcinoma (NPC) and 19 patients without cancer as the control group. The positive rates of B-protein in NPC patients without distant metastasis (107) and with distant metastasis (26) were 78.5% and 84.6% respectively. The overall positive rate of B-protein in NPC patients was 79.7%, which did not correlate with tumor stage and sex. The positive rate of B-protein in the control group was 5.3%. The difference in positive rates between NPC and the control group was significant (p less than 0.001). The quantitative changes of B-protein did not correlate with the tumor burden of NPC patients. Therefore, B-protein assay is not recommended in monitoring the treatment of NPC.

In order to detect the difference in serum gamma-interferon levels between patients with nasopharyngeal carcinoma (NPC) and normal controls, the reversed passive hemagglutination (RPHA) method was used. Serum gamma-interferon level was determined in 93 patients with NPC, of these, 47 were newly diagnosed, untreated patients. Of the treated patients, 15 had received radiotherapy but were proved later to have distant metastasis. Thirty-one patients had received radiotherapy and survived over 5 years without local recurrence or distant metastasis. Another 47 healthy subjects, age and sex matched with fresh NPC cases, were used as control group. The results revealed that the concentration of gamma-interferon in the serum of neither males nor females showed significant difference (p greater than 0.1). Among the NPC fresh cases, the concentration of gamma-interferon also showed no significant difference in patient serum in either early stages (stages I and II) or later stages (stages III-V) (p greater than 0.1). The serum gamma-interferon level was significantly increased in fresh NPC patients compared with normal controls (p less than 0.05). Concerning the irradiated patients, serum gamma-interferon level was not increased in patients who survived over five years, without relapse, compared with normal controls (p greater than 0.1). However, the serum gamma-interferon level in patients with distant metastasis was higher than in normal controls (p less than 0.05). Also, the serum gamma-interferon level was significantly increased in distant metastatic patients compared with patients without relapse (p less than 0.05).