Cells with stem-like properties are associated with the development of HPV18-positive cervical cancer

Misako Kusakabe, Ayumi Taguchi*, Michihiro Tanikawa, Ryota Wagatsuma, Miki Yamazaki, Saki Tsuchimochi, Yusuke Toyohara, Akira Kawata, Satoshi Baba, Toshihide Ueno, Kenbun Sone, Mayuyo Mori-Uchino, Masako Ikemura, Hiroko Matsunaga, Takeshi Nagamatsu, Osamu Wada-Hiraike, Masahito Kawazu, Tetsuo Ushiku, Haruko Takeyama, Katsutoshi OdaKei Kawana, Hiroyuki Mano, Yutaka Osuga

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
JournalCancer Science
DOIs
Publication statusAccepted/In press - 2022

Keywords

  • cell of origin
  • cervical cancer
  • human papillomavirus
  • stem cell
  • tumor immunogenicity

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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