This study aimed to compare trichloroacetic acid (TCA) versus electrocautery (ECA) for the treatment of anal high-grade squamous intraepithelial lesions (HSIL).

This is an observational, single-center study. All subjects with HIV who had anal HSIL treated with TCA or ECA from 2010 to 2022 were included. Effectiveness was evaluated by on-treatment analysis, defining response as the resolution of HSIL and recurrence as a new diagnosis of HSILs during follow-up. A propensity score analysis was used to adjust for confounding factors.

In total, 227 and 260 HSIL episodes were treated with ECA and TCA, respectively. Response was observed in 61.7% (95% CI: 55.3-68) of cases treated with ECA and in 73.1% (95% CI: 67.8-78.5) with TCA (p = .004). The effectiveness of TCA was higher in large and multifocal HSILs. Side effects were common with both treatments, but no serious events were described. Tolerability was good in 77.1% and 80.7% of patients treated with ECA and TCA, respectively. At 24 months, recurrent HSIL were observed in 36.3% (95% CI: 27.3-45) and 28% (95% CI: 20.2-35.8) in the ECA and TCA groups (p = .049). A nadir CD4 cell count ≤200 cells/µl was found to be a risk factor for recurrence (OR: 1.77; 95% CI: 1.12-2.78).

In this study, treatment with TCA showed high effectiveness, low recurrence and good tolerability. Considering the benefits of TCA, it could be considered one of the first-line treatments for anal HSIL.

Anal intraepithelial neoplasia (AIN) appears in three different stages. AIN 1 and AIN 2 (p16 negative) are defined as low risk and unlikely to progress to invasive anal cancer. AIN 2 (p16 positive) and AIN 3 are of high risk and should be treated because progression rates to anal cancer are around 10% and treatment significantly reduces this risk. The correct treatment is still a matter of debate. Human papilloma virus (HPV) plays a role in the development of AIN. Our aim was to assess anal endoscopic dissection (aESD) as an intervention for AIN3.

We retrospectively evaluated patients who underwent aESD for AIN 3 between December 2017 and March 2023. The interventional technique itself (duration, complications, size of specimen) and patient outcomes (recurrence, progression to anal cancer, re-intervention) were analyzed.

Fifteen patients with a median age of 52 years (23-78) underwent aESD for AIN 3. All tested specimens were positive for HPV. Median duration of intervention was 56.1 min, one delayed postinterventional bleeding occurred, and specimen size was 12.05 cm2. Median follow-up was 11.17 months. Three recurrences (20%) appeared: one was resected via biopsy and two were again treated with aESD. There was no progression to invasive anal cancer in the follow-up period.

Anal endoscopic submucosal dissection seems to be a safe and feasible treatment for AIN. Recurrences are seldom and can be treated again with the same method. Nevertheless, indications for resection in comparison to radiofrequency ablation, pharmacological therapy, and watch-and-wait strategy are still unclear.

Ethics commission of Salzburg, Austria, EK-Nr. 1056/2023. Keywords: Endoscopic submucosal dissection, anal intraepithelial neoplasia, anal cancer.

Anal squamous cell carcinoma (SCC) is rare, but it has been commonly detected as an invasive cancer. The standard treatment for anal SCC was surgical resection. However, recent medical advances have enabled the standard treatment to be chemoradiotherapy. Anal intraepithelial neoplasia (AIN) is a premalignant lesion of SCC. The screening test for AIN and human papilloma virus vaccine are important for the following high-risk patients: patients positive for human immunodeficiency virus and men who have sexual intercourse with men. Although cytology can be easily applied for a screening test, the false-negative rate for AIN is high. Instead, high-resolution anoscopy (HRA) has been gaining attention as a promising screening method for high-risk patients. Investigations comparing characteristic findings of HRA with the histology of AIN have demonstrated that HRA is a highly specific test for AIN. Magnifying or image-enhanced endoscopies are also routinely used for colonoscopy, as they allow detailed observations at higher magnifications than those of HRA. Hence, these endoscopic modalities can be applied for assessing AIN. Ablation therapies or topical medications are available as the local treatment for AIN. Although endoscopic submucosal dissection is considered to be feasible to remove AIN, it has a technical difficulty to approach endoscopically invisible areas. Hence, this technique may be useful to resect AIN localized in the endoscopically visible areas, when the localization is confirmed via targeted biopsy.

Ablative treatment of anal high-grade squamous intraepithelial lesions (HSIL) reduces the risk of progression to anal squamous cell carcinoma.

To identify factors that influence the response to treatment of anal HSIL by electrocautery ablation (ECA) in a population of HIV-positive men who have sex with men (MSM).

Retrospective study of ECA treatment response in a prospectively followed anal dysplasia cohort. HIV-positive MSM diagnosed with anal HSIL were included. Demographic and HIV data were recorded. Response to treatment was assessed by biopsy after at least 18 months of follow-up.

One hundred and twenty-eight HSILs in 91 men were included in this study. The overall response rate at 18 months was 70.3%. The number of electrocautery sessions required (2 ECA sessions vs 1: adjusted odds ratio [aOR] = 0.36 (95%CI 0.13-1.01); >=3 sessions vs 1: aOR = 0.10 (95%CI 0.04-0.29); p < 0.001]) and the history of previous HPV-related anal pathology (previous anal lesions vs no previous lesions AOR = 2.83 (95%CI 1.14-7.02), p = 0.024) were independently associated with response at 18 months. No serious adverse events were reported.

Consideration should be given to alternative therapies in patients with unresolved HSIL after 1 ECA treatment.

Anal intraepithelial neoplasia (AIN) is the accepted precursor of anal squamous cell carcinoma (ASCC). There has long been a hypothesis that treating AIN may prevent ASCC. Many different treatment modalities have been suggested and studied. We conducted this systematic review to evaluate their efficacy and the evidence as to whether we can prevent ASCC by treating AIN.

