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Topical 5‐fluorouracil treatment of anal intraepithelial neoplasia in human immunodeficiency virus‐positive men
Author(s) -
Richel O.,
Wieland U.,
De Vries H.J.C.,
Brockmeyer N.H.,
Van Noesel C.,
Potthoff A.,
Prins J.M.,
Kreuter A.
Publication year - 2010
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/j.1365-2133.2010.09982.x
Subject(s) - medicine , anal cancer , prospective cohort study , fluorouracil , gastroenterology , viral load , squamous intraepithelial lesion , surgery , cancer , cervical intraepithelial neoplasia , human immunodeficiency virus (hiv) , cervical cancer , immunology
Summary Background Anal intraepithelial neoplasia (AIN), a human papillomavirus (HPV)‐induced potential precursor lesion of anal cancer, is frequent among human immunodeficiency virus (HIV)‐positive men who have sex with men (MSM). So far, only a few prospective studies have been performed on the topical treatment of AIN, especially at the intra‐anal location. Objectives To evaluate the efficacy and safety of self‐administered topical 5‐fluorouracil (5‐FU) treatment of AIN in HIV‐positive MSM. Methods High‐resolution anoscopy (HRA) was performed and patients with AIN (grade 1–3) were treated with 5‐FU twice weekly for a total of 16 weeks. HRA‐guided lesional biopsies were repeated after 5‐FU treatment for histopathological evaluation. Lesional swabs were obtained before and after treatment for HPV typing and HPV‐DNA load determination of the high‐risk types HPV16, 18, 31 and 33. Responding patients returned 6 months after treatment for follow‐up. Results A total of 46 patients with AIN were included in this open prospective pilot study; 76% had multifocal disease and 74% had high‐grade lesions (AIN 2 or 3). In an intention‐to‐treat analysis, 26 of 46 patients (57%) responded to 5‐FU treatment. Eighteen patients (39%) had a complete clearance of AIN and eight patients (17%) had a partial response. Seventeen patients (37%) did not respond (unchanged grade of AIN in 16 patients and progression from low‐ to high‐grade AIN in one patient). 5‐FU treatment led to a significant decrease of HPV16‐DNA load and cumulative high‐risk HPV‐DNA load in both responding and nonresponding patients. Thirty‐nine patients (85%) experienced side‐effects during therapy, but only two discontinued 5‐FU treatment. One patient was lost to follow‐up. Six months later, 50% of the complete responders had a recurrence. Conclusions A substantial proportion of HIV‐positive MSM with AIN completely cleared their lesions with topical 5‐FU treatment. In those with partial response, pretreatment with topical 5‐FU might facilitate subsequent ablative therapy.