High-grade Anal Intraepithelial Neoplasia Research Articles

Diagnostic and Management Challenges Associated With Vulvar Crohnʼs Disease

Crohn's disease(CD) is an IBD with extra intestinal manifestations such as arthritis, uveitis, erythema nodosum. Crohn's disease of the vulva is a rare and under recognized condition, particularly because it may not involve GI tract. The diagnosis and treatment of this condition remains a challenge. We present a case of Vulvar Crohn's which has been an extremely difficult case to manage. Our patient is a 29 y/o female with 10 year h/o vulvar Crohn's disease presenting as painful fissures, perirectal and labial masses. On physical exam, there was erythema, induration and severe edema of labia majora, minora and perianal area. She underwent biopsy of the lesions which was confirmed to be Crohn's disease. Even though she had no GI symptoms, she underwent colonoscopy to determine the extent of her disease and it was normal. Patient was tried on several medications including metronidazole, steroids, 6-MP, infliximab, adalimumab, methotrexate, azathioprine, certolizumab,ustekinumab and vedolizumab. However, she failed to respond to any of these therapies. Patient was referred to plastic surgery for partial vulvectomy, biopsy of which showed high grade vulvar intraepithelial neoplasia (VIN) in addition to Crohn's (dermal chronic inflammation with granulomas). She was then referred to colorectal surgery for management of perianal disease, and gynecology for evaluation of VIN. She also underwent excision of anal skin tags and anal mapping, with pathology demonstrating positive P16 in squamous epithelium consistent with high grade AIN. Vulvar Crohn's is an under-recognized condition with about 100 cases reported to date. It can occur by direct extension from perianal region or by metastatic spread from bowel. Vulvar CD may precede intestinal involvement in about 25% of cases. It usually presents with edema, ulcerations and fissures of the vulva. Patients may be asymptomatic or present with pain, pruritis, discharge and dyspareunia. Diagnosis requires a high degree of suspicion as it could be mistaken for other conditions like infections, sarcoidosis etc. Diagnosis is confirmed by biopsy. Treatment remains a challenge and no treatment guidelines exist. A multidisciplinary approach is recommended and medications including steroids, thiopurines, TNF-α antagonists could be used. However, patients may not respond to any medications and surgery remains an option. Clinicians must be astute to consider neoplasia in this situation, as was seen in our patient.Figure: Microscopic findings of the epiglottis biopsy demonstrating in the high- and low-power fields ulcerated squamous mucosa with chronic inflammatory changes.

Risk factors of high-grade anal intraepithelial neoplasia recurrence in HIV-infected MSM

To assess risk factors of high-grade anal intraepithelial neoplasia (HGAIN) recurrence in a cohort of HIV-infected MSM. Consecutive HIV-infected 100 MSM with a history of successfully treated intra-anal HGAIN with electrocautery were followed with anal cytology, human papillomavirus (HPV) determination, and high-resolution anoscopy (HRA) at 3-6-month intervals. HGAIN recurrence was analyzed using Kaplan-Meier analysis. Risk factors of recurrence were assessed using Cox proportional hazards regression. The value of different tests for detecting recurrence was also assessed. After a mean follow-up of 17.6 months, 39 of the 100 patients [39%, 95% confidence interval (CI): 29-49] developed recurrent HGAIN, 24 at the previously treated site, and 15 at a different site. The probability of recurrence was 23.5% at 12 months (95% CI: 13.9-33.1) and 53.3% at 24 months (95% CI: 34.3-72.7). Risk factors of recurrence were presence of hepatitis C antibodies (hazard ratio 2.79; 95% CI: 1.04-7.53), nadir CD4 cell count less than 200 cells/μl (hazard ratio 2.61; 95% CI: 1.06-6.44), and HGAIN lesions affecting at least two octants of anal circumference (hazard ratio 8.27; 95% CI: 1.1-62). Infection by at least two HPV oncogenic strains increased the risk of recurrence (hazard ratio 2.3; 95% CI: 0.98-5.42). HRA, anal cytology, and oncogenic HPV determination test showed a sensitivity of 100, 79.4, and 86.7%, and a specificity of 57.7, 36.6, and 34.7%, respectively, for detecting HGAIN recurrence. The risk of HGAIN recurrence in HIV-infected MSM is high. Regular posttreatment follow-up of these patients is mandatory, and performing direct HRA appears to be the best strategy.

