Management Of Anal Intraepithelial Neoplasia Research Articles

Multidisciplinary management of anal intraepithelial neoplasia and rate of progression to cancer: A retrospective cohort study

PurposeTo describe the regional burden of AIN and rate of progression to cancer in patients managed in specialist and non-specialist clinic settings. MethodsPatients with a histopathological diagnosis of AIN between 1994 and 2018 were retrospectively identified. Clinicopathological characteristics including high-risk status (chronic immunosuppressant use or HIV positive), number and type of biopsy (punch/excision) and histopathological findings were recorded. The relationship between clinicopathological characteristics and progression to cancer was assessed using logistic regression. ResultsOf 250 patients identified, 207 were eligible for inclusion: 144 from the specialist and 63 from the non-specialist clinic. Patients in the specialist clinic were younger (<40 years 31% vs 19%, p = 0.007), more likely to be male (34% vs 16%, p = 0.008) and HIV positive (15% vs 2%, p = 0.012). Patients in the non-specialist clinic were less likely to have AIN3 on initial pathology (68% vs 79%, p = 0.074) and were more often followed up for less than 36 months (46% vs 28%, p = 0.134). The rate of progression to cancer was 17% in the whole cohort (20% vs 10%, p = 0.061). On multivariate analysis, increasing age (OR 3.02, 95%CI 1.58–5.78, p < 0.001), high risk status (OR 3.53, 95% CI 1.43–8.74, p = 0.006) and increasing number of excisions (OR 4.88, 95%CI 2.15–11.07, p < 0.001) were related to progression to cancer. ConclusionThe specialist clinic provides a structured approach to the follow up of high-risk status patients with AIN. Frequent monitoring with specialist assessments including high resolution anoscopy in a higher volume clinic are required due to the increased risk of progression to anal cancer.

Management of anal intraepithelial neoplasia and anal squamous cell carcinoma at a tertiary referral centre with a dedicated infectious diseases unit: an 18-year review.

Anal squamous cell carcinoma (ASCC) is a rare malignancy with rising incidence rates. Risk factors include human immunodeficiency virus (HIV) infection, high-risk sexual activity and HPV-related genitourinary dysplasia/neoplasia. There is an overlap between high-risk patients and those attending HIV Medicine/Sexual Health (HMSH) services. We hypothesised that HMSH involvement may facilitate earlier referral to colorectal surgeons, with better outcomes. Retrospective review of all ASCC and anal intraepithelial neoplasia (AIN) treated at a tertiary-referral hospital with a dedicated HMSH clinic between 2000 and 2018. Comparative analysis was performed of demographics, management and outcomes between HMSH and non-HMSH patients. One hundred and nine patients had anal pathology, eighty-five with ASCC (78%) and twenty-four with AIN (22%). Seventy (64%) were male. Median (range) age at ASCC diagnosis was 51 years (26-88). Thirty-six percent of all patients attended HMSH services, 28% were HIV positive, and 41% of males were men-who-have-sex-with-men (MSM). Eighty-one ASCC patients (97.5%) were treated with curative intent. Sixty-seven (80%) had primary chemoradiation therapy. Fifteen (17.5%) had primary surgical excision. Twelve (14%) developed recurrent disease. Ultimately, seven required salvage APR. Overall 3-year survival (3YS) was 76%. HMSH patients were significantly younger at ASCC diagnosis (p < 0.001), with a higher prevalence of HIV, HPV and MSM. HMSH attenders also tended to be diagnosed at earlier stages, were less likely to develop recurrence and achieved better overall outcomes, with a superior overall 3YS than non-HMSH patients (92% vs 72%, p = 0.037). ASCC incidence is increasing worldwide. The HMSH cohort has emerged as a distinct subpopulation of younger, high-risk, male patients. Collaboration between HMSH and colorectal surgeons offers an opportunity for risk reduction strategies and earlier intervention.

Practice parameters for the diagnosis and treatment of anal intraepithelial neoplasia (AIN) on behalf of the Italian Society of Colorectal Surgery (SICCR).

