Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan.
Preeminent Medical Photonics Education and Research Center Institute for NanoSuit Research, Hamamatsu University School of Medicine, 1-20-1 Handayama Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan.
Sci Rep. 2023 Apr 6;13(1):5514. doi: 10.1038/s41598-023-32486-8.
Recurrent respiratory papillomatosis (RRP) has a wide range of severity. We investigate the relationship between human papillomavirus (HPV) particle production and severity of RRP. From September 2005 to June 2021, 68 RRP samples (from 29 patients) were included. HPV type was determined. HPV viral load, physical status, and demographic and clinical characteristics were assessed. Immunohistochemistry (IHC) was performed for p16, Ki-67, L1, and E4. We used NanoSuit-CLEM (correlative light and electron microscopy) and transmission electron microscopy (TEM) to examine the samples. The total number of surgeries in HPV-positive and HPV-negative cases were 3.78 (n = 55/68, range: 1-16) and 1.30 (n = 13/68, range: 1-3), respectively (p = 0.02). IHC showed that L1 and E4 were correlated and expressed on the tumour surface. NanoSuit-CLEM and TEM revealed HPV particles in L1-positive nuclei. L1 IHC-positive cases had a shorter surgical interval (p < 0.01) and more frequent surgeries (p = 0.04). P16 IHC, viral load, and physical status were not associated with disease severity. This study visualised HPV particle production in RRP for the first time. Persistent HPV particle infection was associated with severity. We suggest L1 IHC for evaluating RRP severity in addition to the Derkay score.
复发性呼吸道乳头瘤病 (RRP) 的严重程度差异很大。我们研究了人类乳头瘤病毒 (HPV) 颗粒产生与 RRP 严重程度之间的关系。从 2005 年 9 月至 2021 年 6 月,纳入了 68 例 RRP 样本(来自 29 例患者)。确定 HPV 类型。评估 HPV 病毒载量、物理状态以及人口统计学和临床特征。进行免疫组化 (IHC) 检测 p16、Ki-67、L1 和 E4。我们使用 NanoSuit-CLEM(相关光和电子显微镜)和透射电子显微镜 (TEM) 检查样本。HPV 阳性和 HPV 阴性病例的总手术次数分别为 3.78(n=55/68,范围:1-16)和 1.30(n=13/68,范围:1-3)(p=0.02)。IHC 显示 L1 和 E4 相关并在肿瘤表面表达。NanoSuit-CLEM 和 TEM 显示 HPV 颗粒在 L1 阳性核内。L1 IHC 阳性病例的手术间隔更短(p<0.01)且手术更频繁(p=0.04)。P16 IHC、病毒载量和物理状态与疾病严重程度无关。本研究首次在 RRP 中观察到 HPV 颗粒的产生。持续性 HPV 颗粒感染与严重程度相关。我们建议除了 Derkay 评分外,还使用 L1 IHC 评估 RRP 的严重程度。