Jul 03, 2026

The development of the Association of Coloproctology of Great Britain and Ireland (ACPGBI) guidelines for the treatment and follow-up of patients with an anal high-grade squamous intraepithelial lesion (aHSIL)

DOI
https://dx.doi.org/10.17504/protocols.io.bp2l6objzlqe/v1
  • Tamzin Cuming1,2,
  • Morris Gordon3,
  • Katrina Knight4,
  • Danielle Brogden5,
  • Hema Sekhar6,
  • Ben Cromarty7,
  • Paul Barron7,
  • Erin Walker7,
  • Julie Bowring1,
  • Litza Mtilasi8,
  • Maryam Alfa-Wali9,
  • Noreen Chindawi1,
  • Mhairi Collie10,
  • Ahsan Javed11,
  • David Finch12,13,
  • Yuxin Liu14,
  • Paula Loughlin15,
  • Brett Packham16,
  • Iain Reeves17,
  • Philip Roelandt18,
  • Usama Shahbaz1,
  • Andrew G Renehan12,13
  • 1Department of Surgery, Homerton Healthcare NHS Foundation Trust, London, UK;
  • 2Imperial College London;
  • 3University of Lancashire, Preston, UK;
  • 4Department of Colorectal Surgery, Glasgow, UK;
  • 5Department of Surgery, Maidstone and Tunbridge Wells NHS Trust;
  • 6Department of Surgery, Sandwell and West Birmingham Hospitals NHS Trust;
  • 7Patient representative;
  • 8Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands;
  • 9St Mary's Hospital, The Imperial College Healthcare NHS Trust, London, UK;
  • 10Colorectal Unit, Western General Hospital, Edinburgh;
  • 11Department of Colorectal Surgery, Liverpool, UK;
  • 12Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK;
  • 13Colorectal and Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK;
  • 14Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York, USA;
  • 15Department of Surgery, Connolly and Beaumont Hospital, Dublin, Ireland;
  • 16Leeds Cancer Centre, St. James’s University Hospital, Leeds, UK;
  • 17Department of Sexual Health, Homerton Healthcare NHS Foundation Trust, London, UK;
  • 18Department of Gastroenterology and Hepatology, UZ Leuven, Leuven, Belgium
Lee Malcomson
Icon indicating open access to content
QR code linking to this content
DOI: https://dx.doi.org/10.17504/protocols.io.bp2l6objzlqe/v1
Protocol Citation: Tamzin Cuming, Morris Gordon, Katrina Knight, Danielle Brogden, Hema Sekhar, Ben Cromarty, Paul Barron, Erin Walker, Julie Bowring, Litza Mtilasi, Maryam Alfa-Wali, Noreen Chindawi, Mhairi Collie, Ahsan Javed, David Finch, Yuxin Liu, Paula Loughlin, Brett Packham, Iain Reeves, Philip Roelandt, Usama Shahbaz, Andrew G Renehan 2026. The development of the Association of Coloproctology of Great Britain and Ireland (ACPGBI) guidelines for the treatment and follow-up of patients with an anal high-grade squamous intraepithelial lesion (aHSIL). protocols.io https://dx.doi.org/10.17504/protocols.io.bp2l6objzlqe/v1
License: This is an open access  protocol  distributed under the terms of the  Creative Commons Attribution License,  which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Protocol status: Working
We use this protocol and it's working
Created: July 02, 2026
Last Modified: July 03, 2026
Protocol  Integer ID: 320224
Keywords: anal high-grade intraepithelial lesion, high-resolution anoscopy, anal cancer
Funders Acknowledgements:
ACPGBI
Disclaimer
* This document was edited 6th February 2026; with final checks on 30th June 2026
Abstract
Introduction Anal squamous cell carcinoma (ASCC) is an uncommon malignancy, increasing in incidence globally, and caused in the majority of cases by the human papilloma virus (HPV). The Association of Coloproctology of Great Britain and Ireland (ACPGBI) guidelines on the management of ASCC in 2017 included some recommendations on the management of precursor intra-epithelial lesions, in the main, derived through non-systematic methods and reliant on expert opinion. Here, we describe the development, using systematic evidence-based approaches, of updated and wider-ranging guidelines for the treatment and follow-up of patients with a histological diagnosis of anal high-grade squamous intraepithelial lesion, a precursor lesion of anal cancer.

The LAST consensus divided the former nomenclature of three grades of anal intraepithelial neoplasia (AIN), into a dichotomous anal high-grade squamous intraepithelial lesion (aHSIL) and low-grade squamous intraepithelial lesion (aLSIL), the latter being considered due to HPV types of low oncogenic risk, of very low malignant potential, frequently regress and are not considered further in this guideline.

Two key recent reports form cornerstones to the timing of these guidelines. First, the US-based ANCHOR trial demonstrated proof that ablative treatment of aHSIL lesions, at least in HIV positive individuals, halved the rate of malignant transformation to ASCC, compared with traditional monitoring. Second, a comprehensive meta-analysis, using a unifying anal cancer risk scale, developed a framework in which to stratify patients in very high-risk and high-risk categories. While this categorisation is very important to anal cancer screening (not covered in these guidelines), it might also be relevant for stratification and prioritisation of patients for treatment and in follow-up after aHSIL treatment.

We reviewed current international guidelines and demonstrated substantial variation in recommendations. Against this background, there are variations in practice (including the general under-resourcing of high-resolution anoscopy, HRA), treatment options, and follow-up protocols.

Methods In accordance with the ACPGBI Guidelines Development Framework, we will comply with the Appraisal of Guidelines for Research and Evaluation II (AGREE II) framework and use the GRADE approach and GIN McMaster approach for guideline development. There will be into six steps: (i) establishing the guideline development group (GDG), reflecting geographic and multi-disciplinary diversity, as well as methods expertise; (ii) formulating thematic questions, including the use of the PICO framework to produce specific actionable questions ; (iii) selecting evidence using systematic scoping and then systematic searches (iv) reviewing research evidence using a three-phase approach, including the evidence assessment tool to assess risk of bias of systematic reviews and other appropriate tools for primary studies; (v) developing and wording recommendations, including using the GRADE methodology and agreeing these amongst the GDG; and (vi) finalising and publishing the guidelines.

Throughout all phases, there will be five cross-cutting themes: (i) patient and public involvement and engagement; (ii) equality, diversity and inclusion of multiple interested stakeholders; (iii) encouraging the use of standardised terminology and classification; (iv) consideration of special clinical settings, for example, multi-zonal anogenital HSIL; and (v) identification of research gaps and research recommendations.

Scoping results Preliminary scoping identified three review questions:

Q1. Whether or not to treat aHSIL?

Q2. Treatment: In patients with aHSIL, what is the effectiveness of treatment of topical methods versus ablative methods versus local excision versus doing nothing.

Q3. Follow-up after treatment: In patients who have completed aHSIL treatment, what are the outcomes of surveillance by regimen, intensity and modality required versus doing nothing?

