Microwave hyperthermia represses human papillomavirus oncoprotein activity and induces cell death due to cell stress in 3D tissue models of anogenital precancers and cancers

Conley, M. J. , Epifano, I. , Kirk, A., Stevenson, A. and Graham, S. V. (2023) Microwave hyperthermia represses human papillomavirus oncoprotein activity and induces cell death due to cell stress in 3D tissue models of anogenital precancers and cancers. EBioMedicine, 91, 104577. (doi: 10.1016/j.ebiom.2023.104577) (PMID:37068348) (PMCID:PMC10130467)

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Background: Hyperthermia is a well-accepted cancer therapy. Microwaves provide a very precise, targeted means of hyperthermia and are currently used to treat plantar warts caused by cutaneous-infective human papillomaviruses (HPVs). Other HPV genotypes infecting the anogenital mucosa cause genital warts or preneoplastic lesions or cervical cancer. Effective, non-ablative therapies for these morbid HPV-associated lesions are lacking. Methods: The molecular consequences of microwave treatment were investigated in in vitro cultured three-dimensional HPV-positive cervical tumour tissues, and tissues formed from HPV-infected normal immortalised keratinocytes. Microwave energy delivery to tissues was quantified. Quantitative reverse transcriptase PCR was used to quantify mRNA expression. Immunohistochemistry and fluorescence immunostaining was used to assess protein expression. Findings: Microwave energy deposition induced sustained, localised cell death at the treatment site. There was a downregulation in levels of HPV oncoproteins E6 and E7 alongside a reduction in cellular growth/proliferation and induction of apoptosis/autophagy. HSP70 expression confirmed hyperthermia, concomitant with induction of translational stress. Interpretation: The data suggest that microwave treatment inhibits tumour cell proliferation and allows the natural apoptosis of HPV-infected cells to resume. Precision microwave delivery presents a potential new treatment for treating HPV-positive anogenital precancerous lesions and cancers. Funding: Funding was through an Innovate UK Biomedical Catalyst grant (ID# 92138-556187), a Chief Scientist Office grant (TCS/19/11) and core support from Medical Research Council (MC_ UU_12014) core funding for the MRC-University of Glasgow Centre for Virus Research.

Item Type:Articles
Additional Information:Michaela J. Conley and Ilaria Epifano contributed equally to this study.
Glasgow Author(s) Enlighten ID:Stevenson, Mr Andrew and Graham, Professor Sheila and Conley, Dr Michaela and Kirk, Miss Anna and Epifano, Dr Ilaria
Authors: Conley, M. J., Epifano, I., Kirk, A., Stevenson, A., and Graham, S. V.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:EBioMedicine
ISSN (Online):2352-3964
Published Online:15 April 2023
Copyright Holders:Copyright © 2023 The Authors
First Published:First published in EBioMedicine 91: 104577
Publisher Policy:Reproduced under a Creative Commons License
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
315250MRC PE seed funding - John McLauchlanJohn McLauchlanMedical Research Council (MRC)MC_UU_12014III - Centre for Virus Research
306598MiTAG- Microwave treatment for anogenital diseaseSheila GrahamOffice of the Chief Scientific Adviser (CSO)N/AIII - Centre for Virus Research