title: Systematic review of guidelines for the assessment and management of high-grade anal intraepithelial neoplasia (AIN II/III).
abstract: OBJECTIVE
  There is ambiguity with regard to the optimal management of anal intraepithelial neoplasia (AIN) III. The aim of this review was to assess and compare international/national society guidelines currently available in the literature on the management, treatment and surveillance of AIN III. We also aimed to assess the quality of the studies used to compile the guidelines and to clarify the terminology used in histological assessment.
  
  
  METHODS
  An electronic search of PubMed and Embase was performed using the search terms 'anal intraepithelial neoplasia', 'AIN', 'anal cancer', 'guidelines', 'surveillance' and 'management'. Literature reviews and guidelines or practice guidelines in peer reviewed journals from 1 January 2000 to 31 December 2014 assessing the treatment, surveillance or management of patients with AIN related to human papilloma virus were included. The guidelines identified by the search were assessed for the quality of evidence behind them using the Oxford Centre for Evidence-based Medicine 2011 Levels of Evidence.
  
  
  RESULTS
  The database search identified 5159 articles and two further guidelines were sourced from official body guidelines. After inclusion criteria were applied, 28 full-text papers were reviewed. Twenty-five of these were excluded, leaving three guidelines for inclusion in the systematic review: those published by the Association of Coloproctology of Great Britain and Ireland, the American Society of Colon and Rectal Surgeons and the Italian Society of Colorectal Surgery. No guidelines were identified on the management of AIN III from human papilloma virus associations and societies. All three guidelines agree that a high index of clinical suspicion is essential for diagnosing AIN with a disease-specific history, physical examination, digital rectal examination and anal cytology. There is interchange of terminology from high-grade AIN (HGAIN) (which incorporates AIN II/III) and AIN III in the literature leading to confusion in therapy use. Treatment varies from immunomodulation and photodynamic therapy to targeted destruction of areas of HGAIN/AIN II/III using infrared coagulation, electrocautery, cryotherapy or surgical excision but with little consensus between the guidelines. Recommendations on surveillance strategies are similarly discordant, ranging from 6-monthly physical examination to annual anoscopy ± biopsy. Over 50% of the recommendations are based on Level 3 or Level 4 evidence and many were compiled using studies that were more than 10 years old.
  
  
  CONCLUSIONS
  Despite concordance regarding diagnosis, there is significant variation in the guidelines over recommendations on the treatment and surveillance of patients with HGAIN/AIN II/III. All three sets of guidelines are based on low level, outdated evidence originating from the 1980s and 1990s.
authors.affiliation: Exeter Surgical Health Services Research Unit (HeSRU), Royal Devon and Exeter Hospital, Barrack Road, Exeter, Devon, UK.
authors.forename: N N
authors.initials: NN
authors.lastname: Alam
authors.affiliation: Warwick Medical School, University of Warwick, Coventry, UK.
authors.forename: D A
authors.initials: DA
authors.lastname: White
authors.affiliation: Exeter Surgical Health Services Research Unit (HeSRU), Royal Devon and Exeter Hospital, Barrack Road, Exeter, Devon, UK.
authors.forename: S K
authors.initials: SK
authors.lastname: Narang
authors.affiliation: Exeter Surgical Health Services Research Unit (HeSRU), Royal Devon and Exeter Hospital, Barrack Road, Exeter, Devon, UK.
authors.forename: I R
authors.initials: IR
authors.lastname: Daniels
authors.affiliation: Exeter Surgical Health Services Research Unit (HeSRU), Royal Devon and Exeter Hospital, Barrack Road, Exeter, Devon, UK.
authors.forename: N J
authors.identifier: http://orcid.org/0000-0002-3043-8324
authors.initials: NJ
authors.lastname: Smart
mesh_terms: D001005:Anus Neoplasms / Q000175:diagnosis* / Q000628:therapy*; D002278:Carcinoma in Situ / Q000175:diagnosis* / Q000628:therapy*; D019468:Disease Management; D019983:Guideline Adherence; D006801:Humans; D011159:Population Surveillance / Q000379:methods*; D017410:Practice Guidelines as Topic; D009626:Terminology as Topic
keywords: AIN; Anal intraepithelial neoplasia; HGAIN; anal cancer; guidelines; high grade anal intraepithelial neoplasia