The effectiveness and tolerability of imiquimod suppositories to treat extensive intra-anal high-grade squamous intraepithelial lesions/warts in HIV-infected individuals
Restricted accessResearch articleFirst published online October, 2019
The effectiveness and tolerability of imiquimod suppositories to treat extensive intra-anal high-grade squamous intraepithelial lesions/warts in HIV-infected individuals
Topical imiquimod is a potential treatment for intra-anal condyloma and squamous intraepithelial lesions caused by human papillomavirus (HPV). We aimed to assess the effectiveness and tolerability of imiquimod suppositories for the treatment of anal high-grade intraepithelial lesions (HSIL) and condylomas in HIV-infected patients. We conducted a retrospective analysis in a prospectively followed cohort. High-resolution anoscopy was used for diagnosis and assessment following treatment. Patients’ tolerability was assessed with a self-administered survey. Ninety-five patients (94.7% men) were analyzed. All were on combination antiretroviral therapy. Median CD4 T-cell count was 690 cells/µL, 89% had undetectable plasma viral load. Response to imiquimod was seen in 46.3% (complete: 12.5%, partial: 33.8%) in the intent-to-treat analysis, and in 55.2% (complete: 14.9%, partial: 40.3%) in the on-treatment analysis. Higher response rates were observed for anal condyloma compared with HSIL. A significantly poorer response rate was observed in smokers and in individuals with lower nadir CD4 T-cell counts. Imiquimod tolerability was “good” in 57.1% (n = 36), “acceptable” in 33.3% (n = 21), and “poor” in 9.5% (n = 6). Systemic side effects were reported in 20.7% (n = 13). There was no association between treatment effect and tolerability. In conclusion, imiquimod stands as a well-tolerated option for the treatment of HPV-associated intra-anal pathology in HIV-infected individuals.
DalingJRWeissNSHislopTG, et al.
Sexual practices, sexually transmitted diseases, and the incidence of anal cancer. N Engl J Med1987;
317: 973–977.
2.
Crum-CianfloneNFHullsiekKHMarconiVC, et al.
Anal cancers among HIV-infected persons: HAART is not slowing rising incidence. AIDS2010;
24: 535–543.
3.
WeisSEVecinoIPogodaJM, et al.
Treatment of high-grade anal intraepithelial neoplasia with infrared coagulation in a primary care population of HIV-infected men and women. Dis Colon Rectum2012;
55: 1236–1243.
4.
GassenmaierAFuchsPSchellH, et al.
Papillomavirus DNA in warts of immunosuppressed renal allograft recipients. Arch Dermatol Res1986;
278: 219–223.
5.
SilveraRJSmithCKSwedishKA, et al.
Anal condyloma treatment and recurrence in HIV-negative men who have sex with men. Dis Colon Rectum2014;
57: 752–761.
6.
MoscickiA-BDarraghTMBerry-LawhornJM, et al.
Screening for anal cancer in women. J Low Genit Tract Dis2015;
19: S26–41.
7.
BrownSRSkinnerPTidyJ, et al.
Outcome after surgical resection for high-grade anal intraepithelial neoplasia (Bowen’s disease). Br J Surg1999;
86: 1063–1066.
8.
CranstonRDBakerJRLiuY, et al.
Topical application of trichloroacetic acid is efficacious for the treatment of internal anal high-grade squamous intraepithelial lesions in HIV-positive men. Sex Transm Dis2014;
41: 420–426.
9.
MegillCWilkinT.Topical therapies for the treatment of anal high-grade squamous intraepithelial lesions. Semin Colon Rectal Surg2017;
28: 86–90.
10.
RichelOWielandUde VriesHJC, et al.
Topical 5-fluorouracil treatment of anal intraepithelial neoplasia in human immunodeficiency virus-positive men. Br J Dermatol2010;
163: 1301–1307.
11.
GrimmCPolterauerSNatterC, et al.
Treatment of cervical intraepithelial neoplasia with topical imiquimod: a randomized controlled trial. Obstet Gynecol2012;
120: 152–159.
12.
RichelOde VriesHJCvan NoeselCJM, et al.
Comparison of imiquimod, topical fluorouracil, and electrocautery for the treatment of anal intraepithelial neoplasia in HIV-positive men who have sex with men: an open-label, randomised controlled trial. Lancet Oncol2013;
14: 346–353.
13.
van der SnoekEMden HollanderJCvan der EndeME.Imiquimod 5% cream for five consecutive days a week in an HIV-infected observational cohort up to 32 weeks in the treatment of high-grade squamous intraepithelial lesions: Table 1. Sex Transm Infect2015;
91: 245–247.
14.
KaspariMGutzmerRKaspariT, et al.
Application of imiquimod by suppositories (anal tampons) efficiently prevents recurrences after ablation of anal canal condyloma. Br J Dermatol2002;
147: 757–759.
15.
WielandUBrockmeyerNHWeissenbornSJ, et al.
Imiquimod treatment of anal intraepithelial neoplasia in HIV-positive men. Arch Dermatol2006;
142: 1438–1444.
