Positive keratinocytes in 3D cell culture models: a novel therapy for HPV-associated disease

July 10, 2020

Microwave treatment induces cell stress pathways and inhibits HPV oncoprotein expression that causes tumour progression. Induction of apoptosis and reduced cell proliferation suggest a reversal of the cervical tumour phenotype in the 3D tissues. Access Microbiology, Vol 2, Iss 7A

High-risk human papillomavirus (HPV) is the causative agent of benign, precancerous and cancerous lesions, in both anogenital and oropharyngeal sites. Increased expression of the viral oncoproteins E6 and E7 are responsible for tumour progression. The treatment of these precancerous and cancerous lesions is invasive, painful and with long-term side effects. Localised microwaves have been used successfully in the clinic for the treatment of verrucas, which are caused by low-risk HPV genotypes (>75% success rate versus >33% for cryotherapy). Moreover, local hyperthermia is known to have anti-tumour effects.

Ten-second microwave treatment of 3D in vitro-grown cervical tumour tissues (HPV16-positive SiHa cell) resulted in cell death in the treated zone while the tissue integrity was disrupted in the adjacent area. Microwaves induced apoptosis (induction of cleaved caspase 3) and autophagy (induction of LC3) and inhibited cell proliferation (loss of Ki67 and MCM2) in the entire tissue. Furthermore, HPV16 E6 and E7 expression was reduced in cells in the treated and transition zones, with subsequent induction of expression of the apoptosis-regulator, p53 over a 24 hour period following microwave treatment. Thermal stress, identified with the Heat Shock Protein 70 (HSP70) and translational stress identified by G3BP expression, was observed in the transition zone.

In conclusion, we demonstrate that the microwave treatment induces cell stress pathways and inhibits HPV oncoprotein expression that causes tumour progression. Induction of apoptosis and reduced cell proliferation suggest a reversal of the cervical tumour phenotype in the 3D tissues.

1. College of Medical Veterinary and Life Sciences, Institute of Infection Immunity and Inflammation, Centre for Virus Research

2. Department of Pathology, University of Cambridge, Cambridge

Ilaria Epifano (1), Michaela J. Conley (1), Andrew Stevenson (1), John Doorbar (2), Sheila V. Graham (1)

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A feasibility study of microwave therapy for precancerous actinic keratosis

February 7, 2020

The results of this study conclude that a significantly higher proportion of treated AK areas responded than untreated (90% vs 15%; P < 0.001).

Thin AKs were more responsive than thick AKs. The site did not affect efficacy. Pain was severe, but brief (80% reported pain lasting ‘a few seconds only’). Adverse events were minimal. All participants who would choose microwave therapy over their current treatment cited the shorter discomfort period.

For full access to the published paper, visit Wiley Online.

Microwaves: A Painless, Efficient New Treatment for Plantar Warts

February 6, 2020

This is independent paper describes the challenges patients face when seeking treatment for plantar warts and provides an overview of his experience with Swift microwave therapy, and what it can do for his patients.

Published by Podiatry Management in March 2020, this is independent paper was written by board certified foot surgeon Dr Alec Hochstein for the New Concepts and Studies February forum. Dr Hochstein describes the challenges patients face when seeking treatment for plantar warts and provides an overview of his experience with Swift microwave therapy, and what it can do for his patients.

"With today’s advances in biotechnology, it is time to move past the ‘armamentarium’ of partially-effective treatments for verrucae. A true solution to viral infection can arise only from engaging the body’s own immune response, and Swift offers the best tool to activate that engagement."

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Verrucae: An update and contemporary approaches to management

November 5, 2018

This article provides a clinical update on the subject treating plantar warts and verrucae using newer modalities which are increasingly being used in podiatry.

Plantar warts or verrucae continue to be a common reason for a visit to the podiatrist. Previous CPD articles published on this topic have focused on chemical management and cryosurgery. In the last decade we have seen new research publications and the introduction of novel techniques into mainstream podiatry such as needling and microwave treatment. This article serves to provide a clinical update on the subject whilst focusing on these newer modalities, which are increasingly being used in podiatry.

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Roundtable discussion: Verrucae

September 4, 2018

Ivan Bristow, Anthony Davies, David Calway, Graham Howell, Jean Mooney discuss the latest developments in the treatment of verrucae.

Ivan Bristow, Anthony Davies, David Calway, Graham Howell, Jean Mooney discuss the latest developments in the treatment of verrucae.

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Microwave Therapy for Cutaneous Human Papilloma Virus Infection

September 3, 2017

A pilot study of microwave therapy to the skin in 32 individuals with 52 recalcitrant plantar warts is reported, alongside a molecular characterisation of the effects of microwaves on the skin.

Human papilloma virus (HPV) infection of keratinocytes causes cutaneous warts. Warts induce significant morbidity and disability but most therapies, including cryotherapy, laser and radiofrequency devices show low efficacy. Microwaves induce heating of tissue in a highly controllable, uniform manner and we set out to explore their use in treatment of HPV. We present a pilot study of microwave therapy to the skin in 32 individuals with 52 recalcitrant plantar warts. Additionally, we undertook a molecular characterisation of the effects of microwaves on the skin. Microwave therapy was well tolerated and 75.9% of lesions cleared, which compares favourably to 23-33% success for cryotherapy or salicylic acid. Microwaves specifically induced dendritic cell cross-presentation of HPV antigen to CD8+ T-cells in skin and we show that IL-6 may be important for IRF1 and IRF4 modulation to enhance this process. Keratinocyte-skin dendritic cell cross-talk is integral to host defence against HPV infections, and this study shows that microwave induces anti-HPV immunity which is important for treatment of warts and potentially HPV-related cancers.

Ivan Bristow BSc PhD; Wen Chean Lim BSc PhD; Alvin Lee MBBS (MD); Daniel Holbrook BSc; Natalia Savelyeva PhD; Peter Thomson BSc; Christopher Webb BSc; Marta Polak MSc PhD; Michael R. Ardern-Jones DPhil FRCP (MD PhD)

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The Successful Use of a Novel Microwave Device in the Treatment of a Plantar Wart

July 2, 2017

This case study was drawn from an ongoing project which has been granted full ethical approval from the Faculty of Health Sciences, University of Southampton. Bristow I.R., Webb C., Ardern-Jones M.R.

Plantar warts, caused by the human papilloma virus (HPV), are a commonly encountered condition presenting in clinic. In adults, an array of various therapies exists, frequently with modest results particularly with plantar lesions. Microwaves have had limited uses for medical purposes. Recently a new portable microwave device has been approved for the treatment of skin lesions. Prior research has demonstrated immuno-stimulatory effects against HPV infection. We report the application of a novel portable medical microwave unit to treat a long-standing plantar wart which had failed to respond to other treatment modalities.

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Treating Verruca Effectively with Microwave Energy – Are we getting warmer?

June 1, 2017

The basic science of microwave effects on skin and clinical responses noted suggest a mechanism for the observed action of microwaves in cutaneous warts.

The basic science of microwave effects on skin and clinical responses noted suggest a mechanism for the observed action of microwaves in cutaneous warts, although more research is required to further this knowledge. Our understanding of the molecular mechanisms of hyperthermia provides a strong case for this new technology to be explored further as a local immune response activator therapy. Additionally, it seems likely that there may be many other potential dermatology applications for this exciting technology.

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