Zhejiang Cancer Research Institute, Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China.
Department of Clinical Laboratory, Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China.
J Med Virol. 2023 May;95(5):e28761. doi: 10.1002/jmv.28761.
Persistent high-risk human papillomavirus (HR-HPV) infections cause cervical cancer and a fraction of head and neck cancer. To investigate whether HR-HPV infection might be also involved in the development of gastric cancer (GC), we developed a platform utilizing a rolling circle amplification (RCA)-based nested L1 polymerase chain reaction with Sanger sequencing to genotype the HPV DNA in cancer tissues of 361 GC and 89 oropharyngeal squamous cell carcinomas (OPSCC). HPV transcriptional activity was determined by E6/E7 mRNA expression and a 3' rapid amplification of cDNA ends was performed to identify HPV integration and expression of virus-host fusion transcripts. Ten of 361 GC, 2 of 89 OPSCC, and 1 of 22 normal adjacent tissues were HPV L1 DNA-positive. Five of the 10 HPV-positive GC were genotyped as HPV16 by sequencing and 1 of 2 GC with RCA/nested HPV16 E6/E7 DNA detection exhibited HPV16 E6/E7 mRNA. Two OPSCC displayed HPV16 L1 DNA and E6/E7 mRNA, of which 1 OPSCC tissue showed virus-host RNA fusion transcripts from an intron region of KIAA0825 gene. Together, our data reveal viral oncogene expression and/or integration in GC and OPSCC and a possible etiology role of HPV infections in gastric carcinogenesis.
持续的高危型人乳头瘤病毒（HR-HPV）感染可导致宫颈癌和部分头颈部癌症。为了研究 HR-HPV 感染是否也与胃癌（GC）的发生有关，我们开发了一种平台，利用基于滚环扩增（RCA）的嵌套 L1 聚合酶链反应结合 Sanger 测序，对 361 例 GC 和 89 例口咽鳞状细胞癌（OPSCC）的癌组织中的 HPV DNA 进行基因分型。通过 E6/E7 mRNA 表达来确定 HPV 转录活性，并进行 3'快速 cDNA 末端扩增以鉴定 HPV 整合和病毒-宿主融合转录本的表达。在 361 例 GC 中，有 10 例、89 例 OPSCC 中有 2 例和 22 例正常相邻组织中有 HPV L1 DNA 阳性。测序显示，这 10 例 HPV 阳性 GC 中有 5 例为 HPV16 型，2 例用 RCA/嵌套 HPV16 E6/E7 DNA 检测到 HPV16 E6/E7 mRNA 的 GC 中有 1 例。2 例 OPSCC 显示 HPV16 L1 DNA 和 E6/E7 mRNA，其中 1 例 OPSCC 组织显示来自 KIAA0825 基因内含子区域的病毒-宿主 RNA 融合转录本。总之，我们的数据揭示了 GC 和 OPSCC 中病毒癌基因的表达和/或整合，以及 HPV 感染在胃癌发生中的可能病因作用。
