by Jeffrey T. Kirchner, DO, AAHIVS, AAHIVM Chief Medical Officer

June 16, 2020

Featured Literature:
Poynten, IM et al. The Natural History of Anal High-grade Squamous Intraepithelial Lesions in Gay and Bisexual Men. Clin Infect Dis. 2020 Apr 28; doi: 10.1093/cid/ciaa166.

Gay and bisexual men (GBM) have the highest incidence of anal squamous cell cancer (SCC). The presence of HIV increases the likelihood of SCC, most of which are caused by human papilloma virus (HPV) subtypes 16 and 18. High-grade Squamous Intraepithelial lesions (HSIL) precede anal cancer. However, both prevention and treatment remain hindered by the lack of data on the natural history of HSIL. This Study of the Prevention of Anal Cancer (SPANC) was conducted from 2010 to 2018. It included 617 GBM men of whom 64% were HIV-negative and 36% HIV-positive. All subjects were > 35 years of age with a median age of 49 years. Participants had anal cytology and high-resolution anoscopy (HRA) done at baseline and at three annual visits. A composite HSIL diagnosis (cytology ± histology) was used. There were 124 incident HSIL cases over 1097 person-years of follow-up (11.3 / 100 PY). Major predictors of a higher incidence of HSIL included: age <45 years, HIV positivity, having a prior SIL diagnosis and presence of HPV-16 subtype. During 695 person-years of follow-up, 153 men with high-grade SIL cleared the lesions. Predictors of clearance included: age < 45 years, having anal intraepithelial neoplasia (AIN) 2 rather than AIN-3, having smaller lesions and non-HPV-16 subtype. Clearance was not related to HIV status. Only one patient progressed to anal cancer. The authors believe these data strongly show that not all anal HSIL detected by screening requires intervention. Men who had persistent HPV-16 subtype are less likely to clear HSIL and are more likely to benefit from treating these lesions with surgery or ablation.

Author’s Commentary:

This is the largest published study to date looking at the progression of HSIL in a cohort of GBM. Overall, these data are encouraging in that the progression rate from HSIL to anal cancer was only about 0.2% per year. They can provide a point of shared decision making for some patients regarding treatment versus continued surveillance. However, HPV infection is obviously a dynamic process for many GBM with a potential for both clearance of low-grade lesions but also the risk of new HPV infections. Another recent study from France (CID 2020; 221:1488-93) found 24-month clearance rates of 32% for HPV-16 compared to 54% for HPV-18. Although many HIV programs perform anal Pap smears in their MSM population there are still no formal guidelines regarding this practice. For clinics that are doing anal Pap smears, it is important to have a system for follow-up of abnormal results including availability of high-resolution anoscopy and treatment protocols in place. Continued uptake of HPV vaccination in younger MSM should also decrease the incidence of new infections. 

The author has no conflicts of interest to disclose.

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