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.

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