MEDLINE and EMBASE were electronically searched using relevant search terms. All studies investigating the use of a single treatment for AIN that reported at least one end outcome such as partial or complete response to treatment, recurrence after treatment and/or ASCC diagnosis after treatment were included.

Thirty studies were included in the systematic review investigating 10 treatment modalities: 5% imiquimod, 5-fluorouracil, cidofovir, trichloroacetic acid, electrocautery, surgical excision, infrared coagulation, radiofrequency ablation, photodynamic therapy and HPV vaccination. All treatment modalities demonstrated some initial regression of AIN after treatment; however, recurrence rates were high especially in HIV-positive patients. Many of the studies suffered from significant bias which prevented direct comparison.

Although the theory persists that by inducing the regression of AIN, we may be able to reduce the risk of ASCC, there was no clinical evidence within the literature advocating that treating AIN does prevent ASCC.

Women with a history of human papillomavirus (HPV)-related cervical, vaginal or vulvar high-grade squamous intra-epithelial lesions (HSILs) or cancer are at increased risk of developing anal squamous intra-epithelial lesions (SILs) or a squamous cell carcinoma of the anus (SCCA). Screening for intra-anal SILs with high-resolution anoscopy (HRA) in high-risk populations is a subject of debate. In this study we aimed to answer the following question: what is the prevalence of intra-anal (H)SIL in women with HPV-related vulvar and/or perianal disease using HRA for screening?

A retrospective study was performed to evaluate the prevalence of intra-anal (H)SIL in women with a history of vulvar and/or perianal HSIL or (superficially invasive) squamous cell carcinoma (SCC). This study was performed between 2015 and 2018 following implementation of a protocol for intra-anal screening using HRA.

Twenty-seven patients, 10 with a history of (superficially invasive) SCC (four vulvar, five perianal, one multizonal) and 17 with HSIL as the worst diagnosis (two perianal, 15 multizonal) were screened for intra-anal lesions using HRA. No anal cancer was found at screening, 6 (22%) patients were diagnosed with intra-anal HSIL and 12 (44%) patients with intra-anal low-grade SIL.

We found a high prevalence of intra-anal HSIL in women previously diagnosed with vulvar and perianal HSIL. Given the clear link between HSIL and SCCA, screening for intra-anal lesions in women with HPV-related genital pathology seems warranted. Future studies should focus on the effect of HSIL treatment on the prevention of anal cancer.

Background Anal cancer is a rare malignancy that disproportionately affects men who have sex with men (MSM) and HIV-infected people. Anal cancer is associated with human papillomavirus (HPV) in upward of 90% of cases and is preceded by pre-cancerous changes in cells of the anal canal. High-resolution anoscopy (HRA) is used for the detection, treatment and continued monitoring of anal dysplasia. Practice guidelines regarding anal cancer prevention vary by jurisdiction and institution, and patient engagement is low for high-risk populations such as MSM. The purpose of this study is to characterise perceptions among MSM of barriers to and facilitators of their adherence to HRA follow-up recommendations.

Surveys and in-person focus groups with MSM who were either adherent or non-adherent to HRA follow-up recommendations at a Federally Qualified Health Centre in Boston, MA, which specialises in sexual and gender minority care, were conducted. Facilitators of and barriers to follow-up were identified by deductive content analysis.

Focus group participants identified the following barriers to and facilitators of HRA follow up: (1) patient-level beliefs about HPV-related disease or HRA, ability to engage in care, internalised stigma and physical discomfort; (2) provider-level knowledge and expertise, communication skills and relationship-building with patient; and (3) systems-level societal stigma and healthcare system inefficiencies.

Reinforcing facilitators of and reducing barriers to HRA follow up may improve adherence among MSM. This includes improvements to: patient education, provider training to increase knowledge and cultural sensitivity, public awareness about HPV-related anal cancer, physical discomfort associated with HRA and systems inefficiencies.

Trichloroacetic acid (TCA) and electrocautery ablation (ECA) are 2 of the main treatment options for anal high-grade squamous intraepithelial lesion (HSIL). Our aim was to compare the efficacy and tolerance of TCA vs. ECA for HSIL.

Retrospective uncontrolled study of HIV-infected men who have sex with men who had an anal HSIL treated with TCA or ECA. On-treatment effectiveness was evaluated at 6-8 weeks after treatment. A complete response was defined as resolution of HSIL, a partial response as regression to low-grade lesion, and recurrence as biopsy-proven HSIL during follow-up. A propensity-score analysis was used to adjust efficacy to potential confounding.

From May 2009 to March 2018, 182 and 56 cases of anal HSIL were treated with ECA and TCA, respectively. Comparing ECA with TCA, a complete response was observed in 33.5% (95% confidence interval: 25.8 to 41.6) vs. 60.7% (50.0 to 74.8) and a partial response in 28.0% (20.3 to 36.0) vs. 23.2% (12.5 to 37.3), respectively (P < 0.001). These differences were maintained in the propensity-score analyses. Side effects were common in both treatment, but tolerance was reported as good in 80.6% (74.2 to 89.2) and 82.6% (73.9 to 93.9) of cases treated with ECA and TCA, respectively, and no serious events were described. Recurrence cumulative incidence for the first 12 months was 14.6% (9.1 to 23.1) for ECA episodes and 27.6% (11.5 to 57.7) for TCA (P = 0.183).

Our study showed a higher efficacy of TCA than ECA with similar rates of side effects. In our opinion, considering the benefits of TCA, it should be considered as a first-line therapy for most anal HSIL management.

Antiretroviral therapy (ART) has revolutionized the treatment and prognosis of people living with HIV (PLHIV). With increased survival and improved overall health, PLHIV are experiencing dermatologic issues both specific to HIV and common to the general population. In this new era of ART, it is crucial for dermatologists to have a strong understanding of the broad range of cutaneous disease and treatment options in this unique population. In this review, we outline the most common skin diseases in PLHIV, including HIV-associated malignancies, inflammatory conditions, and infections, and focus on the role of ART in altering epidemiology, clinical features, diagnosis, and treatment of cutaneous conditions.

