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Conclusion: Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) is considered to be a distinct entity in Japan. The combination of both HPV-DNA sequencing analysis and immunohistochemistry (IHC) for p16INK4A is useful to discriminate the OPSCC patients with a better prognosis from other cases, especially in the advanced stage. Surgical treatment is recommended for HPV-negative advanced cancer. Objective: The number of HPV-related OPSCCs has been increasing worldwide. However, the incidence and prognostic significance of this cancer in Japan have not yet been fully elucidated. Methods: Seventy-seven Japanese patients with OPSCC were enrolled in this study. The prevalence of HPV-DNA was assessed by PCR and sequencing. The expression of p16INK4A and p53 was examined by IHC. The clinicopathological parameters and disease-specific survival were analyzed for HPV-positive and -negative patients. Results: HPV-DNA was detected in 32 patients. Thirty-four patients were p16INK4A-positive by IHC. The patients who were positive for HPV infection were significantly younger. Furthermore, in the stage III or IV cases, the 3-year disease-specific survival of the HPV infection-positive group was significantly better than that of the HPV-negative group. Surgical treatment was demonstrated to lead to a good prognosis for the patients with HPV-negative advanced cancer. [ABSTRACT FROM AUTHOR]

Aim: To clarify human papillomavirus (HPV) involvement in carcinogenesis of the upper digestive tract of virological and pathological analyses., Methods: 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., Results: 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., Conclusion: Based on our results, we cannot deny the possibility of HPV16 involvement in the carcinogenesis of the esophagus.