High-grade Anal Intraepithelial Neoplasia Research Articles

Analytical validation and diagnostic performance of the ASCL1/ZNF582 methylation test for detection of high grade anal intraepithelial neoplasia and anal cancer

DNA methylation testing on biopsies can detect high-grade anal intraepithelial neoplasia (HGAIN) in need of treatment and anal cancer. This study aimed to analytically validate and determine the diagnostic performance of a newly developed multiplex quantitative methylation-specific PCR, PreCursor-M AnoGYN(RUO), combining ASCL1, ZNF582 and a reference (ACTB) in one assay. Analytical validation was performed on two qPCR devices using predefined quality criteria. Diagnostic performance was determined on a cross-sectional series of 111 anal biopsies covering all stages of anal disease. Differences in methylation levels were assessed using the Kruskal-Wallis test. Area under the curve was determined using logistic regression analysis. Detection rates were calculated at predefined specificities for the cross-sectional and an additional longitudinal series of 23 HGAIN biopsies preceding anal cancer (i.e., progressive HGAIN).For both devices analytical quality criteria were met. ASCL1 and ZNF582 methylation levels increased with increasing severity of disease (p < 6*10−8). Diagnostic performance for AIN3+ was 0.81. All cancers and virtually all progressive HGAIN were detected at 70% and 80% specificity.In conclusion, the ASCL1/ZNF582 methylation test (PreCursor-M AnoGYN(RUO)) was demonstrated to be highly robust and reproducible. Moreover, it had excellent diagnostic accuracy to detect AIN3+ and can potentially be used to guide HGAIN management.

Prevalence of high-grade anal intraepithelial neoplasia in immunocompetent women treated for high-grade cervical intraepithelial neoplasia

BackgroundThe aim of the study was to evaluate the prevalence of high-grade anal intraepithelial neoplasia (AIN2-3) among immunocompetent women treated for high-grade cervical intraepithelial neoplasia (CIN2-3). Such knowledge is strongly needed to establish whether a screening program should be recommended in this group of patients. MethodsThis prospective study included a cohort of consecutive women with no known causes of immunosuppression treated with LEEP (loop electrosurgical excision procedure) for a histopathological diagnosis of CIN2-3 in our center between 2019 and 2021. Following the procedure, all patients were invited to undergo anal cytology and anal high-risk HPV-DNA testing (aHPV-DNA). In cases in which one or both tests resulted positive, a high-resolution anoscopy with a biopsy of suspicious lesions was performed. All women also completed a questionnaire on sexual habits. ResultsAt total of 100 women were enrolled in the study. Among these, eight patients had a concomitant or past diagnosis of anogenital warts, while one patient had received a previous diagnosis of high-grade vaginal intraepithelial neoplasia. Anal Pap smears were positive for low-grade lesions in three patients, while 73 women tested positive for aHPV-DNA. Histological examinations revealed the presence of AIN2-3 lesions in four patients (6.5%; 95% C.I., 1.8 to 15.7%), who subsequently underwent excisional treatment. ConclusionsWomen with a history of high-grade cervical intraepithelial neoplasia have an intermediate risk of developing high-grade anal intraepithelial neoplasia. Future studies are needed in order to assess an ideal screening approach for this condition.

Therapeutic Vaccination against Human Papillomavirus Type 16 for the Treatment of High-Grade Anal Intraepithelial Neoplasia in HIV+ Men.