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 10 years 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 recommendations are 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.

Data on tissue distribution of human papillomavirus types in anal high-grade squamous intraepithelial lesions are limited and the impact on treatment outcomes poorly understood.

We aimed to investigate potential predictors of treatment failure after electrocautery ablation, including human papillomavirus type(s) isolated from index lesions.

This was a retrospective cohort study.

The study was conducted at a tertiary academic referral center in New York City.

Seventy-nine HIV-infected patients with a diagnosis of anal high-grade squamous intraepithelial lesions between January 2009 and December 2012 were included, and genomic DNA was extracted from biopsy tissue.

The prevalence of human papillomavirus types in index lesions and surveillance biopsies after electrocautery ablation were analyzed to evaluate treatment response.

Of 79 anal high-grade squamous intraepithelial lesions, 71 (90%) tested positive for ≥1 human papillomavirus type; 8 (10%) had no human papillomavirus detected. The most common type was 16 (39%), followed by 33 (15%). Human papillomavirus type 18 was seen in 3%. Sixty-one patients (77%) underwent electrocautery ablation and had subsequent surveillance biopsies. Surveillance biopsies yielded benign findings or low-grade squamous intraepithelial lesions in 31 (51%) of 61 and recurrent high-grade squamous intraepithelial lesions in 30 (49%) of 61 patients (mean follow-up: 35 mo). Ablation response did not differ significantly based on baseline demographics, smoking history, history of anogenital warts, mean CD4 T-cell count, antiretroviral-therapy use, and HIV viral load (<50 copies/mL). The recurrence of high-grade lesions was not significantly associated with high-risk human papillomavirus types detected in index lesions.

Human papillomavirus genotyping in surveillance biopsies was not performed.

Anal high-grade squamous intraepithelial lesions in HIV-infected patients contain a wide range of human papillomavirus types, and individual lesions commonly harbor multiple types concomitantly. Recurrence of anal high-grade squamous intraepithelial lesions after electrocautery ablation occurs frequently and is not affected by high-risk human papillomavirus types. See Video Abstract at http://links.lww.com/DCR/A833.

The Anal Cancer HSIL Outcomes Research (ANCHOR) trial aims to determine whether treating precancerous anal high-grade squamous intraepithelial lesions (HSIL), versus active surveillance, is effective in reducing anal cancer incidence in HIV-infected individuals. We evaluated the reliability (i.e., internal consistency, test-retest) and between-group stability of a 25-item ANCHOR Health-Related Symptom Index (A-HRSI).

ANCHOR participants at least 1-month post-randomization to treatment or active surveillance completed the A-HRSI via telephone. Participants were contacted 7-10 days later to complete the A-HRSI and a participant global impression of change (PGIC) item.

Participants (n = 100) were enrolled (mean age = 51.4, 79% cisgender-male, 73% African American, 9% Hispanic) from five ANCHOR sites. Cronbach's α was good for the physical symptoms (0.82) domain and fair for the physical impacts (0.79) and psychological symptoms (0.73) domains. Intraclass correlation coefficients were good for each of respective domains (i.e., 0.80, 0.85, and 0.82). There were no significant differences in PGIC between the treatment (n = 56) and active surveillance (n = 44) groups (F(1,98) = 2.03, p = 0.16).

The A-HRSI is able to reliably assess participant-reported symptoms and impacts of anal HSIL across a 7-10 days of timeframe. Future work will involve the establishment of construct and discriminant validity prior to inclusion in the full ANCHOR trial.

To determine the impact of expectant management surveillance for patients at risk for squamous cell carcinoma of the anus (SCCA).

Adult patients at risk for anal cancer, specifically those with human immunodeficiency virus (HIV) or known human papilloma virus (HPV) infections (anal dysplasia, anogenital warts, cervical dysplasia, or cervical cancer), underwent expectant management surveillance with targeted therapy of only grossly abnormal or symptomatic anoderm lesions. A retrospective analysis investigated the SCCA incidence in these surveilled populations and in the general population patients without known HIV or HPV infection.

There were 452 incident SCCA in a population of 5,978,510 patients (mean follow-up per patient of 5.4 years). Four hundred ten cancers (90.7%) developed in 5,750,501 HIV-negative patients without documented history of HPV infection (cumulative incidence 0.007%). In at-risk patient populations, the cumulative incidence was 0.69% in patients with anal dysplasia (6 out of 872 patients), 0.14% in HIV+ patients (8 out of 5626 patients), and less than 0.1% in the remaining at-risk groups: cervical cancer (1 out of 1168 patients), cervical dysplasia (14 out of 125,604 patients), and genital warts (14 out of 94,739 patients).

Expectant management surveillance, with targeted treatment for symptomatic or abnormal lesions, is an effective strategy for the diagnosis of anal cancer in at-risk patient populations. In this study, most patients who developed anal cancer had no known risk factors. A screening strategy for the general population needs to be further delineated.

Both ablation and expectant management of high-grade squamous intraepithelial lesions have been proposed. Expectant management would be reasonable if 1) the rate of high-grade squamous epithelial lesion progression to anal squamous cell carcinoma were low, and 2) anal squamous cell carcinoma arising under surveillance had a better prognosis than anal squamous cell carcinoma presenting without an identified precursor.

This study aims to quantify aspects of high-grade squamous epithelial lesion/anal squamous cell carcinoma clinical evolution in a surgical practice.

This is a retrospective cohort study.

This study was performed in 1 colorectal surgeon's practice over a 20-year period.

Consecutive patients with high-grade squamous intraepithelial lesion and anal squamous cell carcinoma were included.

We looked at the rate and timing of progression to anal squamous cell carcinoma, and the stage, treatment, and outcome of anal squamous cell carcinoma. We reviewed a comparison group of HIV-positive patients presenting de novo with anal squamous cell carcinoma (no prior history of high-grade squamous intraepithelial lesion).

