Objectives Anogenital warts (AGW, condylomata acuminata) and intraepithelial neoplasia (IEN) do not only impact health and social well-being, they are also associated with considerable costs for the healthcare systems. Immunocompromised and HIV-positive patients carry the highest epidemiological burden of human papillomavirus (HPV) infection and comprise a population specifically susceptible to treatment failures and recurrences. This systematic review aimed at identifying and appraising the available evidence from controlled studies of interventions for the treatment of AGW and IEN in immunocompromised patients.
Methods We conducted a comprehensive literature search. The Cochrane Collaboration's tool was used to assess risk of bias in included studies. Our confidence in the (pooled) effect-estimates was evaluated according to the Grading of Recommendations Assessment, Development and Evaluation approach. All evaluations were based on data independently extracted by two review authors.
Results Nine randomised controlled trials and two controlled studies were eligible, investigating external AGW, intra-anal and/or vaginal warts, and intra-anal and/or perianal IEN. The identified studies assessed imiquimod, cidofovir, fluorouracil, electrocautery, systemic interferon-α and interferon-β, and the combination of intralesional interferon-α and podophyllin. Four studies combined an ablational intervention with either imiquimod, cidofovir, intralesional or systemic interferon-α. One study investigated an experimental therapeutic vaccination (HPV 16 E7) at different concentrations.
Conclusions The quality of the evidence ranged from ‘very low’ to ‘moderate’ and was limited by the often small samples. Evidence was available for the efficacy of electrocautery for intra-anal IEN, and imiquimod cream for external AGW. Some further interventions should be subjected to investigations in larger samples. No data on some interventions established for the treatment of AGW in immunocompetent patients such as podophyllotoxin, sinecatechins, laser ablation or trichloroacetate were available. Future trials should address these gaps and include relevant patient-reported outcomes such as health-related quality of life.
- ANOGENITAL CONDITIONS
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Handling editor Jackie A Cassell.
Contributors RNW, LW, CD and AN developed the research question and methods section. RNW and LW selected eligible studies during the title/abstract-screening and full-text evaluation, extracted data from the included studies, appraised the quality of the evidence, entered and double-checked data for RevMan and analysed/interpreted the data. AN and CD were involved in cases of dissent with respect to extracted data/evaluations and participated in analysing and interpreting the data and in the final editing of the draft. RNW developed the draft of the manuscript, coordinated contributions of the co-authors and compiled the final draft.
Funding The conduct of the current review was not funded.
Competing interests The Division of Evidence based Medicine (dEBM) received research grants from various entities: The conduct of a previous systematic review and meta-analysis of topical interventions for anogenital warts in immunocompetent patients has been funded with an institutional research grant by Meda Pharma GmbH & Co. KG. The dEBM received research grants not associated with the current work by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V., European Academy of Dermatology and Venereology, Medigene, European Dermatology Forum, Pfizer, Merz, Deutsche Dermatologische Gesellschaft, Deutsche Gesellschaft für Allergologie und klinische Immunologie, Deutsche Dermatologische Akademie and GSK. The dEBM is currently involved in the development of a German clinical practice guideline on the management of HPV-associated anogenital lesions. AN is responsible for the grants given to dEBM. RNW, LW and CD declare to have no further conflicts of interests. AN has received personal honoraria for educational activity with direct or indirect sponsoring from Novartis, Pfizer, Boehringer Ingelheim, Bayer Healthcare, Jansen and Meda.
Provenance and peer review Not commissioned; externally peer reviewed.
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