Methylation of HPV and a tumor suppressor gene reveals anal cancer and precursor lesions.

We studied DNA methylation patterns of human papillomavirus (HPV) and tumor suppressor gene EPB41L3 in 148 anal and perianal biopsies to determine whether high levels of methylation would be associated with anal intraepithelial neoplasia (AIN). The most prevalent HPV type was HPV16, detected in 54% of the 30 benign biopsies, 33% of the 43 low-grade AIN (lgAIN), 82% of the 59 high grade AIN (hgAIN) and 4 of the 5 anal cancers. A methylation score was developed (0.561*HPV16me+0.439*EPB41L3) which had increasing values with severity of disease: the mean was 8.1% in benign, 13.2% in lgAIN, 22.3% in hgAIN and 49.3% in cancers (p < 0.0001). The methylation score as a triage classifier at a cut-off of 8.8 gave a sensitivity of 90.6% (95% CI: 82.8, 96.9), specificity of 50.7% (95% CI: 39.7, 61.6) and area under the curve of 0.82 (95% CI: 0.75–0.89) for separating hgAIN and cancer from benign and lgAIN biopsies. We conclude that methylation of HPV16 and EPB41L3 show highly significant association with increasing severity of AIN and cancer and may be useful as biomarkers in anal disease.

Prevalence and Genotyping of HPV in Women With Cervical and Anal Neoplasia [32E

INTRODUCTION: Persistent human papillomavirus (HPV) infection has been strongly associated with the development of anogenital cancer precursor lesions. Therefore, the objective of this study was to determine the prevalence of oncogenic HPV genotypes and associated factors in women with anal neoplasia. METHODS: A cross-sectional study was conducted in 152 women with anal intraepithelial or invasive neoplasia, to identify HPV genotypes. RESULTS: Fourteen different HPV types were identified. HPV 16 and 18 were found in 53% (n=30) of anal high-grade squamous intraepithelial lesions (HSIL). HPV 31 and 33 were identified in 37% (n=21) of anal HSIL. In the logistic regression analysis, the factors that remained associated with high-risk HPV types were: an anal histopathology report of HSIL or worse (OR=8·96; 95%CI: 3·40-23·57; p &lt; 0·0001) and alcohol consumption (OR: 2·20; 95%CI: 1·01-4·80; p=0·04) as risk factors, and condom use as a protective factor (OR=0·33; 95%CI: 0·12-0·87; p=0·02). CONCLUSION: The prevalence of HR-HPV in women with high grade AIN and cervical neoplasia is high. Fourteen different HPV types were found, and HPV16, 31,33 and 18 were the four major genotypes identified.

Human Papillomavirus Genotyping of Incidental Malignant and Premalignant Lesions on Hemorrhoidectomy Specimens.

Routine histopathologic examination of hemorrhoidectomy specimens is controversial having been described as not useful and expensive with few of these common cases demonstrating incidental lesions. However, unexpected premalignant and malignant lesions have been detected on excised hemorrhoids. The high-risk human papillomavirus (HR-HPV) types associated with these incidentally identified high-grade lesions are presently unknown. We aimed to identify cases of incidental high-grade anal intraepithelial neoplasia (HG-AIN) and anal squamous cell carcinoma incidentally discovered on hemorrhoidectomy specimens, genotype HR-HPVs from these lesions, and assess p53 and p16 expression by immunohistochemistry to identify risk factors for their development. With institutional approval, cases with associated demographics from 1995 to 2015 were reviewed to identify and confirm incidental HG-AIN or squamous cell carcinoma in hemorrhoidectomy specimens. Genotyping for HR-HPV types and immunohistochemical staining for p53 and p16 was performed. Statistical analysis comparing HPV genotypes, p53 and p16 staining, and potential risk factors by the Fisher exact test was performed. In the largest series of incidental high-grade lesions on hemorrhoidectomy, HPV 16 was the most common HR-HPV detected though multiple-type infections were common including some HPV 16/18-negative cases. By genotyping, HPV 39 was significantly associated with IV-drug abuse history (P=0.0015) and HIV-positive status (P=0.037), whereas HPV 58 detection correlated with chemotherapy-induced immunosuppression (P=0.029). There was frequent overlap between p53 staining and HPV positivity, particularly when HPV 31 was detected. We also identified several mimickers of HG-AIN that may present diagnostic challenges in these specimens. Our data support continued routine examination of hemorrhoidectomy specimens and suggest that adjunctive studies such as immunohistochemistry for challenging cases may be useful.