Consultation and dissemination Advanced draft guidelines will be shared with related professional organisations involved in the management of patients with aHSIL. The final guidelines will be disseminated through journal and conference publications to inform clinical teams and patient support groups to raise awareness and implementation of the guidelines.
INTRODUCTION
Anal squamous cell carcinoma (ASCC) is an uncommon malignancy, increasing in incidence globally (1), and caused in the majority of cases by the human papilloma virus (HPV) (2). The Association of Coloproctology of Great Britain and Ireland (ACPGBI) is a professional organisation responsible for the management (mainly surgical) of patients with disease of the colon, rectum and anus. The ACPGBI requested the two senior authors (TC, AGR) to establish guidelines for the diagnosis, treatment and follow-up of patients with anal cancer precursor intra-epithelial lesions.

The starting point in these guidelines is any screened or non-screened population where the diagnosis of anal high-grade intra-epithelial lesion (aHSIL) has already been established. The proposed guidelines aim to provide guidance on the most effective way to treat and follow-up aHSIL, and in doing so, provide information to improve outcomes after treatment, including reducing malignant transformation, recurrence and complications, symptoms and ultimately patient satisfaction.

The ACPGBI guidelines on the management of ASCC in 2017 included some recommendations on the management of precursor intra-epithelial lesions (3). There were four major limitations to the methodology used to develop the 2017 guidelines: (i) there was no systematic review of evidence; (ii) there was no systematic appraisal of the evidence; (iii) recommendations were based on expert opinion; and (iv) there was no consistent methodological training (for example in GRADE assessment) for guideline makers..

Here, we describe the development of updated wider-ranging guidelines for the treatment and follow-up of patients with diagnosed aHSIL, The development of this guideline is in line with key international procedural documents, including the procedures of the GRADE approach as laid out in the GRADE handbook (4), supported by the WHO handbook for guideline development (5). The GDG will use the GIN-McMaster guideline development checklist, an 18-point process map to support the steps in a GRADE-compliant guideline development process (6, 7), and write up will use the Appraisal of Guidelines for Research and Evaluation II (AGREE II) framework (https://www.agreetrust.org/agree-ii/) (8), for best available evidence. This methodology addresses the aforementioned limitations of the previous guidelines. There is empirical evidence that the use of the AGREE II framework is associated with higher quality guidelines (9). To-date, the AGREE II framework has been used in other guidelines on colorectal disease topics – for example, emergency colorectal surgery (10) and haemorrhoidal disease (11). However, this will be the first guideline from ACPGBI to fully employ the GRADE approach for design, planning, synthesis, recommendation formulation, decision making and write up.
Accountability
For pragmatic purposes, the Guideline Development Group (GDG) includes the Project Management Team, PMT (AGR, TC, MG), responsible for maintenance of a deliverable timeline on these guidelines, and the main GDG who will meet (mainly virtually) at key steps in the development of the guidelines and will be responsible for scientific content and final recommendations.

The GDG is accountable to its commissioner, the ACPGBI, and will report and update regularly (for example, each calendar year quarter) to the ACPGBI President, Secretary and the new ACPGBI Guidelines Task Force (through its Chair https://www.acpgbi.org.uk/about/committees/1012/guidelines_committee/public#:~:text=Our%20aims%20are%20to%20support,or%20in%20collaboration%20with%20others ).
Terminology and the Lower Anogenital Squamous Terminology (LAST) consensus
Throughout these guidelines, we will strive to standardise and explain terminology, recognising there are different but equivalent terms used by different clinical specialities and across different geographies in the classification and management of anal cancer and its precursor intraepithelial lesions (12-14). In the 2017 ACPGBI guidelines (3), the histological classification stated that “Anal Intraepithelial neoplasia (AIN) is traditionally graded as AIN I, II and III. To aid management algorithms, the (histological) terminology of high-grade squamous intraepithelial lesion (HSIL) and low-grade squamous intraepithelial lesion (LSIL) were introduced over a decade ago” in the form of the 2-tier LAST consensus (13).

In broad terms, LSIL corresponds to AIN I; HSIL corresponds to AIN III and AIN II, where there is also p16 immunohistochemistry-block positivity (15). AIN II not confirmed by positive p16 immunohistochemistry is downgraded to LSIL. The 2024 guidelines from the Royal College of Pathologists (RCPath) state: “It is generally recognised that a common unified terminology should be applied to anogenital lesions since they share a common aetiology via HPV infection (16). It follows from this that a 3-tier grading system for AIN should be adopted, with the further qualifications of LSIL and HSIL in parentheses (i.e. LSIL/condyloma and AIN1; HSIL/AIN2 and AIN3), in order to maintain uniformity with cervical and vulval neoplasia. This is consistent with recommendations of the Lower Anogenital Squamous Terminology (LAST) project (13).

Furthermore, the RCPath guidelines refer to those of the British Society of Gynaecological Pathologists from 2018 who agree with the LAST criteria, in particular, in the use of p16 for assistance in the diagnosis of HSIL: i.e. the lesion needs to be morphologically HSIL but a block positive p16 immunohistochemistry allows confirmation of AIN2 (HSIL) over LSIL (17). In this guideline we will use ‘AIN’ to refer to all anal intraepithelial neoplasia, ie LSIL and HSIL, and ‘aHSIL’ for recognised anal cancer precursor lesions.
The ANCHOR trial
The 2017 ACPGBI guidelines (3) wrote “The central tenet of management of AIN (analogous to CIN) is that if one can induce regression or eradicate of AIN, then malignant transformation can be prevented”. At that time, there was no direct evidence to support this pathway to prevention of anal SCC (as there is for CIN to invasive cervical carcinoma). The publication of the ANCHOR trial (18) in 2022 changed this.

The ANCHOR trialists conducted a phase 3 trial at 25 centres in the United States. Persons living with HIV who were 35 years of age or older and who had biopsy-proven anal HSIL were randomly assigned (1:1 ratio) to receive either HSIL treatment or active monitoring with high resolution anoscopy (HRA) without treatment. 4459 participants were randomised. The primary outcome measure was progression to cancer in a time-to-event analysis. With a median follow-up of 25.8 months, 9 cases were diagnosed in the treatment group (1.7 per 1,000 person-years) and 21 cases in the active monitoring group (4.0 per 1,000 person-years). The rate of progression to anal cancer was lower in the treatment group compared with that in the active monitoring group by 57% (P = 0.03 by log-rank test).

There are two clear findings with implications for clinical practice:
Treatment of aHSIL resulted in lower rates of progression to anal cancer than active monitoring in patients living with HIV. It is therefore no longer justifiable to offer active monitoring for aHSIL without accompanying aHSIL eradicating treatment, at least in individuals living with HIV. This principle might also apply to those with aHSIL but not living with HIV (19).

The active monitoring group in the ANCHOR trial remarked that the rate of malignant transformation of HSIL into anal cancer is lower than that previously cited in the literature (4 new cancers per 100 people over 10 years). However, in patients with extensive aHSIL (>50% surface area – as defined at HRA with 5 or more octants of the anal canal or perianal involved), the rate of progression was substantially higher (10 new cancers per 100 people over 10 years). This information can be used to inform shared clinical decision making about options for treatment and surveillance. Nonetheless, the trial was stopped early at 25.8 months by the data monitoring committee so the cancer rate with active monitoring for longer periods is not known. The ANCHOR trial results were a key motivation for ACPGBI to develop up-to-date evidence-based guidelines.
Defining high-risk patients
The dichotomous classification of aHSIL and aLSIL is important to classify the risk of anal cancer progression at a lesion-level. However, it is equally important to classify risk at patient level. In 2021, Clifford and colleagues (20), a part of a collaboration between the International Agency for Research in Cancer (IARC) and the International Anal Neoplasia Society (IANS) Screening Task Force, undertook a comprehensive meta-analysis, using a unifying anal cancer risk scale, to provide robust and comparable estimates of anal cancer burden across many patient groups.

