title: High-grade Dysplasia in Anogenital Warts of HIV-Positive Men.
abstract: 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.
  
  
  
  To describe a case series of HIV+ MSM with typical AGW that harbored different grades of dysplasia.
  
  
  
  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-.
  
  
  
  Histopathological analysis, immunohistochemical staining for p16INK4a and Ki67, HPV-typing, and viral load determination in AGWs of HIV+ compared with patients who were HIV-.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Dermatology, Venereology, and Allergology, HELIOS St. Elisabeth Hospital Oberhausen, Oberhausen, University of Witten-Herdecke, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kreuter
authors.affiliation: Department of Dermatology, Venereology, and Allergology, HELIOS St. Elisabeth Hospital Oberhausen, Oberhausen, University of Witten-Herdecke, Germany.
authors.forename: Christos
authors.initials: C
authors.lastname: Siorokos
authors.affiliation: Institute of Pathology, Mülheim an der Ruhr, Mülheim, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Oellig
authors.affiliation: National Reference Center for Papilloma- and Polyomaviruses, Institute of Virology, Uniklinik Köln, University of Cologne, Cologne, Germany.
authors.forename: Steffi
authors.initials: S
authors.lastname: Silling
authors.affiliation: National Reference Center for Papilloma- and Polyomaviruses, Institute of Virology, Uniklinik Köln, University of Cologne, Cologne, Germany.
authors.forename: Herbert
authors.initials: H
authors.lastname: Pfister
authors.affiliation: National Reference Center for Papilloma- and Polyomaviruses, Institute of Virology, Uniklinik Köln, University of Cologne, Cologne, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Wieland
mesh_terms: D000328:Adult; D001005:Anus Neoplasms / Q000175:diagnosis* / Q000517:prevention & control; D003218:Condylomata Acuminata / Q000473:pathology* / Q000821:virology*; D055088:Early Detection of Cancer; D005260:Female; D005832:Genital Diseases, Male / Q000473:pathology* / Q000821:virology*; D006679:HIV Seropositivity / Q000150:complications*; D018451:Homosexuality, Male; D006785:Hospitals, University; D006801:Humans; D016867:Immunocompromised Host; D008297:Male; D008875:Middle Aged; D027383:Papillomaviridae / Q000302:isolation & purification; D012189:Retrospective Studies; D012307:Risk Factors