To define minimum standards for provision of services and clinical practice in the investigation of anal cancer precursors.
Currently, patient assessment for anal cancer precursors consists of the digital anorectal examination (DARE), anal cytology and high-resolution anoscopy (HRA) examination. However, the final arbiter in the detection of an anal cancer precursor is with histological verification of an HRA-directed biopsy sample indicating HSIL. This document focuses on HRA examination and the biopsy procedures that help procure an accurate histological diagnosis of high-grade squamous intraepithelial lesions (HSILs). Treatment of anal cancer precursors is not addressed.
Anal squamous cell carcinoma (ASCC) is a stigmatized condition that frequently presents late, with corresponding poor prognosis, and typically requires chemoradiotherapy.1 Although rare in the general community, it occurs more commonly in specific populations, such as in HIV-infected men who have sex with men (MSM), who have rates more than 80 times higher than HIV-uninfected men.2 Women with previous human papillomavirus (HPV)–associated anogenital disease also have higher rates.3 Furthermore, the annual incidence of ASCC is increasing, particularly in these high-risk populations.4
There are many epidemiologic, virologic, cytological, and histological similarities between ASCC and cervical cancer, including the presence of the precursor, high-grade squamous intraepithelial lesion. Such similarities have fostered requests for the introduction of screening programs, striving to replicate the public health successes of the cervical cancer/cervical HSIL screening programs. Although estimated progression rates from HSIL to squamous cell carcinoma are lower in the anus compared with the cervix,5,6 identifying anal HSIL in an accurate and reproducible manner potentially allows for early diagnosis and interventions aimed at reducing anal cancer rates in high-risk populations.
After discussions between experts in the field at the International Papillomavirus meeting in Lisbon, September 17 to 21, 2015, a first version of proposed guidelines for practice standards in the detection of anal cancer precursors was developed. This was sent to key international stakeholders and a complete draft discussed at a Board meeting of the International Anal Neoplasia Society (IANS) in March 2016. A draft was then uploaded to the IANS Web site and an email sent to all IANS members for comments. These comments were included, and following further discussions, the final draft was ratified by the IANS Board at their meeting on June 22, 2016.
What Is HRA and Why Do We Need Standards?
Anal cytology has been used to predict those at risk of HSIL, but the limited sensitivity restricts its usefulness as a potential screening technique.7 High-resolution anoscopy with directed biopsy, a technique similar to cervical colposcopy,8 is currently the gold standard against which anal cytology and other diagnostic procedures are compared. High-resolution anoscopy developed simultaneously in several countries and has been used to help identify anal HSIL for more than 2 decades.9 However, the procedure for HRA is not standardized, and variations in HRA procedural techniques worldwide are not well documented. Most of these clinical HRA services are recent developments, suggesting that the numbers and locations of these services may be continuing to grow. For example, the International Anal Neoplasia Society (http://ians.memberlodge.org/) newly created in 2013 has members from at least 21 countries, including the following: Australia, Belgium, Brazil, Canada, Dominican Republic, France, Greece, Indonesia, Italy, Japan, The Netherlands, Philippines, Poland, Portugal, Puerto Rico, Russian Federation, Spain, Switzerland, Thailand, United Kingdom, the United States, and Venezuela. In addition to this geographical spread, there is also a considerable diversity in the professional backgrounds of HRA practitioners, including those from infectious diseases, HIV and sexual health, colorectal surgery, gynecology, family medicine, and dermatology. A survey of colon and rectal surgeons found that less than half who state they perform HRA have ever been formally trained. An analysis of their techniques showed that most did not conform to basic recommendations for HRA established by recognized experts in the field.10 Moreover, the procedure itself is not always completely described in publications, making comparison between reports difficult. Finally, a number of ablative and pharmacologic treatments for anal HSIL are currently used, requiring additional training beyond the purview of this guideline. However, it is well recognized that HRA-guided identification of HSIL can be pivotal to successful eradication of HSIL.
The establishment of common standards for HRA would therefore potentially be valuable to the following:
- ensure minimum competencies for the clinical practice of HRA
- define minimum acceptable standards for professional continuing clinical practice and contribution to research studies
- allow more meaningful comparison of research data. This is particularly relevant after the recent development of uniform histological reporting standards for anogenital HPV-associated squamous lesions11
- assess the value of individual components of training, including the effect of experience, techniques used, equipment, and length of time performing HRA on developing proficiency12–15
High-resolution anoscopy is the examination of the anal canal and perianus using a colposcope for lighting and magnification, after application of 5% acetic acid and Lugol iodine solutions to identify anal lesions.
