Lack of Regression of Anal Squamous Intraepithelial Lesions despite Immune Restoration under cART.

aAP-HP-Service d'Immunologie Clinique, Hôpital Européen Georges Pompidou, Paris bAP-HP- Service d'Anatomie et Cytologie Pathologiques, Hôpital Lariboisière, Université Denis Diderot, Paris cINSERM U943 - Paris dUMPC Paris Univ 06 UMR S 943 Paris eAP-HP-Laboratoire de Virologie, Hôpital Européen Georges Pompidou, Paris fAP-HP, Groupe hospitalier Pitié-Salpêtrière, Service de Maladies Infectieuses et Tropicales, Paris, France gAP-HP-Service des Maladies Infectieuses, Hôpital Saint Antoine, Paris hUniversité Paris Descartes, Sorbonne Paris Cité, Paris, France.
AIDS (London, England) (Impact Factor: 6.56). 10/2012; DOI: 10.1097/QAD.0b013e32835ad2cb
Source: PubMed

ABSTRACT BACKGROUND:: A high prevalence of anal squamous intraepithelial lesions (ASIL) and HPV infections were observed in HIV-infected MSM in the pre-cART (combined antiretroviral therapy) era. The impact of cART on the natural history of HPV infection and ASIL is poorly documented. METHODS:: 94 HIV-infected MSM naïve of cART were enrolled in a longitudinal study before starting cART. Patients were evaluated for anal cytology, histology and anal HPV DNA at baseline, month 12 and month 24 of cART. HPV DNA genotyping was performed by Linear Array assay. Anal cytologic samples were processed by the Thin Prep™ method. RESULTS:: Analyses included 76 patients with at least two visits with available cytology. The median age was 39.4 years. The median (interquartile range) CD4 cell count was 301/mm (242-339) at baseline and 545/mm at month 24, when 93% of patients had plasma HIV-RNA ≤50 copies/ml.Abnormal result was observed in 45 of 76 patients at baseline (59%) with prevalent LSIL in 27 patients (36%) and HSIL in 7 patients (9%) and in 36 of 69 patients assessed at month 24 (52%) with LSIL in 23 patients (33%) and HSIL in 6 patients (9%). At month 24, regression of the severity of lesions was observed in 44% of patients, whereas a lesion occurred in 37% of patients. CONCLUSION:: Our results show a high prevalence and incidence of ASIL in HIV-infected MSM despite immune restoration under cART. These data emphasize that HIV-positive MSM although receiving effective cART remain at high risk of anal SIL.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Squamous cell carcinoma of the anus (SCCA) is a rare disease, but its incidence has been increasing dramatically since the 1970s. Men who have sex with men (MSM) and infection with human immunodeficiency virus (HIV) are the two main risk factors. Risk of developing SCCA is increased more than 100-fold in HIV-seropositive MSM. We review here how immunodeficiency could promote SCCA and how restoration of immunity since the advent of combined antiretroviral therapy can influence the natural history and incidence of SCCA. We also review the prognostic and therapeutic implications of immunosuppression in these patients. Finally, we show how, with anti-HPV vaccines, immunity is a target in the prevention of SCCA and could in the future be used in its treatment.
    Gastroentérologie Clinique et Biologique 08/2013; · 0.80 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To quantify incidence of, and risk factors for, progression to and spontaneous regression of high-grade anal squamous intraepithelial lesions (ASILs). Retrospective review of patients at St Vincent's Hospital Anal Cancer Screening Clinic during a period when high-grade ASILs were not routinely treated (2004-2011). All patients who had an anal Papanicolaou smear or high-resolution anoscopy were included, except for patients with previous anal cancer. High-grade anal intraepithelial neoplasia (HGAIN) was defined as a composite of histologically confirmed grade 2 or 3 anal intraepithelial neoplasia (AIN2/3) and/or high-grade squamous intraepithelial lesion on anal cytology. Analyses were repeated restricting to histologically confirmed AIN3. There were 574 patients: median age 45 years (interquartile range, IQR 36-51), 99.3% male and 73.0% HIV-infected [median HIV duration was 13.8 years (IQR 6.4-19.8), median CD4 T-lymphocyte count was 500 cells/μl (IQR 357-662), 83.5% had undetectable plasma HIV viral load]. Median follow-up was 1.1 years (IQR 0.26-2.76). Progression rate to HGAIN was 7.4/100 person-years (95% confidence interval, CI 4.73-11.63). No risk factor for progression to HGAIN was identified; progression to AIN3 was more likely with increasing age (Ptrend = 0.004) and in those who were HIV-infected [hazard ratio 2.8 (95% CI 1.18-6.68) versus HIV-uninfected; P = 0.019], particularly in those whose nadir CD4 T-lymphocyte count was less than 200 cells/μl (Ptrend = 0.003). In 101 patients with HGAIN, 24 (23.8%) patients had spontaneous regression [rate 23.5/100 person-years (95% CI 15.73-35.02)], mostly to AIN1. Regression was less likely in older patients (Ptrend = 0.048). Two patients with HGAIN developed anal cancer. High-grade ASILs frequently spontaneously regress. Longer-term, prospective studies are required to determine whether these regressions are sustained.
    AIDS (London, England) 09/2013; 27(14):2233-43. · 6.56 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: HIV infection is one of the strongest risk factors for anal squamous cell cancer (ASCC). Most ASCC are caused by HPV, and most HPV-associated ASCC are caused by HPV-16. Anal HPV infections are very common in men who have sex with men (MSM), and nearly universal among HIV-infected MSM. High-grade anal intraepithelial neoplasia (HGAIN), the precursor for ASCC, is present in about 30 % of HIV+ MSM, but neither the progression rate to ASCC nor the regression rate are known. The incidence rate of ASCC among HIV-infected people has risen in the first decade after cART became available, but appears to be plateauing recently. Anal cytology has poor sensitivity and specificity. High resolution anoscopy (HRA) is advocated by some as a screening tool in high-risk groups, but is cumbersome and time-consuming and it is unknown whether HRA followed by treatment of HGAIN prevents ASCC. More research is needed on progression and regression rates of HGAIN, on effective therapy of HGAIN, and on biomarkers that predict HGAIN or anal cancer. HPV vaccination and earlier start of cART may prevent most anal cancers in the long run.
    Current HIV/AIDS Reports 07/2014;


Available from
Jul 28, 2014