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The Accuracy of Anal Swab-Based Tests to Detect High-Grade Anal Intraepithelial Neoplasia in HIV-Infected Patients: A Systematic Review and Meta-analysis.

ABSTRACT: Background:The incidence of high-risk human papillomavirus (HR-HPV)-induced anal cancer is increasingly problematic among HIV-positive patients. Anal cancer is preceded by precursor lesions, anal intraepithelial neoplasia (AIN). AIN detection requires high-resolution anoscopy, a cumbersome and time-consuming procedure. We aggregated evidence on anal swab-based tests to detect AIN in HIV-positive patients. Methods:We searched MEDLINE and EMBASE for cross-sectional studies on AIN detection with anal cytology, HR-HPV DNA detection, HPV E6/E7 mRNA analysis, and P16INK4a and Ki-67 immunostaining. Summary estimates of sensitivity and specificity were calculated using bivariate logistic regression. Cytology was reported using the terms squamous intra-epithelial lesion (SIL) for AIN and high-grade SIL (HSIL) for high-grade AIN (HGAIN). Results:We included 22 studies. Using cytology with a cutoff of any SIL to detect HGAIN, we detected a sensitivity of 82% (95% CI, 74%-87%) and specificity of 45% (95% CI, 44%-66%); with the cutoff of HSIL, the sensitivity was 44% (95% CI, 45%-67%) and the specificity was 79% (95% CI, 69%-87%). The sensitivity of HPV DNA to detect HGAIN was 91% (95% CI, 82%-95%) and the specificity was 27% (95% CI, 21%-33%). For MSM, the positive predictive value (PPV) of cytology with a cutoff of any SIL was 36% (95% CI, 23%-50%) and the negative predictive value (NPV) was 87% (95% CI, 78%-93%), whereas cytology with a cutoff of HSIL had a PPV of 62% (95% CI, 50%-73%) and an NPV of 78% (95% CI, 65%-87%). The PPV of HR-HPV DNA detection was 37% (95% CI, 20%-57%) and the NPV was 87% (95% CI, 79%-93%). Conclusions:Given its sensitivity, cytology with a cutoff of any SIL could be considered as a triaging method, whereas cytology with a cutoff of HSIL had better specificity and could be used for quality assurance. HR-HPV DNA detection had poor specificity and PPV, making it unsuitable for triage.

SUBMITTER: Dias Goncalves Lima F

PROVIDER: S-EPMC6524827 | biostudies-other | 2019 May

REPOSITORIES: biostudies-other

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Project description:BACKGROUND:The aim of the present study was to evaluate patient factors that affect the progression of anal dysplasia in human immunodeficiency virus (HIV)-positive individuals. METHODS:A retrospective cohort study of HIV-positive adults with human papilloma virus related anal lesions was performed from 2012 to 2017. All patients underwent surgical excision or biopsy and fulguration of lesions in the operating room without using high resolution anoscopy. Patients with initial presentation of squamous cell carcinoma were excluded. The study was designed to investigate progression between the first available histology and either the follow up histology or a negative examination. Patient files were reviewed and data was collected. A bivariate analysis of continuous and categorical variables was performed. RESULTS:One hundred and sixty-one patients met the inclusion criteria. Ninety-seven percent were male. Mean age was 41 years. Thirty-five percent were African American and 47% were Caucasian. After a median follow-up interval of 331 days (IQR 120-615 days) 14 (9%) of patients had progression of disease. Visible lesions on initial presentation, as opposed to lesions found in patients undergoing examination under anesthesia because of HSIL on anal pap smear, was associated with progression (p = 0.0.2). A lower initial CD4 count (p?=?0.01) and initial surgical pathology of anal condylomata (p?=?0.01) were also associated with progression. High-risk serotype was associated with no change or regression (p?=?0.01). CONCLUSIONS:In our large cohort of HIV-positive patients treated without high resolution anoscopy the rate of progression was low. Most notably, visible lesions at initial presentation and CD4 count when lower were associated with progression. Initial surgical pathology of anal condylomata was associated with progression, while high-risk serotypes correlated with regression or stability. Identification of risk factors has important implications concerning postoperative surveillance and counseling of HIV-positive patients with anal condylomata/ anal dysplasia.

