scholarly journals Characterisation of anal intraepithelial neoplasia and anal cancer in HIV ‐positive men by immunohistochemical markers p16, Ki‐67, HPV‐E4 , and DNA methylation markers

2021 ◽  
Author(s):  
Ramon P. Zee ◽  
Chris J.L.M. Meijer ◽  
Tamzin Cuming ◽  
Alexander Kreuter ◽  
Miekel M. Sandt ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Anal Cancer ◽  
Intraepithelial Neoplasia ◽  
Anal Intraepithelial Neoplasia ◽  
Hiv Positive ◽  
Ki 67 ◽  
Immunohistochemical Markers ◽  
Hiv Positive Men

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

2019 ◽  
Vol 6 (5) ◽  
Author(s):  
Fernando Dias Gonçalves Lima ◽  
Janine D Viset ◽  
Mariska M G Leeflang ◽  
Jacqueline Limpens ◽  
Jan M Prins ◽  
...  
Keyword(s):  
Anal Cancer ◽  
Predictive Value ◽  
Dna Detection ◽  
Intraepithelial Neoplasia ◽  
Anal Intraepithelial Neoplasia ◽  
Hiv Positive ◽  
High Grade ◽  
Ki 67 ◽  
Hpv Dna ◽  
Anal Swab

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.

Progression From Perianal High-Grade Anal Intraepithelial Neoplasia to Anal Cancer in HIV-Positive Men Who Have Sex With Men

2016 ◽  
Vol 59 (9) ◽  
pp. 836-842 ◽  
Author(s):  
Jill Tinmouth ◽  
Valentina Peeva ◽  
Henok Amare ◽  
Sandra Blitz ◽  
Janet Raboud ◽  
...  
Keyword(s):  
Anal Cancer ◽  
Intraepithelial Neoplasia ◽  
Anal Intraepithelial Neoplasia ◽  
Hiv Positive ◽  
High Grade ◽  
Sex With Men ◽  
Hiv Positive Men

Prevalence and predictors of high-grade anal intraepithelial neoplasia in a community-based sample of homosexual men

Sexual Health ◽  
2012 ◽  
Vol 9 (6) ◽  
pp. 574 ◽  
Author(s):  
Richard J. Hillman ◽  
Marina T. van Leeuwen ◽  
Claire M. Vajdic ◽  
Leo McHugh ◽  
Garrett P. Prestage ◽  
...  
Keyword(s):  
High Risk ◽  
Intraepithelial Neoplasia ◽  
Anal Intraepithelial Neoplasia ◽  
Hiv Positive ◽  
Homosexual Men ◽  
High Grade ◽  
Community Based ◽  
Cytological Abnormalities ◽  
Hiv Negative ◽  
Hiv Positive Men

Background We report the prevalence and predictors for high-grade anal intraepithelial neoplasia (HGAIN) in community-based cohorts of HIV-negative and HIV-positive homosexual men in Sydney, Australia. Methods: A cross-sectional study of consecutive participants in both cohorts was performed in 2005 (204 HIV-negative and 128 HIV-positive men). Anal swabs collected by a research nurse underwent cytological analysis, using the ThinPrep procedure, and human papillomavirus (HPV) testing. Participants who had cytological abnormalities other than low-grade squamous epithelial lesions (SIL) were referred for high resolution anoscopy (HRA). Results: A total of 114 men had cytological abnormalities (24.3% of HIV-negative and 57.5% of HIV-positive men, odds ratio (OR) = 4.21, 95% confidence interval (CI) 2.57–6.90). However, only three (2.3%) HIV-positive men and no HIV-negative men had high-grade SIL on anal cytology. Seventy-seven men were referred for HRA, of whom 63 (81.8%) attended. Histologically confirmed HGAIN was detected in 21 (33.3%). The prevalence of HGAIN was higher in HIV-positive men (10.8%) than in HIV-negative men (5.0%, OR = 2.29, 95% CI 0.93–5.63, P = 0.071). HGAIN was not related to age but was strongly associated with the detection of high-risk types of anal HPV (OR = 10.1, 95% CI 1.33–76.2) rather than low-risk types (OR = 1.97, 95% CI 0.74–5.25). Conclusion: HGAIN was prevalent in homosexual men across all age groups and was more than twice as common in HIV-positive men compared with HIV-negative men. The presence of high-risk anal HPV was highly predictive of HGAIN.

scholarly journals Cancer Risk Stratification of Anal Intraepithelial Neoplasia in Human Immunodeficiency Virus–Positive Men by Validated Methylation Markers Associated With Progression to Cancer

2020 ◽  
Author(s):  
Ramon P van der Zee ◽  
Olivier Richel ◽  
Carel J M van Noesel ◽  
Iuliana Ciocănea-Teodorescu ◽  
Annina P van Splunter ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cancer Risk ◽  
Risk Stratification ◽  
Cancer Progression ◽  
Anal Cancer ◽  
Intraepithelial Neoplasia ◽  
Anal Intraepithelial Neoplasia ◽  
Multivariable Logistic Regression Analysis ◽  
Cross Sectional ◽  
Progression Risk

Abstract Background High-grade anal intraepithelial neoplasia (HGAIN; AIN2–3) is highly prevalent in HIV+ men, but only a minority of these lesions progress towards cancer. Currently, cancer progression risk cannot be established; therefore, no consensus exists on whether HGAIN should be treated. This study aimed to validate previously identified host cell DNA methylation markers for detection and cancer risk stratification of HGAIN. Methods A large independent cross-sectional series of 345 anal cancer, AIN3, AIN2, AIN1, and normal control biopsies of HIV+ men was tested for DNA methylation of 6 genes using quantitative methylation-specific PCR. We determined accuracy for detection of AIN3 and cancer (AIN3+) by univariable and multivariable logistic regression analysis, followed by leave-one-out cross-validation. Methylation levels were assessed in a series of 10 anal cancer cases with preceding HGAIN at similar anatomic locations, and compared with the cross-sectional series. Results Methylation levels of all genes increased with increasing severity of disease (P < .05). HGAIN revealed a heterogeneous methylation pattern, with a subset resembling cancer. ZNF582 showed highest accuracy (AUC = 0.88) for AIN3+ detection, slightly improved by addition of ASCL1 and SST (AUC = 0.89), forming a marker panel. In the longitudinal series, HGAIN preceding cancer displayed high methylation levels similar to cancers. Conclusions We validated the accuracy of 5 methylation markers for the detection of anal (pre-) cancer. High methylation levels in HGAIN were associated with progression to cancer. These markers provide a promising tool to identify HGAIN in need of treatment, preventing overtreatment of HGAIN with a low cancer progression risk.

Sign in / Sign up

Export Citation Format

Share Document