In the recently published IANS anal cancer screening guidelines (21), high-risk patients are classified into category A and category B. This will be the basis for discussions in this guideline development for how to follow-up patients after treatment for aHSIL. There is evidence that higher risk groups on the Clifford scale progress faster to anal cancer, and hence the assessment of patient risk may in turn influence advice on the prioritisation of aHSIL patients for treatment and surveillance (22).
Guidelines for the management of aHSIL
In 2021, Brogden and colleagues (23) updated a previous review of aHSIL management guidelines by Alam et al from 2016 (24). They identified guidelines from eight different societies organisations and institutes. For this protocol, we updated the summary tables of the guidelines discussed in the Brogden and Alam papers into two categories. First, those from colorectal surgical and oncological societies, namely the Association of Coloproctology of Great Britain and Ireland (ACPGBI, 2017 (3)); the American Society of Colon and Rectal Surgeons (ASCRS, 2018 (25)); the Italian Society of Colorectal Surgery (SCCR, 2019 (26)); and the Hellenic Society of Medical Oncology (HESMO, 2021 (27)). These are tabulated in Second, guidelines from HIV and dermatology societies, namely German Society of Dermatology (GSD, 2015 (28)); National Comprehensive Cancer Network: People Living with HIV (NCCN, 2018 (29)); European AIDS Clinical Society (EACS, 2023 (30)); and New York State Department of Health AIDS Institute (NYS-DOH, 2024 (31)). Here, we add the National Institute for Health (NIH), 2024 (32)). These apply mainly to HIV population of patients with screen-detected aHSIL. Screening recommendations are not within the scope of the current guideline development, but these guidelines do offer recommendations on treatments and surveillance and may be relevant to research question no. 3. A recent systematic review identified additional guidelines on anal cancer screening from the French National Society of Coloproctology (33), Brazilian Society for Surgical Oncology (34), Portuguese Society for Coloproctology (35) and the International Anal Neoplasia Society (IANS) (21). Our initial searches also identified published guidelines for the management and/or screening of high-risk populations including patients with solid organ transplants (36). These will not be explored further in this guideline. As above, screening recommendations are not within the scope of the current guideline development, but these guidelines do offer recommendations on treatments and surveillance and may be relevant for the research questions.

In addition, we did not include the ESMO (2021) (37) guidelines as their guidance on the management of AIN was very brief and mirrored those from ACPGBI (2017) (3). We were aware of the French guidelines (38) on the management of anal cancer, but these did not include recommendations for the management of aHSIL
Current clinical practice - High-resolution anoscopy (HRA)
Against these backgrounds, there are variations in current clinical practice after a diagnosis of aHSIL. Historically, practice has been standard anoscopy with random biopsy and mapping to evaluate the extent of the HSIL lesions. However, this has often been a substitute for treatment, with regular appointments for mapping used as a means of early cancer detection rather than aHSIL treatment. By contrast in the ANCHOR trial, all cases were screened, monitored and treated with HRA guidance. Additionally, contemporary reviews (39, 40) on management emphasise that high-resolution anoscopy (HRA) is the gold standard for diagnosis. At present, this investigative modality is under-resourced in the UK and worldwide.

HRA is the evaluation of the perianal area and anal canal with magnification 30 to 50 times plus staining with 5% acetic acid plus or minus the use of aqueous (Lugol’s) iodine for the visual identification of HSIL and its targeted biopsy. It is a replacement for random biopsies/ mapping. The anal canal is accessed via an anoscope, and the mucosa visualised with magnification which can be achieved through a binocular scope identical to those used for colposcopy usually with live video projection on to a screen or through digital anoscopes where the camera is attached to the end of the anoscope and the image projected on to a screen directly. Binocular vision via a colposcope was used universally in the ANCHOR study and in the vast majority of the published literature. Digital imaging anoscopes are generally considered to generate equivalent quality images and videos.

The term “HRA”, or high-resolution anoscopy, will be used for any technique using 5% acetic acid (+/- aqueous iodine) staining and magnification to at least x 30 to inspect the perianal area and squamous epithelium of the anal canal. Different modalities for HRA exist – for example, colposcopy and digital imaging HRA – but differences between these are beyond the scope of these guidelines.
Treating aHSIL
At present, treatment is not universally employed for aHSIL in colorectal departments in the UK. Although the ANCHOR trial was restricted to people with HIV (36), and cancer did develop in the treatment arm, the trial was stopped early due to the ‘public health implications’ of the significant reduction in cancer incidence in the treatment arm (57%). In addition, 50% of the anal cancers in the ANCHOR study were Stage 1 compared to 12% in those cancers that present symptomatically in the UK.

Furthermore, even if it were ever again deemed ethical to have a trial with long term non-treatment of anal HSIL, it is unlikely that a trial of the size of ANCHOR (10,000 people screened) would be repeated in HIV-negative populations due to the substantial funding implications and relatively lower prevalence of disease.
Despite the excess risk of anal cancer in the population of gay and bisexual men and transwomen with HIV, in absolute numbers more women than men develop anal cancer in the UK population (and worldwide) (1) and it is this group, predominantly women with no known risk factors or with a minor cervical smear abnormality in their history in whom cancer is rising the fastest (42). While screening at present is not feasible for this group, diagnosed HSIL is an opportunity potentially to prevent anal SCC and in the light of the ANCHOR (18) study’s findings, treating aHSIL now needs to be considered.
Regression and progression
Regression of aHSIL was noted in the SPANC study (43), a screen-detected aHSIL observational study, and was calculated to be 25% at six months in those with AIN3 and 30% of those with AIN2 (p16 positive) HSIL. This natural history study followed over 650 gay men in Sydney, one third of whom had HIV, whose aHSIL had been found by community and HIV clinic screening. New lesions occurring during the surveillance – all of which was done with HRA – were those more likely to regress, as were those of smaller size.

Combined with the evidence from ANCHOR, larger lesions (>50% of the anal or perianal zone), those with more advanced aHSIL e.g. AIN3 vs AIN2 and prevalent lesions rather than those identified during surveillance should be prioritised for treatment. As noted above, patient factors may also play a role. Older gay or bisexual men (>45 years), especially those with HIV are at particular risk of aHSIL progression to cancer. There is evidence that those with HIV are more likely to develop anal cancer if they have a history of one or more opportunistic illness (i.e.an AIDS history) or a low CD4 nadir (<200). Cis men with HIV and no anoreceptive sex history but at least one opportunistic illness are more likely to develop anal cancer than gay and bisexual men with HIV and no episodes of opportunistic illness (44).

Any symptomatic aHSIL e.g. itching, mucus discharge, bleeding should be prioritised as these are likely to be severe lesions and may contain early anal cancers within them. Almost all aHSIL is asymptomatic and almost all anal cancer is symptomatic while arising from a background of aHSIL.

