Topical 5-fluorouracil treatment of anal intraepithelial neoplasia in human immunodeficiency virus-positive men.
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.


OBJECTIVE
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.
Richel
O
O
Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. o.richel@amc.uva.nl
Wieland
U
U
de Vries
H J C
HJ
Brockmeyer
N H
NH
van Noesel
C
C
Potthoff
A
A
Prins
J M
JM
Kreuter
A
A
D017088:AIDS-Related Opportunistic Infections / Q000150:complications; D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D001005:Anus Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use*; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D008297:Male; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000150:complications / Q000821:virology; D010865:Pilot Projects; D011446:Prospective Studies
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil