Low‐ and high‐risk human papillomavirus genotype infections in intra‐anal warts in HIV ‐positive men who have sex with men

Abstract

SummaryBackground Anogenital warts are often presumed to represent nondysplastic or low-grade anal intraepithelial neoplasia (LGAIN). We previously demonstrated that up to 20% of intra-anal warts in HIV-positive men who have sex with men (MSM) contain regions of high-grade AIN (HGAIN). Objectives To determine the causative human papillomavirus (HPV) types of lowand high-grade dysplastic areas in warts from HIV-positive MSM. Methods A total of 42 intra-anal warts from 41 HIV-positive MSM were graded as nondysplastic, LGAIN or HGAIN. Whole-tissue sections (WTS) were analysed with the SPF10 polymerase chain reaction/LiPA25 HPV genotyping system. If the WTS contained multiple HPV types, dysplastic regions were isolated by laser capture microdissection (LCM) for HPV genotyping. Results Overall, 38 of 42 (91%) WTS tested positive for HPV DNA. Of these, 23 (61%) contained a single HPV type and 15 (39%) contained multiple HPV types. All LCM-selected regions contained no more than one HPV type. Ten of 42 (24%) WTS contained HGAIN disease, of which six (60%) were associated with a high-risk HPV (hrHPV) genotype. Twenty-three of 42 WTS contained LGAIN disease, of which two (9%) were associated with hrHPV. AIN lesions containing hrHPV types were identified using p16 staining. Conclusions LGAIN lesions can be caused by high-risk HPV genotypes and vice versa. We therefore recommend routine follow-up and treatment of all dysplastic intra-anal warts for HIV-positive MSM.

Grading immunohistochemical markers p16 INK4a and HPV E4 identifies productive and transforming lesions caused by low‐ and high‐risk HPV within high‐grade anal squamous intraepithelial lesions

“…In the case of HIV+ MSM, the clinical implications of HSILs associated with lrHPV are uncertain. 31 Such HSILs/AIN2 lesions showing extensive patchy p16 staining in the absence of E4 might represent an abortive, nonproductive lrHPV infection overexpressing HPV E7 and not completing the HPV life cycle. The mechanism for strong patchy expression of p16 in lrHPV infections is unclear.…”

“…In this set of biopsies (176 of 183 from HIV+ MSM, 96·2%), few LSILs (nine of 60, 15%) were associated with hrHPV, and only six of 86 HSILs (7%) were associated with lrHPV. In the case of HIV+ MSM, the clinical implications of HSILs associated with lrHPV are uncertain . Such HSILs/AIN2 lesions showing extensive patchy p16 staining in the absence of E4 might represent an abortive, nonproductive lrHPV infection overexpressing HPV E7 and not completing the HPV life cycle.…”

“…25 Immunohistochemistry FFPE sections 4-lm thick were used for IHC staining with p16 INK4a and panHPV E4 using heat-induced epitope retrieval with citrate buffer (Dako/Agilent Technologies, Santa Clara, CA, U.S.A.) and a primary mouse monoclonal antibody anti-p16 INK4a clone E6H4 [Ventana Medical Systems Inc. (Roche Diagnostics), Mannheim, Germany], and XR-E4-1 (Labo Biomedical Products BV, Rijswijk, the Netherlands). The panHPV E4 antibody has been found to be reactive against at least HPV genotypes 6,11,16,18,31,33,35,39,45,51,52,53,56,58,59, 66, 67 and 70. 17,22 Reactivity was visualized using the EnVision Detection System (Dako/Agilent Technologies).…”

Condylomata acuminata of HIV-positive men may harbour focal areas of dysplasia: relevant implications for the management of human papillomavirus-induced disease in high-risk patients

“…These observations strongly argue for early detection and treatment of all HPV‐induced anogenital lesions. The second interesting finding is that low‐risk HPV types can induce high‐grade dysplasia, as shown in four of the analysed warts . Accordingly, low‐risk HPVs are not completely innocent in immunosuppressed individuals, as also seen in giant condylomata of Buschke and Löwenstein.…”

“…In this issue of the BJD , Siegenbeek van Heukelom et al . add relevant new information to our knowledge of HPV‐driven carcinogenesis in HIV‐positive MSM . They have performed HPV genotyping of 42 lesions that clinically appeared as intra‐anal warts.…”