Association between human papillomavirus particle production and the severity of recurrent respiratory papillomatosis

Satoshi Yamada; Toshiya Itoh; Taro Ikegami; Atsushi Imai; Daiki Mochizuki; Hiroshi Nakanishi; Ryuji Ishikawa; Junya Kita; Yuki Nakamura; Yoshinori Takizawa; Jun Okamura; Yoshihiro Noda; Toshihide Iwashita; Takahiko Hariyama; Mikio Suzuki; Kiyoshi Misawa; Hideya Kawasaki

doi:10.1038/s41598-023-32486-8

Association between human papillomavirus particle production and the severity of recurrent respiratory papillomatosis

Sci Rep. 2023 Apr 6;13(1):5514. doi: 10.1038/s41598-023-32486-8.

Authors

Satoshi Yamada^{1

2}, Toshiya Itoh^{2

3}, Taro Ikegami⁴, Atsushi Imai¹, Daiki Mochizuki¹, Hiroshi Nakanishi¹, Ryuji Ishikawa¹, Junya Kita¹, Yuki Nakamura¹, Yoshinori Takizawa¹, Jun Okamura⁵, Yoshihiro Noda⁶, Toshihide Iwashita⁷, Takahiko Hariyama², Mikio Suzuki⁴, Kiyoshi Misawa⁸, Hideya Kawasaki^{9

10}

Affiliations

¹ Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan.
² 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.
³ Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
⁴ Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
⁵ Department of Otorhinolaryngology, Seirei Hamamatsu General Hospital, Hamamatsu, Japan.
⁶ Department of Otorhinolaryngology, Seirei Mikatahara General Hospital, Hamamatsu, Japan.
⁷ Department of Regenerative and Infectious Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
⁸ Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan. kiyoshim@hama-med.ac.jp.
⁹ 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. gloria@hama-med.ac.jp.
¹⁰ Department of Regenerative and Infectious Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan. gloria@hama-med.ac.jp.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Human Papillomavirus Viruses
Human papillomavirus 11
Human papillomavirus 6
Humans
Papillomavirus Infections*
Respiratory Tract Infections*

Supplementary concepts

Recurrent respiratory papillomatosis