High-Grade Anal Intraepithelial Neoplasia in HIV+ MSM
Objective To assess the value of several factors to predict the risk of progression to high-grade anal intraepithelial neoplasia (HGAIN) in a cohort of HIV-infected MSM.
Design Longitudinal study of 556 HIV-infected MSM who underwent screening for anal dysplasia (include anal cytology and high-resolution anoscopy at each visit).
Methods Progression rate to HGAIN was estimated by Kaplan–Meier analysis. Predictors of progression were assessed by Cox-proportional hazards regression.
Results Sixty-eight incidents HGAIN cases over 649 person-years of follow-up were diagnosed, resulting in a progression rate of 10.5 cases/100 person-years [95% confidence interval (CI), 8.1–13.3). The cumulative incidence of HGAIN was 7.2% at 12 months (95% CI, 4.3–10.1) and 16.2% at 24 months (95% CI, 11.7–20.7). Independent risk factors for progression were as follows: abnormal cytology [hazard ratio (HR), 2.5 (95% CI, 1.2–4.9) if low-grade squamous intraepithelial lesion, HR 2.76 (95% CI, 1.4–5.3) if atypical squamous cells of uncertain significance and HR 7.73 (95% CI, 2.3–25.4) if high-grade squamous intraepithelial lesion], abnormal high-resolution anoscopy (HR 3.57; 95% CI, 2–6.4) and infection by 16 or 18 human papillomavirus (HR 1.63; 95% CI, 1–2.6). To be receiving HAART (HR 0.4; 95% CI, 0.2–0.7) and have stable sexual couple (HR 0.62; 95% CI, 0.4–0.9) were protective factors. Patients with favorable predictors had an incident rate of 2.86 cases/100 person-years (95% CI, 3.5–10.3).
Conclusion The rate of progression to HGAIN varies according to different predictors that should be considered when assessing the particular risk of each patient. Patients with low risk of progression could be screened at longer intervals.
Brief summary We describe the risk of progression to HGAIN in a cohort of 556 HIV-infected MSM. The incidence rate of HGAIN varies widely according to different predictors. These factors should be considered when assessing the particular risk of each patient.
Invasive anal cancer is considered infrequent in the general population and accounts for approximately 2% of all gastrointestinal malignancies. However, in HIV-infected MSM anal cancer occurs at rising rates, and nowadays it has become the most common non-AIDS defining cancer in this group of population. According to recent data, the incidence of anal cancer among HIV-positive MSM ranges from 65 to 130 cases/100 000 person-years, a rate 30–100 times higher than in the general population. The natural history of anal cancer is not fully understood. The infection by oncogenic human papillomavirus (HPV) is considered the main etiological agent of this cancer. HPV infection is able to induce a series of changes in the transitional epithelium that lead to the development of anal intraepithelial neoplasia (AIN), which may eventually evolve to invasive anal cancer. This process occurs in a progressive manner, initially causing low-grade anal intraepithelial neoplasia (LGAIN), which in turn progress to high-grade anal intraepithelial neoplasia (HGAIN), considered to be the direct precursor of invasive anal cancer. Although the exact rate of progression of HGAIN to invasive carcinoma is unclear, it has been estimated to be 1.3–3.2% at 5 years. The propensity for LGAIN to transform to high-grade lesions and anal cancer is even less clear. It has been suggested that many LGAIN are associated with low-risk HPV genotypes and that the risk of progression to malignancy is therefore lower. Moreover, the risk of progression from normality to HGAIN is also poorly understood.
Despite that there are no universal recommendations for the management of HGAIN, many authors have encouraged advocates of screening for these dysplasic changes in order to treat premalignant lesions, and hence reducing the incidence of anal cancer in HIV-positive MSM. Many of these recommendations are extrapolated from the cervical cancer screening in women. These programmes recommend to perform anal cytology and high-resolution anoscopy (HRA) annually and more frequently if any abnormality is observed. However, the scientific evidence for this advice is limited.
To more comprehensively study the risk of progression to HGAIN we conducted a longitudinal study on the natural history of AIN in a cohort of HIV-positive MSM. We assessed the value of several factors to predict development of HGAIN and the risk of progression according to the results of the anal cytology and HRA.