Anal cancer is increasing in HIV+ men who have sex with men (MSM). Treatment options for its precursor, high-grade anal intraepithelial neoplasia (HGAIN), are suboptimal. In this phase I to II dose-finding study, we assessed the safety and efficacy of the human papillomavirus type 16 (HPV16) synthetic long peptide vaccine (SLP-HPV-01) in HIV+ MSM with HPV16-positive HGAIN. Four dosage schedules (1-5-10; 5-10-20; 10-20-40; and 40-40-40-40 μg) of SLP-HPV-01 were administered intradermally with a 3-week interval in 10 patients per dose level (DL). In each dose group, 5 patients also received 1 μg/kg pegylated IFNα-2b subcutaneously. Primary endpoints were safety and regression of HGAIN at 3, 6, and 12 months. Eighty-one of 134 screened patients (60%) had HPV16-negative HGAIN lesions, leaving 53 eligible patients. Thirteen patients were excluded, leaving 40 men. The vaccine was well tolerated. One patient developed a generalized rash. The highest dosage level induced the strongest immune responses. There was no indication for stronger reactivity in the IFNα groups. Up to 18 months of follow-up, 8/38 intention-to-treat patients had a complete clinical and histologic response and one had a partial response (in total 9/38, 23.7%). At the highest dosage level, the clinical response was 4/10 (40%). Stronger immune responses were detected among clinical responders. The highest DL is safe, immunogenic, and associated with clinical responses to HPV16-induced lesions. However, as the majority of HGAIN is caused by the other HPV types, further studies should aim at pan-HPV vaccination to prevent or treat HGAIN.

Human papillomavirus in the setting of immunodeficiency: Pathogenesis and the emergence of next-generation therapies to reduce the high associated cancer risk.

Human papillomavirus (HPV), a common sexually transmitted virus infecting mucosal or cutaneous stratified epithelia, is implicated in the rising of associated cancers worldwide. While HPV infection can be cleared by an adequate immune response, immunocompromised individuals can develop persistent, treatment-refractory, and progressive disease. Primary immunodeficiencies (PIDs) associated with HPV-related disease include inborn errors of GATA, EVER1/2, and CXCR4 mutations, resulting in defective cellular function. People living with secondary immunodeficiency (e.g. solid-organ transplants recipients of immunosuppression) and acquired immunodeficiency (e.g. concurrent human immunodeficiency virus (HIV) infection) are also at significant risk of HPV-related disease. Immunocompromised people are highly susceptible to the development of cutaneous and mucosal warts, and cervical, anogenital and oropharyngeal carcinomas. The specific mechanisms underlying high-risk HPV-driven cancer development in immunocompromised hosts are not well understood. Current treatments for HPV-related cancers include surgery with adjuvant chemotherapy and/or radiotherapy, with clinical trials underway to investigate the use of anti-PD-1 therapy. In the setting of HIV co-infection, persistent high-grade anal intraepithelial neoplasia can occur despite suppressive antiretroviral therapy, resulting in an ongoing risk for transformation to overt malignancy. Although therapeutic vaccines against HPV are under development, the efficacy of these in the setting of PID, secondary- or acquired- immunodeficiencies remains unclear. RNA-based therapeutic targeting of the HPV genome or mRNA transcript has become a promising next-generation therapeutic avenue. In this review, we summarise the current understanding of HPV pathogenesis, immune evasion, and malignant transformation, with a focus on key PIDs, secondary immunodeficiencies, and HIV infection. Current management and vaccine regimes are outlined in relation to HPV-driven cancer, and specifically, the need for more effective therapeutic strategies for immunocompromised hosts. The recent advances in RNA-based gene targeting including CRISPR and short interfering RNA (siRNA), and the potential application to HPV infection are of great interest. An increased understanding of both the dysregulated immune responses in immunocompromised hosts and of viral persistence is essential for the design of next-generation therapies to eliminate HPV persistence and cancer development in the most at-risk populations.

DNA Methylation Analysis to predict Regression of high-grade anal Intraepithelial Neoplasia in HIV+ men (MARINE): a cohort study protocol

IntroductionAnal cancer precursors, or high-grade anal intraepithelial neoplasia (HGAIN), are highly prevalent in HIV-seropositive (HIV+) men who have sex with men (MSM). Around 30% of lesions regress within 1 year,...

