Is Proflavine Exposure Associated with Disease Progression in Women with Cervical Dysplasia? A Brief Report

Abstract

Proflavine is an acridine dye used with high‐resolution microendoscopy for in vivo diagnostic evaluation of cervical epithelial cells. However, there are concerns that even short‐term exposure of cervical tissue to dilute proflavine may increase cervical cancer risk. We performed a retrospective analysis of women referred for colposcopy to Barretos Cancer Hospital comparing the risk of cervical disease progression in those whose cervical tissue was (n = 232) or was not exposed (n = 160) to proflavine. Patients in both groups underwent treatment and follow‐up based on histopathologic results and per the local standards of care. Progression of disease was evaluated by comparing histopathology from the initial visit to the worst subsequent histopathology result from all follow‐up visits. Mean duration of follow‐up was 18.7 and 20.1 months for the proflavine‐exposed and controls groups, respectively. There were no significant differences in disease progression from normal/CIN1 to CIN2/3 or from any initial diagnosis to invasive cancer between the proflavine exposed and control groups overall. Risks of cervical dysplasia progression observed in this study are in agreement with those of the natural history of cervical cancer. Our results suggest that cervical exposure to dilute proflavine does not increase the risk of cervical precancer and cancer.

Comparative Study Regarding the Properties of Methylene Blue and Proflavine and Their Optimal Concentrations for In Vitro and In Vivo Applications

“…It was observed that there were no noticeable differences in disease progression from the initial diagnostic to invasive cancer between the proflavine exposed and control groups overall. Some risks of cervical dysplasia progression were observed, but these findings were in good correlation with those observed for the natural cases of cervical cancer [35]. These findings are thus promising for using PRO in early diagnostic.…”

“…The basis of its antibacterial property is its action as a nucleic acid intercalator. As a result of this important property, PRO is routinely used for umbilical cord care in newborn infants in the United States, with rare episodes of toxicity reported thus far [35].…”

“…Different authors reported the use of both dyes for diagnostic procedures including: in vivo confocal laser endomicroscopy [37,38], in vivo microscopy to identify Barrett's esophagus [39], pathological changes in oral mucosa [40], colon [9], stomach [41], duodenum, upper gastrointestinal tract [41] and central airway, cervical tissue [35,42], cervix [35], sarcoma [43], urinary fistula [44], sentinel node (SN)'s, head and neck cancers [45], breast cancer [17], and gastrointestinal and thyroid surgery [10]. Apart from MB and PRO's ability to stain nuclei, the latter also stains non-specifically the membranes of adipocyte cells, making it possible to identify adipocytes without using a contrast agent [43].…”

“…If combined with in vivo microscopy, the injection of PRO in tissue allows the assessment of precancerous lesions [35]. Thus, only 1 mL of 0.01% PRO solution topically applied and associated with digital photography helped the surgeons to determine the most suitable places for performing biopsies [36].…”

“…injected in mouse and human cells increases antiviral immunity via the STING mechanism. If this amount of dye was applied for 3 successive days, the viral titers drop about 100-fold [35].…”