Preliminary results of a screening program for anal cancer and its precursors for HIV-infected men who have sex with men in Vigo-Spain

Men who have sex with men (MSM) infected with human immunodeficiency virus (HIV) have the highest risk of developing anal cancer (AC). The objective of this study was to describe our screening implementation program in this population, and report the prevalence of human papillomavirus (HPV) anal infection, and cytological and histological findings in a Spanish medium-size community (Vigo, Spain). Prospective cohort analysis of 240 HIV-infected MSM. Cellular anal sample and high risk HPV (HR-HPV)-tests were performed to study cytological changes and HPV genotyping. High resolution anoscopy (HRA) was performed in 209 patients. Results were analyzed with respect to epidemiological, clinical and analytical factors. Of 209 patients selected for HRA, the prevalence of HR-HPV anal infection, cytological and histological alterations was 85.6%, 47.5%, and 39.8%, respectively. Sensitivity and specificity for ≥ ASCUS (atypia of squamous cells of undetermined significance) cytology in relation to histological alterations were 61% and 85%, (OR: 8.7; IC 95%: 4.4-17.2), respectively. Observed concordance between high-grade squamous intraepithelial lesion (HSIL) cytology and HSIL anal intraepithelial neoplasia types 2 and 3 (AIN-2/3) histology was 64% (OR: 11.4; IC 95%: 3.6-36.7). One patient with HSIL cytology presented a prevalent anal squamous carcinoma. HRA was feasible with similar results to relevant groups. There was a high prevalence of anal HR-HPV infection, and cytological and histological alterations.

Factors Associated With High-Grade Anal Intraepithelial Neoplasia in HIV-Positive Men in an Urban Setting

Factors Associated With High-Grade Anal Intraepithelial Neoplasia in HIV-Positive Men in an Urban Setting

CK17 and GATA-3 Expression in High-Grade Anal Intraepithelial Neoplasia Subtypes

CK17 and GATA-3 Expression in High-Grade Anal Intraepithelial Neoplasia Subtypes

High-grade anal intraepithelial neoplasia: Progression to invasive cancer is not a certainty

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

Efectividad del genotipado del virus del papiloma humano frente a la citología anal en la identificación de neoplasia intraepitelial de alto grado

IntroductionThe incidence of high-grade anal intraepithelial neoplasia (HGAIN) -with an aetiological based on high-risk types of human papillomavirus- is increasing in some high-risk groups. Screening for HGAIN includes routine anal cytology and, more recently, HPV genotyping. The main objective of this study was to determine the sensitivity and specificity of anal cytology and HPV genotyping for the detection of HGAIN. Materials and methodsThis is a study to determine the correlation of cytological and microbiological findings with anal biopsy findings in a cohort of patients at high risk of developing AIN referred to the department of sexually transmitted infections of the Hospital Costa del Sol, Spain, between January 2008 and December 2014. ResultsOf the 151 patients subjected to screening, a total of 92 patients, all of them with the result of three screening test (anal cytology, genotyping and biopsy) were included in the study. Just under two-thirds (62%) of them were HIV-positive. The sensitivity and specificity of anal cytology to detect HGAIN were 52.8 and 85.7%, respectively (k: 0.328), and 78 and 62.8% to detect two or more HPV oncogenic genotypes (k: 0.417). The detection of oncogenic HPV genotypes allowed the identification of 23 new cases of HGAIN that had been underdiagnosed with anal cytology, with 14 cases containing at least three high-risk genotypes. ConclusionAnal cytology did not show enough sensitivity in HGAIN screening. HPV genotyping has shown to be a useful tool to detect HGAIN cases, although it could lead to an over-diagnosis as a solitary screening procedure.

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.

Colorectal Disorders in Acute Human Immunodeficiency Virus Infection: A Case Series.