O091 Social deprivation and malignant progression of anal intraepithelial neoplasia

Abstract Introduction Social deprivation is known to be a risk factor for cervical cancer but its influence on progression rate to invasive cancer is less clear. This study aimed to investigate whether deprivation was a risk factor for high grade anal intra-epithelial neoplasia (AINIII) progression to anal squamous cell carcinoma (ASCC). Methods Retrospective analysis of AINIII patients in Southeast Wales between 2000–2021. Deprivation was calculated from postcodes at time of referral, divided into five quintiles (Welsh Index of Multiple Deprivation 2019). Welsh Clinical Portal and Cancer Network Information System Cymru (CaNISC) were utilised to collect patient demographics, histopathology and clinical outcomes. Results Eighty-six AINIII patients were identified. Twenty-nine presented with synchronous ASCC and AINIII. Thirteen progressed to cancer (median 23 months). The proportion of patients in each deprivation quintile was calculated. The association between deprivation and incidence of ASCC at presentation (p=0.93) and AIN transformation to ASCC (p=0.65) were not statistically significant (chi-square analysis). Conclusion No correlation between presentation of anal ASCC or AINIII progression and social deprivation was observed. Due to small sample size, multicentre research is required to investigate this further. Take-home message Social deprivation was not observed to be a risk factor for anal Intra-epithelial Neoplasia III or anal cancer in our cohort. However, further research across a larger sample size is required to investigate this association further.

Gene methylation of CADM1 and MAL identified as a biomarker of high grade anal intraepithelial neoplasia

Human papillomavirus (HPV) is detected in up to 96% of anal squamous cell cancers, where screening programs needed. However, the best methodology is still undetermined. Host DNA methylation markers CADM1, MAL and miR124 have been identified in cervical disease, but not anal disease. Anal swabs varying by disease grade were assessed for DNA methylation of CADM1, MAL and miR124-2. Each marker was compared across disease grades, stratified by HPV and HIV status. Receiver operating characteristic curves identified the predictive value of significant gene candidates. CADM1 methylation was significantly higher in high-grade squamous intraepithelial lesions (HSIL) compared with low-grade (LSIL) (p = 0.005) or normal (p < 0.001) samples with 67.2% correctly identified as HSIL. MAL methylation was significantly (p = 0.002) increased in HSIL compared with LSIL in HIV positive participants with 79.8% correctly indicated as HSIL. Gene miR124-2, showed no difference between disease grades. Biomarkers with established diagnostic value in cervical disease have limited utility in the prediction of anal disease, with CADM1 identified as a marker with screening potential in a gay and bisexual men (GBM) population and MAL in HIV positive GBM population. New markers specific to the anal mucosa are required to improve triage of high-risk individuals.

Trends in incidence and survival from anal cancer and incidence of high-grade anal intraepithelial neoplasia in Denmark

ObjectiveThe aim of the current study was to assess temporal trends in incidence of anal squamous cell carcinomas (SCC) and high-grade anal intraepithelial lesions (AIN2/3), and estimate survival from anal cancer and factors related to 5-year mortality in Denmark. MethodsWe analyzed anal SCC and AIN2/3 cases in the period of 1998–2018 from the Danish Cancer Register and the Danish Registry of Pathology, respectively. Overall, period, gender, and histology specific age-standardized incidence rates, average annual percentage change (AAPC), and 5-year relative survival were estimated. Cox proportional hazards models were applied to evaluate the effect on 5-year mortality of period, age, gender, and stage of disease. ResultsAltogether 2580 anal cancers and 871 AIN2/3 were identified. The AIN2/3 incidence increased for women 1998–2007 (AAPC: 3.5% (95% CI −0.7, 8.0)) and then tended to decrease during 2008–2018(AAPC: −5.2% (95% CI −9.6, −0.6)). A similar pattern was observed for men, although at a lower incidence with the decrease starting later (2008–2012) and the trend not reaching statistical significance. The anal SCC incidence increased over the whole study period for both women and men (women AAPC: 4.0% (95% CI 3.2%, 4.9%) and men AAPC: 3.6% (95% CI 2.3%, 4.9%)). The relative survival improved over time (from 61% to 72%). Being older and male was associated with a higher risk of dying within 5 years. ConclusionsThere is a need to focus attention on anal cancer and its precursor lesions, as the cancer incidence continues to increase. Actions could include screening and gender-neutral HPV vaccination.

