Effects of photodynamic therapy using topical applied hexylaminolevulinate and methylaminolevulinate upon the integrity of cervical epithelium.
OBJECTIVE
Cervical intraepithelial neoplasia (CIN) is associated with genital human papillomavirus (HPV) infection and represents the precursor of cervical cancer. Established ablative treatment methods may cause substantial complications in following pregnancies including premature delivery and the birth of low-weight babies. Photodynamic therapy (PDT) of CIN using esters of 5-aminolevulinic acid (5-ALA) represents a promising alternative. However, it has not been analyzed yet if the PDT itself leads to sustained damage of the cervical tissue. This study aims at evaluating the effect of hexylaminolevulinate (HAL) and methylaminolevulinate (MAL) PDT on cervical tissue.


METHODS
Twenty-five patients underwent 1-2 PDT cycles for CIN 1-3 applying topical HAL and MAL. Before and 6 months after PDT, biopsies were obtained from the cervix. Macroscopic changes of the cervix were evaluated. We assessed H&E slides for signs of sustained tissue damage. Furthermore, expression profiles of p16(INK4a), Ki67, Bcl-2, Bax, and CD31 were evaluated.


RESULTS
PDT was performed satisfactory in all patients. No macroscopic changes of the cervix were encountered and histological evaluation revealed no signs of apoptosis, necrosis, irritation, vascular changes and fibroses 6 months after PDT. Ki67 and p16(INK4a) were useful for the prediction of response to PDT. Bcl-2 and Bax showed no significant expression profile changes after PDT and the micro-vessel pattern was not altered.


CONCLUSIONS
HAL and MAL PDT do not leave any sustained damage in normal cervical tissue. This is of paramount importance as cervical insufficiency or stenosis may have implications on pregnancy and cervical cancer screening.
Soergel
Philipp
P
University Women's Clinic, Hannover Medical School, 30625 Hannover, Germany. soergel.philipp@mh-hannover.de
Loehr-Schulz
Regine
R
Hillemanns
Marija
M
Landwehr
Sandra
S
Makowski
Lars
L
Hillemanns
Peter
P
D000287:Administration, Topical; D000328:Adult; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015331:Cohort Studies; D004311:Double-Blind Method; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*
D014408:Biomarkers, Tumor; D017319:Photosensitizing Agents; C475457:methyl 5-aminolevulinate; D000622:Aminolevulinic Acid; C419924:5-aminolevulinic acid hexyl ester