@article{d47a1208826148d8803985743c4f8b41,
title = "Cells with stem-like properties are associated with the development of HPV18-positive cervical cancer",
abstract = "The cellular origins of cervical cancer and the histological differentiation of human papillomavirus (HPV)-infected cells remain unexplained. To gain new insights into the carcinogenesis and histological differentiation of HPV-associated cervical cancer, we focused on cervical cancer with mixed histological types. We conducted genomic and transcriptomic analyses of cervical cancers with mixed histological types. The commonality of the cellular origins of these cancers was inferred using phylogenetic analysis and by assessing the HPV integration sites. Carcinogenesis was estimated by analyzing human gene expression profiles in different histological types. Among 42 cervical cancers with known HPV types, mixed histological types were detected in four cases, and three of them were HPV18-positive. Phylogenetic analysis of these three cases revealed that the different histological types had a common cell of origin. Moreover, the HPV-derived transcriptome and HPV integration sites were common among different histological types, suggesting that HPV integration could occur before differentiation into each histological type. Human gene expression profiles indicated that HPV18-positive cancer retained immunologically cold components with stem cell properties. Mixed cervical cancer has a common cellular origin among different histological types, and progenitor cells with stem-like properties may be associated with the development of HPV18-positive cervical cancer.",
keywords = "cell of origin, cervical cancer, human papillomavirus, stem cell, tumor immunogenicity",
author = "Misako Kusakabe and Ayumi Taguchi and Michihiro Tanikawa and Ryota Wagatsuma and Miki Yamazaki and Saki Tsuchimochi and Yusuke Toyohara and Akira Kawata and Satoshi Baba and Toshihide Ueno and Kenbun Sone and Mayuyo Mori-Uchino and Masako Ikemura and Hiroko Matsunaga and Takeshi Nagamatsu and Osamu Wada-Hiraike and Masahito Kawazu and Tetsuo Ushiku and Haruko Takeyama and Katsutoshi Oda and Kei Kawana and Hiroyuki Mano and Yutaka Osuga",
note = "Funding Information: The authors thank Yuko Aoki (Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo) and Naoko Suzuki (Department of Life Science and Medical Bioscience, Waseda University) for technical support with the experiments. We also thank Iwao Kukimoto (Pathogen Genomics Center, National Institute of Infectious Diseases) for HPV genotyping. The supercomputing resource was provided by the Human Genome Center, The University of Tokyo. Funding Information: This study was supported by a grant to A.T. by AMED (Grant Number: 22wm0325014h0003) and JSPS KAKENHI (Grant Number: 20K18157). This research was partially supported by the Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research, BINDS) from AMED (Grant Number: JP21am0101104 and Research Support Project for Life Science and Drug Discovery (BINDS) under Grant Number JP22ama121055). The funders did not have any role in the study design, collection, analysis, and interpretation of the data, preparation of the manuscript, or decision to submit the article for publication. Publisher Copyright: {\textcopyright} 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.",
year = "2023",
month = mar,
doi = "10.1111/cas.15664",
language = "English",
volume = "114",
pages = "885--895",
journal = "Cancer Science",
issn = "1347-9032",
publisher = "Wiley-Blackwell",
number = "3",
}