Younger people <30, with small volume AIN2 may be monitored, ideally with HRA, for regression. Suggested timelines are over six months to one year. There is evidence that persistent HPV 16 is also a risk factor for progression (45) so where this is available, this can be used to judge the timing of treatment of diagnosed anal HSIL. Given the median time to progression of 27 months in the ANCHOR study, persistent aHSIL for over one year should be considered for treatment according to the guidelines that will be elaborated in the final guidelines document.

At present the literature is predominantly in populations of gay and bisexual men with and without HIV, with the literature in women, particularly those with no known risk factors lagging behind. A meta-analysis found that anal HSIL was associated with cervical high-risk HPV in HIV negative women, at a level of 2% (11/527 women) to 24% (33/138 women) in those with HPV 16 on the cervix (46). Although, little is known about progression to cancer in women with aHSIL, around 2/3 of anal cancers worldwide are in women, most of whom (97%) are HIV negative (47).
Current treatment options
Treatment options fall into in two broad categories:
1. Topical medical therapies including: imiquimod ("Aldara"); sinecatechins under the brand name "Catephen" = "Veregen" (Eur., US); 5FU = topical 5-fluorouracil; cidofovir topical or intralesional, interferon. These are patient-applied and are recommended for 3-4 months. None are licensed for use in the anal canal or for use against HSIL as opposed to warts.  Also potentially useful are: artesunate suppositories, cryosurgery.
2. Surgical treatments, which include ablative techniques: electrocautery; hyfrecation (an outpatient version of electrocautery); CO2 and diode laser; infra-red coagulation; cryotherapy/liquid nitrogen treatment; radiofrequency ablation; photodynamic therapy; photochemotherapy; light/photo coagulation; argon beam ablation; "Plasmajet"; and clinician-applied topical ablation with TCA, (trichloroacetic acid); and endoscopic submucosal dissection and local excision. Other than local excision, many procedures are routinely carried out in the outpatient clinic/ ‘office’ in clinical practice. Use of laser generally requires specific regulation and approval by a laser liaison officer with a health organisation.
Some of these techniques are still experimental and have little literature to support their use. Electrocautery was used in 83.6% of ANCHOR treatment cases, with infra-red coagulation in 4.8% and excision in 2.3% (18). Therapeutic vaccines have also been trialled as treatments for anal HSIL. Ablative treatment is recognised to require multiple visits [see ANCHOR protocol] and in the ANCHOR trial most of this was carried out in the outpatient clinic/ ‘office’ with local anaesthesia (noting that 87% of aHSIL were less than 50% of the anal canal or perianal regions. Local anaesthesia is not required for TCA application. However, for ablation (excepting radiofrequency ablation), surgical excision and TCA techniques, HRA visualisation is required. Topical treatments are applied to the general area in question (e.g. anal canal) but are not targeted at the identified lesion.

There are at least two subject-relevant and comprehensive systematic reviews on interventions for aHSIL published in the last five years and will be important resources in this guideline development – one from Brogden et al. (2021) (48) and a recent Cochrane review (2025) (49).
Surveillance after treatment completion
Follow-up protocols vary in frequency and duration. In the active monitoring arm of the ANCHOR trial, progression to ASCC was only 4.0 per 1,000 person-years (18) albeit the trial was stopped early, not reaching the planned 5 years of follow up. This guideline will take this study’s outcomes as the most evidence-based. The follow-up regimen after treatment completion in the ANCHOR study was an HRA every six months until 5 years – however, this was in the setting of a research study.

Brogden and colleagues (23) reviewed six guidelines on the management of AIN and summarised follow-up as “apart from the ASCRS guidelines who state that treated patients do not require follow-up unless visible or palpable disease develops, (most) recommend some regimen of follow-up ………… between  3–6  monthly  for  3–5 years”.
METHODS
The team will employ the GIN-McMaster guideline development checklist, an 18-point process map, to support each of these steps within a GRADE-compliant guideline development process (6, 7). These will be based on ployment for recent UK guidelines from BSG led by MG as the methods chair (50, 51). Broadly this has been structured into six steps: (i) establishing the guideline development group (GDG), reflecting geographic and multi-disciplinary diversity, as well as methods expertise; (ii) formulating thematic questions, including the use of the PICO framework to produce specific actionable questions ; (iii) selecting evidence using systematic scoping and then systematic searches (iv) reviewing research evidence using a three-phase approach, including the evidence assessment tool to assess risk of bias of systematic reviews and other appropriate tools for primary studies; (v) developing and wording recommendations, including using the GRADE methodology and agreeing these amongst the GDG; and (vi) finalising and publishing the guidelines.
Intended audience
The intended audience for these guidelines includes: (i) health professionals from several disciplinary backgrounds – colorectal surgeons, clinical oncologists, medical oncologists, cancer nurse specialists and stoma nurses, gynaecologists, genito-urinary clinicians, HIV  clinicians, gastroenterologists, and dermatologists; (ii) patients with anal cancer and with precursor intra-epithelial lesions, and their carers, patients at high-risk of having anal intra-epithelial lesions including women with vulval and vaginal intra-epithelial lesions, HIV positive individuals, gay and bisexual men, transwomen and non-binary individuals assigned male at birth who have anorectal intercourse, and immune-comprised individuals, such as transplant recipients; and (iii) policy makers and commissioners.
Step 1- establishing the guideline development group (GDG)
The GDG will be inclusive of the five countries within the ACPGBI – namely England, Wales, Scotland, Northern Ireland and the Republic of Ireland. The aim of the GDG membership is to be inclusive (in terms of geographic, gender, ethnic, career stage, speciality) with as many panel members as possible to increase the reliability of the group’s judgement. There will be at least two patient representatives. In composing the GDG, the group considered that all clinical members had to have expert working knowledge in the diagnosis and treatment of early anal cancer or its precursor intra-epithelial lesion. The GDG will be advised by methodologist (MG) covering input from information gathering, quality assurance and evidence review and grading. He will act a co-chair and co-first author and remains free of conflicts of interest. He will be non-voting, in line with GIN guidance (6).
Step 2 – formulating thematic and then actionable questions
The two clinical leads (TC and AGR) have drafted a set of thematic review questions and then refined them to produce key actionable questions, which have been ratified by the rest of the GDG. The review questions/ recommendations were modified according to the GDG’s knowledge of clinical practice shortcomings and variations in practice. The review questions/ recommendations will formulated within the PICO framework for treatments. A similar framework will be used for other types of review questions – for example, surveillance.
A core outcome set is currently being developed for future studies assessing the treatment of anal intraepithelial lesions, the CORSiCA project (leads: AGR, DF, and Ms Rebecca Fish, Manchester). https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023429661.

The core outcomes are crucial for application of the GRADE methodology for assessment of the strength of the evidence, which in turn leads to the appropriate wording of the recommendations. For GRADE methodology, we require the key outcomes (small number of outcomes) for decision making.
Step 3 - selecting evidence using systematic scoping and then systematic searches
We will use a search strategy designed and checked by an information specialist with Cochrane expertise. We will search: the Cochrane Central Register of Controlled Trials (CENTRAL) (via Ovid EBMR) (inception to present); MEDLINE (via Ovid) (1946 to present); Embase (via Ovid) (1974 to present); PsycINFO (via Ovid) (1987 to present); AMED (via Ovid) (Allied and Complementary Medicine) (1985 to present); and CINAHL (via EBSCO) (Cumulative Index to Nursing and Allied Health Literature) (1984 to present).