Vroegtijdige opsporing van voorstadia van een anaal carcinoom bij hiv-seropositieve patiënten

Early detection of precursor lesions of anal cancer in HIV-seropositive patients Although anal cancer is rare in the overall population, its incidence is increasing in the last decades. Especially HIV-seropositive patients have an increased risk of developing anal squamous cell carcinoma (SCC), mainly because of the high prevalence of high-grade anal intraepithelial neoplasia (AIN) among these patients. High-grade AIN is a precursor lesion for anal SCC associated with human papillomavirus (HPV) infection. Despite the lack of direct evidence demonstrating that AIN identification reduces the risk of anal cancer, experts think that screening and treatment of high-risk patients will prevent the disease. This article aims to review the current literature about AIN and discusses the screening options, including digital rectal examination, anal cytology and high-resolution anoscopy.

Anal cancer screening and prevention: a review for dermatologists.

The incidence of and mortality from anal cancer, predominantly squamous cell carcinoma (SCC), have been increasing since the 1980s, during an era when many common malignancies have seen decreases in mortality. Dermatologists may be more likely to see patients at an increased risk for anal SCC, such as those living with HIV, MSM and those presenting for management of anogenital warts, yet there is little guidance in the field on how to manage these patients. We underwent a project to review the evidence surrounding screening and prevention of anal SCC. HPV vaccination, the main preventative measure for anal SCC, is often underutilized and may not be effective for those most at risk. Screening methods currently include high-risk HPV and anal cytology testing, with high-resolution anoscopy (HRA) reserved for biopsy and confirmatory testing. High-risk HPV testing has been associated with high sensitivity for intraepithelial neoplasia, but low specificity in high-risk groups. Recent meta-analyses examining AIN detection using anal cytology estimate a similarly high sensitivity of 74-87%, with a relatively higher specificity (44-66%) for identifying high-grade AIN. HRA is the gold standard for diagnosis, but its accessibility and cost are deterrents from its use as a screening tool. Cervical cancer screening, initially adopted without significant evidence of its impact, has significantly decreased cervical cancer rates. The argument can be made that rates of anal SCC may also benefit from appropriate screening methods, particularly anal cytology. It is prudent for dermatologists to be aware of the methods available to them in the management of at-risk patients, the data supporting them, and the potential benefits of screening in order to counsel patients appropriately and address the increasing burden of disease.

Incidence of HPV-related Anogenital Intraepithelial Neoplasia and Cancer in Men With Diabetes Compared With the General Population.

Diabetes may increase risk of human papillomavirus (HPV)-related precancer and cancer. We estimated incidence of penile and anal high-grade intraepithelial neoplasia (hgPeIN, hgAIN) and squamous cell carcinoma (SCC) in men with diabetes compared with the entire Danish male population without diabetes. In this registry-based cohort study, we included all men born 1916-2001 and residing in Denmark (n = 2,528,756). From nationwide registries, we retrieved individual-level information on diabetes, educational level, and diagnoses of hgPeIN, hgAIN, penile SCC, and anal SCC. We used Poisson regression models to estimate incidence of hgPeIN, hgAIN, penile SCC, and anal SCC as a function of diabetes status, attained age, calendar period, and education. We estimated incidence rate ratios (IRRs) of each outcome in men with diabetes compared with nondiabetic men, both for diabetes overall and separately for type 1 (T1D) and type 2 diabetes (T2D). Men with diabetes had increased incidence rate of penile SCC compared with nondiabetic men (IRR = 1.5, 95% CI = 1.2, 1.9). We saw similar trends for anal SCC, hgPeIN, and hgAIN. The combined incidence rate of penile and anal SCC was increased in men with T2D (IRR = 1.5, 95% CI = 1.3, 1.8), but not with T1D (IRR = 0.53, 95% CI = 0.20, 1.4) compared with men without diabetes. The incidence of penile and anal high-grade intraepithelial neoplasia and SCC in men with diabetes was increased compared with men without diabetes. For penile and anal SCCs, this was primarily due to an increased risk in men with T2D.

