High-grade Dysplasia in Anogenital Warts of HIV-Positive Men

Abstract

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 p16 INK4a 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 p16 INK4a-negative, whereas 25 of 31 (81%) AGWs with high-grade lesions or an anal carcinoma were p16 INK4a-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 p16 INK4a-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 these lesions may only contain low-risk HPV-types. Anogenital warts in patients who are HIV+ should be evaluated histopathologically to exclude cancer precursors.

Recommendations Favoring Anal Cytology as a Method for Anal Cancer Screening: A Systematic Review

“…Three societies have specifically identified HIV-positive patients with anogenital condylomas as a risk group for screening [17,19,23]. Several studies have described that a significant percentage of anal condylomas in HIV-positive patients harbor high-grade lesions [38][39][40][41]. Individuals with condylomas also have a long-term increased risk of HPV-associated anogenital cancers [42].…”

New Insights into the Role of Human Papillomavirus in Anal Cancer and Anal Wart Development

“…The larger published study that included 319 HIV-positive and -negative patients submitted to anogenital wart surgical excision, found that in HIV-positive MSM, occult HSIL/cancer was found in 47, and 26% of HIV-negative MSM [16]. Other studies have reported a similar high trend [17-19]. …”

HIV-Associated Anal Dysplasia and Anal Carcinoma

“…However, condylomata acuminata indicate persistent HPV infection and therefore show an association with anal malignancy as discussed above. Moreover, recent data demonstrated high-grade lesions in genital warts including early cancer [39]. The cytological examination follows the revised Bethesda classification from 2001 [40].…”