We will place no restrictions on language of publication. Searches will be produced for all three questions as the evidence base is relatively small, with categorisation of evidence to each of the three core guideline questions for further consideration.
Step 4 – reviewing research evidence
A sub-group of the team will independently perform data extraction using piloted data extraction forms on the Covidence software or on a spreadsheet. Appraisal will be used as per the included paper – the AMSTAR 2 tool for reviews (52); the Cochrane risk of bias tool for RCTs or the ROBINS-I for observational studies (53). The QUADAS-2 tool will be used for diagnostic test accuracy studies (54).
Measures of treatment effect
We will express treatment effect as RRs with corresponding 95% CIs for dichotomous outcomes, and mean difference (MD) with 95% CI for continuous outcomes. Where endpoint and change score were both reported, we will use endpoint scores for data analysis. However, if the studies assessed the same continuous outcome in different ways, we would estimate the treatment effect using the standardised mean difference (SMD).
Unit of analysis issues
The unit of analysis will be the participants. In studies comparing more than two intervention groups, we intend to perform multiple pairwise comparisons between all possible pairs of intervention groups. To prevent double counting, we will evenly distribute shared intervention groups among these comparisons. For dichotomous outcomes, we plan to divide both the number of events and the total number of participants. For continuous outcomes, we will only divide the total number of participants, keeping the means and SDs unchanged. Cross-over studies will be included in quantitative analysis only if data are reported separately for before and after the cross-over, using pre-cross-over data exclusively. We do not anticipate encountering any cluster RCTs; however, if such trials are identified, we will only use their data if the authors have employed appropriate statistical methods to account for the clustering effect. In a sensitivity analysis, we will also exclude cluster RCTs to evaluate their impact on the results.
Dealing with missing data
In instances of missing data or studies that have not reported data in sufficient detail, we will proactively reach out to study authors. We will make efforts to estimate missing SDs using appropriate statistical tools and calculators available within Cochrane Review Manager 5.4. If the studies have reported standard errors (Review Manager 2020 https://revman.cochrane.org/info). Studies that do not provide measures of variance will be considered at high risk of reporting bias.
Assessment of heterogeneity
We will assess the included studies to evaluate their homogeneity in terms of participants, intervention, comparator and outcome. To assess statistical heterogeneity, we will use a χ2 test with a significance level set at p<0.1 to indicate the presence of heterogeneity. Inconsistency will be quantified and expressed through the I² statistic. We will interpret the thresholds as follows (55):
0% to 40%: might not be important.
30% to 60%: may represent moderate heterogeneity.
50% to 90%; may represent substantial heterogeneity.
75% to 100%: considerable heterogeneity.
Assessment of reporting biases
Most reporting biases can be mitigated using an inclusive search strategy. We intend to explore the possibility of publication bias by employing a funnel plot when we have 10 or more studies available for analysis. The extent of publication bias will be assessed through visual examination of funnel plot asymmetry.
Additionally, we will test funnel plot asymmetry by conducting a linear regression of the intervention effect estimate against its SE, applying weighting based on the inverse of the variance of the intervention effect estimate (56).
Data synthesis
To summarise the characteristics of the included studies, we will initially conduct a narrative synthesis encompassing all of them. Subsequently, we will perform a meta-analysis of interventional outcomes if two or more studies have assessed similar populations, interventions and outcomes. We plan to analyse studies involving children, adults and different sub-intervention types separately.

We will use Cochrane Review Manager 5.4 (Review Manager 2020 https://revman.cochrane.org/info) for our data synthesis. The random-effects model will be used to combine study data. Effect estimates from studies reporting data in a similar manner will be pooled in the meta-analysis. For dichotomous outcomes, we will pool RRs, whereas for continuous outcomes, we will pool MDs or SMDs. These results will be presented alongside 95% CIs. In cases where conducting a meta-analysis is not feasible, typically due to variations in data reporting, we will provide a narrative summary of the included studies.
Subgroup analysis and investigation of heterogeneity
If we identify heterogeneity, we will investigate possible causes and address them using the methods described in the Cochrane Handbook for Systematic Reviews of Interventions (57). We plan to undertake subgroup analyses of potential effect modifiers if sufficient data were available.
Sensitivity analysis
We plan to conduct a sensitivity analysis focused on the primary outcomes to assess the robustness of our review findings concerning decisions made during the review process. This analysis will involve excluding studies with a high or unclear risk of bias from our analyses. In instances where data analyses include studies with both reported and estimated SDs, we will exclude studies with estimated SDs to examine the impact on our review’s findings. Furthermore, we will explore whether the choice of model (fixed-effect vs random-effects) influences the results. In cases of unexplained heterogeneity, we will perform a targeted investigation of key factors within any outlier studies to better understand and potentially define the source of this heterogeneity.
Step 5 – developing and wording recommendations
Summary of findings and assessment of the certainty of the evidence
Where appropriate evidence exists, we will present our primary outcomes results in ‘Summary of findings’ tables for all forms of studies. Based on risk of bias, inconsistency, imprecision, indirectness and publication bias, we will grade the certainty of the evidence for each outcome as high, moderate, low or very low. This will use the targeted and outcome specific thresholds to support imprecision judgements. Please see the table from the recent BSG IBD guidelines that clarifies the levels of certainty and associated pivotal language that is proposed in the GRADE handbook. Such tables will primarily employ RCTs. As part of the scoping and main searches, observational studies will be considered if they meet minimum scope (greater than 100 patients and 6 months follow up) and quality standards on ROBINS-I appraisal.

However, initial searching suggests pervasive issues with confounding not being controlled, variable and poorly defined outcomes and missing data will lead to critical judgements. As such, this data does not support GRADE analysis and needs to be considered as insufficient to make conclusions with.

There is precedent to make decisions with GRADE when there is no evidence (58). When direct published literature is absent, an expert evidence survey of panel members can be taken about their unpublished observations and case series. If there is consensus, this data can be published to support a GRADE recommendation.

We will justify all decisions to downgrade the certainty of analyses using footnotes and make comments to aid the reader’s understanding of the review where necessary.
Thresholds of treatment effect
When comparing two interventions or approaches, all RRs will be supplemented with absolute risk difference and appropriate confidence intervals of absolute effects. These will be categorised according to the thresholds that have been defined by the GDG to aid interpretation of the clinical significance of the finding.
Development of recommendations
The complete technical summary will be provided to voting members after conducting an updated search to incorporate any new studies and integrate them into the existing evidence. There will be three potential forms of statement. GRADE, Good Practice Statements and Expert opinion. Where appropriate, the data and GRADE summary of findings tables will be incorporated into frameworks following the ‘evidence to decision’ approach facilitating the consideration of key factors to inform decision-making (59).

GRADE recommendations should be considered in the context of prespecified and standardised GRADE language. This may be particularly novel to the reader as this has not been applied in such a fashion within previous ACPGBI guidelines. It is therefore important to remember that the language used has not been devised ad hoc and is informed by the key factors—namely, the effectiveness and safety of interventions, the certainty of these findings and the magnitude of effects seen—in an objective manner. There are clearly opportunities where borderline or complex decisions on such recommendations could be challenged, but the use of language is consistent with these decisions.