With consideration of only HIV-positive patients, 341 patients had a mean 5.6 years follow-up from high-grade squamous intraepithelial lesion diagnosis to the most recent documented anal examination. Twenty-four of these surveillance patients developed anal squamous cell carcinoma, yielding a progression rate of 1.3% per patient-year. Mean follow-up was 7.3 years from the initial cancer diagnosis to the most recent contact. Forty-seven patients who presented de novo with anal squamous cell carcinoma developed 74 lesions, with a mean follow-up of 5.7 years after initial diagnosis. This de novo group had higher anal squamous cell carcinoma-specific mortality (3% per patient-year vs 0.05%). Our study did not show a significantly higher rate of high stage (stage III or IV) at anal squamous cell carcinoma diagnosis in the de novo group in comparison with the surveillance group (25.5% vs 8.3% (p = 0.09)).

This study was retrospective in nature and had a predominately male population.

The progression of untreated high-grade squamous intraepithelial lesion to anal squamous cell carcinoma approximates 1% per patient-year. Anal squamous cell carcinoma developing under surveillance tends to be of an earlier stage and to require fewer major interventions than anal squamous cell carcinoma presenting de novo. Cancer-specific mortality was lower for malignancies that developed under surveillance. We suggest that expectant management of patients with high-grade squamous intraepithelial lesion is a rational strategy for preventing anal cancer morbidity. See Video Abstract at http://links.lww.com/DCR/A699.

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.

High-resolution anoscopy (HRA) is a form of low-resolution anal microscopy currently utilized in the screening and management of anal squamous dysplasia. No randomized controlled trials, national or international guidelines exist on the use of HRA for this purpose. Much of our understanding of this entity has been adapted from the literature on cervical squamous dysplasia, including the technique of HRA itself. Epidemiologic evidence has shown that the prevalence and incidence of anal dysplasia is highest in HIV-positive populations. The history of this technique parallels the evolution of our understanding of anal dysplasia. To understand the history of the use of HRA and its place in the screening and management of anal squamous dysplasia, we discuss key advances in the understanding of human papillomavirus-related squamous dysplasia. We begin with early reports in the field establishing the link between this virus and squamous dysplasia, through the marked increase in anal cancer seen with the onset of the HIV epidemic, the identification of relevant populations at risk, the performance of the test itself, to its use today.

Anal cancer, caused by oncogenic types of human papillomavirus, is a growing problem in the United States. A key focus of anal cancer prevention has been screening for and treating precancerous high-grade squamous intraepithelial anal lesions (HSILs).

To develop a health-related symptom index for HSIL using qualitative techniques because anal HSIL and its treatment may have a negative impact on health-related quality of life (HRQOL), and no HRQOL measure specific to this condition and treatment currently exists.

Expert consultation was used to guide one-on-one concept elicitation interviews with participants to identify HRQOL aspects they attribute to their anal HSIL and its treatment. This resulted in a draft instrument, which was administered to an independent participant sample, where cognitive interview techniques assessed comprehension.

Eighteen anal HSIL-related concepts were identified by the expert panel. Across the 41 concept elicitation interviews, 23 items representing physical symptoms, physical impacts, and psychological symptoms were identified to comprise the initial measure, which was then evaluated during three rounds of cognitive interviews (n = 45). Several questionnaire aspects were refined on the basis of participant input, with three additional items added per expert/participant recommendation. One item was removed because of poor comprehension, resulting in a 25-item measure.

Using state-of-the-art qualitative methodology, we have established the content validity of this new instrument, the ANCHOR Anal HSIL Health-Related Symptom Index. Quantitative validation efforts are currently underway. The participant-driven process of developing this tool will facilitate a participant-centered evaluation of the impact on morbidity for treatment of anal HSIL or observation without treatment.

Anal cancer incidence and mortality have been increasing over the past decade. Although the incidence in the general population remains low, it is much higher in certain subgroups, including those living with human immunodeficiency virus and men who have sex with men. Approximately 90% of anal squamous cell cancers are caused by infection with carcinogenic human papillomavirus (HPV). Given the common etiology between anal and cervical carcinogenesis, screening for anal cancer has been proposed in certain high-risk populations using strategies adapted from cervical cancer prevention. In this review, the authors discuss important differences in anal and cervical cancer regarding the populations at risk, disease natural history, and clinical procedures and outcomes that need to be considered when evaluating strategies for anal cancer screening. They also performed a systematic review and meta-analysis of the performance of anal cytology, anal HPV testing, and various biomarkers for the detection of anal precancers and cancers. The implications of these performance estimates are summarized in the context of risk-based screening and management of anal precancers, and important research gaps are highlighted that need to be addressed to fully understand the benefits and harms of anal cancer screening. Cancer Cytopathol 2018. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

Anal intraepithelial neoplasia (AIN) is a precursor of anal carcinoma. Conventional therapy is based on topical and local ablative approaches. However, the recurrence rates are very high, leading to repetitive treatment sessions and need for long-term surveillance. Endoscopic submucosal dissection (ESD) is an established treatment for malignant early neoplasias of the gastrointestinal tract, especially in the esophagus, stomach, and colorectum. Japanese centers have reported few cases of ESD for early anal carcinoma. We report a case of high-grade AIN diagnosed with magnifying narrow-band imaging and chromoendoscopy that was resected R0 with ESD en bloc.

Anogenital human papillomavirus is the most common sexually transmitted infection acquired through skin-to-skin contact. Most infections are cleared by an intact immune system. Persistence of these infections results in precancerous lesions and, eventually, to cancers of the cervix, vagina, vulva, and perianal area. The introduction of the prophylactic human papilloma virus (HPV) vaccinations may reduce the incidence of these infections, but the effect of these vaccinations will be seen only in the decades that follow. In the meantime, multiple therapies such as immune modulators, ablative modalities, and surgical excision are used in an attempt to treat precancerous lesions and hence prevent cancer. There is an increase in multicentric disease in young women, especially with the HIV epidemic and in women who are immune compromised. This article aims to address the challenges and management options in women who have a field effect of HPV-associated disease.

