MRC-University of Glasgow Centre for Virus Research; School of Infection and Immunity; College of Medical, Veterinary and Life Sciences, University of Glasgow, Garscube Estate, Glasgow, G61 1QH, Scotland, UK.
MRC-University of Glasgow Centre for Virus Research; School of Infection and Immunity; College of Medical, Veterinary and Life Sciences, University of Glasgow, Garscube Estate, Glasgow, G61 1QH, Scotland, UK.
EBioMedicine. 2023 May;91:104577. doi: 10.1016/j.ebiom.2023.104577. Epub 2023 Apr 15.
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.
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.
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.
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 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.
热疗是一种被广泛认可的癌症治疗方法。微波提供了一种非常精确、靶向的热疗手段，目前用于治疗由皮肤感染型人乳头瘤病毒（HPV）引起的足底疣。感染肛门生殖器黏膜的其他 HPV 基因型会引起生殖器疣或癌前病变或宫颈癌。目前缺乏针对这些 HPV 相关病变的有效、非消融性治疗方法。
在体外培养的 HPV 阳性宫颈肿瘤组织和 HPV 感染的正常永生化角质形成细胞形成的组织中研究微波治疗的分子后果。定量逆转录酶 PCR 用于定量 mRNA 表达。免疫组织化学和荧光免疫染色用于评估蛋白表达。
微波能量沉积在治疗部位诱导持续的局部细胞死亡。HPV 癌蛋白 E6 和 E7 的水平下调，同时细胞生长/增殖减少，凋亡/自噬增加。HSP70 表达证实了热疗，同时诱导了翻译应激。
数据表明，微波治疗抑制肿瘤细胞增殖，并允许 HPV 感染细胞的自然凋亡恢复。精确的微波传递为治疗 HPV 阳性肛门生殖器癌前病变和癌症提供了一种新的潜在治疗方法。
资助来自英国创新署生物医学催化计划（ID# 92138-556187）、首席科学家办公室资助（TCS/19/11）和医学研究委员会（MRC）-格拉斯哥大学病毒研究中心核心资金的核心支持（MC_ UU_12014）。