HPV vaccination to prevent recurrence of anal intraepithelial neoplasia in HIV+ MSM.

Objective:Anal cancer precursor lesions high-grade anal intraepithelial neoplasia (HGAIN) are highly prevalent among HIV+ MSM. Treatment of HGAIN is frustrated by high recurrence rates. We investigated the efficacy of the quadrivalent human papillomavirus (qHPV) vaccine as posttreatment adjuvant in preventing HGAIN recurrence in HIV+ MSM.Design:Randomized, double-blind, placebo-controlled, multicentre trial.Setting:Three HIV outpatient clinics in Amsterdam, the Netherlands.Subjects:HIV+ MSM with CD4+ cell count more than 350 cells/μl, biopsy-proven intra-anal HGAIN successfully treated in the past year, and lesions still in remission at enrolment, as assessed by high-resolution anoscopy (HRA).Intervention:Participants were randomized to three doses of qHPV (Gardasil-4, MSD) or placebo with vaccinations at 0, 2, and 6 months. HRA was repeated at 6, 12, and 18 months.Main outcome measure:The primary outcome was cumulative, biopsy-proven HGAIN recurrence rate at 18 months, evaluated in an intention-to-treat (ITT) (received all vaccinations) and per-protocol analysis (all vaccinations and complete follow-up).Results:We randomized 126 participants of which 64 (50.8%) received qHPV and 62 (49.2%) placebo. All participants received three vaccinations, and in both groups for two participants follow-up was incomplete. We found no difference (P = 0.38) in cumulative HGAIN recurrence rates between the qHPV (44/64, 68.8%) and placebo group (38/62, 61.3%) in the ITT analysis [absolute risk reduction −7.5 (95% confidence interval (CI) −24.1 to 9.2)]. This was similar in the per-protocol analysis.Conclusion:Despite adequate serological responses to qHPV vaccination, short-term recurrence of HGAIN was not prevented. These findings do not support qHPV vaccination as a treatment adjuvant to prevent HGAIN recurrence in HIV+ MSM.

Evaluation of high-risk human papillomavirus testing and anal cytology to detect high-grade anal intraepithelial neoplasia

Optimal screening for detection of anal precancer has not been established, and most studies involve very high-risk populations. We evaluated high-risk human papillomavirus (HPV) testing and anal cytology to detect high-grade anal intraepithelial neoplasia (≥AIN2) in a cohort with mostly moderate risk factors for AIN. Patients ≥35 years old undergoing anal biopsy for various lesions received HPV testing by Roche cobas and a subset by Hologic APTIMA HPV assays with concurrent anal ThinPrep cytology. Biopsies were blindly reviewed by 3 authors, and consensus diagnosis was compared with HPV and cytology results. Sensitivity and specificity for ≥AIN2 detection by HPV testing and cytology (≥ASC-US) were calculated. Among 64 patients, 19 (29.7%) showed ≥AIN2 on biopsy. All patients were tested by cobas, and 35 (54.7%) were positive. A subset of 39 patients were also tested by APTIMA, and 18 (46.2%) were positive. Positive cytology (≥ASC-US) was present in 37 (57.8%) patients, with 27 (73.0%) of these positive by cobas. HPV testing alone yielded 75.0% and 84.2% sensitivity for APTIMA and cobas, respectively; specificity was 66.7% and 57.8%. Sensitivity and specificity of cytology alone was 78.9% and 51.1%. Combined HPV testing and cytology had a sensitivity and specificity of 91.7% and 37.0% for APTIMA and 94.7% and 40.0% for cobas. Combined HPV testing and cytology had the highest sensitivity for ≥AIN2 detection, with a performance comparable to cervical cancer screening tests, suggesting this strategy may represent a viable screening option in a population with moderate risk factors for AIN.