Over the last few decades, incidence of anal cancer among HIV-positive men has been on the rise. In this context, programmes of screening and treatment of anal dysplasia which is a precursor of anal cancer have been developed. The aim of our study was to describe the efficiency, side effects and outcome of anal dysplasia treatment in a population of HIV-positive men who have sex with men (MSM).

We performed a retrospective study of HIV-positive MSM who received treatment for anal dysplasia between May 2010 and February 2014 in the Saint-Pierre University Hospital, Brussels. The different treatments used were electrocautery (ECA), infrared coagulation (IRC), surgical treatment and imiquimod.

Seventy-three HIV-infected MSM were included in the study, counting 62% of HGAIN. Median age was 41 years. Eighty-one per cent were on HAART. Median CD4 cell count was 525 cell/mm³, and 65% had undetectable viral loads. A total of 139 therapeutic interventions were recorded during the study period, and two-thirds of the enrolled patients received more than one treatment. At 540 days of follow-up, the rate of treatment response was 62%. Fifty per cent of the persistent HGAIN were metachronous lesions. No severe adverse events were recorded but frequent treatment-associated discomfort was reported, such as pain, self-limited bleeding, infection and anal irritation.

Treatment of anal dysplasia appears to be safe and to offer short-term efficiency. However, its long-term efficiency remains unknown, especially in the HIV-positive population in which spontaneous clearance is lower and rate of recurrence higher.

The incidences of high-grade anal intraepithelial neoplasia (HSIL) and superficially invasive squamous cell carcinomas (SISCCA) related to human papillomavirus (HPV) have increased. These lesions can progress to invasive anal cancer. The aim of the study was to assess the clinical outcome with a special focus on the healing rate.

Forty-six consecutive patients (M/F: 35/11; HIV+: 30) with histologically proven HSIL lesions (N=41) or SISCCA (N=5) were enrolled in a follow-up survey.

Of the 46 patients, 40 were treated by excision (n=9), electrocoagulation (n=13), topical treatment (n=2) or combined strategies (n=16). After a mean follow-up of 35 (27-43) months, only one patient progressed to an invasive cancer. Regression and healing were observed in 14 (30%) and 15 (33%) patients. The cumulative probabilities of healing were 14%, 49% and 74% after 1, 3 and 5 years. None of the current smokers healed. Heterosexual patients, sexual abstinence, patients older than 44 years old, non-smokers, patients without any past history of condyloma and those with less than 2 high-risk HPVs at baseline were more likely to heal.

Progression to invasive cancer is a rare event. Large, prospective cohort studies are needed to plan coherent strategies for both follow-up and treatment.

Human papillomavirus (HPV) infections belong to the most common sexually transmitted infections. To date, more than 200 completely classified HPV-types have been reported, and those belonging to the genus alpha predominantly infect the anogenital region. Condylomata acuminata are caused by the two low-risk types HPV6 and HPV11 in more than 90 % of cases. Treatment of genital warts might be either ablative (e.g. electrocautery, surgical excision, or laser therapy) or topical (e.g. podophyllotoxine, trichloroacetic acid, or imiquimod), and depends on the size, location, morphology and anatomical region. Recurrences after treatment are frequent. Therefore, combination therapies (e.g. topical and ablative) play an important role in daily routine. HIV-infected individuals, especially HIV-positive MSM, have a strongly increased risk for anal dysplasia and anal cancer. Condylomata acuminata and a large proportion of anal dysplasia and anal carcinoma are preventable by prophylactic HPV-vaccination.

The prevalence of anal intraepithelial neoplasia has been increasing, especially in high-risk patients, including men who have sex with men, human immunodeficiency virus positive patients, and those who are immunosuppressed. Several studies with long-term follow-up have suggested that rate of progression from high-grade squamous intraepithelial lesions to invasive anal cancer is ∼ 5%. This number is considerably higher for those at high risk. Anal cytology has been used to attempt to screen high-risk patients for disease; however, it has been shown to have very little correlation to actual histology. Patients with lesions should undergo history and physical exam including digital rectal exam and standard anoscopy. High-resolution anoscopy can be considered as well, although it is of questionable time and cost-effectiveness. Nonoperative treatments include expectant surveillance and topical imiquimod or 5-fluorouracil. Operative therapies include wide local excision and targeted ablation with electrocautery, infrared coagulation, or cryotherapy. Recurrence rates remain high regardless of treatment delivered and surveillance is paramount, although optimal surveillance regimens have yet to be established.

The impact of the treatment of precursor lesions of anal cancer (anal intraepithelial neoplasia) on health-related quality of life has not been investigated.

This study aimed to evaluate the impact of 3 treatment options for anal intraepithelial neoplasia on health-related quality of life and sexual functioning in HIV-positive men who have sex with men.

The prospective cohort was embedded in a randomized clinical trial evaluating the optimal treatment of anal intraepithelial neoplasia.

This study was performed at the HIV outpatient clinic of the Academic Medical Center, Amsterdam, the Netherlands.

Included in the study were HIV-positive men who have sex with men with anal intraepithelial neoplasia.

Treatment with imiquimod (n = 54), topical fluorouracil (n = 48), or electrocautery (n = 46) was given for 16 weeks.

Health-related quality of life and sexual functioning were assessed before, during, and 4 weeks after treatment. Health-related quality of life was assessed using the EQ5D, sexual functioning was assessed using items derived from the International Index of Erectile Function, and the female sexual function index adapted for anal intercourse.

One hundred forty-five patients (98%) completed at least 1 questionnaire. There was a significant different pattern of change over time in health-related quality of life among the 3 treatment groups. Patients in the imiquimod group were more likely to report pain/discomfort at week 8 than patients in the electrocautery group. Patients in the electrocautery group were more likely to report anxiety/depression and were less satisfied with their overall sex life at week 16 than patients in the imiquimod and fluorouracil groups, and patients in the electrocautery group were also more likely to report pain/discomfort and problems with usual activities at week 20 than patients in the fluorouracil group.

