Noninvasive Physical Plasma as Innovative and Tissue-Preserving Therapy for Women Positive for Cervical Intraepithelial Neoplasia

Simple Summary The treatment of cervical intraepithelial neoplasia (CIN) is still associated with the use of invasive therapeutic procedures. Although CIN 1/2 lesions show high remission rates, treatment is necessary in individual cases and noninvasive and oncologically safe therapeutic options should be available for these patients. Here, we characterized the antineoplastic properties of noninvasive physical plasma (NIPP) at the in vitro, ex vivo and in vivo levels and performed a prospective, single-armed phase-IIb trial on 20 patients with CIN1/2 (NCT03218436). NIPP-treated dysplastic cell models exhibited significant cell growth retardation due to DNA damage, cell cycle arrest and apoptosis. A tissue level analysis showed a transmucosal tissue devitalization while preserving the tissue morphology. Within 24 weeks of follow-up, treatment success was achieved in 19 (95%) participants with CIN 1/2 without peri- or postinterventional complications. Therefore, NIPP may be a sufficient treatment alternative for CIN, other mucosal dysplasia and beyond. (1) Background: Cervical intraepithelial neoplasia (CIN) of long-term persistence or associated with individual treatment indications often requires highly invasive treatments. These are associated with risks of bleeding, infertility, and pregnancy complications. For low- and middle-income countries (LMICs), standard treatment procedures are difficult to implement and manage. We characterized the application of the highly energized gas "noninvasive physical plasma" (NIPP) for tissue devitalization and the treatment of CIN. (2) Methods: We report the establishment of a promising tissue devitalization procedure by NIPP application. The procedure was characterized at the in vitro, ex vivo and in vivo levels. We performed the first prospective, single-armed phase-IIb trial in 20 CIN1/2 patients (NCT03218436). (3) Results: NIPP-treated cervical cancer cells used as dysplastic in vitro model exhibited significant cell growth retardation due to DNA damage, cell cycle arrest and apoptosis. Ex vivo and in vivo tissue assessments showed a highly noninvasive and tissue-preserving treatment procedure which induces transmucosal tissue devitalization. Twenty participants were treated with NIPP and attended a 24-week follow-up. Treatment success was achieved in 19 (95%) participants without postinterventional complications other than mild to moderate discomfort during application. (4) Conclusions: The results from this study preliminarily suggest that NIPP could be used for an effective and tissue-preserving treatment for CIN without the disadvantages of standard treatments. However, randomized controlled trials must confirm the efficacy and noninferiority of NIPP compared to standard treatments.