Incidence of Recurrent High-Grade Anal Dysplasia in HIV-1-Infected Men and Women Following Infrared Coagulation Ablation: A Retrospective Cohort Study.

This single-center, retrospective cohort study sought to estimate the cumulative incidence in HIV-1-infected patients of biopsy-proven high-grade anal intraepithelial neoplasia (HGAIN) recurrence after infrared coagulation (IRC) treatment. The study was based on data from a prospectively compiled database of 665 HIV-1-infected outpatients who attended a hospital Clinical Proctology/HIV Unit between January 2012 and December 2015. Patient records were checked to see which ones had received IRC treatment but later experienced a recurrence of HGAIN. Cytology samples were also checked for the presence of human papilloma virus (HPV). A total of 81 of the 665 patients (12%, 95%CI: 10–15%), of whom 65 were men and 16 women, were diagnosed with HGAIN and again treated with IRC. Of these 81, 20 (25%) experienced recurrent HGAIN, this incidence being true of both men (16/65, 95%CI: 19–57%) and women (4/16, 95%CI: 10–50%). The median time to recurrence was 6 (2–19) months overall, 6 (2–19) months in men, and 4 (2–6) months in women. HPV infection was detected in all patients except two, with HPV-16 being the most common genotype. This rate of incidence of recurrent HGAIN following IRC treatment is consistent with other reports and highlights the importance of continued post-treatment surveillance, particularly in the first year.

Evaluation of High-Risk Human Papillomavirus Testing and Anal Cytology to Detect High-Grade Anal Intraepithelial Neoplasia

Evaluation of High-Risk Human Papillomavirus Testing and Anal Cytology to Detect High-Grade Anal Intraepithelial Neoplasia