Background. The gastrointestinal (GI) tract is important in the pathogenesis of human immunodeficiency virus (HIV) infection. We report a case series of lower GI endoscopic and histopathologic findings of HIV-infected individuals after presentation with acute infection. Methods. We performed a retrospective case review of individuals infected with HIV who enrolled between August 2010 and April 2013 in a primary infection treatment trial. All participants started the trial during acute infection and underwent colonoscopy with biopsies at baseline and after the start of antiretroviral treatment. Results. Twenty acutely infected individuals were included in the study (mean age, 33 years; range, 20-54 years). All participants were male who reported having receptive anal sex as an HIV risk factor. Nine individuals (45%) had at least 1 finding by colorectal pathology; 1 person had 2 diagnoses (diverticulosis and focal active proctitis). The histopathological findings revealed anal dysplasia in 3 cases: 2 had high-grade anal intraepithelial neoplasia (AIN) and 1 had low-grade AIN. Two persons had a colorectal polyp, 1 hyperplastic and 1 adenomatous. Three persons were diagnosed with diverticulosis, and 2 persons were diagnosed with proctitis, including 1 with focal active proctitis and 1 with cytomegalovirus proctitis. Conclusions. To our knowledge, this is the first case series report of lower GI disorders in acute HIV-infected individuals. Although the causal relationship remains uncertain, we describe the endoscopic findings that were observed during acute HIV infection among men who have sex with men. Understanding the prevalence of these pathologies may likely shed light on how acute HIV infection damages the lower GI tract.

The effectiveness of electrocautery ablation for the treatment of high-grade anal intraepithelial neoplasia in HIV-infected men who have sex with men.

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 6-8weeks 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 12.1months, 14 of 55 patients with a response (25.4%; 95% CI 15.8-38.3%) developed recurrent HGAIN within a mean time of 29.9months (95% CI 22-37.7months). 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.

Loss of histone variant macroH2A2 expression associates with progression of anal neoplasm

AimsThe macroH2A histone variants are epigenetic marks for inactivated chromatin. In this study, we examined the expression of macroH2A2 in anal neoplasm from anal intraepithelial neoplasia (AIN) to anal squamous...

P17.17 Anal human papillomavirus (hpv) infection and anal intraepithelial neoplasia (ain) among men who have sex with men (msm) in kuala lumpur, malaysia

Introduction MSM in particular HIV positive MSM have an increased risk of anal cancer. There is a paucity of data regarding anal HPV infection and high grade anal intraepithelial neoplasia (HGAIN) among MSM in Malaysia. The study is part of a larger regional collaboration with sites in Bangkok, Bali and Jakarta. The aims of the study were to determine the prevalence, incidence and risk factors associated with high risk anal HPV infection and HGAIN among a cohort of MSM attending a screening site in Kuala Lumpur. Methods 3 doctors received training in high resolution anoscopy (HRA). 52 MSM participants, 26 HIV positive and 26 HIV Negative, were enrolled into the study. Participants were screened at 3 time points – at baseline, 6 months and 12 months. Each participant completed a questionnaire on demographics, smoking and sexual history. Anal sample collection was then undertaken for liquid based anal cytology and anal HPV genotyping (Linear Array). This was followed by HRA and biopsy of abnormal areas. Patients with AIN 2 or 3 were offered treatment. Each participant was also screened for syphilis (RPR nad TPPA) at each visit. Results The baseline results are presented. There were no anal cancers. The most common HPV genotype was HPV 16 in 17/52 (33%) participants. 39 (75%) had at least one high risk HPV infection. 26 (50%) had abnormal cytology. 9/52 (17%) had HGAIN (AIN 2 or 3). HGAIN correlated with high grade anal cytology (ASC-H or HSIL) in 6/9 patients. There was 1 newly diagnosed HIV infection. There were 6 incident syphilis infections. Demographic and sexual behaviour data and correlates of HGAIN will be presented. Conclusion High risk anal HPV infection and HGAIN was highly prevalent at baseline within this cohort of Asian MSM reinforcing the importance of screening within this population. Disclosure of interest The study was funded by grant from TreatAsia.

