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Original Investigation |

High-Grade Dysplasia in Anogenital Warts of HIV-Positive Men ONLINE FIRST

Alexander Kreuter, MD1; Christos Siorokos, MD1; Frank Oellig, MD2; Steffi Silling, PhD3; Herbert Pfister, PhD3; Ulrike Wieland, MD3
[+] Author Affiliations
1Department of Dermatology, Venereology, and Allergology, HELIOS St. Elisabeth Hospital Oberhausen, Oberhausen, University of Witten-Herdecke, Germany
2Institute of Pathology, Mülheim an der Ruhr, Mülheim, Germany
3National Reference Center for Papilloma- and Polyomaviruses, Institute of Virology, Uniklinik Köln, University of Cologne, Cologne, Germany
JAMA Dermatol. Published online July 27, 2016. doi:10.1001/jamadermatol.2016.2503
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Importance  Human papillomavirus (HPV)-induced anogenital lesions are very frequent in men who have sex with men (MSM) who are HIV-positive (HIV+). Anogenital warts (AGWs) are considered benign lesions caused by low-risk HPV-types, whereas anogenital dysplasias are potential cancer precursors associated with high-risk HPV-types. Both types of lesions can usually be distinguished clinically.

Objective  To describe a case series of HIV+ MSM with typical AGW that harbored different grades of dysplasia.

Design, Setting, and Participants  For this retrospective virological analysis, we recruited 25 HIV+ MSM with AGWs (n = 38) harboring areas of dysplasia and 22 patients who were HIV-negative (HIV−) with AGWs seen between February 2013 and March 2015 at a tertiary dermatological referral center for anal cancer screening. Dysplasia-containing AGW tissue of HIV+ MSM were compared with randomly selected AGWs of patients who were HIV−.

Main Outcomes and Measures  Histopathological analysis, immunohistochemical staining for p16INK4a and Ki67, HPV-typing, and viral load determination in AGWs of HIV+ compared with patients who were HIV−.

Results  Overall, 25 HIV+ MSM with AGWs (mean [SD] age, 47.3 [11.1] years) harboring areas of dysplasia and 22 patients who were HIV− (5 women, 17 men; mean [SD] age, 35.5 [12.8] years) with AGWs were included in this study. The 38 dysplasia-containing AGWs of HIV+ MSM harbored low-grade dysplasia in 6 cases (16%), high-grade dysplasia in 31 cases (81%), and areas of invasive anal carcinoma in 1 (3%) case. With the exception of 1 biopsy, all low-grade lesions were p16INK4a-negative, whereas 25 of 31 (81%) AGWs with high-grade lesions or an anal carcinoma were p16INK4a-positive. Only low-risk HPV-types were present in 11 samples (29%; 2 low-grade lesions and 9 high-grade lesions), low-risk and high-risk types were found in 19 samples (50%; 1 low-grade lesion and 18 high-grade lesions), and only high-risk HPV-types were present in 8 samples (21%; 3 low-grade lesions, 4 high-grade lesion, and 1 cancer-containing lesion). High low-risk HPV DNA loads were found in low-grade and high-grade lesions, while high high-risk HPV DNA loads were only found in AGWs harboring high-grade lesions. The 22 AGWs of patients who were HIV− showed no signs of dysplasia, and p16INK4a-staining was always negative. All of these samples carried low-risk HPV types, and in 2 cases high-risk HPV-types were detected additionally.

Conclusions and Relevance  In contrast to immunocompetent patients, AGWs of HIV+ MSM may harbor high-grade dysplasia or even invasive squamous cell carcinoma. A substantial proportion of theses lesions may only contain low-risk HPV-types. Anogenital warts in patients who are HIV+ should be evaluated histopathologically to exclude cancer precursors.

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Figure 1.
High-Resolution Anoscopy of a Human Papillomavirus-Induced Intraanal Lesion that Clinically Appears as Anogenital Wart

Terminal capillaries present in the lesion are a typical clinical sign for benign anogenital warts.

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Figure 2.
Immunohistochemical Analysis of p16INK4a Expression in an Intraanal Lesion that Clinically Appeared as Anogenital Warts, but Histopathologically Revealed Focal Areas of High-Grade Dysplasia

The lesion clinically appeared as an anogenital wart, but histopathologically revealed focal areas of high-grade dysplasia. p16INK4a is an indirect marker of high-risk human papillomavirus E7 oncogene expression. Strong nuclear and cytoplasmic p16INK4a expression is present in the areas of high-grade dysplasia, whereas p16INK4a staining is negative in the anogenital wart part of the lesion (hematoxylin-eosin, original magnification ×100).

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