S1803 Extramammary Paget’s Disease of the Anal Canal: A Rare Diagnosis

INTRODUCTION: Extramammary Paget's disease (EMPD) is an uncommon intraepithelial malignancy that often involves areas of skin with high apocrine gland density. Cases of EMPD involving the anal canal are extremely rare. We present a case of anal EMPD where subsequent work up was unsuccessful in locating the primary site of the associated gastrointestinal (GI) cancer. CASE DESCRIPTION/METHODS: 76 year old male with history of diabetes, hypertension, immune thrombocytopenic purpura treated with rituximab, and chronic lymphocytic leukemia in remission after treatment with chemotherapy, presented with chronic constipation. He denied hematochezia, weight loss, or family history of GI malignancy. He underwent colonoscopy where one polyp was removed from the cecum with pathology revealing a tubular adenoma as well as a one centimeter whitish area of abnormal-appearing mucosa in the anal canal extending proximally into the anal transition zone and initial biopsy demonstrated invasive EMPD (BerEP4, CK7, CK20 & mucicarmine positive) (Image 1). A second biopsy of the lesion showed anal intraepithelial neoplasia (AIN 2–3) with EMPD (CK7, CK20, CDX2 & mucicarmine positive) (Image 2). Later, PET/CT scan showed linear FDG uptake in the anorectal region and several FDG-avid lymph nodes in the right external iliac chain and inguinal region. Subsequent excisional biopsy of the right inguinal lymph nodes showed metastatic tumor, with an immunohistochemistry profile similar to prior EMPD biopsies (Image 3). Patient underwent a repeat colonoscopy which did not reveal any new findings. An EGD and capsule endoscopy were also done which did not show any suspicious masses or lesions. Wide local excision with lymph node dissection was recommended, but the patient declined further management. Two months later, the patient got a CT abdomen and pelvis due to increasing abdominal pain which showed worsening metastatic disease in the liver and abdominal lymph nodes. Patient opted for hospice care and died a few weeks afterwards. DISCUSSION: To our knowledge, EMPD involving the anal canal is a rare finding with only a handful of cases reported in the literature. It was an incidental diagnosis and most likely associated with an unidentified colorectal adenocarcinoma. Surgery is the treatment of choice for localized disease, provided there is no evidence of dermal invasion or distant metastasis. Radiation and chemotherapy may be trialed in advanced cases, but efficacy remains poor.Figure 1.: Colonoscopy (A &B) showing mucosal lesion in anal canal (arrows), extending proximally into the anal transition zone. Anus biopsy on H & E stain (C ) showing invasive extramammary Paget’s disease with nests of malignant epithelial cells showing a high nuclear-to-cytoplasmic ratio with arrows indicating invasive carcinoma which is confirmed with BerEP4 immunohistochemistry stain (D) confirming in situ (red arrows) and invasive extramammary Paget's disease (blue arrows).Figure 2.: Anus biopsy (20X) with H & E stain (B) showing foci of extramammary Paget’s disease (black arrows) in tissue composed of high grade anal intraepithelial neoplasia (AIN 2-3). CDX2 immunohistochemistry stain (C) and Mucicarmine stain (D) highlighting extramammary Paget's disease.Figure 3.: PET/CT (A) shows FDG-avid lymph nodes in the right external iliac chain and inguinal region (white arrow). Right inguinal lymph node biopsy shows metastatic extramammary Paget's disease (40X) with H & E stain (B), confirmed with CK 7 immunohistochemistry stain expression (10X) in (C) and CDX2 immunohistochemistry expression (40X) in (D).

Cytology-based screening for anal intraepithelial neoplasia in women with a history of cervical intraepithelial neoplasia or cancer.

High-risk human papillomavirus (HPV) has been identified in the pathogenesis of anal cancer. The purpose of this study was to assess the prevalence of abnormal anal cytology and HPV in women aged ≥40 years who have a history of high-grade cervical squamous intraepithelial lesion (SIL) or cancer and to estimate the prevalence of anal intraepithelial neoplasia (AIN) using cytology as the primary screening modality. Women who had a history of high-grade cervical SIL or cancer and were ≥40 years of age were included in this prospective study. Anal cytology with HPV-DNA testing was performed. All patients with abnormal anal cytology were referred for high-resolution anoscopy (HRA), and abnormal lesions were biopsied and treated if pathologically confirmed. Abnormal anal cytology correlated with HPV status, HRA findings, and clinical and demographic characteristics. A total of 317 women completed the study. Of these, 96 (30.3%) had abnormal anal cytology (high-grade SIL, 12.5%; low-grade SIL, 19.8%; atypical squamous cells, cannot exclude high-grade SIL, 6.3%; atypical squamous cells of undetermined significance, 61.5%) and 101 (31.9%) were HPV-DNA-positive. There was a significant association between abnormal cytology results and the presence of high-risk HPV. Of the 96 patients with abnormal cytology, 30 (31.3%) had biopsy-proven AIN on HRA, representing 9.5% of the total patient cohort; of these, 10 (33.3%) had low-grade AIN and 20 (66.7%) had high-grade AIN. Older age and smoking were significant risk factors for abnormal anal cytology. Women aged ≥40 years with a history of high-grade cervical SIL or cancer have a high rate of AIN. Screening for anal cancer may therefore be considered in this patient population. The optimal screening approach should be addressed in future studies.

