Nasopharyngeal Brush Biopsies and Detection of Nasopharyngeal Cancer in a High-Risk Population

Tune, Cathryn E.; Liavaag, Per Gunnar; Freeman, Jeremy L.; Brekel, M.W.M. van den; Shpitzer, Tommy; Kerrebijn, Jeroen D. F.; Payne, David G.; Irish, Jonathan C.; Ng, Raymond; Cheung, Roy K.; Hm, Dosch

doi:10.1093/jnci/91.9.796

Cited by 61 publications

(60 citation statements)

References 32 publications

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“…Of nine patients with recurrent or residual disease, only two patients were positive for EBV; therefore, scarring change after irradiation may reduce the overall ability of nasopharyngeal brushing to detect EBV positivity in patients with recurrent NPC. 25 However, the fact that 98% of the swab samples obtained successfully from the nasopharynx contained sufficient DNA for the amplification of the LMP-1 gene did not appear to be a problem in this study. One reason for this phenomenon may be that radiation-treated patients were encouraged to irrigate their nasopharynx vigorously, even during radiation treatment, to prevent crust formation.…”

Section: Discussionmentioning

confidence: 55%

Presence of the latent membrane protein 1 gene in nasopharyngeal swabs from patients with mucosal recurrent nasopharyngeal carcinoma

Tsang

Chuang

Tseng

et al. 2003

Cancer

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BACKGROUNDNasopharyngeal carcinoma (NPC) is the most common head and neck malignancy in southeastern China and Taiwan. Early detection of the local disease followed by timely and appropriate treatment is essential to increasing cure and survival rates. Detection of Epstein–Barr virus (EBV) genomic DNA, such as the latent membrane protein 1 gene (LMP‐1), in patients postirradiation during follow‐up may indicate mucosal recurrence.METHODSSeventy‐one patients with NPC underwent serial nasopharyngeal swabs for LMP‐1 polymerase chain reaction assay before, during, and after irradiation. All of patients achieved a complete disease remission of the LMP‐1 gene after irradiation that lasted for at least 6 months.RESULTSThe median LMP‐1 disease remission time after the beginning of irradiation was 4.3 weeks. Patients with early LMP‐1 disease remission (≤ 4 weeks after the beginning of irradiation) and delayed LMP‐1 disease remission (> 4 weeks) had 3‐year local control rates of 93.5% and 76.9%, respectively (P = 0.0529). The LMP‐1 gene was detected again (reexpression of LMP‐1 [re‐LMP‐1]) in 10 patients after irradiation with at least 6 months of follow‐up. Nine of 10 patients (90%) in the re‐LMP‐1 positive group and 2 of 61 patients (3.3%) in the re‐LMP‐1 negative group developed local recurrence. Mucosal recurrence developed in nine patients, and all displayed re‐LMP‐1. By detecting re‐LMP‐1 using nasopharyngeal swabs, mucosal recurrence was diagnosed with a sensitivity of 100% (9 of 9 patients) and a specificity of 98.4% (61 of 62 patients). The 3‐year overall survival rate, the disease free survival rate for the entire group, and the estimated local mucosal control rates in the re‐LMP‐1 positive and re‐LMP‐1 negative groups were 86.5%, 76.5%, 19.4%, and 96.7%, respectively.CONCLUSIONSExpression of EBV LMP‐1 in nasopharyngeal swab specimens from patients with irradiated/treated NPC can provide a highly sensitive and specific method of forecasting mucosal recurrence. This investigation confirmed the reliability and feasibility of nasopharyngeal swabs in screening for mucosal recurrences in patients with NPC. Cancer 2003. © 2003 American Cancer Society.