P10.03 Anal human papillomavirus (hpv) infection and anal intraepithelial neoplasia (ain) among men who have sex with men (msm) in kuala lumpur, malaysia

Introduction MSM in particular HIV positive MSM have an increased risk of anal cancer. There is a paucity of data regarding anal HPV infection and high grade anal intraepithelial neoplasia (HGAIN) among MSM in Malaysia. The study is part of a larger regional collaboration with sites in Bangkok, Bali and Jakarta. The aims of the study were to determine the prevalence, incidence and risk factors associated with high risk anal HPV infection and HGAIN among a cohort of MSM attending a screening site in Kuala Lumpur. Methods 3 doctors received training in high resolution anoscopy (HRA). 52 MSM participants, 26 HIV positive and 26 HIV Negative, were enrolled into the study. Participants were screened at 3 time points – at baseline, 6 months and 12 months. Each participant completed a questionnaire on demographics, smoking and sexual history. Anal sample collection was then undertaken for liquid based anal cytology and anal HPV genotyping (Linear Array). This was followed by HRA and biopsy of abnormal areas. Patients with AIN 2 or 3 were offered treatment. Each participant was also screened for syphilis (RPR nad TPPA) at each visit. Results The baseline results are presented. There were no anal cancers. The most common HPV genotype was HPV 16 in 17/52 (33%) participants. 39 (75%) had at least one high risk HPV infection. 26 (50%) had abnormal cytology. 9/52 (17%) had HGAIN (AIN 2 or 3). HGAIN correlated with high grade anal cytology (ASC-H or HSIL) in 6/9 patients. There was 1 newly diagnosed HIV infection. There were 6 incident syphilis infections. Demographic and sexual behaviour data and correlates of HGAIN will be presented. Conclusion High risk anal HPV infection and HGAIN was highly prevalent at baseline within this cohort of Asian MSM reinforcing the importance of screening within this population. Disclosure of interest The study was funded by grant from TreatAsia.

S17.4 Using data on pathogenesis and epidemiology to inform anal cancer screening strategies: data from the study of prevention of anal cancer (spanc)

Background HPV vaccination of school-aged boys will prevent anal cancer in future generations. Vaccination of gay men up to age 26 is recommended in several jurisdictions, but vaccination is generally not recommended at older ages because of a concern of possible lack of efficacy due to past or current HPV infection. Anal cancer screening, based on the model of cervical cancer screening, has also been proposed as a means to reduce morbidity. Methods The Study of the Prevention of Anal Cancer (SPANC) is a three-year prospective study of the natural history of anal HPV infection and cancer precursors in HIV-negative and -positive gay men aged ≥35 years. At each visit all men receive an anal swab for cytology and HPV genotyping, followed by high resolution anoscopy-directed biopsy for histological assessment. Results At the end of June 2015, 595 men had been enrolled. Median age was 49 and 35.3% were HIV-positive. Men of all ages enrolled in SPANC were likely to report multiple sexual partners in the past 6 months (overall 73.4% of 35–44 year olds decreasing to 62.1% of 65+ year olds, p trend = 0.03). The prevalence of HPV16, the genotype responsible for >90% of anal cancer, was 29.4% in 35–44, 30.8% in 45–54, 34.2% in 55–64 and 19.0% in 65+ year olds (p trend = 0.54), with no difference by HIV status. The incidence of HPV16 decreased with age from 5.6/100 person years (PY) in 35–44 year olds to 2.9/100PY in 55–64 year olds. There was no incident HPV16 in men aged 65+ (p trend = 0.059). At baseline, the prevalence of anal high grade intraepithelial neoplasia (HSIL) was higher in HIV-positive than in the HIV-negative participants (46.9% vs 32.3%, p Conclusions Gay men in SPANC reported multiple sexual partners across the adult age-range, and incident HPV16 continued to be detected in men up to their seventh decade of life. This suggests that HPV vaccination of adult gay men may prevent infection and have a role in cancer prevention. Anal HSIL is highly prevalent, particularly among HIV-positive men, but there are high rates of clearance without treatment. These data suggest that a screening test which can distinguish persistent from transient HSIL is required. The role of HPV biomarkers in identifying those HSIL lesions most likely to persist should be investigated.

Human papillomavirus status, anal cytology and histopathological outcome in HIV-positive patients.

