Correlation of Radiation Response of Cervical Cancer Stem Cells with Their Initial Number before Treatment and Molecular Genetic Features of Papillomavirus Infection

Bull Exp Biol Med. 2020 Dec;170(2):241-245. doi: 10.1007/s10517-020-05043-w. Epub 2020 Dec 2.

Abstract

The proportion of CD44+CD24low cancer stem cells (CSC) was determined in cervical scrapings of 41 patients with squamous cell carcinoma of the uterine cervix before treatment and after irradiation in a total focal dose of 10 Gy. The relationship of quantitative changes in the CSC population with such parameters of papillomavirus infection as genotype, viral load, and physical status of HPV DNA (the absence or presence of HPV DNA integration into the cell genome and the degree of integration) was studied. Single- and multi-factor analysis revealed 2 independent indicators affecting the radiation response of CSC: initial number of these cells before treatment and physical status of HPV DNA. The increase in the CSC proportion after radiation exposure was observed 4.5-fold more often in patients with an initially low proportion of CSC (<3%) than that in other patients (p=0.001). The CSC proportion increased by on average 3% after irradiation in patients with complete integration of HPV 16/18 DNA and decreased by 3.8 % in patients with partial integration or no integration (p=0.03).

Keywords: cancer stem cells; cervical cancer; human papillomavirus; integration of viral DNA; radiotherapy.

MeSH terms

  • Adult
  • Aged
  • Alphapapillomavirus
  • CD24 Antigen / biosynthesis
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / radiotherapy*
  • Carcinoma, Squamous Cell / virology
  • Cervix Uteri / virology
  • DNA, Viral / metabolism
  • Female
  • Genotype
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 18 / genetics
  • Humans
  • Hyaluronan Receptors / biosynthesis
  • Middle Aged
  • Molecular Biology
  • Neoplastic Stem Cells / radiation effects*
  • Papillomavirus Infections / complications
  • Papillomavirus Infections / genetics
  • Radiation Tolerance
  • Treatment Outcome
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / radiotherapy*
  • Uterine Cervical Neoplasms / virology
  • Viral Load
  • Virus Integration
  • Young Adult

Substances

  • CD24 Antigen
  • CD24 protein, human
  • CD44 protein, human
  • DNA, Viral
  • Hyaluronan Receptors