Improving the screening of precancerous anal lesions in high-risk subjects with normal cytology: A longitudinal cohort study using simple tests

For patients at high risk of anal cancer, annual screening strategies using invasive evaluation methods are stressful. According to a normal examination at baseline using simple and non invasive tests, the aim of the work was to quantify neoplastic events. Patients and methodData from patients with a normal evaluation at the first visit were retrospectively extracted from a prospective database. The individual follow-up period was at least two years and three evaluations. Patients with abnormal cytology were assessed using high-resolution anoscopy and targeted biopsies. ResultsA total of 182 subjects (F/M: 10/90, aged 48.1(10.6) years, HIV: 81%) were followed for 41(11) months. Anal cytology remained normal in 94 patients (52%), but high-grade anal neoplasms occurred in 28 patients (15%). Patients with a negative HPV16 status at baseline had cumulative probabilities of high-grade AIN of 0.4%(0.1%-1.9%), 2.6%(1.2%-5.9%) and 7.5%(4.5%-12.2%) after 1 year, 2 years and 3 years of follow-up, respectively. These probabilities were lower than those of patients with a positive HPV16 at baseline and those with a previous history of AIN. ConclusionIn patients with normal cytology and negative HPV16 at baseline, a three-year interval screening may be a less cumbersome alternative to traditional annual screening.

Giant Acuminated Condyloma in a HIV Positive Migrant Patient: Is There a Benefit on Giving the HPV Vaccine To the Men Who Have Sex With Men Population? Case Report and Literature Review

Anal cancer is a serious health problem in HIV-positive Men who have Sex with Men (MSM), and precursor lesions like anal intraepithelial neoplasia; are well defined. Anal intraepithelial neoplasia (AIN), a human papillomavirus (HPV)- associated anal cancer precursor lesion, is frequent among human immunodeficiency virus (HIV)-positive men who have sex with men and women (MSMW). There is a paucity of data published on the progression of high-grade AIN to invasive cancer as well as on clinical and virological characteristics comparing anal margin and anal canal carcinoma. Men who are infected with HIV and MSM are at particularly high risk for persistent HPV infection and HPV-induced lesions. The treatment of high-grade squamous intraepithelial lesions (HISL) in HIV positive MSM associating the adjuvant vaccine against HPV is likely to be cost-effective, with benefits reported in the age group above 38 years. It is convenient to design large controlled studies that enroll the MSM population infected with HIV, as in our patient; to evaluate the benefits of the HPV vaccine.

Anal PAP, HPV tests and magnifying chromoendoscopy with biopsies in the diagnosis of anal intraephitelial neoplasia

IntroductionAnal intraepithelial neoplasia (AIN) is the most likely precursor of squamous cells cancer which represents 90% of anal cancers. The use of biomolecular tests as a screening method has been extended by gynecology. Given the similarities that exist between the HPV disease in the lower genital tract and anorectal sectors, it is expected that HPV tests can provide information for the diagnosis, treatment and follow-up for AIN-affected patients. ObjectivesComparing the performance of anal cytology, PAP and HPV tests (Hybrid Capture and Papillocheck) against the histology of the diagnosis of low- and high-grade AIN in risk groups. Material and methodsA cross-sectional study was carried out to evaluate diagnostic methods for low- and high-grade AIN in 73 patients. Samples for anal PAP, Papillocheck and Hybrid Capture were taken from all patients who then, regardless of the results, underwent magnifying chromoendoscopy (MCE) along with biopsy. Diagnostic test performances and their 95% confidence intervals (CI: 95%) were calculated as well as the likelihood ratio for each test. ResultsOf the 73 patients, 49 (67%) were women. The average age of the patients was 38 years. In 38 patients (52%), the histology was positive with 10 (14%) grade II AIN or higher. There were no statistically significant differences in sensitivity nor in specificity for low- and high-grade AINs between any of the tests. ConclusionAnal PAP, the Hybrid Capture test (HC2, Qiagen) and PapilloCheck (Greiner Bio One) were highly sensitive but not specific for low- and high-grade AINs. Therefore, a biopsy should be conducted against a positive result of any of the tests to confirm AIN and the degree of dysplasia. The screening method selection depend on the availability but also costs of the test should be considered, since all the diagnostic tests have similar performance.