The squamo-columnar junction (SCJ) is the junction where the squamous anal epithelium abuts the colonic columnar epithelium.
The anal transformation zone (AnTZ) is the zone where all aspects of squamous metaplasia are currently found and have occurred.
A complete and satisfactory HRA is one in which the anus is completely visualized, including the following:
- entire anal canal from the SCJ at the border of the distal rectum
- distal canal
- anal verge
As with cervical colposcopy, HRA relies on the clinician’s ability to recognize abnormalities in the acetic acid and Lugol staining patterns of the epithelium, changes in vessel patterns, and morphologic features such as friability, ulceration and mass effect. In this manner, it is possible to identify and distinguish the presence of potential HSIL and early, non-palpable cancers, from other benign findings.
Details of how to perform an examination are available elsewhere.16 As a minimum, this requires a good quality colposcope with adequate lighting and magnification, together with an examination table and provider seat, that allow for reasonable examination ergonomics and comfortable positions for both examiner and patient.
High-resolution anoscopy can be a technically and physically challenging examination. Specific features include the following:
- a) the clinician must hold the anoscope in position throughout the examination, adjusting where necessary, to fully visualize the entire AnTZ, including the SCJ, while refocusing and repositioning the colposcope as needed;
- b) the large surface area of the AnTZ, anal canal, and perianus, together with anatomical obstacles, such as mucosal folds and papillae, can be challenging to fully visualize;
- c) microscopic features helping to identify anal HSIL may be subtle, requiring higher magnification compared with the cervix, and can differ from those seen on the cervix8;
- d) widespread, multifocal disease is often present;
- e) coexisting pathology may be present, such as condyloma, hemorrhoids, anal fissure, and fistula in ano;
- f) changes may be present from treatment-related scar tissue, strictures, and irradiation changes from previous radiotherapy—potentially adding complexity to the interpretation of patterns seen;
- g) the psychosocial and emotional state of the patient being examined may either facilitate or make the exam even more challenging.
Most published data are from studies in MSM, particularly those who are HIV positive. However, in the general population, women develop anal cancer more commonly than men, and rates of anal cancer and HSIL are also elevated in other immunosuppressed populations groups.17–19 It is currently unknown whether optimum HRA practices or specific findings differ between these groups, and the only way that this can be investigated is to compare clinical findings from HRA tests that have been carried out to set quality standards.
What Comparable Specialties Do
Both colposcopy and endoscopy have established and validated quality standards, complemented by robust training and ongoing quality criteria for individuals and for clinical service units that are subject to inspection20–23 (Table 1). Ensuring a standard of performance is a valuable quality assurance measure for inclusion in screening programs aiming to prevent cancer. It is therefore appropriate that, before such a program can be introduced to prevent anal and other lower anogenital tract cancers, similar stringent standards need to be validated and implemented.
Proposed Minimum Standards for HRA Services
In the absence of data indicating optimum practice, the International Anal Neoplasia Society has developed guidance among current HRA practitioners. Although this may vary somewhat according to the size of the clinic population, referral pattern, case mix, level of expertise, training commitments, and research activities, the key components should include the following:
Set Up of HRA Services
- The room for conducting examinations must permit adequate privacy, confidentiality and dignity, and have nearby toilet facilities.
- The position of the patient during the procedure can be left (or right)-lateral, prone or lithotomy. Whichever is used, the patient’s comfort during examination should be ensured.
- Adequate resuscitation facilities for local anesthetic overdose, vasovagal reactions and for allergic reactions should be readily available and staffed trained in their administration. Adequate equipment and training of staff in procedures to stop excessive bleeding should be available.
- Patient information should be given, detailing the procedure, ideally before the examination. The information should outline the purposes of the examination, any preparation necessary, likely pain and bleeding that may be involved, as well as the potential benefits.
- Informed consent, as required by local regulations and customary practice, should be obtained at all times. Depending on local practices, this may be verbal consent. However, consideration should be given to using a written consent process, perhaps in conjunction with a preprocedural information leaflet.
