Department of Surgical Oncology and Digestive Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Oncol Rep. 2010 Apr;23(4):1085-92. doi: 10.3892/or_00000736.
A number of studies have reported the presence of human papillomavirus (HPV) in lung carcinoma. Interestingly, its detection rate appears to differ histologically and geographically. The present study examined 30 adenocarcinomas and 27 squamous cell carcinomas of the lung in a southern area of Japan, and detected high-risk HPV genome in 9 (30%) adenocarcinomas and 2 (7%) squamous cell carcinomas, using PCR with SPF10 primers and INNO-LiPA HPV genotyping assay. The difference of HPV detection rates in adenocarcinomas and squamous cell carcinomas was statistically significant (P=0.044, Fisher's exact test). HPV-16 was the most prevalent HPV genotype, and was detected in 27% (8/30) of adenocarcinomas and in 7% (2/27) of squamous cell carcinomas. High-risk-HPV positive carcinomas had decreased proportions of pRb (P=0.107) and significantly increased proportions of p16INK4a expressing cells (P=0.031) when compared to HPV-negative lung carcinomas. All HPV-16-positive cases were considered to have an integrated form of HPV-16 but its viral load was low (geometric mean = 0.02 copy per cell). In 20 additional adenocarcinomas treated with gefitinib, a tyrosine kinase inhibitor specific for epidermal growth factor receptor, the presence of HPV was examined. Note that East Asian ethnicity is a predictive factor of gefitinib response. High-risk HPV genome was found in 75% (6/8) of adenocarcinomas with complete or partial response to gefitinib but was not found in the remaining 12, which did not respond to gefitinib. In conclusion, the present study suggests that high-risk HPV may be more strongly related to adenocarcinomas, particularly gefitinib-responsive adenocarcinomas, when compared to squamous cell carcinomas. However, its low viral load makes it difficult to determine the etiological significance of these findings.
一些研究报道了人乳头瘤病毒（HPV）在肺癌中的存在。有趣的是，其检测率似乎在组织学和地域上有所不同。本研究在日本南部地区检查了 30 例腺癌和 27 例鳞状细胞癌，并使用 SPF10 引物和 INNO-LiPA HPV 基因分型检测试剂盒在 9 例（30%）腺癌和 2 例（7%）鳞状细胞癌中检测到高危 HPV 基因组。腺癌和鳞状细胞癌中 HPV 检测率的差异具有统计学意义（P=0.044，Fisher 确切检验）。HPV-16 是最常见的 HPV 基因型，在 27%（8/30）的腺癌和 7%（2/27）的鳞状细胞癌中被检测到。与 HPV 阴性的肺癌相比，高危 HPV 阳性的癌中 pRb 的比例降低（P=0.107），p16INK4a 表达细胞的比例显著增加（P=0.031）。所有 HPV-16 阳性病例均被认为具有 HPV-16 的整合形式，但病毒载量较低（几何平均值为 0.02 拷贝/细胞）。在另外 20 例接受吉非替尼治疗的腺癌中，一种针对表皮生长因子受体的酪氨酸激酶抑制剂，检查了 HPV 的存在。需要注意的是，东亚人种是吉非替尼反应的预测因素。在对吉非替尼完全或部分有反应的 8 例腺癌中有 75%（6/8）发现高危 HPV 基因组，但在其余 12 例无反应的腺癌中未发现。综上所述，本研究表明，与鳞状细胞癌相比，高危 HPV 可能与腺癌，特别是对吉非替尼有反应的腺癌关系更密切。然而，其低病毒载量使得确定这些发现的病因学意义变得困难。
