Gastro-Intestinal Viral Oncology Group, Ingham Institute for Applied Medical Research, Liverpool, Sydney, New South Wales, Australia; South Western Sydney Clinical School, University of New South Wales, Kensington, Sydney, New South Wales, Australia; Department of Gastroenterology and Hepatology, Bankstown-Lidcombe Hospital, South Western Sydney Local Health Network, Bankstown, Sydney, New South Wales, Australia.
Gastro-Intestinal Viral Oncology Group, Ingham Institute for Applied Medical Research, Liverpool, Sydney, New South Wales, Australia; South Western Sydney Clinical School, University of New South Wales, Kensington, Sydney, New South Wales, Australia.
Clin Gastroenterol Hepatol. 2015 Jul;13(7):1364-1368.e5. doi: 10.1016/j.cgh.2014.11.017. Epub 2014 Nov 21.
We investigated the role of high-risk human papillomavirus (hr-HPV) in patients with Barrett's dysplasia and adenocarcinoma (EAC). Clearance vs persistence of HPV (DNA, E6 or E7 mRNA, and p16INK4A protein) and overexpression or mutation of p53 were determined for 40 patients who underwent endotherapy for Barrett's dysplasia or EAC. After ablation, dysplasia or neoplasia was eradicated in 34 subjects (24 squamous, 10 intestinal metaplasia). Six patients had detectable lesions after treatment; 2 were positive for transcriptionally active hr-HPV, and 4 had overexpression of p53. Before endotherapy, 15 patients had biologically active hr-HPV, 13 cleared the infection with treatment, and dysplasia or EAC was eliminated from 12 patients. One patient who cleared HPV after ablation acquired a p53 mutation, and their cancer progressed. Of 13 patients with overexpression of p53 before treatment, 10 cleared the p53 abnormality after ablation with eradication of dysplasia or neoplasia, whereas 3 of 13 had persistent p53 mutation-associated dysplasia after endotherapy (P = .004). Immunohistochemical and sequence analyses of p53 produced concordant results for 36 of 40 samples (90%). Detection of dysplasia or neoplasia after treatment was associated with HPV persistence or continued p53 overexpression.
我们研究了高危型人乳头瘤病毒（hr-HPV）在 Barrett 异型增生和食管腺癌（EAC）患者中的作用。对 40 例接受 Barrett 异型增生或 EAC 内镜治疗的患者进行了 HPV（DNA、E6 或 E7mRNA 和 p16INK4A 蛋白）清除与持续、p53 过表达或突变的检测。消融后，34 例（24 例为鳞状细胞、10 例为肠上皮化生）患者的异型增生或肿瘤被消除。6 例治疗后仍可检测到病变；其中 2 例为转录活性 hr-HPV 阳性，4 例为 p53 过表达。内镜治疗前，15 例患者存在具有生物活性的 hr-HPV，13 例经治疗清除了感染，12 例异型增生或 EAC 被消除。1 例消融后 HPV 清除的患者获得了 p53 突变，且癌症进展。治疗前 13 例 p53 过表达的患者中，10 例在消融后 p53 异常清除，异型增生或肿瘤被消除，而 13 例中有 3 例在 EAC 后仍持续存在 p53 突变相关的异型增生（P =.004）。p53 的免疫组化和序列分析在 40 例样本中的 36 例（90%）中产生了一致的结果。治疗后发现异型增生或肿瘤与 HPV 持续存在或 p53 持续过表达有关。
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