The follow-up method differed slightly among treatment groups. There is no standardized, validated sexual functioning questionnaire for HIV-positive men who have sex with men.

All treatment options have a negative impact on aspects of health-related quality of life. Electrocautery has significantly more negative effects on health-related quality of life than imiquimod and fluorouracil and also has a negative effect on sexual functioning.

Electrocautery is one of the main treatment options for high-grade anal intraepithelial neoplasia (HGAIN). However, data regarding its efficacy are scarce. The aim of the study was to evaluate the effectiveness of electrocautery for the treatment of HGAIN.

An observational study of HIV-infected men who have sex with men (MSM) who underwent screening for anal dysplasia was carried out. The on-treatment effectiveness of electrocautery was evaluated (according to biopsy findings measured 6-8 weeks after treatment) in patients with HGAIN. A complete response was defined as resolution of anal intraepithelial neoplasia (AIN), a partial response as regression to low-grade AIN and recurrence as biopsy-proven HGAIN during follow-up.

From May 2009 to November 2014, 21.9% (126 of 576) of patients screened were found to have HGAIN. Electrocautery effectiveness was evaluated in 83 patients. A complete response was observed in 27 patients [32.5%; 95% confidence interval (CI) 23.4-53.2%], a partial response in 28 patients (33.7%; 95% CI 24.5-44.4%) and persistence in 28 patients (33.7%; 95% CI 24.5-44.4%). The patients with the most successful results (81.8%) required two to four sessions of electrocautery. After a mean follow-up of 12.1 months, 14 of 55 patients with a response (25.4%; 95% CI 15.8-38.3%) developed recurrent HGAIN within a mean time of 29.9 months (95% CI 22-37.7 months). No patient progressed to invasive cancer during the study or developed serious adverse events after treatment. No factors associated with poor response or recurrences were observed.

Although electrocautery is the standard treatment for anal dysplasia, almost 50% of patients with HGAIN in our study did not respond or relapsed. New treatment strategies are necessary to optimize the management of anal dysplasia.

Anal cancer may be an emerging clinical problem in HIV-infected women particularly in resource-limited settings. Human papillomavirus (HPV) infection is a precursor to anal cancer and is prevalent in HIV-infected women, but the natural history of HPV infection and anal cancer precursors is not well described in this population. It is not known which specific dysplastic lesions in the anus are most likely to progress, and whether treatment of high grade squamous intraepithelial lesion reduces the incidence of anal cancer in women. Cervical HPV infection and associated lesions may be related to the pathogenesis and natural history of anal disease. Cervical screening is resource intensive but some limited infrastructure exists in most areas where cervical cancer is prevalent. Anal screening, however is not performed. It may be that the infrastructure for cervical screening may be leveraged in developing the appropriate research, screening and treatment tools for anal dysplasia.

Infection with the human immunodeficiency virus (HIV) remains associated with a greater risk of anal cancer, despite widespread use of combination antiretroviral therapy. Evidence concerning the acceptability of anal cancer screening gives little attention to women. Because HIV-infected women have a high prevalence of depression and history of sexual trauma, understanding acceptability among this group is critical.

We sought to assess barriers and motivators to participation in anal cancer screening research among a racial/ethnically diverse HIV-infected female population.

We conducted a survey based on the Health Belief Model to identify characteristics of women willing to participate in anal cancer screening research (n = 200). Bivariate analyses examined associations between willingness to participate and sociodemographics, clinical characteristics, and health beliefs. Logistic regression modeled willingness to participate in research.

Of the women who participated, 37% screened positive for depression, 43% reported a high trauma history, and 36% screened positive for posttraumatic stress disorder. Overall, 65% reported willingness to participate in research. Those likely to participate were older, reported intravenous drug use as their HIV risk factor, and had a history of prior high-resolution anoscopy (HRA) compared with those unwilling to participate. The most commonly reported barrier to anal Pap testing was fear of pain. In adjusted analyses, a lack of fear of pain and prior experience with HRA significantly predicted willingness to participate.

Findings suggest that, to increase participation in anal Pap and HRA-related research for HIV-infected women, a single approach may not be adequate. Rather, we must harness patients' previous experiences and address psychosocial and financial concerns to overcome barriers to participation.

To assess the efficacy of topical 80% trichloroacetic acid (TCA) to treat internal anal high-grade squamous intraepithelial lesions (HSILs) in HIV-positive individuals.

All patients who attended the University of Pittsburgh Anal Dysplasia Clinic for treatment of biopsy-proven internal anal HSIL with topical TCA between July 1, 2009, and June 30, 2012, and who had 1 or more follow-up visits to assess treatment efficacy were included in the analysis. Recurrence of HSIL was assessed in July 1, 2013.

A total of 98 HSILs from 72 patients were treated, and 77 (78.6%) resolved to normal epithelium or low-grade SIL during follow-up. Forty-eight (49.0%) and 27 (27.6%) of lesions resolved with 1 and 2 TCA treatments, respectively, whereas 1 lesion (1%) each resolved with 3 and 4 TCA treatments. Twenty-one (21.4%) lesions in 20 patients remained without resolution after TCA treatments. These patients were offered an alternative treatment. During follow-up, 8 (15.1%) of 53 patients had a lesion that recurred at the index site (11/53 [20.8%], inclusive of adjacent lesions) and 17 patients had new lesions diagnosed.

Topical TCA is an efficacious treatment of internal anal HSIL in an anal dysplasia clinic setting with high-resolution anoscopy capacity. Advantages of TCA for this recurrent disease process include the following: low cost, no requirement for special equipment beyond that for high-resolution anoscopy, and painless application procedure. A larger prospective comparative study would better define efficacy and patient acceptability between treatment methods.