It may be initially unusual to see key therapies recommended ‘conditionally’. This does not mean they are ineffective or should not be used. In line with the GRADE approach and language guidance discussed, this is a reflection of the likelihood that future research may change the current findings. A change does not mean that an effective treatment is ineffective (or vice versa), instead, it may simply mean that the certainty of evidence may change with further research, owing to increased quality, reduced inconsistency and increased precision. From this perspective, it is clear that many (if not most) therapies have the potential to be conditional as we constantly evolve the evidence base and increase the quality and precision of findings.

It is also GRADE recommendations are supplemented by Good Practice Statements (GPS). In line with best international practice, such statements are only made when there are strong sources of non-traditional evidence (expert knowledge and eminent experience, patient voices, observational bodies of evidence) or when standard studies would simply not be feasible. These should not be used as a mechanism to state unsupported recommendations where no forms of evidence exist. GPS must be ACTIONABLE and of a substantial net benefit to the user. As such, the GDG does not suggest that GRADE recommendations are more truthful or important than GPS statements. Rather, these respond to the unique context and reality of clinical research. The novel approach of this guideline is to present both, transparently displaying the rationale for the different approaches, but acknowledging the importance of both groups of guidance to the field.
In cases where evidence is limited or do not follow the PICO format but are descriptive in nature, we will present a narrative summary to support best practice statements or similar formulations and if these need direct statements of utility to users, expert opinion statements will be made. These will be clearly labelled and presented as the consensus view of the GDGD from their expert perspective and as such allow more latitude for different focus and structure to the other statements. As they are clearly labelled, they do not mislead the readers of the guideline.
Decision making
A face-to-face meeting will be convened to thoroughly discuss, explore and critically evaluate the components of the completed technical review and the ETD frameworks. Prior to this, question leads will review the selected and appraised evidence and work with the methods chair to pre-prepare recommendations. These will be shared with the group and feedback considered prior to a synchronous decision-making meeting. Three online sessions will be convened to decide on final recommendations of all three types. When clear agreement is reached, voting to confirm consensus. In instances of disagreement, the ETD framework will guide the voting process and help identify the underlying reasons for such disagreement.

Voting will be based on a clear GRADE statement with accompanying justification and implementation statements or similarly GPS, along with magnitude and certainty data where relevant. The votes will be dichotomous (Yes or No) and must reach 75% agreement to approve the item. This will be done using Poll Everywhere (https://www.polleverywhere.com/) to allow live anonymous voting. All conflicted members will be asked to abstain from voting. If an agreement is not reached, further discussion will be conducted, amendments made, and both the original and amended statements will be voted on sequentially. If neither attains 75%, the discussion will be temporarily halted and resumed later in the day to allow time for reflection. The team will gather and refocus the evidence, followed by another round of discussion.

Expert opinion statements will not be voted on. Voting will not be prominent in the published guideline and the percentage agreement or any Likert agreement system (https://en.wikipedia.org/wiki/Likert_scale) will not be used as this have no validity and are not supported in GRADE methodology.
SCOPING RESULTS - Scope of guidelines
Following initial discussions with the GDG, the project management team propose that the following are outside the scope of these guidelines, while recognising that with time, these ‘out of scope’ areas may be re-visited. These exclusions include:  

  • Anal cancer screening (in asymptomatic patients). The GDG recognise that in clinical practice, the histological diagnosis of HSIL might be arrived at through ‘opportunistic’ screening in addition to any asymptomatic screening programmes that may be introduced.

  • The management of women with multi-zonal disease is complex and is currently being addressed in a series of consensus documents from the British Society for Colposcopy and Cervical Pathology (BSCCP) and is out of scope for this guideline.

  • Anal cancer screening in HIV positive individuals is being address the British HIV Association (BHIVA) and is out of scope for this guideline.

  • Currently, there is no recognised staging system to identify ‘severe’ aHSIL likely to progress to cancer other than the histological division between AIN2 and AIN3. The GDG recognises the importance of developing such a system however will only advise on patient and lesions characteristics on which to judge prioritisation decisions based on the available evidence in the literature.

  • We will exclude studies that are about the aHSIL detection rate via screening with cytology and high-risk HPV which are then used to proceed to HRA.

  • We will not include the management of early anal squamous carcinoma as these guidelines will be revised in the setting of the evidence from the PLATO trials when completed.
Review questions
Following initial discussions with the GDG, the project management team propose three review questions using a PICO structure:

Q1. Whether to treat aHSIL or not?
In patients with aHSIL what is the evidence behind any treatment of the condition vs observation (with HRA or without) alone?
Sub question: 1.1: what is the recommended timing of initial treatment?

PICO:
Population – all with aHSIL however sub populations – patients in high-risk groups versus others

Intervention: any treatment for aHSIL

Comparison: not treating aHSIL (‘watch and wait’ strategies; observation; active monitoring)

Outcome: the incidence of ASCC.

Key sources: Data from the ANCHOR trial (18) will likely form a key source of evidence.
Q2. Treatment: There are broadly two questions:
In patients with aHSIL (population – with sub populations), what is the success of treatment (intervention) with the measurement (Outcome) of:
aHSIL eradication to biopsy proven normal; or
HSIL downgrading to biopsy proven LSIL; or
Progression to ASCC
and how safe is the treatment/ intervention for topical medical therapies (outlined earlier) versus ablative methods of HSIL versus excision versus doing nothing (active surveillance/watchful waiting), with a six, 12-month, 2 year or longer follow up? (comparisons)
How many treatment episodes were required over what period of time for the treatments described in 2.1?
Key sources: Data from updates on Brogden systematic review (48)  on treatments will likely form a key source of evidence. We will also consider the recently published (August 2025) and comprehensive Cochrane review (49) – limited to randomised controlled trials only.
Q3. Follow-up after treatment: In patients who have completed aHSIL treatment (defined as eradication of HSIL to normal or downgrading of HSIL to LSIL) what are the outcomes (defined as recurrence of HSIL or progression to cancer) of surveillance (description of regimen, intensity and modality required) vs doing nothing (comparison)?

Key sources: Data from updates on guidelines identified in the Brogden review (23) will  likely form a key source of evidence.
Outcome measures
A core outcome set is currently being developed for future trials regarding the treatment of anal intra-epithelial lesions, in the CORSiCA project (leads: AGR, RF, and DF). https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023429661.
There were some 22 outcomes at the end of the CORCISA project (as presented at the IANS conference, London, June 2025). The PMT deemed this number too many and for pragmatic reasons opted for four ‘oncological’ outcomes within the physiology/ clinical domain. Primary outcomes for the review questions in these guidelines:
Progression of aHSIL to cancer
Regression of aHSIL to aLSIL
Resolution of aHSIL to histologically negative disease
Occurrence of major or significant adverse outcomes
CONSULTATION AND DISSEMINATION: Step 6 – finalising and publishing guidelines
An advanced draft version of the guidelines will be posted on the ACPGBI website for consultation with registered stakeholders and respondents.
The ACPGBI will inform registered stakeholders and respondents that the draft is available and will invite them to comment by a deadline.

Questions for stakeholders will be posted with the draft guidelines. The ACPGBI will also ask stakeholders to comment on recommendations identified as likely to increase costs, and their justification, and to consider whether any other draft recommendations are expected to add substantial costs. These costs should consider the cost of anal cancer management including advanced anal cancer management vs the cost of preventative measures.