Squamous cell carcinoma (SCC) of the anus is a human papilloma virus (HPV) related malignancy that is preceded by anal intraepithelial neoplasia (AIN) making this cancer, at least theoretically, a preventable disease. In the past 10years the diagnosis, management and nomenclature of AIN has dramatically changed. Increased life expectancy in human immunodeficiency virus (HIV) positive patients due to highly active antiretroviral therapy (HAART) has caused an increase in the incidence of SCC of the anus. While many experts recommend screening and treatment of anal high-grade squamous intraepithelial lesion (HSIL), there is no consensus on the optimal management these lesions. Therefore, there is a need to review the current evidence on diagnosis and treatment of AIN and formulate recommendations to guide management. Surgeons who are members of the Italian Society of Colorectal Surgery (SICCR) with a recognized interest in AIN were invited to contribute on various topics after a comprehensive literature search. Levels of evidence were classified using the Oxford Centre for Evidence-based Medicine of 2009 and the strength of recommendation was graded according to the United States (US) preventive services task force. These recommendationsare among the few entirely dedicated only to the precursors of SCC of the anus and provide an evidence-based summary of the current knowledge about the management of AIN that will serve as a reference for clinicians involved in the treatment of patients at risk for anal cancer.

Multidisciplinary Approach to the Management and Treatment of Anal Dysplasia.

The incidence of anal intraepithelial neoplasia (AIN) has been increasing over the years. AIN acts as a precursor lesion for anal squamous cell cancer. Factors leading to progression of AIN into malignancy are complex and involve grade of the lesion, human papillomavirus and HIV coinfection, as well as patient-related risk factors such as immunocompromised state and men who have sex with men. The multifaced aspects of this disease make its management challenging, as it involves several disciplines including pathology, primary care, infectious disease, and colorectal specialties. Each of these fields brings its own expertize to the management of AIN, and their collaborative, coordinated work culminates into best practice and optimized outcomes in the care of the AIN patient.

Systematic review of guidelines for the assessment and management of high‐grade anal intraepithelial neoplasia (AIN II/III)

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. 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. 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. 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.

PTU-198 Systematic review of the assessment and management of anal intraepithelial neoplasia grade iii

Introduction Anal Intraepithelial Neoplasia (AIN) is dysplasia in the squamous epithelium of the anus and is a precursor for anal squamous cell carcinoma. AIN is associated with many risk factors particularly infection with the Human Papilloma Virus (HPV), which is found in 90% of cases. There is ambiguity with regards to the optimal management of AIN III and there are significant variations in the published guidelines produced by official bodies. Therefore the optimal treatment and long term management of AIN III is yet to be standardised. The aim of this review is to assess the evidence behind national society guidelines currently available in the literature available on AIN III management, surveillance and treatment. Method An electronic search of Pubmed 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 st January 2000 to 31 st December 2014, assessing the treatment, surveillance or management of patients with AIN related to HPV 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 4473 articles and 2 guidelines were sourced from official body guidelines (ACPGBI and ASCRS). After inclusion criteria were applied, 22 abstracts were reviewed and 10 were excluded as they were not relevant to AIN III or anal cancer, and a further 6 were excluded as they were earlier versions of current guidelines. Three guidelines (American College of Radiology, NCCN and the European Society for Medical Oncology) were excluded as they were recommendations for anal cancer leaving three guidelines for review. Guidelines published by ACPGBI, ASCRS Italian Society of Colorectal Surgery (SICCR) were included for the systematic review. Conclusion All 3 guidelines agree that a high index of clinical suspicion is necessary for diagnosing AIN III. A disease specific history focussing on signs, symptoms and predisposing risk factors as well as a perianal examination, digital rectal examination and anal cytology is essential for assessment. However, there is significant variation amongst the guidelines with regards to surveillance, medical treatment, surgical excision and follow-up of patients with AIN III. The quality of evidence used to form the guidelines is of a low level with the majority based on Level 3 or 4 evidence. This review highlights that the current guidelines available are based on out-dated evidence of low quality and standardised registry data is needed to standardise assessment, treatment and surveillance to improve overall outcome. Disclosure of interest None Declared.

Current treatment options for management of anal intraepithelial neoplasia.

