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Association between human papillomavirus particle production and the severity of recurrent respiratory papillomatosis ヒトパピローマウイルス粒子産生と再発性呼吸器乳頭腫症の重症度との関連性 山田, 智史 ヤマダ, サトシ Yamada, Satoshi open access (C) The Author(s) 2023 This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. doctoral 医学系研究科 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. Springer Nature 2023-04-06 eng doctoral thesis VoR http://hdl.handle.net/10271/0002000197 https://hama-med.repo.nii.ac.jp/records/2000197 37024540 https://doi.org/10.1038/s41598-023-32486-8 2045-2322 Scientific Reports 13 13 5514 甲第951号 博士（医学） 2023-09-22 13802 浜松医科大学 https://hama-med.repo.nii.ac.jp/record/2000197/files/DT_951ronbun.pdf application/pdf 3.5 MB 2024-07-19