Abstract
Vulvar cancer (VC) is a specific form of malignancy accounting for 5–6% of all gynaecologic malignancies. Although VC occurs most commonly in women after 60 years of age, disease incidence has risen progressively in premenopausal women in recent decades. VC demonstrates particular features requiring well-adapted therapeutic approaches to avoid potential treatment-related complications. Significant improvements in disease-free survival and overall survival rates for patients diagnosed with post-stage I disease have been achieved by implementing a combination therapy consisting of radical surgical resection, systemic chemotherapy and/or radiotherapy. Achieving local control remains challenging. However, mostly due to specific anatomical conditions, the need for comprehensive surgical reconstruction and frequent post-operative healing complications. Novel therapeutic tools better adapted to VC particularities are essential for improving individual outcomes. To this end, cold atmospheric plasma (CAP) treatment is a promising option for VC, and is particularly appropriate for the local treatment of dysplastic lesions, early intraepithelial cancer, and invasive tumours. In addition, CAP also helps reduce inflammatory complications and improve wound healing. The application of CAP may realise either directly or indirectly utilising nanoparticle technologies. CAP has demonstrated remarkable treatment benefits for several malignant conditions, and has created new medical fields, such as “plasma medicine” and “plasma oncology”. This article highlights the benefits of CAP for the treatment of VC, VC pre-stages, and postsurgical wound complications. There has not yet been a published report of CAP on vulvar cancer cells, and so this review summarises the progress made in gynaecological oncology and in other cancers, and promotes an important, understudied area for future research. The paradigm shift from reactive to predictive, preventive and personalised medical approaches in overall VC management is also considered.
Highlights
Cold atmospheric plasma (CAP) is a highly reactive ionised physical state containing a mixture of physical and biologically active agents
As the surgical treatment of vulvar squamous cell carcinomas (VSCC) is associated with significant morbidity and high recurrence rates, which are related to the limited ability to distinguishmalignant from healthy tissue, there is a need for new tools for the real-time detection of occult tumour lesions and the localisation of cancer margins in patients with VSCC
Taking into consideration a highly heterogeneous cohort of patients suffering from impaired healing, individualised profiling as a predictive diagnosis is instrumental for cost-effective targeted secondary prevention, as demonstrated in the multi-professional publication “Wound Healing: Proof-of-Principle Model for the Modern Hospital—Patient Stratification, Prediction, Prevention and Personalisation of Treatment” [314]
Summary
Cold atmospheric plasma (CAP) is a highly reactive ionised physical state containing a mixture of physical and biologically active agents. Plasma-derived reactive species are free radicals, including oxygen forms (ozone O3, superoxide anion O2−), hydroxyl radical (OH), hydrogen peroxide (H2O2), nitrogen dioxide radical (NO2), nitric oxide (NO), peroxynitrite (ONOO−), organic radicals, electrons, energetic ions, and charged particles [2,3,4,5,6,7] Study of their interaction with biological cell or tissue components revealed that biological plasma effects are mediated via reactive oxygen (ROS) and nitrogen species (RNS) which affect cellular redox-regulated processes [8,9], initiating many cellular responses with selectively-targeted anti-tumour effects (e.g., inhibition of cell adhesion, selective apoptosis, necrosis or the inhibition of cell proliferation by disrupting the S-phase of cell replication in tumour cells, suppression of metastatic cell migration, induction of membrane permeation or inducing lethal DNA damage) [10]. Non-thermally operated plasma sources could be a suitable alternative for the treatment of precancerous and cancerous lesions in gynaecological oncology especially, due to small size and high flexibility of the application probes
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