- Staffing levels should be adequate. In addition to the HRA practitioner, a health-care professional (such as a trained nurse or medical assistant) is desirable. If another staff member is present during the HRA, they should undergo appropriate training re language and behavior during the procedure.
- Cleaning of the room between cases must comply with local infection control policies. Although HRA is not a sterile procedure, avoidance of cross-contamination is important. This is best carried out in consultation with the Infection Control department of your institution.
- Sterilization of biopsy forceps should similarly be discussed with Infection Control.
- HRA findings should be accurately recorded in the medical notes and include anatomical location and a detailed description of lesions, using accepted descriptors. Annotated digital photography may be considered to supplement drawings
- Clear policies must be in place to ensure accurate reporting of examinations, follow-up arrangements, communication of results, and the expediting of care for urgent or cancer cases. It is highly recommended to provide each patient with concise information on what to do post-HRA and ways of contacting the nurse/physician or institution in case of adverse events.
- Follow-up information should be solicited from patients, regarding their experiences during and after the procedures. If this cannot be done as a routine, it would be beneficial for the service to obtain feedback at least annually.
- A close working relationship with surgical colleagues is required for the prompt management of complications and complex or advanced cases. After consultation with the colleagues, there should be clear policies guiding processes for both internal and external referrals.
- Those units managing anal cancer should have access to health-care providers with specialized knowledge and be able to advise patients and their relatives.
- Diagnosis and treatment of anal HSIL and ASCC requires the input of clinicians from multiple specialties. It is important to have a team approach, with clinicians working closely for the benefit of good patient care. Specialties potentially involved include medical oncologists, colorectal surgeons, HIV/sexual health physicians, radiation oncologists, and histopathologists/cytopathologists.
Standard anatomical location reporting is crucial to orient any subsequent care or reexamination by different providers. Figure 1 illustrates that the anus is divided into the anal canal and perianus. The anal canal is divided into distal/proximal regions:
- distal rectum
- squamocolumnar junction
- dentate line
- distal canal
- anal verge
The perianum extends 5 cm laterally from the anal verge (margin) and is visualized by gentle retraction of the buttocks.
The location descriptors used must be independent of the position of the patient, with the use of “o’clock” terminology avoided wherever possible. This is because of the marked differences in meaning, depending on whether the patient is in a left lateral, prone, or lithotomy position.
The canal into can be divided into octants, circumferentially, as illustrated in Figure 2.
Lesion location can additionally be recorded in the anal canal with respect to its proximal/distal extent as at/near the SCJ, mid-canal, distal canal, and perianus. This allows the anal canal to be described by smaller sections, which may assist in the assessing of the extent of disease. Consideration should be given documenting the anatomical area of HSIL (both intra-anal and perianal lesions), in the form of photographs and/or diagrams to further provide a record of volume of disease as this may be important in monitoring progress and may be a marker for disease progression.
General HRA Descriptors
After direct, repeated, and comprehensive application of 5% acetic acid to the entire anal canal (+/− Lugol iodine for the intra-anal canal), the details in Table 2 should be recorded.
It is recommended that lesions are seen using the terminologies listed in Table 3.
Depending on their jurisdiction, colposcopists may need to initially satisfy a number of training requirements, including E-learning, attendance at courses, preceptorships, mentorships, and completion of practice log books. Until further data are available, training in HRA practice could ideally include a number of components:
- i. attendance at a basic HRA course, organized by a recognized professional society;
- ii. knowledge of anorectal anatomy and physiology, epidemiologic characteristics of HPV-associated anal disease, cyto/histopathologic terminology, and clinical features of anal HPV-associated disease, together with their diagnosis and management;
- iii. observation of an experienced HRA practitioner;
- iv. preceptorship—a formal program of visits by expert to observe practice as part of a specifically designed training program;
- v. mentorship—discussing cases with identified experts, focused on the acquisition of practical clinical competencies;
- vi. multidisciplinary discussions with cytologists, pathologists and clinicians, to improve clinicopathologic correlations and refine lesion identification; and
- vii. regular patient feed-back of the service and care.
Continuous learning and review of performance are an integral part of developing and maintaining practice techniques.
Once a defined training syllabus and assessment metrics have been developed and evaluated, further work will be required to identify which aspects of training yield the highest quality outcomes.
