Effects of Epstein-Barr Virus Infection on the Risk and Prognosis of Primary Laryngeal Squamous Cell Carcinoma: A Hospital-Based Case-Control Study in Taiwan

Abstract

Mounting molecular evidence supports Epstein–Barr virus (EBV) involvement in the pathogenesis of laryngeal squamous cell carcinoma (LSCC); however, the epidemiological data are inconsistent. In this retrospective case-control study, we aimed to determine whether EBV infection underlies the risk and prognosis of LSCC. The prevalence of EBV infection, as analyzed using an EBV DNA polymerase chain reaction assay, was significantly higher in 42 Taiwanese patients with newly diagnosed primary LSCC, compared to 39 age- and sex-matched control patients without cancer (48% vs. 19%). Furthermore, most of the EBER signals detected using in situ hybridization were localized to the nuclei of tumor-infiltrating lymphocytes. In multivariate analysis, EBV DNA positivity, age ≥ 55 years, cigarette smoking, and high BCL-2, B2M, and CD161 expression (assessed using immunohistochemistry) were identified as independent risk factors for LSCC. Furthermore, five-year local recurrence and disease-free survival rates were 34% and 58%, respectively, with a high EBER signal and low CD3 expression independently predicting five-year local recurrence and disease-free survival. Our comprehensive profiling data accurately identified patients at risk for LSCC development, local recurrence, or disease-free survival. The information obtained in this study improves our understanding of EBV infection in LSCC, and may guide precision medicine for patients with LSCC.

Laryngeal Helicobacter pylori Infection and Laryngeal Cancer-Case Series and a Systematic Review

“…Using an Aperio ScanScope scanner (Leica Biosystems, Richmond, IL, USA), the stained slides were digitized at 40× magnification. The presence of H. pylori and the cellular expression levels of E-cadherin and CD1d were digitally assessed in four specified regions of interest via semi-quantitative image analysis (Tissue Studio v2.1; Definiens AG, Münich, Germany) [ 44 ]; the selected regions contained the laryngeal mucosal lesion and submucosal tissue, and passed the filtering process because of a cell count ≥ 15 [ 44 , 45 ]. A histological score (1 × percentage of cells positive for low brown chromogen intensity) + (2 × percentage of cells positive for medium brown chromogen intensity) + (3 × percentage of cells positive for high brown chromogen intensity) [ 46 ] was calculated for cellular staining by the scientific team members (T.-C.C.…”

Emerging Oncogenic Viruses in Head and Neck Cancers from Romanian Patients

“…The highest prevalence of the viruses we tested was for EBV1 (61.63%) and EBV2 was detected in fewer samples (3.8%). Therefore, we are mentioning Lee LA et al, who detected using Real Time PCR a 48% EBV prevalence in Primary Laryngeal Squamous Cell Carcinoma, from Formalin-fixed paraffinembedded (FFPE) tissue sections [23]. Deng Z et al analyzed the prevalence and prognostic values of EBV infections in Japanese patients with different types of HNSCC from fresh frozen samples, using PCR.…”

“…A total of 67 infectious agents were detected by a type-specific multiplex genotyping (TS-MPG) assay, which combines multiplex polymerase chain reaction (PCR) and beadbased assay using the Luminex ® 100/200™ system (Luminex Corp., Austin, TX, USA), as described previously [18][19][20]. Multiplex type-specific PCR uses specific primers for the detection of 19 probable/high-risk alpha-HPV types (HPV 16,18,26,31,33,35,39,45,51,52,53,56,58,59, 66, 68a, 68b, 70, 73, and 82), 2 low-risk alpha-HPV types (HPV 6, 11), 25 genus-beta HPV types (HPV 5,8,9,12,14,15,17,19,20,21,22,23,24,25,36,37,38,47,49,75,76,80,92,93, and 96) from the Papillomaviridae family, 12 polyomaviruses (JCV-John Cunningham virus, BKV, KIV-Karolinska Institute Virus, WUV-Washington University Virus, MCV-Merkel Cell Polyomavirus, HPyV6, HPyV7, TSV-Trichodysplasia Spinulosa Polyomavirus, HPyV9, HPyV10, HPyV12, SV40-Simian Virus 40) from the Polyomaviridae family, and 9 herpesviruses: HSV1 (HHV1), HSV2 (HHV2), varicella zoster virus (HHV3), EBV (HHV4) with EBV1 and EBV2 types, CMV (HHV5), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), HHV8 (KSHV or Kaposi's sarcoma-associated herpesvirus) from the Herpesviridae family…”

Epstein-Barr Virus-Associated Carcinoma of the Larynx: A Systematic Review with Meta-Analysis

“…The 31 systematically reviewed studies were carried out in 19 different countries in Europe (n = 12) [6,[10][11][12][13][14][15][16][17][18][19][20], Asia (n = 8) [21][22][23][24][25][26][27][28], North America (n = 5) [3,[29][30][31][32], Eurasia (n = 3) [4,5,33], Oceania (n = 1) [34], South America (n = 1) [2], and concomitantly in North America and Europe (n = 1) [35] (Table 1).…”

“…The studies have detected EBV by PCR-based techniques (n = 16) [3][4][5]12,13,15,17,18,21,23,25,28,[31][32][33][34], in situ hybridization (ISH) (n = 14) [2,10,12,14,16,19,20,22,[26][27][28]31,32,35], or immunological methods (n = 10) [5,10,12,14,16,24,[28][29][30]35]. In seven studies, two techniques were used for viral detection, with five studies combining immunological assays and hybridization [4,10,14,16,35]: a study using immunological and PCR-based techniques [5] and another study applying ISH and PCR-based techniques [32].…”