Abstract and Introduction
Abstract
Objective To assess the value of several factors to predict the risk of progression to high-grade anal intraepithelial neoplasia (HGAIN) in a cohort of HIV-infected MSM.
Design Longitudinal study of 556 HIV-infected MSM who underwent screening for anal dysplasia (include anal cytology and high-resolution anoscopy at each visit).
Methods Progression rate to HGAIN was estimated by Kaplan–Meier analysis. Predictors of progression were assessed by Cox-proportional hazards regression.
Results Sixty-eight incidents HGAIN cases over 649 person-years of follow-up were diagnosed, resulting in a progression rate of 10.5 cases/100 person-years [95% confidence interval (CI), 8.1–13.3). The cumulative incidence of HGAIN was 7.2% at 12 months (95% CI, 4.3–10.1) and 16.2% at 24 months (95% CI, 11.7–20.7). Independent risk factors for progression were as follows: abnormal cytology [hazard ratio (HR), 2.5 (95% CI, 1.2–4.9) if low-grade squamous intraepithelial lesion, HR 2.76 (95% CI, 1.4–5.3) if atypical squamous cells of uncertain significance and HR 7.73 (95% CI, 2.3–25.4) if high-grade squamous intraepithelial lesion], abnormal high-resolution anoscopy (HR 3.57; 95% CI, 2–6.4) and infection by 16 or 18 human papillomavirus (HR 1.63; 95% CI, 1–2.6). To be receiving HAART (HR 0.4; 95% CI, 0.2–0.7) and have stable sexual couple (HR 0.62; 95% CI, 0.4–0.9) were protective factors. Patients with favorable predictors had an incident rate of 2.86 cases/100 person-years (95% CI, 3.5–10.3).
Conclusion The rate of progression to HGAIN varies according to different predictors that should be considered when assessing the particular risk of each patient. Patients with low risk of progression could be screened at longer intervals.
Brief summary We describe the risk of progression to HGAIN in a cohort of 556 HIV-infected MSM. The incidence rate of HGAIN varies widely according to different predictors. These factors should be considered when assessing the particular risk of each patient.
Introduction
Invasive anal cancer is considered infrequent in the general population and accounts for approximately 2% of all gastrointestinal malignancies. However, in HIV-infected MSM anal cancer occurs at rising rates, and nowadays it has become the most common non-AIDS defining cancer in this group of population. According to recent data, the incidence of anal cancer among HIV-positive MSM ranges from 65 to 130 cases/100 000 person-years, a rate 30–100 times higher than in the general population. The natural history of anal cancer is not fully understood. The infection by oncogenic human papillomavirus (HPV) is considered the main etiological agent of this cancer. HPV infection is able to induce a series of changes in the transitional epithelium that lead to the development of anal intraepithelial neoplasia (AIN), which may eventually evolve to invasive anal cancer. This process occurs in a progressive manner, initially causing low-grade anal intraepithelial neoplasia (LGAIN), which in turn progress to high-grade anal intraepithelial neoplasia (HGAIN), considered to be the direct precursor of invasive anal cancer. Although the exact rate of progression of HGAIN to invasive carcinoma is unclear, it has been estimated to be 1.3–3.2% at 5 years. The propensity for LGAIN to transform to high-grade lesions and anal cancer is even less clear. It has been suggested that many LGAIN are associated with low-risk HPV genotypes and that the risk of progression to malignancy is therefore lower. Moreover, the risk of progression from normality to HGAIN is also poorly understood.
Despite that there are no universal recommendations for the management of HGAIN, many authors have encouraged advocates of screening for these dysplasic changes in order to treat premalignant lesions, and hence reducing the incidence of anal cancer in HIV-positive MSM. Many of these recommendations are extrapolated from the cervical cancer screening in women. These programmes recommend to perform anal cytology and high-resolution anoscopy (HRA) annually and more frequently if any abnormality is observed. However, the scientific evidence for this advice is limited.
To more comprehensively study the risk of progression to HGAIN we conducted a longitudinal study on the natural history of AIN in a cohort of HIV-positive MSM. We assessed the value of several factors to predict development of HGAIN and the risk of progression according to the results of the anal cytology and HRA.
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