An advanced draft version of the guidelines will be shared for comment and endorsement from several related professional organisations including:


The proposed timeline is for presentation to ACPGBI conference in July 2026.
Authors’ contributions
AGR, and TC contributed to conception and design. AGR, TC, and MG form the project management team, who coordinate steering group meeting and the systematic literature searches. All authors contributed to the final editing of the protocol.
Declaration of Interests
AGR has received conference fees, travel, accommodation and hospitality from THD. TC is the current President of the International Anal Neoplasia Society (IANS); the opinions in this protocol do not reflect those of IANS. All other authors have no conflicts of interest to declare. All authors have submitted an approved conflicts of interest statement prior to involvement in the guideline development group.
Funding
ACPGBI have undertaken to provide the funds for the methodologist to assist in the production of these guidelines.
Protocol references
1. Islami F, Ferlay J, Lortet-Tieulent J, Bray F, Jemal A. International trends in anal cancer incidence rates. Int J Epidemiol. 2017;46(3):924-38. 2. Lin C, Franceschi S, Clifford GM. Human papillomavirus types from infection to cancer in the anus, according to sex and HIV status: a systematic review and meta-analysis. Lancet Infect Dis. 2018;18(2):198-206. 3. Geh I, Collins S, Renehan A, Scholefield J, Govindarajah N, et al. Association of Coloproctology of Great Britain and Ireland (ACPGBI): Guidelines for the Management of Cancer of the Colon, Rectum and Anus (2017) - Anal Cancer. Colorectal Dis. 2017;19 Suppl 1:82-97. 4. GRADE handbook. https://gdt.gradepro.org/app/handbook/handbook.html [accessed 03 Dec 2025] 5. WHO handbook for guideline development, 2nd Edition. http://www.who.int/publications/i/item/9789241548966 [accessed 03 Dec 2025] 6. McMaster GRADE Centre. GIN-McMaster guideline development checklist. https://cmggrade.mcmaster.ca/ [accessed 03 Dec 2025] 7. Schünemann HJ, Wiercioch W, Etxeandia I, Falavigna M, Santesso N, Mustafa R, et al. Guidelines 2.0: systematic development of a comprehensive checklist for a successful guideline enterprise. CMAJ. 2014;186(3):E123-42. 8. Brouwers MC, Kho ME, Browman GP, Burgers JS, Cluzeau F, Feder G, et al. AGREE II: advancing guideline development, reporting and evaluation in health care. CMAJ. 2010;182(18):E839-42. 9. Mares-Carballo M, García-García M, Gómez-Fandiño Y, De-Dios-de-Santiago D, Martínez-Martínez C, Bueno-Cavanillas A, Khan KS. Guidance documents for colorectal and anal cancer treatment: A systematic quality and reporting assessment. Colorectal Dis. 2022;24(12):1472-90. 10. Miller AS, Boyce K, Box B, Clarke MD, Duff SE, Foley NM, et al. The Association of Coloproctology of Great Britain and Ireland consensus guideline on emergency perianal surgery. Colorectal Dis. 2021;23(4):746-57. 11. van Iersel R, Kleijnen J, Watson AJM, Joseph J, Smart NJ, et al. European Society of ColoProctology: guideline for haemorrhoidal disease. Colorectal Dis. 2020;22(6):650-62. 12. Albuquerque A, Golightly MA, Zappacosta C, Pesola F, Bowring J, Cuming T, et al. Multizonal anogenital neoplasia in women: a cohort analysis. Br J Cancer. 2025. 13. Chapprah TM, Colgan TJ, Cox JT, Heller DS, Henry MR, Luff RD, et al. The Lower Anogenital Squamous Terminology Standardization Project for HPV-Associated Lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology. Arch Pathol Lab Med. 2012;136(10):1266-97. 14. Bowden SJ, Ellis IB, Cuming T, Brogden D, Shephard SM, Finch DA, et al. Multizonal intraepithelial neoplasia of the lower genital tract and anus in women: terminology for defining the disease, an introduction by the British Society for Colposcopy and Cervical Pathology (BSCCP), International Anal Neoplasia Society (IANS), European Federation for Colposcopy (EFC) and British Society for the Study of Vulval Disease (BSSVD). British Journal of Cancer. 2025. 15. Liu Y, McCaughey WG, Darapri SM, Farhat N, Blakey M, Sigel K, et al. p16 Immunoreactivity Correlates With Morphologic and HPV-Associated Anal Intraepithelial Neoplasia: A Study of 100 Biopsies. Am J Surg Pathol. 2021;45(11):1573-8. 16. Monaghan M, Wang NASCB. Guidelines for histopathological reporting of anal cancer. Available at: https://www.rcpath.org/static/2fd8f2d16c-d5bb-4b9b-b147b/3a5a40a60e2eb3f1-87b9-4bd1-9c6889300d949827/16156-Dataset-for-histopathological-reporting-of-anal-cancer.pdf [accessed 17 April 2025] 17. Singh N, Cocks C, Wong RWY, McCluggage WG, Herrington CS. The British Association of Gynaecological Pathologists. Interpretation of p16 immunohistochemistry in lower anogenital tract neoplasia. PGD 0604824 24 V2 Final Available at: www.thebagp.org/download/edbagp-guidelines-clc-project-interpretationguide-2018 [accessed 17 April 2025] 18. Palefsky JM, Lee JY, Jay N, Goldstone SE, Darragh TM, Dunlevy HA, et al. Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer. N Engl J Med. 2022;386(24):2273-82. 19. Palefsky JM. CDC and NIH’s Guidelines 26 ANCHOR Implications for People without HIV, IANS webinar 14 January 2025. https://iansoc.org/jss/ojcm?26returnUrl=IANS%2FwebRounds-Recording [accessed 17 April 2025] 20. Clifford GM, Georges D, Shiels MS, Engels EA, Albuquerque A, Poynten IM, et al. A meta-analysis of anal cancer incidence by risk group: Toward a unified anal cancer risk scale. Int J Cancer. 2021;149(8):843-7. 21. Stier EA, Clarke MA, Deshmukh AA, Wentzensen N, Liu Y, Poynten IM, et al. International Anal Neoplasia Society’s consensus guidelines for anal cancer screening. J Cancer. 2022;154(10):1690-704. 22. Brasanac D, Weinberg SE, Finkinen JS, Johnson JS, Krogh K, Kim S, et al. The effect of human immunodeficiency virus and human papillomavirus strain diversity on the progression of anal squamous intraepithelial lesions. Hum Pathol. 2022;128:20-30. 23. Brogden DJ, Luip MEE, Warrogan N, Koyountoums CS, Luip CS. Comparing and contrasting clinical consensus and guidelines for anal intraepithelial neoplasia in different geographical regions. Colorectal Dis. 2022;57(4):207-58. 24. Alam NN, White DA, Narang SK, Daniels IR, Smart NJ. Systematic review of guidelines for the assessment and management of high-grade anal intraepithelial neoplasia (AIN) (UK guidelines). Br J Surg. 2016;103(7):852-66. 25. Stewart DB, Gaertner WB, Glasgow SC, Herline AJ, Ricciardi R, Steele SR. The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for Anal Squamous Cell Cancers (Revised 2018). Dis Colon Rectum. 2018;61(7):755-74. 