Nasopharyngeal carcinoma screening
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Nasopharyngeal carcinoma Microchapters |
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Differentiating Nasopharyngeal carcinoma from other Diseases |
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Diagnosis |
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Treatment |
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Case Studies |
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Nasopharyngeal carcinoma screening On the Web |
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American Roentgen Ray Society Images of Nasopharyngeal carcinoma screening |
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Risk calculators and risk factors for Nasopharyngeal carcinoma screening |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Homa Najafi, M.D.[2]Faizan Sheraz, M.D. [3]
Overview
There is insufficient evidence to recommend routine screening for [disease/malignancy].
OR
According to the [guideline name], screening for [disease name] is not recommended.
OR
According to the [guideline name], screening for [disease name] by [test 1] is recommended every [duration] among patients with [condition 1], [condition 2], and [condition 3].
Screening
Screening for nasopharyngeal carcinoma only is done in endemic areas, the screning methods which can be used are:
- Measurement the titre levels of
- antibody against EBV immunoglobulin A capsod antigen (IgA VCA)
- Antibody against EBV immunoglobulin A early antigen (IgA EA)
- Antibody against EBV nuclear antigen 1 (EBVNA1-IgA)
- Antibody against EBV-specific DNase antibodies
- Plasma EBV DNA quantitation by real-time PCR
- Endoscopic examination of nasopharynx
The titre levels of antibodies to EBV immunoglobulin A viral capsid antigen (IgA VCA) and early antigen (IgA EA) have been widely used as screening and diagnostic markers for NPC, even though these markers lack specificity [5]. Furthermore, IgA VCA/EA levels usually remain elevated even after disease remission is achieved. In contrast, quantitation of EBV DNA using a real-time PCR technique is highly sensitive and specific for NPC and correlates well with tumour burden [6, 7]. Pre-treatment plasma EBV DNA levels have been shown to complement TNM (tumour–node–metastasis) staging [8], and elevated EBV DNA levels at 6 weeks after treatment is a powerful prognosticator of recurrence and survival [9, 10]. EBV DNA can be used clinically to monitor disease response and recurrence [11, 12], while ongoing studies are addressing the use of EBV DNA as a screening tool as well as a risk stratification marker guiding therapy [13].
Nasopharynx cancer often is not detected until a tumor has grown large enough to invade a critical structure. The association of EBV and NPC might play a role in screening for
tumors. A study from China of 338,868 patients who underwent serologic screening for EBV titer revealed that of nearly 10,000 patients who had antibodies to EBV, NPC was
detected in 113 (approximately 1.2%). Most (>85%) were early-stage cancers.20 qPCRtechniquesmay be helpful in detecting early nasopharyngeal cancer. Screening
for LMP1 in nasopharyngeal swabs was shown to be a promising screening tool in highrisk populations, with a sensitivity of 87%and a specificity of 98%.21 Technological advances
and other genetic or environmental markers proving useful in the detection of early NPC may lead to the identification of populations benefitting from rigorous screening or chemoprevention.
Based on this, there is an ongoing, prospective screening program of all siblings in Singapore to all patients with newly diagnosed NPC, who will be examined clinically, including an endoscopic examination of the nasopharynx, measurements of IgA—viral capsid anti-gen, IgA—early antigen, and plasma EBV DNA.The data on screening is, for obvious reasons, limited to populations where NPC is endemic . In a study from South China, EBV serology (IgA against the viral capsid antigen)was used and 1136 individuals with positive findings were identified and followed up . During 4 years,35 individuals were diagnosed with NPC, of which 92%were stage 1 or 2. This translates to a detection rate per annum that was almost 32
times higher than in the background population.156 Similar data was reported in a subsequent study of a Chinese population(Guangdong).157 It has been suggested that the positive predictive value may been enhanced by testing against several anti-EBV-Ig (EBNA 1 IgA,EBNA 1 IgG,and zta IgG). In a large epidemiological study from Taiwan, close to 10,000 individuals were tested for IgA against EBV capsid antigen and neutralizing antibodies against EBV-specific DNase and assessed with data in cancer and death registries for 15 years. The cumulative risk of NPC per 100,000 person- years was 11 for subjects who tested positive for neither serologic marker,45 fort hose who were positive for 1 marker and 371 for those who were positive for both markers.After adjustment for age and the presence or absence of a family history of nasopharyngeal carcinoma, the relative risk was 32.8 for subjects positive for both markers and 4.0 for subjects positive for 1 when compared with subjects who were negative for both markers. 159 There are no prospective screening studies that have proven a decreased mortality from NPC.
In view of the prevalence of nasopharyngeal carcinoma in southern China, population screening presents an attractive strategy for early diagnosis and, consequently, better outcomes. Immunoserology (IgA antibodies against EBV capsid antigen [VCA-IgA], early antigen [EA-IgA], EBV nuclear antigen 1 [EBNA1-IgA], and EBV-specific DNase antibodies) and EBV DNA-based screening methods have been studied. From the early studies consisting of case-control and prospective testing, immunoseropositivity is estimated to be predictive of nasopharyngeal carcinoma susceptibility after a year, and detection sensitivity is enhanced when combining a panel of markers (appendix).28 Nonetheless, false-positive rates of 2–18% have been reported with serological testing alone.29 A promising method to reduce false-positive rates could entail use of a confi rmatory non-invasive test after positive serology. In a study that incorporated this strategy, the combination of serum VCA-IgA antibody and circulating EBV DNA had an overall sensitivity (defi ned as positive result of either marker) of 99%, but EBV DNA accurately identifi ed 75% of false-positive VCA-IgA-detected cases.30 A large-scale prospective screening study (NCT02063399) for nasopharyngeal carcinoma with use of plasma EBV DNA is in progress and plans to recruit almost 20 000 healthy men aged between 40 and 60 years (appendix).