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Section: Discussionmentioning

confidence: 55%

Presence of the latent membrane protein 1 gene in nasopharyngeal swabs from patients with mucosal recurrent nasopharyngeal carcinoma

Tsang

Chuang

Tseng

et al. 2003

Cancer

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“…The technique and procedure of the PCR for EBV and HPV DNA detection have been described previously. [17][18][19][20][21] Genomic regions in the EBNA-1 were amplified by primer sets of 5 0 -TGAATACCACCAAGAAGGTG-3 0 and 5 0 -AGTTCCTTCGTCGGTAGTC-3 0 or 5 0 -GTA-GAAGGCCATTTTTCCAC-3 0 and 5 0 -TTTCTACGT-GACTCCTAGCC-3 0 . Negative control samples containing water were also processed in parallel to tissue samples.…”

Section: Methodsmentioning

confidence: 99%

Use of combined molecular biomarkers for prediction of clinical outcomes in locally advanced tonsillar cancers treated with chemoradiotherapy alone

Chung¹,

Lee²,

Horng

et al. 2008

Head & Neck

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Background. Environmental exposures to tobacco, alcohol, human papillomavirus (HPV) and/or Epstein-Barr virus (EBV), all of which can perturb multiple cell cycle proteins or tumor suppressors, have been implicated in the pathogenesis of different subsets of head and neck cancers. The aim of this study was to investigate to which extent the virus infection by itself, and/or the altered cell cycle proteins, contributes to prognosis in locally advanced tonsillar squamous cell carcinomas (TSCCs) treated with concurrent chemoradiotherapy (CCRT) alone.Methods. Serial tumor tissue arrays from archival samples were tested for the presence of HPV genome integration or EBV episome by means of DNA sequencing, realtime polymerase chain reaction (PCR), and in situ hybridization. Alterations of cell cycle proteins (p53, pRb, and p21) were evaluated by immunohistochemical staining. The association of viral presence with altered cell cycle proteins was correlated to clinical outcomes.Results. Of the 46 patients with the same T2N2bM0 stage IVA among consecutive patients with TSCC, 23 (50%) had integrated HPV DNA and only 1 (2%) had EBV episome. The HPV types detected were almost all HPV-16. A reduced expression pattern of p53, pRb, and p21 was noted in HPVpositive tumors, and the incremental number of alterations in the 3 proteins was significantly associated with HPV-negative tumors. The presence or absence of HPV together with the number of altered expression of the 3 cell cycle markers resulted in further identification of 4 biologically and clinically distinct subgroups with different outcomes after CCRT.Conclusions. Use of combined biomarkers of oncogenic HPV and tumor suppressors of p53, pRb, and p21 in advanced TSCC provides prognostic molecular classification superior to the TNM stage system and identifies low-risk patients for organ preservation by CCRT alone and high-risk patients who might benefit from planned tonsillectomy and neck dissection before

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“…24,26 This may be because of insensitive, qualitative (multiplex) PCR assays 24 or insufficient brushing of the NP epithelium in these controls. In contrast, several other studies 25,45 and our present study using sensitive quantitative real-time PCR, have found EBV DNA in brushing specimens from most healthy carriers, albeit at low levels.…”

Section: Np Brushings Of Npc Patients Contain Extremely High Ebv Dna mentioning

confidence: 99%

“…This is indicated by recent reports, showing elevated EBV DNA loads in NP swab samples of NPC patients using nonstandardized PCR techniques. [24][25][26][27] Thus, we investigated in more detail the diagnostic value of EBV DNA load quantification and EBV mRNA detection, in particular BARF1 and EBNA1 mRNA, in NP brushing specimens from consecutive Indonesian ENT patients with suspected NPC and various controls. In all patients suspected for NPC a biopsy was taken from the same site to confirm presence or absence of NPC by using EBER in situ hybridisation (EBER-RISH) and immunohistochemical staining for EBNA1 and LMP1.…”

mentioning

confidence: 99%

Noninvasive diagnosis of nasopharyngeal carcinoma: Nasopharyngeal brushings reveal high Epstein‐Barr virus DNA load and carcinoma‐specific viral BARF1 mRNA