26. Paladino G, Gasparini G, Da Costa AM, Van Nessaw F, Caselli S, Perrotti E, et al. Practice parameters for the diagnosis and treatment of anal intraepithelial neoplasia (AIN) on behalf of the Italian Society of Colorectal Surgery (SICCR). Tech Coloproctol. 2019;23(5):513-28. 27. Gowers N, Goutasyrmenis S, Kalogeropila M, Tsagoulakis D, Youn L, Xynos E. Hellenic society of medical oncology (HESMO) guidelines for anal cancer. Updates Surg. 2021;73(1):47-55. 28. Kreitor A, Dete M, Gimeglamos A, Semith M, et al. German-Austrian guidelines on anal dysplasia and anal cancer in HIV-positive individuals: prevention, diagnosis, and treatment. S Dtsch Dermatol Ges. 2015;13(12):1302-19. 29. de Suñer G, Arbynider RF, Adk B, Bacchot R, Batten SK, et al. Cancer in People Living with HIV, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Cancer Netw. 2018;16(9):960-71. 30. EACS European AIDS Clinical Society Guidelines Version 12.0. https://www.eacsociety.org/media/guidelines-12.0.pdf [accessed 17 April 2025] 31. New York State Department of Health AIDS Institute. Screening for Anal Dysplasia and Cancer in Adults with HIV. https://www.hivguidelines.org/ol/edline/hiv-anal-cancer/ [accessed 17 April 2025] 32. NIH. Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents With HIV. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/hivans?view=full [accessed 17 April 2025] 33. Spindler L, Etienney I, Abramowitz L, de Parades V, Pigot F, Siproudhis L, et al. Screening for precancerous anal lesions linked to human papillomavirus: French recommendations for clinical practice. Tech Coloproctol. 2024;28(1):3-7. 34. Vallado M, Reichenbach RM, Silva J, Mai J, Alvarez C, Auglis S, et al. Brazilian Society of Surgical Oncology: Guidelines for the management of anal canal cancer. J Surg Oncol. 2024;130(3):810-29. 35. Leal C, Catano AC, Limper M. Portuguese Society for Coloproctology. Anal cancer and precursor lesions - Recommendations. chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.spcp.pt/protocolos/ref/ cancer-anal.pdf [accessed 17 April 2025] 36. Chinch-Hoy PJ, Reid GP. Human papillomavirus infections in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2022;36(7):100-7. 37. Rao S, Green MG, Khan K, Brown G, Crean R, Singh S, Sete et al. Anal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up(1). Ann Oncol. 2021;32(7):1007-100. 38. Mourad-Zabotto L, Vendrely V, Abramowitz L, Gerard JP, Francois E, Gomez D, et al. Anal cancer: French Intergroup Clinical Practice Guidelines for diagnosis, treatment and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, SNFCP). Dig Liver Dis. 2017;49(9):831-40. 39. Leeds IL, Fang SH. Anal cancer and intraepithelial neoplasia screening: A review. World J Gastrointest Surg. 2016;8(1):41-51. 40. Loughrey MB, Shepherd NA. Anal and Perianal Preneoplastic Lesions. Gastroenterol Clin North Am. 2002;53(1):201-20. 41. Goldstone SE, Lensing SY, Stier EA, Darragh T, Lee JY, van Zante A, et al. A Randomized Clinical Trial of Infrared Coagulation Ablation Versus Active Monitoring of Infra-anal High-grade Dysplasia in Adults With Human Immunodeficiency Virus Infection: An AIDS Malignancy Consortium Trial. Clin Infect Dis. 2019;68(7):1204-12. 42. Albuquerque A, Brogden D, Howell AM, Tekks P, Mills S, Kontovounisios C. Anal Cancer in High-Risk Women: The Lost Tribe. Cancers (Basel). 2022;15(1). 43. Poynten IM, Jin F, Roberts JM, Templeton DJ, Law C, Cornall AM, et al. The Natural History of Anal High-grade Squamous Intraepithelial Lesions in Gay and Bisexual Men. Clin Infect Dis. 2021;72(5):853-61. 44. Deshmukh AA, Lin Y, Dronavalli H, Shiels M, Chesson H, Dosum B, Liang R, et al. Recent and projected incidence trends and risk of anal cancer among people with HIV in North America. J Natl Cancer Inst. 2024;116(9):1450-8. 45. Liu Y, Sigel K, Gaisa MM. Human Papillomavirus Genotypes Predict Progression of Anal Low-Grade Squamous Intraepithelial Lesions. J Infect Dis. 2018;218(11):1746-52. 46. Lin C, Slama J. Cervical determinants of anal HPV infection and high-grade anal lesions in women: a collaborative pooled analysis. Lancet Infect Dis. 2019 Aug;19(8):888-891. doi: 10.1016/S1473-3099(19)30164-1. Epub 2019 Jun 13. PMID: 31204304; PMCID: PMC6656696. 47. Deshmukh AA, Boangiu AC. Global burden of HPV-attributable squamous cell carcinoma of the anus in 2020, according to sex and HIV status: a worldwide analysis. Int J Cancer. 2023 Feb 1;152(3):417-428. 48. Kontovounisios C, Pellino G, Kontovounisios C, Tekkis P, Mills S. Evaluating the efficacy of treatment regimens for anal intraepithelial neoplasia: a systematic review. Int J Colorectal Dis. 2021;36(2):213-26. 49. Pedersen TB, Pachler FR, Rosenberg J, Andresen K. Interventions for anal canal intraepithelial neoplasia. Cochrane Database Syst Rev. 2025;(8):CD029044. 50. East JE, Gordon N, Nigam G, Sinopoulou V, Bateman AC, Din S, et al. British Society of Gastroenterology guidelines on colorectal surveillance in inflammatory bowel disease in adults: 2025. Gut. 2025;74(Suppl 2):s1-s101. 51. Moran GW, Gordon N, Simopoulou V, Radford SJ, Barie AM, Vuyyuru SK, et al. British Society of Gastroenterology guidelines on inflammatory bowel disease in adults: 2025. Gut. 2025;74(Suppl 2):s1-s101. 52. Shea BJ, Reeves BC, Wells G, Thuku M, Hamel C, Moran J, et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. Bmj. 2017;358:j4008. 53. Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. Bmj. 2016;355:i4919. 54. Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011;155(8):529-36. 55. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539-58. 56. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. Bmj. 1997;315(7109):629-34. 57. Cumpston M, Li T, Page MJ, Chandler J, Welch VA, Higgins JP, Thomas J. Updated guidance for trusted systematic reviews: a new edition of the Cochrane Handbook for Systematic Reviews of Interventions. Cochrane Database Syst Rev. 2019;10(1):ED000142. 58. Mustafa RA, Garcia CAC, Bhatt M, Riva JJ, Vesely S, Wiercioch W, et al. GRADE notes: How to use GRADE when there is “no” evidence? A case study of the expert evidence approach. J Clin Epidemiol. 2021;137:231-5. 59. Alonso-Coello P, Schünemann HJ, Moberg J, Brignardello-Petersen R, Akl EA, Davoli M, et al. GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 1: Introduction. Bmj. 2016;353:i2016.
Acknowledgements
AGR is supported by the Manchester NIHR Biomedical Research Centre (NIHR203308). The authors would like to acknowledge the support and assistance of Ms Lisa Massey, Consultant Colorectal Surgeon and Chair of the Guideline Development Committee of the ACPGBI.