Anal squamous cell cancer is an uncommon malignancy caused by infection with oncogenic strains of Human papilloma virus. Anal cancer is much more common in immunocompromised persons, including those infected with Human immunodeficiency virus. High-grade anal intraepithelial neoplasia (HGAIN), the precursor of anal cancer, is identified by clinicians providing care for patients with anorectal disease, and is increasingly being identified during screening of immunosuppressed patients for anal dysplasia. The traditional treatment for HGAIN has been excision of macroscopic disease with margins. This approach is effective for patients with small unifocal HGAIN lesions. Patients with extensive multifocal HGAIN frequently have recurrence of HGAIN after excision, and may have postoperative complications of anal stenosis or fecal incontinence. This led to the suggestion by some that treatment for HGAIN should be delayed until patients developed anal cancer. Alternative approaches in identification and treatment have been developed to treat patients with multifocal or extensive HGAIN lesions. High-resolution anoscopy combines magnification with anoscopy and is being used to identify HGAIN and determine treatment margins. HGAIN can then be ablated with a number of modalities, including infrared coagulation, CO2 laser, and electrocautery. These methods for HGAIN ablation can be performed with local anesthesia on outpatients and are relatively well tolerated. High-resolution anoscopy-directed HGAIN ablation is evolving into a standard approach for initial treatment and then subsequent monitoring of a disease which should be expected to be recurrent. Another treatment approach for HGAIN is topical treatment, principally with 5-fluorouracil or imiquimod. Topical therapies have the advantage of being nonsurgical and are well suited for treating widespread multifocal disease. Topical treatments have the disadvantage of requiring extended treatment courses and causing a symptomatic inflammatory response. Successful treatment requires adherence to a regime that is uncomfortable at best and at worst painful. Topical treatments can be successful in motivated adherent patients willing to accept these side effects.

Interventions for anal canal intraepithelial neoplasia

Anal canal intraepithelial neoplasia (AIN) is a pre-malignant condition of the anal canal transitional epithelium that is associated with human papillomavirus (HPV) infection. The incidence and prevalence of AIN and anal cancer are increasing rapidly in HIV-positive men who have sex with men (MSM). Other groups like HIV-negative MSM, immunosuppressed patients and people affected by other HPV diseases like genital warts and cervical intraepithelial neoplasia (CIN) may also develop AIN. The condition is complicated by its multicentric and multifocal nature and high rates of relapse and morbidity. Targeted excisions using ablative treatments such as cautery, infrared coagulation (IRC) and cryotherapy have been used as first-line therapeutic strategies, and there are many other options. There is no consensus about the optimal management of AIN. To evaluate the effects of therapeutic interventions for anal canal intraepithelial neoplasia (AIN). We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2011, Issue 4), MEDLINE and EMBASE (to October 2011). We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies, and contacted experts in the field and manufacturers of any AIN and HPV-specific treatments. Randomized controlled trials (RCTs) that assessed any type of intervention for AIN. Two review authors independently abstracted data and assessed risk of bias. If it was possible, the data were synthesised in a meta-analysis. We found only one RCT, which included 53 patients, that met our inclusion criteria. This trial reported data on imiquimod versus placebo. There was no statistically significant difference in the risk of disease cure but there was a trend for imiquimod to downgrade the AIN to a low-risk stage. The lack of statistical power of the trial may be due to the small number of patients in each group. The risk of bias was estimated as moderate. The included trial failed to demonstrate any statistically significant efficacy of imiquimod in the management of anal intraepithelial neoplasia (AIN). The absence of reliable evidence for any of the interventions used in AIN precludes any definitive guidance or recommendations for clinical practice. Prospective cohort studies and retrospective studies have not been included in this review as they are considered to provide lower quality evidence. Well designed RCTs are needed.

Guidelines for Management of Anal Intraepithelial Neoplasia

Guidelines for Management of Anal Intraepithelial Neoplasia

Evaluation and Management of Anal Intraepithelial Neoplasia in HIV-Negative and HIV-Positive Men Who Have Sex with Men

The incidence of human papillomavirus (HPV)–associated anal cancer in men who have sex with men (MSM) is striking and has not been mitigated by the use of highly active antiretroviral therapy. Detection and treatment of high-grade anal intraepithelial neoplasia (HGAIN) may reduce the incidence of anal cancer. Anal cytology is a useful tool to detect HGAIN; annual screening of HIV-positive MSM and biennial screening of HIV-negative MSM appears to be cost-effective. MSM with abnormal cytology should be referred for high-resolution anoscopy and biopsy. Individuals with HGAIN should receive treatment; treatment modalities for HGAIN demonstrate moderate efficacy and are usually well tolerated, but greater study is required to determine which treatment is optimal. Large prospective studies are needed to document the efficacy of screening and treatment of HGAIN on anal cancer incidence. The HPV vaccine holds promise for primary prevention of anal cancer in MSM, but significant implementation challenges remain.