Human papillomavirus (HPV) are responsible for a broad spectrum of mucocutaneous infections and may cause squamous cell carcinoma following long-standing infection . Oncogenic HPV, most commonly HPV 16, are detectable in over 90% of cervical intraepithelial neoplasia and anal intraepithelial neoplasia (AIN). Human immunodeficiency virus (HIV) infection is strongly associated with a higher prevalence of chronic HPV infection, a higher incidence of AIN and an increased risk for anal cancer (AC). In September 2013, guidelines concerning prevention, screening and treatment of AIN for patients affected by HIV were issued by the German AIDS society. In order to validate the suggested screening procedure, we analysed data from 123 male and female patients with HIV infection that regularly present in our outpatient clinic. Anal cytology, HPV typing and high-resolution anoscopy (HRA) were performed. Our results show that screening by anal cytology only identifies a minority of patients with high grade AIN (AIN 3) histology. Patients with normal cytology (NILM, cytology graded negative for intraepithelial lesion or malignancy; n=5, 29.4%), atypical squamous cells of undetermined significance (ASCUS; n=5, 71.4%) and low grade squamous intraepithelial lesion (LSIL; n=8, 44.5%) showed highly dysplastic lesions (AIN 2 and 3) in the histological workup more frequently than expected. Additionally, high-grade squamous intraepithelial lesion (HSIL) was strongly associated with detection of high-risk oncogenic HPV. Anal cytology as the solitary screening tool for anal cancer fails to detect anal dysplasia in a considerable number of patients. Additionally, HPV typing and possibly further biomarkers might be applied to identify those patients with a higher risk of developing anal carcinoma, in order to monitor them more closely or directly transfer them to HRA.

Long-Term Outcomes of Adding HPV Vaccine to the Anal Intraepithelial Neoplasia Treatment Regimen in HIV-Positive Men Who Have Sex With Men

Recent evidence shows that quadrivalent human papillomavirus (qHPV) vaccination in men who have sex with men (MSM) who have a history of high-grade anal intraepithelial neoplasia (HGAIN) was associated with a 50% reduction in the risk of recurrent HGAIN. We evaluated the long-term clinical and economic outcomes of adding the qHPV vaccine to the treatment regimen for HGAIN in human immunodeficiency virus (HIV)-positive MSM aged ≥27 years. We constructed a Markov model based on anal histology in HIV-positive MSM comparing qHPV vaccination with no vaccination after treatment for HGAIN, the current practice. The model parameters, including baseline prevalence, disease transitions, costs, and utilities, were either obtained from the literature or calibrated using a natural history model of anal carcinogenesis. The model outputs included lifetime costs, quality-adjusted life years, and lifetime risk of developing anal cancer. We estimated the incremental cost-effectiveness ratio of qHPV vaccination compared to no qHPV vaccination and decrease in lifetime risk of anal cancer. We also conducted deterministic and probabilistic sensitivity analyses to evaluate the robustness of the results. Use of qHPV vaccination after treatment for HGAIN decreased the lifetime risk of anal cancer by 63% compared with no vaccination. The qHPV vaccination strategy was cost saving; it decreased lifetime costs by $419 and increased quality-adjusted life years by 0.16. Results were robust to the sensitivity analysis. Vaccinating HIV-positive MSM aged ≥27 years with qHPV vaccine after treatment for HGAIN is a cost-saving strategy. Therefore, expansion of current vaccination guidelines to include this population should be a high priority.

Which lesions should be biopsied during high-resolution anoscopy? Prospective descriptive study of simple morphological criteria.

High-resolution anoscopy (HRA) is a useful screening tool for anal intraepithelial neoplasia (AIN), although reputedly challenging for interpretation of suspected lesions. All consecutive patients who underwent biopsies for at least 1 lesion suspicious for AIN during HRA from November 2010 to March 2012 were prospectively included. The characteristics (borders, staining with acetic acid and Lugol iodine solution, and patterns of epithelium and vascularization) of the lesions detected during HRA were compared with histology. A total of 168 suspicious anal lesions were biopsied and analyzed in 103 patients (68% men, mean age ± standard deviation = 49.8 ± 9 y, 57% positive status on human immunodeficiency virus infection). According to histology, 41.7% of the lesions were high grade, 34.5% were low grade, and 23.8% were nondysplastic. Lesions with irregular epithelial pattern (or irregular vascularization) were twice as likely to be high grade compared with lesions with regular epithelial pattern (or regular vascularization). The incidences of acetic acid-induced whitening were 91.4%, 94.8%, and 70% among the high-grade AIN, low-grade AIN, and nondysplastic samples, respectively. Among the high-grade AIN, 62.9% were not stained by Lugol solution (vs 31% of the low-grade AIN). The positive predictive value of a combination of these simple morphological criteria was 68.6%. Several simple morphological criteria are significantly associated with high-grade AIN and are found less often in low-grade AIN. A combination of these morphological criteria provides sufficient positive predictive value to guide biopsy placement during HRA.