LAUSR

Although the incidence of many cancers are decreasing in the United States, the incidence of anal squamous cell cancer (ASCC) increased at approximately 2.7% per year between 2001 and 2015. What is perhaps even more troubling is that the observed ASCC mortality increased 3.1% per year from 2001 through 2016, outpacing the increased incidence in the number of new cases. Furthermore, patients are presenting with more advanced disease. We are increasingly unable to prevent anal cancer and are doing a poorer job of keeping these patients alive. We are failing our patients. We must do better. Much of my career has focused on developing a better understanding of anal dysplasia, including the diagnosis and treatment of patients with high-grade squamous intraepithelial lesions (HSILs) as a means to prevent ASCC. When I began working in the field in the mid-1990s, we knew little, and there was a general reticence to label anal HSILs as the ASCC precursor. Now, few doubt that ASCC derives from HSIL. Using the cervical cancer model as a guidepost, Jay et al adapted colposcopy to the anal canal to identify HSILs. The procedure, high-resolution anoscopy (HRA), uses acetic acid, Lugol iodine solution, and magnification to highlight the vascular and morphologic changes typical of premalignant lesions. HRA became the first monumental step in the anal cancer prevention puzzle. Although we believed that treating HSIL could prevent progression to cancer, similar to in the cervix, we had no proof. Initial treatments focused on targeted ablation, first with infrared coagulation and laser and now, more commonly, with electrocoagulation. But would treatment prevent cancer? I am thrilled to report that in this issue of Cancer, Gaisa et al have presented data that point to the prevention of anal cancer by electrocautery ablation (EA). In a large series of >300 people living with HIV (PLWH), the authors conducted a rigorous, albeit retrospective, study of their treatment results with EA from 2009 to 2016. Not only did participants have a median follow-up of >1 year, but the study was rigorously conducted with thorough demographic data extracted, including smoking status and HIV-related parameters. All procedures were performed by the first author, and human papillomavirus (HPV) typing results were available for a large percentage of the participants. Follow-up was based on HRA with biopsy of lesions suspicious for HSIL and histology was adjudicated. To be included, all participants underwent at least 1 postablation HRA to a maximum of 8, thereby allowing the authors to calculate the probability of disease recurrence after EA out to >3 years. The cumulative probability of local recurrence (at the site of the primary ablation) at 12 months and 36 months was 38% and 53%, respectively. The calculated probability of any recurrence (local or metachronous at a site different from that of the primary HSIL) was 50% and 68%, respectively, at 12 months and 36 months. Some argue against treating HSILs because recurrence rates after ablation are >50%. Although preventing recurrent HSIL would be wonderful, the primary goal of treatment always has been the prevention of ASCC. Although the authors reported a high rate of HSIL recurrence after ablation, no patients in their relatively large treatment series developed ASCC. More and more data continue to emerge demonstrating that untreated anal HSIL leads to ASCC. Berry et al reported on 27 patients with untreated anal HSIL who progressed to ASCC at the HSIL site. A recent study by Arens et al of progression from HSIL to anal cancer (which included some of the authors from the study by Gaisa et al) merged the Surveillance, Epidemiology, and End Results database with Medicare claims to identify PLWH who were diagnosed with HSIL prior to ASCC. In a population that should mirror that in the study by Gaisa et al, the authors identified an incidence of anal cancer of 1.2%, 3.7%, and 5.7%, respectively, at 1 year, 3 years, and 5 years. Gaisa et al found no cases of cancer after a median follow-up of >1 year but out to as long as 7.8 years in >300 participants. Another very recent series from Barcelona examined >3000 patients with HIV who either were screened and treated for HSIL or