HIV infection is one of the strongest risk factors for anal squamous cell cancer (ASCC). Most ASCC are caused by HPV, and most HPV-associated ASCC are caused by HPV-16. Anal HPV infections are very common in men who have sex with men (MSM), and nearly universal among HIV-infected MSM. High-grade anal intraepithelial neoplasia (HGAIN), the precursor for ASCC, is present in about 30 % of HIV+ MSM, but neither the progression rate to ASCC nor the regression rate are known. The incidence rate of ASCC among HIV-infected people has risen in the first decade after cART became available, but appears to be plateauing recently. Anal cytology has poor sensitivity and specificity. High resolution anoscopy (HRA) is advocated by some as a screening tool in high-risk groups, but is cumbersome and time-consuming and it is unknown whether HRA followed by treatment of HGAIN prevents ASCC. More research is needed on progression and regression rates of HGAIN, on effective therapy of HGAIN, and on biomarkers that predict HGAIN or anal cancer. HPV vaccination and earlier start of cART may prevent most anal cancers in the long run.

The incidence of anal cancer is increasing especially in HIV-positive men having sex with men. Screening for the cancer precursor, high-grade squamous intraepithelial lesions (HSIL), is challenging, as current treatment is suboptimal. The aim of this prospective study was to establish the efficacy of five consecutive days a week self-administered treatment with imiquimod 5% cream for both perianal and intra-anal HSIL and to assess the adverse effects and burden of this regimen.

44 patients with histologically proved perianal or intra-anal HSIL were treated with a five consecutive days a week imiquimod 5% cream regimen. When no response could be confirmed after the first 16 weeks of therapy, patients were encouraged to continue the use of the cream for a further 16 weeks. Side effects were routinely assessed.

Complete or partial response was observed in 20 (45%) of 44 patients with HSIL after 16 weeks of treatment; another nine patients showed complete or partial response after an additional 16 weeks of treatment, resulting in a response rate of 29 (66%) out of 44 patients.

Topical imiquimod 5% cream is useful in HSIL. A five consecutive days treatment regimen with imiquimod 5% cream for HSIL does not seem to be more effective compared with the customary prescription for 3 days a week. A prolonged course of imiquimod 5% cream is warranted for intra-anal HSIL. Adverse effects are comparable between 3 and 5 days treatment regimen.

Men who have sex with men have increased prevalence of both human papillomavirus and anogenital condyloma.

Risk factors for multiple treatment and recurrence of anal condyloma were examined.

This is a retrospective study of HIV-negative men who have sex with men who were treated for anal condyloma.

This study was conducted in a private surgical practice.

The patients were HIV-negative men who have sex with men, aged 18 years or older.

Ablation with electrocautery or CO2 laser was performed, as well as excision and topical imiquimod condyloma treatment adjuvant.

Primary clearance, defined as 4 months of condyloma-free survival posttreatment, and recurrence, defined as any anal condyloma diagnosis after primary clearance.

Of 231 participants, 207 achieved primary clearance (median age, 32.0 years) and were followed (median, 18.2 months) after primary treatment. Most had intra-anal and perianal condyloma (56%), were treated with electrocautery ablation (79.2%), and required 1 treatment (range, 1-6) for clearance. There were 57 recurrences (median, 12 months). One-third each had minimal, moderate, or extensive disease. Forty-six percent of patients received imiquimod posttreatment adjuvant. High-grade dysplasia was found in 31% at presentation and 43% during follow-up. Factors associated with requiring multiple treatments for clearance were participants having moderate disease (adjusted odds ratio, 6.0 (1.7-21.4)) and receiving imiquimod adjuvant (adjusted odds ratio, 4.7 (2.0-10.6)). No single factor predicted recurrence, but those with moderate disease experienced recurrences significantly sooner (median, 25 months of follow-up).

This was a retrospective chart review, it was limited to a single practice, and it excluded those who did not achieve primary clearance.

Most men who have sex with men have intra-anal and perianal condyloma and concomitant high-grade dysplasia is common. Most achieved clearance with 1 treatment. Having both intra-anal and perianal condyloma, increased severity of disease, and imiquimod adjuvant were significant predictors of requiring multiple treatments for clearance. No identified risk factors proved a significant predictor of recurrence.

Diagnosis, follow up, and treatment of anal intraepithelial neoplasia are complex and not standardized. This may be partly caused by poor communication of biopsy and cytology findings between pathologists and clinicians as a result of a disparate and confusing terminology used to classify these lesions. This article focuses on general aspects of epidemiology and on clarifying the current terminology of intraepithelial squamous neoplasia, its relationship with human papilloma virus infection, and the current methods that exist to diagnose and treat this condition.

The incidence of anal cancer is elevated in human immunodeficiency virus (HIV)-infected men-who-have-sex-with-men (MSM) compared to the general population. Anal high-grade squamous intraepithelial lesions (HSIL) are common in HIV-infected MSM and the presumed precursors to anal squamous cell cancer; however, direct progression of HSIL to anal cancer has not been previously demonstrated. The medical records were reviewed of 138 HIV-infected MSM followed up at the University of California, San Francisco, who developed anal canal or perianal squamous cancer between 1997 and 2011. Men were followed up regularly with digital anorectal examination (DARE), high-resolution anoscopy (HRA) and HRA-guided biopsy. Although treatment for HSIL and follow-up were recommended, not all were treated and some were lost to follow-up. Prevalent cancer was found in 66 men. Seventy-two HIV-infected MSM developed anal cancer while under observation. In 27 men, anal cancer developed at a previously biopsied site of HSIL. An additional 45 men were not analyzed in this analysis due to inadequate documentation of HSIL in relation to cancer location. Of the 27 men with documented progression to cancer at the site of biopsy-proven HSIL, 20 men progressed from prevalent HSIL identified when first examined and seven men from incident HSIL. Prevalent HSIL progressed to cancer over an average of 57 months compared to 64 months for incident HSIL. Most men were asymptomatic, and cancers were detected by DARE. Anal HSIL has clear potential to progress to anal cancer in HIV-infected MSM. Early diagnosis is facilitated by careful follow-up. Carefully controlled studies evaluating efficacy of screening for and treatment of HSIL to prevent anal cancer are needed.

