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Use of Human Papillomavirus DNA, E6/E7 mRNA, and p16 Immunocytochemistry to Detect and Predict anal High-Grade Squamous Intraepithelial Lesions in HIV-Positive and HIV-Negative Men Who Have Sex with Men

BACKGROUND: Men who have sex with men (MSM) are at high risk of having anal cancer. Anal high-grade squamous intraepithelial lesion (HSIL) is the precursor of anal cancer. We explored the use of different biomarkers associated with human papillomavirus (HPV) infection and HPV-mediated cell transform...

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Autores principales: Phanuphak, Nittaya, Teeratakulpisarn, Nipat, Keelawat, Somboon, Pankam, Tippawan, Barisri, Jiranuwat, Triratanachat, Surang, Deesua, Amornrat, Rodbamrung, Piyanee, Wongsabut, Jiratchaya, Tantbirojn, Patou, Numto, Saranya, Ruangvejvorachai, Preecha, Phanuphak, Praphan, Palefsky, Joel M., Ananworanich, Jintanat, Kerr, Stephen J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3827039/
https://www.ncbi.nlm.nih.gov/pubmed/24265682
http://dx.doi.org/10.1371/journal.pone.0078291
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author Phanuphak, Nittaya
Teeratakulpisarn, Nipat
Keelawat, Somboon
Pankam, Tippawan
Barisri, Jiranuwat
Triratanachat, Surang
Deesua, Amornrat
Rodbamrung, Piyanee
Wongsabut, Jiratchaya
Tantbirojn, Patou
Numto, Saranya
Ruangvejvorachai, Preecha
Phanuphak, Praphan
Palefsky, Joel M.
Ananworanich, Jintanat
Kerr, Stephen J.
author_facet Phanuphak, Nittaya
Teeratakulpisarn, Nipat
Keelawat, Somboon
Pankam, Tippawan
Barisri, Jiranuwat
Triratanachat, Surang
Deesua, Amornrat
Rodbamrung, Piyanee
Wongsabut, Jiratchaya
Tantbirojn, Patou
Numto, Saranya
Ruangvejvorachai, Preecha
Phanuphak, Praphan
Palefsky, Joel M.
Ananworanich, Jintanat
Kerr, Stephen J.
author_sort Phanuphak, Nittaya
collection PubMed
description BACKGROUND: Men who have sex with men (MSM) are at high risk of having anal cancer. Anal high-grade squamous intraepithelial lesion (HSIL) is the precursor of anal cancer. We explored the use of different biomarkers associated with human papillomavirus (HPV) infection and HPV-mediated cell transformation to detect and predict HSIL among HIV-positive and HIV-negative MSM. METHODOLOGY/PRINCIPAL FINDINGS: A total of 123 HIV-positive and 123 HIV-negative MSM were enrolled and followed for 12 months. High-resolution anoscopy (HRA) with biopsies were performed at every visit along with anal sample collection for cytology, high-risk HPV DNA genotyping, HPV E6/E7 mRNA, and p16 immunocytochemistry. Performance characteristics and area under the receiver operator characteristics curve were calculated for these biomarkers at baseline, and Cox regression compared the usefulness of these biomarkers in predicting incident HSIL. High-risk HPV DNA, E6/E7 mRNA, and p16 immunocytochemistry each identified 43–46% of MSM whose baseline test positivity would trigger HRA referral. E6/E7 mRNA had the highest sensitivity (64.7%) and correctly classified the highest number of prevalent HSIL cases. With the exception of p16 immunochemistry, most tests showed significant increases in sensitivity but decreases specificity versus anal cytology, while the overall number of correctly classified cases was not significantly different. Baseline or persistent type 16 and/or 18 HPV DNA was the only test significantly predicting incident histologic HSIL within 12 months in models adjusted for HIV status and low-grade squamous intraepithelial lesions at baseline. CONCLUSIONS/SIGNIFICANCE: Countries with a high HIV prevalence among MSM and limited HRA resources may consider using biomarkers to identify individuals at high risk of HSIL. E6/E7 mRNA had the highest sensitivity for prevalent HSIL detection regardless of HIV status, whereas type 16 and/or 18 HPV DNA performed best in predicting development of incident HSIL within 12 months.