Stevens

Verkuijlen

Hariwiyanto

et al. 2006

Intl Journal of Cancer

106

130

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Nasopharyngeal carcinoma (NPC) is the most prevalent ENTtumour in Indonesia. We investigated the primary diagnostic value of Epstein-Barr virus (EBV) DNA load and mRNA detection in noninvasive nasopharyngeal (NP) brushings, obtained prospectively from consecutive Indonesian ENT-patients with suspected NPC (N 5 106) and controls. A subsequent routine NP biopsy was taken for pathological examination and EBER-RISH, yielding 85 confirmed NPC and 21 non-NPC tumour patients. EBV DNA and human DNA load were quantified by real-time PCR. NP brushings from NPC patients contained extremely high EBV DNA loads compared to the 88 non-NPC controls (p < 0.0001). Using mean EBV DNA load in controls plus 3 SD as cut-off value, specificity, sensitivity, positive and negative predictive values were 98, 90, 97 and 91%, respectively. Epstein-Barr nuclear antigen 1 (EBNA1) and the carcinoma-specific BARF1 mRNA were detected by nucleic acid sequence based amplification and found in 86 and 74% of NP brushings, confirming NPC tumour cell presence. EBV RNA positivity was even higher in fresh samples stored at 280°C until RNA expression analyses (88% for both EBNA1 and BARF1). EBV RNA-negative NP brushings from proven NPC cases had the lowest EBV DNA loads, indicating erroneous sampling. No EBV mRNA was detected in NP brushings from healthy donors and non-NPC patients. In conclusion, EBV DNA load measurement combined with detection of BARF1 mRNA in simple NP brushings allows noninvasive NPC diagnosis. It reflects carcinoma-specific EBV involvement at the anatomical site of tumour development and reduces the need for invasive biopsies. This procedure may be useful for confirmatory diagnosis in large serological NPC screening programs and has potential as prognostic tool. ' 2006 Wiley-Liss, Inc.Key words: EBV; NPC; diagnosis; viral load; oncogene; carcinoma Undifferentiated nasopharyngeal carcinoma (NPC WHO type III) is virtually 100% associated with Epstein-Barr virus (EBV) and has a reported high incidence in most of South-East Asia and intermediate incidence in North-African populations and in Inuit. [1][2][3] In Indonesia, with an ethnically diverse population of 225 million people, NPC is the most common ENT tumour with high prevalence among native populations and a yearly overall incidence estimated at 6.2/100,000. 4 Extremely high incidence was recently documented in native populations living on the island of Sulawesi. 5 In Yogyakarta, Central Java, NPC is the most prevalent tumour among man and 4th most prevalent among females, with a male/female ratio of 2.4, constituting respectively 22 and 8% of all diagnosed malignancies. 4 The strong etiological link between EBV and NPC has been known for over 3 decades [1][2][3]6 and is reflected by abnormal anti-EBV antibody profiles, increased circulating EBV DNA levels and by distinct EBV gene expression in the tumour cells. 7-11 Classically, NPC is considered to have a latency type 2 EBV transcription, with expression of EBV-encoded small RNAs 1 and 2 (EBER1/2), BamHI A rightward transcript...

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Nasopharyngeal Brush Biopsies and Detection of Nasopharyngeal Cancer in a High-Risk Population

Cited by 61 publications

References 32 publications

Presence of the latent membrane protein 1 gene in nasopharyngeal swabs from patients with mucosal recurrent nasopharyngeal carcinoma

Presence of the latent membrane protein 1 gene in nasopharyngeal swabs from patients with mucosal recurrent nasopharyngeal carcinoma

Use of combined molecular biomarkers for prediction of clinical outcomes in locally advanced tonsillar cancers treated with chemoradiotherapy alone

Noninvasive diagnosis of nasopharyngeal carcinoma: Nasopharyngeal brushings reveal high Epstein‐Barr virus DNA load and carcinoma‐specific viral BARF1 mRNA

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