Project description: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, but current histopathological assessment is unable to distinguish between HGAIN likely to regress and HGAIN likely to persist or progress to cancer. We aim to assess if host cell DNA methylation markers can predict regression of HGAIN, thus determining the need for immediate treatment or active surveillance. This could reduce overtreatment and the associated anal and psycho-sexual morbidity.Methods and analysisThis is an active surveillance cohort study in three centres located in Amsterdam, the Netherlands, in 200 HIV+ MSM diagnosed with HGAIN. Participants will not be treated, but closely monitored during 24 months of follow-up with 6 monthly visits including cytology, and high-resolution anoscopy with biopsies. The primary study endpoint is histopathological regression of each baseline HGAIN lesion at the end of the study. Regression is defined as ≤low grade anal intraepithelial neoplasia in the exit biopsy at 24 months. Regression proportions in lesions with low versus high methylation levels (ASCL1, ZNF582), other biomarkers (HPV genotype, HPV-E4, p16INK4A, Ki-67) and immunological markers at baseline will be compared. Main secondary endpoints are the histological and clinical outcome (ie, the number of octants affected by HGAIN) of each baseline HGAIN lesion and overall HGAIN disease (i.e., all lesions combined) after each visit. The health-related quality of life of the study group will be compared with that of a control group of 50 HIV+ MSM receiving regular HGAIN treatment.Ethics and disseminationEthics approval was obtained from the Institutional Review Board of the Academic Medical Center (Amsterdam, The Netherlands; reference no. 2021_099). Participants are required to provide written informed consent. Findings will be disseminated through publication in peer-reviewed scientific journals and presentations at international scientific conferences; dissemination to policy makers and the target patient group will be achieved through our (inter-)national network, professional associations and collaboration with a patient representative organisation.Trial registration numberNL9664.

Project description:BackgroundThe incidence of anal cancer is substantially higher among persons living with the human immunodeficiency virus (HIV) than in the general population. Similar to cervical cancer, anal cancer is preceded by high-grade squamous intraepithelial lesions (HSILs). Treatment for cervical HSIL reduces progression to cervical cancer; however, data from prospective studies of treatment for anal HSIL to prevent anal cancer are lacking.MethodsWe conducted a phase 3 trial at 25 U.S. sites. Persons living with HIV who were 35 years of age or older and who had biopsy-proven anal HSIL were randomly assigned, in a 1:1 ratio, to receive either HSIL treatment or active monitoring without treatment. Treatment included office-based ablative procedures, ablation or excision under anesthesia, or the administration of topical fluorouracil or imiquimod. The primary outcome was progression to anal cancer in a time-to-event analysis. Participants in the treatment group were treated until HSIL was completely resolved. All the participants underwent high-resolution anoscopy at least every 6 months; biopsy was also performed for suspected ongoing HSIL in the treatment group, annually in the active-monitoring group, or any time there was concern for cancer.ResultsOf 4459 participants who underwent randomization, 4446 (99.7%) were included in the analysis of the time to progression to cancer. With a median follow-up of 25.8 months, 9 cases were diagnosed in the treatment group (173 per 100,000 person-years; 95% confidence interval [CI], 90 to 332) and 21 cases in the active-monitoring group (402 per 100,000 person-years; 95% CI, 262 to 616). The rate of progression to anal cancer was lower in the treatment group than in the active-monitoring group by 57% (95% CI, 6 to 80; P = 0.03 by log-rank test).ConclusionsAmong participants with biopsy-proven anal HSIL, the risk of anal cancer was significantly lower with treatment for anal HSIL than with active monitoring. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02135419.).

Project description:BackgroundVulval intraepithelial neoplasia (VIN) is a pre-malignant condition of the vulval skin; its incidence is increasing in women under 50 years. VIN is graded histologically as low grade or high grade. High grade VIN is associated with infection with human papilloma virus (HPV) infection and may progress to invasive disease. There is no consensus on the optimal management of high grade VIN. The high morbidity and high relapse rate associated with surgical interventions call for a formal appraisal of the evidence available for less invasive but effective interventions for high grade VIN.ObjectivesTo evaluate the effectiveness and safety of medical interventions for high grade VIN.Search strategyWe searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE (up to September 2010). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field.Selection criteriaRandomised controlled trials (RCTs) that assessed medical interventions, in adult women diagnosed with high grade VIN.Data collection and analysisTwo review authors independently abstracted data and assessed risk of bias. Where possible the data were synthesised in a meta-analysis.Main resultsFour trials met our inclusion criteria: three assessed the effectiveness of topical imiquimod versus placebo in women with high grade VIN; one examined low versus high dose indole-3-carbinol in similar women. Meta-analysis of three trials found that the proportion of women who responded to treatment at 5 to 6 months was much higher in the group who received topical imiquimod than in the group who received placebo (relative risk (RR) = 11.95, 95% confidence interval (CI) 3.21 to 44.51). A single trial showed similar results at 12 months in (RR = 9.10, 95% CI 2.38 to 34.77). Only one trial reported adverse events, which were more common in the imiquimod group. One trial found no significant differences in quality of life (QoL) or body image between the imiquimod and placebo groups.Authors' conclusionsImiquimod appears to be effective, but its safety needs further examination. Its use is associated with side effects which are tolerable, but more extensive data on adverse effects are required. Long term follow-up should be mandatory in view of the known progression of high grade VIN to invasive disease. Alternative medical interventions, such as cidofovir, should be explored.

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The Accuracy of Anal Swab-Based Tests to Detect High-Grade Anal Intraepithelial Neoplasia in HIV-Infected Patients: A Systematic Review and Meta-analysis.

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