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spelling pubmed-38270392013-11-21 Use of Human Papillomavirus DNA, E6/E7 mRNA, and p16 Immunocytochemistry to Detect and Predict anal High-Grade Squamous Intraepithelial Lesions in HIV-Positive and HIV-Negative Men Who Have Sex with Men Phanuphak, Nittaya Teeratakulpisarn, Nipat Keelawat, Somboon Pankam, Tippawan Barisri, Jiranuwat Triratanachat, Surang Deesua, Amornrat Rodbamrung, Piyanee Wongsabut, Jiratchaya Tantbirojn, Patou Numto, Saranya Ruangvejvorachai, Preecha Phanuphak, Praphan Palefsky, Joel M. Ananworanich, Jintanat Kerr, Stephen J. PLoS One Research Article BACKGROUND: Men who have sex with men (MSM) are at high risk of having anal cancer. Anal high-grade squamous intraepithelial lesion (HSIL) is the precursor of anal cancer. We explored the use of different biomarkers associated with human papillomavirus (HPV) infection and HPV-mediated cell transformation to detect and predict HSIL among HIV-positive and HIV-negative MSM. METHODOLOGY/PRINCIPAL FINDINGS: A total of 123 HIV-positive and 123 HIV-negative MSM were enrolled and followed for 12 months. High-resolution anoscopy (HRA) with biopsies were performed at every visit along with anal sample collection for cytology, high-risk HPV DNA genotyping, HPV E6/E7 mRNA, and p16 immunocytochemistry. Performance characteristics and area under the receiver operator characteristics curve were calculated for these biomarkers at baseline, and Cox regression compared the usefulness of these biomarkers in predicting incident HSIL. High-risk HPV DNA, E6/E7 mRNA, and p16 immunocytochemistry each identified 43–46% of MSM whose baseline test positivity would trigger HRA referral. E6/E7 mRNA had the highest sensitivity (64.7%) and correctly classified the highest number of prevalent HSIL cases. With the exception of p16 immunochemistry, most tests showed significant increases in sensitivity but decreases specificity versus anal cytology, while the overall number of correctly classified cases was not significantly different. Baseline or persistent type 16 and/or 18 HPV DNA was the only test significantly predicting incident histologic HSIL within 12 months in models adjusted for HIV status and low-grade squamous intraepithelial lesions at baseline. CONCLUSIONS/SIGNIFICANCE: Countries with a high HIV prevalence among MSM and limited HRA resources may consider using biomarkers to identify individuals at high risk of HSIL. E6/E7 mRNA had the highest sensitivity for prevalent HSIL detection regardless of HIV status, whereas type 16 and/or 18 HPV DNA performed best in predicting development of incident HSIL within 12 months. Public Library of Science 2013-11-12 /pmc/articles/PMC3827039/ /pubmed/24265682 http://dx.doi.org/10.1371/journal.pone.0078291 Text en © 2013 Phanuphak et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Phanuphak, Nittaya
Teeratakulpisarn, Nipat
Keelawat, Somboon
Pankam, Tippawan
Barisri, Jiranuwat
Triratanachat, Surang
Deesua, Amornrat
Rodbamrung, Piyanee
Wongsabut, Jiratchaya
Tantbirojn, Patou
Numto, Saranya
Ruangvejvorachai, Preecha
Phanuphak, Praphan
Palefsky, Joel M.
Ananworanich, Jintanat
Kerr, Stephen J.
Use of Human Papillomavirus DNA, E6/E7 mRNA, and p16 Immunocytochemistry to Detect and Predict anal High-Grade Squamous Intraepithelial Lesions in HIV-Positive and HIV-Negative Men Who Have Sex with Men
title Use of Human Papillomavirus DNA, E6/E7 mRNA, and p16 Immunocytochemistry to Detect and Predict anal High-Grade Squamous Intraepithelial Lesions in HIV-Positive and HIV-Negative Men Who Have Sex with Men
title_full Use of Human Papillomavirus DNA, E6/E7 mRNA, and p16 Immunocytochemistry to Detect and Predict anal High-Grade Squamous Intraepithelial Lesions in HIV-Positive and HIV-Negative Men Who Have Sex with Men
title_fullStr Use of Human Papillomavirus DNA, E6/E7 mRNA, and p16 Immunocytochemistry to Detect and Predict anal High-Grade Squamous Intraepithelial Lesions in HIV-Positive and HIV-Negative Men Who Have Sex with Men
title_full_unstemmed Use of Human Papillomavirus DNA, E6/E7 mRNA, and p16 Immunocytochemistry to Detect and Predict anal High-Grade Squamous Intraepithelial Lesions in HIV-Positive and HIV-Negative Men Who Have Sex with Men
title_short Use of Human Papillomavirus DNA, E6/E7 mRNA, and p16 Immunocytochemistry to Detect and Predict anal High-Grade Squamous Intraepithelial Lesions in HIV-Positive and HIV-Negative Men Who Have Sex with Men
title_sort use of human papillomavirus dna, e6/e7 mrna, and p16 immunocytochemistry to detect and predict anal high-grade squamous intraepithelial lesions in hiv-positive and hiv-negative men who have sex with men
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3827039/
https://www.ncbi.nlm.nih.gov/pubmed/24265682
http://dx.doi.org/10.1371/journal.pone.0078291
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