Before commencing independent clinical practice of HRA, clinicians should be able to perform all of the competencies listed in Table 4.
Definition of an Adequate HRA Examination
A HRA can only be considered to have been adequately performed if the all the components in Table 5 have been achieved.
Quality Assurance Metrics
The aims of quality assurance (QA) metrics are as follows:
- a) to maximize the likelihood of the accurate detection of the presence and extent of HSIL and early cancers, and
- b) to capture patient experience to minimize discomfort.
Good QA standards aim to achieve high levels of correlation between cytology, HRA descriptions, and histological diagnoses. This may be especially relevant when a patient is referred with previously established cytological or histological evidence of HSIL.
To support the measurement of quality indicators, the terms auditable outcome (an important indicator, based on expert opinion, for which no clear evidence base exists) and quality standard (an auditable outcome for which there is an evidence base that can support a minimum standard) have been identified for colonscopy.24 With respect to the individual components of performing HRA, no clear evidence currently exists to support the setting of clinical practice standards. Nevertheless, there are key performance indicators that are based on a consensus of expert opinion and could potentially be monitored in the future, to obtain that evidence.
These metrics are proposed as a means of establishing initial benchmarks, against which data can be collected in a prospective fashion and the metrics modified in response to experience. These are suggested minimum standards. Individual units may choose to set higher standards.
It is likely that the ability to achieve these metrics will vary with the population being examined. For example, a true screening population will have lower rates of HSIL, whereas a group already identified for treatment is likely to have higher rates. Although the prevalence of HSIL clearly differs between various risk groups, clinical experience does not currently suggest that there is likely to be any significant variation in the performance of HRA and appearance of lesions.
Volume of Practice
The time taken to become proficient is inversely proportional to the volume of practice12,15 and ideally would involve a minimum of 5 HRAs examinations per week. Volume of practice criteria are given in Table 6.
Anal Cytological Sampling
Recommended proportions of technically unsatisfactory anal cytological sampling rates are given in Table 7.
High-resolution anoscopy performance metrics are based on the assumption that cytological changes of HSIL (cHSIL) strongly suggest that histologically verifiable HSIL (hHSIL) is present. There may be rare exceptions, such as profound immunosuppression, post radiotherapy, and very early on in the development of HSIL lesions when these associations differ. These metrics are currently based on expert opinion but will be reviewed as evidence is generated. Table 8 lists the recommended metrics.
Patient Experience (for diagnostic HRA only)
Ensuring minimal levels of discomfort for patients undergoing procedures is a key component of high-quality services and helps with maintaining follow-up. Recommended metrics are given in Table 9.
Possible Additional Metrics
Depending on the clinical or research contexts and availability of resources, consideration may be given to the additional metrics listed in Table 10.
The completion of a deidentified log book in an ongoing fashion is strongly recommended. This facilitates reflective learning, allows the collection of the above metrics, and can be audited, if required.
An example of a logbook is given in Figure 3.
Rising rates of anal cancer, greater understanding of the natural history of HSIL, the precursors to anal cancer, and increasing abilities to intervene, have meant growing interest in the provision of related diagnostic and therapeutic procedures. These opinions and guidelines are currently delivered by a diverse group of professionals from varying backgrounds. We await the outcomes a number of large clinical trials (eg, ANCHOR [https://clinicaltrials.gov/ct2/show/NCT02135419], SPANC,25 LOPAC http://www.hra.nhs.uk/news/research-summaries/lopac-laser-ablation-versus-observation-to-prevent-anal-cancer-v-1-0/ etc.) to provide the evidence base for optimum screening and management of hHSIL. However, an increasing number of clinical services are being introduced in response to the pressing clinical need to identify and closely monitor those at very high risk of anal cancer.
Competent practitioners should be able to find most histological HSIL present, most of the time. Agreed criteria for what constitutes adequate HRA examination and acceptable levels of clinical service will greatly facilitate the interpretation of clinical and research data, together with the development of multicenter, multinational trials designed to address this growing clinical problem.
This guideline proposes initial minimum competencies for the clinical practice of HRA, against which professionals can judge themselves and providers can evaluate the effectiveness of training. Once standards have been agreed upon and validated, it may be possible to develop certification methods for individual practitioners and accreditation of sites.
The authors thank all IANS members for the valuable feedback.
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