Phototheranostics of Cervical Neoplasms with Chlorin e6 Photosensitizer

Abstract

(1) Purpose: Improving the treatment effectiveness of intraepithelial neoplasia of the cervix associated with human papillomavirus infection, based on the application of the method of photodynamic therapy with simultaneous laser excitation of fluorescence to clarify the boundaries of cervical neoplasms. (2) Methods: Examination and treatment of 52 patients aged 22 to 53 years with morphologically and cytologically confirmed mild to severe intraepithelial cervix neoplasia, preinvasive, micro-invasive, and squamous cell cervix carcinoma. All patients were carriers of human papillomavirus infection. The patients underwent photodynamic therapy with simultaneous laser excitation of fluorescence. The combined use of video and spectral fluorescence diagnostics for cervical neoplasms made it possible to control the photodynamic therapy process at all stages of the procedure. Evaluation of the photodynamic therapy of intraepithelial cervical neoplasms was carried out with colposcopic examination, cytological conclusion, and morphological verification of the biopsy material after the photodynamic therapy course. The success of human papillomavirus therapy was assessed based on the results of the polymerase chain reaction. (3) Results. The possibility of simultaneous spectral fluorescence diagnostics and photodynamic therapy using a laser source with a wavelength of 660 nm has been established, making it possible to assess the fluorescence index in real-time and control the photobleaching of photosensitizers in the irradiated area. The treatment of all 52 patients was successful after the first photodynamic therapy procedure. According to the PCR test of the discharge from the cervical canal, the previously identified HPV types were not observed in 48 patients. Previously identified HPV types were absent after repeated PDT in four patients (CIN III (n = 2), CIS (n = 2)). In 80.8% of patients, regression of the lesion was noted. (4) Conclusions. The high efficiency of photodynamic therapy with intravenous photosensitizer administration of chlorin e6 has been demonstrated both in relation to eradication therapy of human papillomavirus and in relation to the treatment of intraepithelial lesions of the cervix.

Keywords: cervical cancer; cervical dysplasia; human papillomavirus; organ-preserving treatment; photodiagnostics; photodynamic therapy; phototheranostics.

Figure 1

Scheme of video fluorescence diagnostics of areas of pathologically altered tissue.

Figure 2

Scheme of video fluorescence diagnostics of areas of pathologically altered tissue.

Figure 3

Scheme of spectral fluorescence diagnostics of areas of pathologically altered tissue.

Figure 4

Images of cervical tissue from a patient with CIN III associated with HPV 6 and 16. (1) Before PDT. (2) After PDT. (a) Black-and-white mode. (b) Color mode. (c) Combined mode (in the upper left corner of the image is the fluorescence index in rel. units).

Figure 5

Results of spectral fluorescence diagnostics of cervical tissues of a patient with CIN III. The fluorescence spectra normalized to the laser line of the healthy and pathologically altered cervical tissue of the patient with CIN III before and after PDT using a laser with a wavelength of 660 nm in the investigated zones. (a) Zone 1. (b) Zone 2. (c) Zone 3. (d) Zone 4. (e,f) Zone 5.

Figure 6

Fluorescence indices of healthy and pathologically altered tissue of the patient cervix with CIN III before and after PDT in the investigated zones 1–5.

Figure 7

Cervix of the patient with CIN. (a) Before PDT. (b) Immediately after the end of PDT.

Figure 8

Results of histological examination of cervical biopsies of a 41-year-old patient with HSIL. (a–c) Lesion before PDT. (d–f) Lesion after PDT.