Anal Intraepithelial Neoplasia (AIN), a pre-cursor of anal squamous carcinoma, is increasingly detected in individuals with impaired immune function. However, choices for effective, low morbidity treatment are limited. Photodynamic Therapy (PDT) is promising as it is known to ablate more proximal gastrointestinal mucosa with safe healing, without damage to underlying muscle. It can also ablate skin with safe healing and minimal scarring.

Pharmacokinetics: Normal rats were sensitised with 200mg/kg 5-aminolaevulinic acid (ALA) and killed 1-8h later. Anal tissues were examined by fluorescence microscopy to quantify the concentration of PPIX (protoporphyrin IX, the active derivative of ALA) in anal mucosa and in the underlying sphincter. PDT: Normal rats were sensitised similarly 3h later, laser light (635 nm) was delivered. Anal canal: 50-150 J/cm using 1cm diffuser fibre; for peri-anal skin, 50-200 J/cm(2), using microlens fibre. In each group, 2 rats were killed 3, 7, 14 and 28 days later and the anal region removed for histological examination.

Pharmacokinetics: Peak concentration of PPIX in mucosa was at 3h, peak ratio mucosa: muscle, 6, seen at same time. PDT. Anal canal 50 J/cm: complete mucosal ablation by 3 days, complete regeneration by 28 days. Higher energies caused muscle damage with scarring. Peri-anal skin: 200 J/cm(2); complete ablation of skin, including appendages, complete healing by 28 days. Minimal effect with lower energy.

ALA-PDT can ablate anal mucosa and peri-anal skin with safe healing and no underlying damage. However, over treatment can damage the sphincters. This technique is ready to undergo clinical trials.

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.

Anal cancer is an increasing issue in HIV-positive men who have sex with men (MSM). Screening for its precursor, anal intraepithelial neoplasia (AIN), is subject of discussion. Current treatment options are suboptimum and have not been compared in a prospective trial. We compared efficacy and side-effects of imiquimod, topical fluorouracil, and electrocautery for the treatment of AIN.

In this open-label randomised trial, we included HIV-positive MSM older than 18 years visiting the HIV outpatient clinic of the Academic Medical Center, Amsterdam, Netherlands. Patients with histologically confirmed AIN were randomly assigned to receive either 16 weeks of imiquimod (three times a week), 16 weeks of topical fluorouracil (twice a week), or monthly electrocautery for 4 months. Randomisation was done with random block sizes of three and six, stratified for AIN grade (AIN grades 1, 2, or 3) and AIN location (peri-anal or intra-anal). Participants were assessed by high-resolution anoscopy 4 weeks after treatment. Responding patients returned for follow-up 24 weeks, 48 weeks, and 72 weeks after treatment. The primary endpoint was histological resolution of AIN measured 4 weeks after treatment and AIN recurrence at week 24, week 48, and week 72 after treatment. The primary analysis was done in a modified intention-to-treat population, including all patients who had received their assigned treatment at least once. The trial is registered at the Netherlands Trial Register, number NTR1236.

Between Aug 12, 2008, and Dec 1, 2010, we screened 388 HIV-positive MSM for AIN by high resolution anoscopy. Of the 246 (63%) patients who had AIN, 156 (63%) were randomly assigned to either receive imiquimod (54 patients), topical fluorouracil (48 patients), or electrocautery (46 patients) following withdrawing of consent by eight patients. Modified intention-to-treat analysis showed a complete response in 13 (24%, 95% CI 15-37) patients in the imiquimod group, eight (17%, 8-30) of patients in the fluorouracil group, and 18 (39%, 26-54) of patients in the electrocautery group (p=0·027). At week 24, 11 (22%) of 50 responders had recurrence; at week 48, 22 (46%) of 48 had recurred; and at week 72, 30 (67%) of 45 had recurred. Recurrence was observed at 72 weeks in 10 (71%) of 14 patients treated with imiquimod, seven (58%) of 12 patients treated with fluorouracil, and 13 (68%) of 19 patients treated with electrocautery. Grade 3-4 side-effects were noted in 23 (43%) of 53 patients in the imiquimod group, 13 (27%) of 48 patients in the fluorouracil group, and eight (18%) patients in the electrocautery group (p=0·019). The most common side-effects were pain, bleeding, and itching. Seven serious adverse events occurred, all not related to the study.

Electrocautery is better than imiquimod and fluorouracil in the treatment of AIN, but recurrence rates are substantial.

Anna Maurits de Cock foundation provided funding for the video colposcope.

To evaluate the safety and efficacy of topical cidofovir for treatment of high-grade squamous perianal intraepithelial neoplasia (PAIN) and vulvar intraepithelial neoplasia (VIN) lesions in HIV-positive individuals.

Phase IIa prospective multicenter trial conducted at eight clinical sites through the AIDS Malignancy Consortium.

: HIV-positive patients with biopsy-proven high-grade PAIN that was at least 3 cm were enrolled. PAIN biopsy specimens were assessed for human papillomavirus (HPV) using PCR and type-specific HPV probing. Participants applied 1% topical cidofovir to PAIN and VIN (if present) for six 2-week cycles. Results were designated as complete response (CR), partial response (PR) (>50% reduction in size), stable disease, or progressive disease (PD).

Twenty-four men and nine women (eight with high-grade VIN as well) were enrolled. Mean age was 44 years and mean CD4 cell count was 412 cells/μl. HPV DNA (most commonly HPV16) was detected in all pretreatment study specimens. Twenty six (79%) participants completed treatment per protocol: CR, five (15%); PR, 12 (36%), stable disease, seven (21%); PD, two (6%) (one with a superficially invasive cancer and one with new area of high-grade PAIN). Treatment was well tolerated with most common adverse events being mild to moderate affecting lesional skin: pain/burning/irritation (25 patients) and ulceration (13 patients).

Topical cidofovir had 51% efficacy in the short-term treatment of high-grade PAIN and VIN with acceptable toxicity in HIV-positive individuals. Randomized control studies with more prolonged treatment courses and longer follow-up to assess the durability of the response are needed.

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.