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High Anal Intraepithelial Neoplasia Progression in Spanish Gay/Bisexual Men
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52nd ICAAC, September 9-12, 2012, San Francisco
Mark Mascolini
Progression from low-grade to high-grade anal intraepithelial neoplasia (LGAIN to HGAIN) measured 14.9 per 1000 patients per month in HIV-positive men who have sex with men (MSM) at a Spanish hospital [1]. Anal cytology and high-risk human papillomavirus (HPV) testing had 100% sensitivity and 100% negative predictive value in screening for HGAIN or anal cancer in this 163-man study.
Rates of anal intraepithelial neoplasia and anal cancer are high in men who have sex with men (MSM) with and without HIV. A 2012 meta-analysis calculated pooled prevalence of histological HGAIN at 29.1% and incidence of 8.5% to 15.4% per year in HIV-positive MSM [2]. In HIV-negative MSM pooled prevalence of histological HGAIN stood at 21.5% and incidence at 3.3% to 6.0% per year. Rates of progression from LGAIN to HGAIN in MSM are poorly understood.
This prospective study at Virgen de las Nieves University Hospital in Granada, Spain involved 163 HIV-positive MSM seen from December 2008 through April 2012 [1]. At the baseline visit and every follow-up visit, men had anal cytology, PCR for HPV, and anoscopy. Men with LGAIN (AIN 1) had yearly follow-up with these three tests. HGAIN is AIN 2 or 3.
The 163 men studied averaged 36.2 years in age (+/- 9.5) and had a median of only 1 sex partner in the past 12 months (interquartile range [IQR] 1 to 6). Almost three quarters of these men (117) reported using condoms, and 35 men had anal warts. While 153 men were European, 10 were South American. Median time since HIV diagnosis stood at 54 months (IQR 32.3 to 105.7), and current CD4 count averaged 601 (+/- 221). Three quarters of the study group were taking antiretroviral therapy for a median of 30 months (IQR 10 to 76), and 105 men had a viral load below 50 copies.
Of the 163 MSM studied, 121 (74%) tested positive for HPV and 91 (56%) had a high-risk HPV genotype. Median number of high-risk HPV types was 1 (IQR 0 to 2). HPV type 16 was the most prevalent high-risk genotype, detected in 34 men (21%). The researchers counted 105 abnormal cytologic results (64%), including 74 men with low-grade squamous intraepithelial lesion (LSIL), 3 with high-grade squamous intraepithelial lesion (HSIL), and 28 with ASCUS (atypical cells of undetermined significance). Among 87 men who had anoscopy, results were normal in 24 (28%), while showing LGAIN in 41 (47%), HGAIN in 15 (17%), and anal cancer in 7 (8%).
HGAIN incidence (the new detection rate) was 14.9 cases per 1000 patients per month over a median of 11 months. In other words, about 15 of 1000 MSM in this group (1.5%) progressed to HGAIN every month. Anal cancer incidence was 3.3 cases per 1000 patients per month. Among 41 men with LGAIN when follow-up began, 21 completed a median of 11 months of follow-up. One third of those 21 had progression to HGAIN and 5% had progression to anal cancer. In this subgroup, incidence of progression from LGAIN to HGAIN was 14.3 per 1000 patients per month, and progression from LGAIN to anal cancer was 2 per 1000 patients per month.
The researchers could identify only two factors associated with progression from LGAIN: younger age (average 29.5 versus 34.1, P = 0.046) and shorter median time since HIV diagnosis (44 versus 60 months, P = 0.03). Factors that did not affect progression in this analysis were number of sex partners in the past year, baseline CD4 or CD8 count, nadir CD4 count, baseline viral load, antiretroviral treatment, antiretroviral treatment duration, virologic failure, history of syphilis, HCV, or HBV, smoking or alcohol use, HPV infection, and high-risk HPV infection.
Anal cytology plus high-risk HPV detection had high sensitivity for detecting any degree of anal dysplasia (98.2%). Positive predictive value of the combined assessments (76.4%) and negative predictive value (80%) were lower, and specificity was only 19%. (Sensitivity is the ability of a test to single out people who have a certain condition. Specificity is the ability of the test to classify people who do not have the condition as negative.) For detecting HGAIN or anal cancer, anal cytology plus high-risk HPV detection had 100% sensitivity and 100% negative predictive value, with 7.9% specificity and 19.4% positive predictive value.
The researchers concluded that combining anal cytology and high-risk HPV detection virtually eliminates the risk that a man has anal dysplasia and thus makes anoscopy unnecessary in these men. The researchers cautioned that their analysis is limited by the relatively short follow-up (median 11 months) and the small number of men who completed even that much follow-up. And despite the high progression rate from LGAIN in these men, the presenting author said the group still plans only yearly follow-up for men with LGAIN.
References
1. Hidalgo Tenorio C, Rivero Rodriguez M, Gil Anguita C, et al. Risk factors in the progression of low grade intraepithelial neoplasia (LGAIN) to high grade intraepithelial neoplasia (HGAIN) In a cohort of HIV-MSM. 52nd Interscience Conference on Antimicrobials and Chemotherapy (ICAAC). September 9-12, 2012. San Francisco. Abstract H-1921.
2. Machalek DA, Poynten M, Jin F, et al. Anal human papillomavirus infection and associated neoplastic lesions in men who have sex with men: a systematic review and meta-analysis. Lancet Oncol. 2012;13:487-500.
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