Risk factors for ≥high-grade anal intraepithelial lesions in MSM living with HIV and the response to topical and surgical treatments

Abstract

Background The objective of this study in MSM living with HIV was to determine the incidence of HSIL and ASCC, related factors, and the response to treatment. Patients and methods Data were gathered in 405 consecutive HIV-infected MSM (May 2010-December 2018) at baseline and annually on: sexual behavior, anal cytology, and HPV PCR and/or high-resolution anoscopy results. They could choose mucosectomy with electric scalpel (from May 2010) or self-administration of 5% imiquimod 3 times weekly for 16 weeks (from November 2013). A multivariate logistic regression model was developed for ≥HSIL-related factors using a step-wise approach to select variables, with a significance level of 0.05 for entry and 0.10 for exit, applying the Hosmer-Lemeshow test to assess the goodness of fit. Results The study included 405 patients with a mean age of 36.2 years; 56.7% had bachelor´s degree, and 52.8% were smokers. They had a mean of 1 (IQR 1–7) sexual partner in the previous 12 months, median time since HIV diagnosis of 2 years, and mean CD4 nadir of 367.9 cells/uL; 86.7% were receiving ART, the mean CD4 level was 689.6 cells/uL, mean CD4/CD8 ratio was 0.77, and 85.9% of patients were undetectable. Incidence rates were 30.86/1,000 patient-years for ≥high squamous intraepithelial lesion (HSIL) and 81.22/100,000 for anal squamous cell carcinoma (ASCC). The ≥HSIL incidence significantly decreased from 42.9% (9/21) in 2010 to 4.1% (10/254) in 2018 (p = 0.034). ≥HSIL risk factors were infection with HPV 11 (OR 3.81; 95%CI 1.76–8.24), HPV 16 (OR 2.69, 95%CI 1.22–5.99), HPV 18 (OR 2.73, 95%CI 1.01–7.36), HPV 53 (OR 2.97, 95%CI 1.002–8.79); HPV 61 (OR 11.88, 95%CI 3.67–38.53); HPV 68 (OR 2.44, CI 95% 1.03–5.8); low CD4 nadir (OR1.002; 95%CI 1–1.004) and history of AIDS (OR 2.373, CI 95% 1.009–5.577). Among HSIL-positive patients, the response rate was higher after imiquimod than after surgical excision (96.7% vs 73.3%, p = 0.009) and there were fewer re-treatments (2.7% vs 23.4%, p = 0.02) and adverse events (2.7% vs 100%, p = 0.046); none developed ASCC. Conclusions HSIL screening and treatment programs reduce the incidence of HSIL, which is related to chronic HPV infection and poor immunological status. Self-administration of 5% imiquimod as first-line treatment of HSIL is more effective than surgery in HIV+ MSM.

Evaluation of the validity of the HPV viral load compared to conventional techniques for the detection of high-grade anal intraepithelial lesions in men with HIV who have sex with men

“…However, these data must be interpreted with caution because very few cases with HPV-18-VL and HSILs have been studied, and so these results are difficult to extrapolate. Notwithstanding, other studies have suggested that HPV-18 could also be a useful biomarker for the detection of anal lesions ( Hidalgo-Tenorio et al, 2021 ).…”

A phase I study of intra-anal artesunate (suppositories) to treat anal high-grade squamous intraepithelial lesions

“…electrocautery (overall complete and partial response rates for imiquimod, 5-FU, and electrocautery were 46%, 42%, and 69%, respectively) and Grade 3-4 adverse events common in the topical treatment groups (43% in the imiquimod and 27% in the 5-FU group), [14,15]. However, a recent small, single center, longitudinal cohort study of MSM living with HIV and diagnosed with HSIL found excellent response rates and tolerability of imiquimod with less recurrence compared to surgical treatment [4]. In a systematic review of 14 studies of intraanal imiquimod, complete response in 211 patients with HSIL was observed in 35%, partial response 20.9% and recurrence in 15% [16].…”

“…Local recurrence or new, metachronous anal HSIL may occur with all treatment modalities, especially as the underlying persistent HPV infection may not be cured. Smoking, poor HIV control (low CD4 cell count or HIV viremia), persistent infection with HPV16/18 or chronic mixed HPV infections can increase the risk for recurrent disease [2][3][4]. Novel approaches to expand the therapeutic armamentarium against HPV related anogenital dysplasia are needed.…”

Update on the Epidemiological Features and Clinical Implications of Human Papillomavirus Infection (HPV) and Human Immunodeficiency Virus (HIV) Coinfection

“…Regarding anal dysplasia, several prospective cohorts have reported a relationship between a low nadir CD4 lymphocyte count and a higher risk for HSIL [ 96 , 97 ]. Indeed, a retrospective study cohort comprising 2800 HIV-infected male or female patients reported a lower risk of progression of LSIL to HSIL among those who presented virological suppression (defined as HIV RNA levels <400 copies/mm 3 ) or CD4 lymphocyte counts >350 cells/µL [ 98 ].…”