Anal Neoplasia in Inflammatory Bowel Disease: Classification Proposal, Epidemiology, Carcinogenesis, and Risk Management Perspectives

Abstract

Patients with inflammatory bowel disease [IBD] may develop, similarly to individuals from general population, rare cases of human papilloma virus [HPV]-related anal canal squamous cell carcinoma [SCC] and intra-epithelial precursor lesions, as well as very rare cases of anal canal adenocarcinoma. Patients with chronic perianal Crohn's disease [CD] are at substantial risk of developing SCC or adenocarcinoma from the fistula-lining epithelium, as well as SCC or adenocarcinoma arising from chronic anorectal ulcerations or strictures. Based on this lesion stratification, we provide in this review tailored incidence estimates and we propose an IBD-specific classification of all types of anal neoplasia that may occur in patients with IBD. After reviewing putative carcinogenesis of all types of neoplasia, we conclude that HPV vaccination could reduce the incidence of HPV-related lesions, although an anal screening programme related to these lesions is not mandatory on the sole basis of IBD. By contrast, we point out that all patients with chronic perianal CD should be explored in depth, including biopsies under anaesthesia and fistula curettage when necessary, in case of any change in anal symptoms ─in particular new, increasing, unexplained pain. Finally, we conclude that there is an urgent need for elaborating and evaluating surveillance algorithms in patients with chronic perianal CD, in order to avoid cancers with late diagnosis and poor prognosis.

High Risk of Anal and Rectal Cancer in Patients With Anal and/or Perianal Crohn’s Disease

“…2 This excess incidence is attributed to a conjunction of HPV infection and chronic local inflammation. 3,4,13 The resulting incidence remains low, but could be attenuated in the future by the impact of HPV vaccination, 14 and does not justify per se surveillance programs. 3 By contrast, the burden of anal cancers that are diagnosed in patients with Crohn's anal and/or perianal disease raises challenging questions of clinical practice.…”

“…3,4,13 The resulting incidence remains low, but could be attenuated in the future by the impact of HPV vaccination, 14 and does not justify per se surveillance programs. 3 By contrast, the burden of anal cancers that are diagnosed in patients with Crohn's anal and/or perianal disease raises challenging questions of clinical practice. We also observed a high rate of rectal cancer in patients with anal and/or rectal Crohn's lesions, exceeding that observed in patients with ulcerative colitis at highest risk of colorectal cancer (ie, those with long-standing extensive colitis).…”

“…At this time, optimal frequency and modalities of surveillance are unknown. 3,16 In addition, the frequent presence of anorectal impassable strictures, 17 and initial location of malignant lesions in inaccessible fistula tracts make the surveillance difficult, if not, in some cases, impossible. 18,19 Dedicated consensus and guidelines regarding the detection of advanced anorectal neoplasia in patients with anal and/or perianal Crohn's disease are now eagerly awaited.…”

“…1 A mild increase in this risk has been reported in patients with Crohn's disease in a meta-analysis of inflammatory bowel disease (IBD) referral center series, 2 possibly attributable to human papilloma virus (HPV) infection and chronic inflammation of anal mucosa. 3,4 Patients with perianal fistulizing Crohn's disease are also at risk of perianal fistula-related SCC and adenocarcinoma. 5 Because anal and/or perianal Crohn's disease is associated in most cases with chronic inflammation of rectal mucosa, patients with chronic anal and/or perianal Crohn's disease also theoretically are at increased risk of rectal cancer.…”

High Prevalence of Anal Canal High-Risk Human Papillomavirus Infection in Patients With Crohn's Disease

“…CD-related anal cancers may be driven by HPV infection, 33 associated with other specific disease-related mechanisms that include local and systemic chronic inflammation, 34 tobacco use, and a possible contribution of drug-induced immunosuppression. 35 The role of immunosuppression on HPV-related diseases has already been addressed in HIV patients 36,37 or renal transplant recipients. 38 Recently, Shah et al 39 failed to demonstrate the influence of immunosuppressive therapy on the presence of anal cytological lesions in IBD patients but only few abnormal anal smears were reported in this cohort, all of them showing atypical squamous cells of undetermined significance, which limits the conclusions.…”