September 11, 2017
Yearly cytology or anoscopy could substantially cut incidence of anal cancer in HIV-positive men who have sex with men (MSM), according to a modeling simulation by Swiss HIV Cohort Study (SHCS) investigators. Wider antiretroviral therapy (ART) coverage would also contribute to lower anal cancer incidence.
Incidence of anal cancer in HIV-positive MSM ranges from 78 to 168 cases per 100,000 person-years in the combination ART era, much higher than the 5 per 100,000 in HIV-negative MSM or about 1 per 100,000 in the general population. In previous SHCS research low CD4 count six to seven years before anal cancer diagnosis emerged as the strongest predictor. Screening for grade 2 or 3 anal intraepithelial neoplasia (AIN) and treating detected lesions can prevent anal cancer. But the value of routine screening and treating for HIV-positive people remains, pending clinical outcome data. SHCS investigators conducted a modeling study to assess the impact of different screening strategies and increasing ART coverage on anal cancer incidence.
The individual-based mathematical model aimed to predict anal cancer incidence in HIV-positive MSM in Switzerland from 1980 through 2030. The model had an anal cancer layer, which depends on a CD4 count layer. The anal cancer layer incorporated four stages of anal cancer progression (no precursor lesion, AIN 1, AIN 2/3, anal cancer), while the CD4 layer considered five CD4 ranges (<100, 100 to 199, 200 to 349, 350 to 499 and ≥500 cells/mm3).
The CD4 layer of the model used CD4 trajectories recorded for HIV-positive MSM in the SHCS in six periods (1980-1989, 1990-1994, 1995-1999, 2000-2004, 2005-2009, 2010-2015). The anal cancer layer of the model used data from the literature. The simulation examined the impact of 100% ART coverage and AIN2/3 screening and treatment on anal cancer incidence in four screening scenarios: no screening, yearly anal cytology, yearly anoscopy and anoscopy targeted five years after the CD4 count fell below 200 cells/mm3. Based on clinical data, the researchers assumed a response rate of 49% one year after electrocautery or infrared coagulation for AIN 2/3.
The model plugged in CD4 count data from 6,411 MSM with three or more CD4 counts between February 1983 and August 2015. Combination ART coverage rose from 0% in 1980-1989 to 83.4% in 2010-2015. In the base scenario -- with no anal cancer screening and ART coverage staying at the 2010-2015 level -- simulated anal cancer incidence peaked at 81.7 new cases per 100,000 person-years in 2009, plateaued over the following five years and fell to 58.7 per 100,000 in 2030. With 100% ART coverage from 2016 onward, incidence dropped to 52.0 per 100,000 in 2030, even with no screening. Screening with CD4 count-dependent anoscopy lowered anal cancer incidence to 51.3 per 100,000 in 2030; yearly cytology cut incidence to 38.2 per 100,000; and yearly anoscopy lowered incidence to 32.8 per 100,000.
In a hypothetical set of 10,000 MSM seen from 2016 through 2030, the model predicted providers would have to screen 384 men with yearly cytology for 15 years to prevent one case of anal cancer and 30.9% of cases would be prevented. Screening with yearly anoscopy for 15 years would lower the number needed to screen to 313 to prevent one case of anal cancer and 37.9% of cases would be prevented. CD4 count-dependent anoscopy performed once would reduce the number needed to screen to 242 to prevent one anal cancer, but only 13.0% of cases would be prevented.
The SHCS team believes their study is the first to predict anal cancer incidence in MSM with HIV while accounting for ART coverage and individual CD4-count trajectories. They cite evidence indicating that the number needed to screen to prevent one anal cancer case compares well with number needed to screen to prevent cervical cancer, breast cancer or colorectal cancer.
Mark Mascolini writes about HIV infection.
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