Human papilloma virus in lung and esophageal carcinoma. Molecular pathology of Japan and Asia

人乳头瘤病毒（HPV）与子宫颈癌、生殖器官癌和肛门癌有因果关系。另一方面，由于HPV在各机构和地区的检出率存在差异，其与肺癌和食管癌的关系尚未明确。在本研究中，我们调查了日本和亚洲国家的肺癌和食管癌中HPV感染的情况，以阐明HPV感染的意义并评估地区差异。对日本东京、高知、鹿儿岛、冲绳4个机构、韩国2个机构、台湾和新加坡各机构的肺癌和食管癌标本（共483份）进行福尔马林固定和石蜡包埋的HPV-DNA原位杂交和PCR检测。HPV-DNA的存在频率较低，如6.9%的肺鳞状细胞癌（12/174），7.1%的肺腺癌（9/127）和8.8%的食管癌（16/182）。在阳性病例中，HPV阳性信号在部分细胞核中稀疏分布。这一发现表明，这种稀疏分布是先前报告中HPV感染频率变化的原因之一。日本、韩国、台湾和新加坡的肺鳞状细胞癌阳性率分别为8.1、8.6、5.6和0%。肺腺癌的发生率分别为5.0、7.1、13.3%和0%。在食管癌中，日本、韩国和台湾的阳性率分别为10.5%、8.0%和6.4%。比较日本各地区食管癌发病频率，鹿儿岛食管癌发病频率最高（24.1%,7/29），差异有统计学意义。除此之外，肺癌无区域差异。

Human papilloma virus (HPV) is causally associated with carcinoma of the uterine cervix, genital organs, and anus. On the other hand, its relation to the lung and esophageal carcinomas has not been clarified yet, since the detection rates of HPV have been variable in the institutions and regions. In the present study, we investigated the HPV infection in lung and esophageal carcinomas in Japan and Asian countries in order to clarify the significance of HPV infection and to evaluate the regional differences.In situ hybridization and PCR detection of HPV-DNA were applied to the formalin-fixed and paraffin-embedded specimens of lung and esophageal carcinomas (total 483 samples), which were collected from four institutions of Japan (Tokyo, Kochi, Kagoshima and Okinawa), two institutions of Korea and each of Taiwan and Singapore.The presence of HPV-DNA was demonstrated in low frequencies, such as 6.9% of squamous cell carcinomas of the lung (12/174), 7.1% of adenocarcinomas of the lung (9/127) and 8.8% of esophageal carcinomas (16/182). The positive signals for HPV were sparsely distributed in some of the nuclei of the carcinoma cells in positive cases. The finding suggests that this sparse distribution is one of causes for the variability of the frequencies of the HPV infection in the previous reports.The positive frequencies in lung squamous cell carcinomas were 8.1, 8.6, 5.6 and 0% in Japan, Korea, Taiwan, and Singapore, respectively. The frequencies in lung adenocarcinomas were 5.0, 7.1, 13.3 and 0%, respectively. In esophageal carcinoma, the positive rates were 10.5, 8.0 and 6.4% in Japan, Korea, and Taiwan, respectively.When the frequencies were compared among the regions in Japan, the highest frequency was observed in that of esophageal carcinomas of Kagoshima (24.1%, 7/29), which was statistically significant. Otherwise, there was no regional difference in lung carcinomas.