16.
FoxPANathanMFrancisN, et al.
A double-blind, randomized controlled trial of the use of imiquimod cream for the treatment of anal canal high-grade anal intraepithelial neoplasia in HIV-positive MSM on HAART, with long-term follow-up data including the use of open-label imiquimod. AIDS2010;
24: 2331–2335.
17.
Salas-MárquezCRepiso-JiménezJBPadilla-EspañaL, et al.
Imiquimod anal tampons treatment of anal intraepithelial neoplasia. J Eur Acad Dermatol Venereol2018;
32: e334–e336.
18.
WillemsNLiboisANkuizeM, et al.
Treatment of anal dysplasia in HIV-positive men who have sex with men in a large AIDS reference centre. Acta Clin Belg2017;
72: 29–35.
19.
CranstonRDBakerJRSiegelA, et al.
A pilot study of the immunologic, virologic, and pathologic consequences of intra-anal 5% imiquimod in HIV-1-infected men with high-grade squamous intraepithelial lesions. Dis Colon Rectum2018;
61: 298–305.
20.
KreuterABrockmeyerNHWeissenbornSJ, et al.
5% imiquimod suppositories decrease the DNA load of intra-anal HPV types 6 and 11 in HIV-infected men after surgical ablation of condylomata acuminata. Arch Dermatol2006;
142: 243–244.
21.
SantorelliCLeoCABaldelliF, et al.
Response to imiquimod 5% cream as treatment for condyloma and anal intraepithelial neoplasia in HIV-positive and HIV-negative patients. Sex Transm Infect2017;
93: 229.
22.
SanclementeGHerreraSTyringSK, et al.
Human papillomavirus (HPV) viral load and HPV type in the clinical outcome of HIV-positive patients treated with imiquimod for anogenital warts and anal intraepithelial neoplasia. J Eur Acad Dermatol Venerol2007;
21: 1054–1060.
23.
SauderDNSkinnerRBFoxTL, et al.
Topical imiquimod 5% cream as an effective treatment for external genital and perianal warts in different patient populations. Sex Transm Dis2003;
30: 124–128.
24.
SaiagPBauhoferABouscaratF, et al.
Imiquimod 5% cream for external genital or perianal warts in human immunodeficiency virus-positive patients treated with highly active antiretroviral therapy: an open-label, noncomparative study. Br J Dermatol2009;
161: 904–909.
25.
PerryCMLambHM.Topical imiquimod: a review of its use in genital warts. Drugs1999;
58: 375–390.
26.
TawadaCOshitaniYKimuraM, et al.
Successful treatment of anal and perianal condyloma acuminata with imiquimod. Acta Derm Venereol2014;
94: 118–119.
27.
Serra-GuillenCNagoreEHuesoL, et al.
A randomized comparative study of tolerance and satisfaction in the treatment of actinic keratosis of the face and scalp between 5% imiquimod cream and photodynamic therapy with methyl aminolaevulinate. Br J Dermatol2011;
164: 429–433.
28.
JayNBerryJMHogeboomCJ, et al.
Colposcopic appearance of anal squamous intraepithelial lesions: relationship to histopathology. Dis Colon Rectum1997;
40: 919–928.
29.
TongWWYShepherdKGarlandS, et al.
Human papillomavirus 16–specific T-cell responses and spontaneous regression of anal high-grade squamous intraepithelial lesions. J Infect Dis2015;
211: 405–415.
30.
MacayaAMuñoz-SantosCBalaguerA, et al.
Interventions for anal canal intraepithelial neoplasia. Cochrane Database Syst Rev2012;
12:CD009244.
31.
KumarBNarangT.Local and systemic adverse effects to topical imiquimod due to systemic immune stimulation. Sex Transm Infect2011;
87: 432.
32.
International Collaboration of Epidemiological Studies of Cervical Cancer, ApplebyPBeralV, et al.
Carcinoma of the cervix and tobacco smoking: collaborative reanalysis of individual data on 13,541 women with carcinoma of the cervix and 23,017 women without carcinoma of the cervix from 23 epidemiological studies. Int J Cancer2006;
118: 1481–1495.
33.
WielandUHellmichMWetendorfJ, et al.
Smoking and anal high-risk human papillomavirus DNA loads in HIV-positive men who have sex with men. Int J Med Microbiol2015;
305: 689–696.
34.
ConleyLBushTDarraghTM, et al.
Factors associated with prevalent abnormal anal cytology in a large cohort of HIV-infected adults in the United States. J Infect Dis2010;
202: 1567–1576.
35.
de PokomandyARouleauDGhattasG, et al.
HAART and progression to high-grade anal intraepithelial neoplasia in men who have sex with men and are infected with HIV. Clin Infect Dis2011;
52: 1174–1181.
36.
PikettyCDarraghTMDa CostaM, et al.
High prevalence of anal human papillomavirus infection and anal cancer precursors among HIV-infected persons in the absence of anal intercourse. Ann Intern Med2003;
138: 453–459.
