Virologic, Immunologic, and Clinical Parameters in the Incidence and Progression of Anal Squamous Intraepithelial Lesions in HIV-Positive and HIV-Negative Homosexual Men

Abstract

Anal cancer may be preceded by anal squamous intraepithelial lesions (ASIL), but the natural history of ASIL is poorly understood. In this report, we characterize the 2-year incidence and progression of low-grade SIL (LSIL) and high-grade SIL (HSIL) in a cohort study in 346 HIV-positive and 262 HIV-negative homosexual or bisexual men. Subjects were studied at defined intervals using anal cytology, anoscopy with biopsy of visible lesions, human papillomavirus (HPV) testing, HIV serostatus, CD4 level, and data on medical history and lifestyle. The incidence of HSIL within 2 years was 20% in HIV-positive men and 8% in HIV-negative men who were normal at baseline. In total, 62% of HIV-positive and 36% of HIV-negative men with LSIL at baseline progressed to HSIL. The relative risk (RR) for anal disease progression in HIV-positive men was 2.4 (95% confidence interval [CI], 1.8-3.2) when compared with HIV-negative men. The RR increased to 3.1 (95% CI, 2.3-4.1) in HIV-positive men with CD4 counts <200/mm3. Infection with multiple HPV types was a risk factor for anal disease progression in both HIV-positive (RR = 2.0; 95% CI, 1.0-4.1) and HIV-negative (RR = 5.1; 95% CI, 2.3-11) men. The incidence of anal HSIL and progression of LSIL to HSIL within 2 years of follow-up is high in HIV-positive homosexual or bisexual men and to a lesser extent, in HIV-negative men. Men with the above risk factors may be at increased risk of developing anal cancer.

Human papillomavirus genotypes in anal intraepithelial neoplasia and anal carcinoma as detected in tissue biopsies

“…Several studies have reported a two to six times greater prevalence of HPV infection in immunosuppressed patients [23][24][25][26][27][28] and twice the risk of progression from low-grade AIN to high-grade AIN. [27][28][29][30] AIN lesions are known to advance from low-grade to high-grade AIN within 2 years of diagnosis in 36-66% of individuals with progression occurring more rapidly and more frequently in immunodeficient individuals. 27,30 Our study confirms the increasing prevalence of high-risk HPV with worsening dysplasia: 56% of AIN I, 80% of AIN II, and 88% of AIN III, findings earlier reported by Varnai et al 31 32 In our study, six (60%) of AIN II lesions were non-16 high-risk HPV types; five of which on follow-up showed less severe lesions.…”

“…[27][28][29][30] AIN lesions are known to advance from low-grade to high-grade AIN within 2 years of diagnosis in 36-66% of individuals with progression occurring more rapidly and more frequently in immunodeficient individuals. 27,30 Our study confirms the increasing prevalence of high-risk HPV with worsening dysplasia: 56% of AIN I, 80% of AIN II, and 88% of AIN III, findings earlier reported by Varnai et al 31 32 In our study, six (60%) of AIN II lesions were non-16 high-risk HPV types; five of which on follow-up showed less severe lesions. One AIN II with HPV 16 had followup and progressed to AIN III.…”

Anal Cancer: An Overview

“…This is likely a result of the fact that HIVpositive patients are more likely to be infected with HPV, often with more than one subtype [15]. Additionally, HIV patients are more likely to have HPV-associated squamous intraepithelial lesions (SILs), particularly those considered high grade [15][16][17]. Development of these HSILs appears to be inversely related to CD4 count [16 -18].…”

Histopathologic and Cytologic Follow-Up in High Risk Male Patients with Unsatisfactory Anal Cytology

“…The role of viral load, medication status, and CD4 count was not assessed, and there is one limitation in this study. Studies have also demonstrated that HIV-positive patients with AIN I were more likely to progress to higher grade lesions, while HIV-negative patients were more likely to have no disease at two-year follow-up [16]. Despite these findings, AIN II/III is less likely to regress regardless of HIV status [17].…”