5-Aminolevulinic Acid-Mediated Photodynamic Therapy of Intraepithelial Neoplasia and Human Papillomavirus of the Uterine Cervix-A New Experimental Approach

Abstract

The aim of this study was to treat patients for ectocervical dysplasia [cervical intraepithelial neoplasia (CIN) grades 1 and 2] and associated human papilloma virus (HPV) infections with photodynamic therapy (PDT). In 20 patients, 5-aminolevulinic acid (5-ALA, 12% w/v) was applied topically with a cervical cap 8 h prior to illumination. A thermal light source (150 W halogen lamp) emitting a broadband red light (total energy: 100 J/cm2, fluence rate: 90 mW/cm2) was used for superficial illumination of the portio. In addition, an Nd:YAG pumped dye laser (652 nm) was used to illuminate the cervical canal (total energy: 50 J/cm2, fluence rate: 300 mW/cm2). Preliminary results of follow-ups at 1, 3, 6, and 9 months posttherapy showed a cytological improvement in the grading of the PAP smears in 19 patients and the eradication of cervical HPV in 80%. These results demonstrate that ectocervical dysplasia and associated HPV infections can be treated by PDT.

Photodynamic Therapy for Cervical Intraepithelial Neoplasia

“…Finally, HPV-DNA was not detected in 75, 74 and 72% at 3, 6 and 12 months after PDT. These data are consistent with Wierrani et al’s [17] report of 19 patients undergoing PDT. One year after PDT, 16 of 57 (28%) patients in our study still had HPV-DNA in cervical smears.…”

“…It may be because she worked in the sunshine during the summer season just after being discharged. In other reports of PDT using 5-ALA, cutaneous photosensitivity was not reported despite light exposure [15,16,17,18,19,20]. However, we believe the superior therapeutic profile of PHE justifies its use despite the increased phototoxicity.…”

“…Only three patients ultimately developed recurrent disease. There are several studies reporting disappointing results using PDT for the treatment of CIN [15,16,17,18,19,20]; however, these investigators used 5-aminolevulinic acid for a sensitization agent which we believe is inferior to the agent used in our study. For example, Hillemanns et al [16] performed PDT using 5-aminolevulinic (5-ALA) for sensitization and an argon-ion-pumped dye laser in 7 women with high grade CIN.…”

Fluorescence detection of cervical intraepithelial neoplasia for photodynamic therapy with the topical agents 5-aminolevulinic acid and benzoporphyrin-derivative monoacid ring

“…Dihematoporphyrin ether administered intravenously in earlier studies resulted in significant cutaneous photosensitivity, whereas topical administration required longer application times than the photosensitizers evaluated in this study. [12][13][14][15] The advantages of using newer, second-generation agents such as 5-ALA and BPD-MA include rapid plasma and tissue clearance, increased selectivity in dysplastic cells, and improved light absorp-tion in the visible red and near-infrared region of the electromagnetic spectrum. BPD-MA is activated at 690 nm, and 5-ALA (after its conversion to protoporphyrin IX) results in effective photosensitization at excitation wavelengths of 630 to 635 nm.…”

“…Wierrani et al 12 observed cytologic improvement in the grading of Papanicolaou smears in 19 of 20 patients with biopsy-proven low-grade lesions (human papillomavirus and cervical intraepithelial neoplasia [CIN] I) and CIN II after photodynamic therapy with topically applied aminolevulinic acid (ALA). 12 Monk et al 13 reported that 68% of 24 patients with CIN (grades I to III) were disease free 12 months after photodynamic therapy after 24-hour exposure to topical Photofrin with subsequent illumination with an argon-pumped dye laser at 635 nm. Finally, Muroya et al 14 treated 56 patients with cervical dysplasia and carcinoma in situ with photodynamic therapy with a systemically administered photosensitizer followed by laser with an excimer dye laser.…”