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Human papillomavirus in upper digestive tract tumors from three countries.

ABSTRACT: To clarify human papillomavirus (HPV) involvement in carcinogenesis of the upper digestive tract of virological and pathological analyses.The present study examined the presence of HPV in squamous cell carcinomas of the oral cavity (n = 71), and esophagus (n = 166) collected from Japan, Pakistan and Colombia, with different HPV exposure risk and genetic backgrounds. The viral load and physical status of HPV16 and HPV16-E6 variants were examined. Comparison of p53 and p16(INK4a) expression in HPV-positive and HPV-negative cases was also made.HPV16 was found in 39 (55%) oral carcinomas (OCs) and 24 (14%) esophageal carcinomas (ECs). This site-specific difference in HPV detection between OCs and ECs was statistically significant (P < 0.001). There was a significant difference in the geographical distribution of HPV16-E6 variants. Multiple infections of different HPV types were found in 13 ECs, but multiple infections were not found in OCs. This difference was statistically significant (P = 0.001). The geometric means (95% confidence interval) of HPV16 viral load in OCs and ECs were 0.06 (0.02-0.18) and 0.12 (0.05-0.27) copies per cell, respectively. The expression of p16(INK4a) proteins was increased by the presence of HPV in ECs (53% and 33% in HPV-positive and -negative ECs, respectively; P = 0.036), and the high-risk type of the HPV genome was not detected in surrounding normal esophageal mucosa of HPV-positive ECs.Based on our results, we cannot deny the possibility of HPV16 involvement in the carcinogenesis of the esophagus.

SUBMITTER: Castillo A

PROVIDER: S-EPMC3247694 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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Human papillomavirus in upper digestive tract tumors from three countries.

Castillo Andres A Koriyama Chihaya C Higashi Michiyo M Anwar Muhammad M Bukhari Mulazim Hussain MH Carrascal Edwin E Mancilla Lida L Okumura Hiroshi H Matsumoto Masataka M Sugihara Kazumasa K Natsugoe Shoji S Eizuru Yoshito Y Akiba Suminori S

World journal of gastroenterology 20111201 48

<h4>Aim</h4>To clarify human papillomavirus (HPV) involvement in carcinogenesis of the upper digestive tract of virological and pathological analyses.<h4>Methods</h4>The present study examined the presence of HPV in squamous cell carcinomas of the oral cavity (n = 71), and esophagus (n = 166) collected from Japan, Pakistan and Colombia, with different HPV exposure risk and genetic backgrounds. The viral load and physical status of HPV16 and HPV16-E6 variants were examined. Comparison of p53 and ...[more]

PMID: 22219599

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Project description:Guanine nucleotide exchange factor T (GEFT), a member of the Rho guanine nucleotide exchange factor family, is expressed in a variety of tumors. In the present study, the expression and clinical significance of GEFT in malignant digestive tract tumors was assessed. Tumor and adjacent control samples from 180 patients were tested. Positive GEFT expression rates were 80, 83.33 and 86.67% in esophageal squamous carcinoma (ESCC), gastric carcinoma (GC) and colorectal cancer (CRC), respectively. GEFT expression was associated with diffuse type carcinoma according to the Lauren classification (χ2=12.525, P=0.002) and tumor-node-metastasis (TNM) stages III/IV (χ2=4.033, P=0.045) in GC, and with vessel carcinoma embolus (χ2=7.890, P=0.005) and lymph node metastasis (χ2=5.455, P=0.020) in CRC, but was not associated with other clinicopathological parameters. Patients with high levels of GEFT protein expression had a less favorable outcome compared with patients with low levels of GEFT expression in patients with CRC (χ2=3.876, P=0.049). However, a significant association was not found between GEFT expression and overall survival in patients with ESCC (χ2=0.040, P=0.842) or GC (χ2=0.501, P=0.479). The rate of human epidermal growth factor receptor 2 upregulation in patients with GC was 13.33% and it was associated with nerve invasion (χ2=4.005, P=0.045) and TNM stages III/IV (χ2=5.600, P=0.018). Mismatch repair protein (MMRP) defect was observed in six cases, and the KRAS mutation rate was 26.67% in patients with CRC. GEFT expression was significantly correlated with MMRP (r=-0.285, P=0.027) and KRAS mutation in patients with CRC (r=0.697, P<0.001). These findings revealed frequent GEFT upregulation in malignant digestive tract tumors, which may have promoted tumor development. GEFT expression in CRC may be associated with microsatellite instability and KRAS mutation status, suggesting that GEFT may be a potential therapeutic target for patients with CRC.

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Human papillomavirus in upper digestive tract tumors from three countries.

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Human papillomavirus in upper digestive tract tumors from three countries.

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