{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T11:14:38Z","timestamp":1781090078731,"version":"3.54.1"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"4","funder":[{"name":"Intramural Research Program of the National Institutes of Health"},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["#Z01 CP010124-21"],"award-info":[{"award-number":["#Z01 CP010124-21"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Human papillomavirus (HPV)-related biomarkers have shown good cross-sectional performance for anal precancer detection in human immunodeficiency virus\u2013positive (HIV+) men who have sex with men (MSM). However, the long-term performance and risk stratification of these biomarkers are unknown. Here, we prospectively evaluated high-risk (HR) HPV DNA, HPV16\/18 genotyping, HPV E6\/E7 messenger RNA (mRNA), and p16\/Ki-67 dual stain in a population of HIV+ MSM.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We enrolled 363 HIV+ MSM between 2009\u20132010, with passive follow-up through 2015. All had anal cytology and a high-resolution anoscopy at baseline. For each biomarker, we calculated the baseline sensitivity and specificity for a combined endpoint of high-grade squamous intraepithelial lesion (HSIL) and anal intraepithelial neoplasia grade 2 or more severe diagnoses (HSIL\/AIN2+), and we estimated the 2- and 5-year cumulative risks of HSIL\/AIN2+ using logistic and Cox regression models.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>There were 129 men diagnosed with HSIL\/AIN2+ during the study. HR-HPV testing had the highest positivity and sensitivity of all assays, but the lowest specificity. HPV16\/18 and HPV E6\/E7 mRNA had high specificity, but lower sensitivity. The 2- and 5-year risks of HSIL\/AIN2+ were highest for those testing HPV16\/18- or HPV E6\/E7 mRNA\u2013positive, followed by those testing dual stain\u2013positive. Those testing HR-HPV\u2013 or dual stain\u2013negative had the lowest 2- and 5-year risks of HSIL\/AIN2+.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>HPV-related biomarkers provide long-term risk stratification for anal precancers. HR-HPV\u2013 and dual stain\u2013negativity indicate a low risk of HSIL\/AIN2+ for at least 2 years, compared with negative anal cytology; however, the high positivity of HR-HPV in HIV+ MSM may limit its utility for surveillance and management in this population.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciy970","type":"journal-article","created":{"date-parts":[[2018,11,8]],"date-time":"2018-11-08T23:13:32Z","timestamp":1541718812000},"page":"631-638","source":"Crossref","is-referenced-by-count":33,"title":["5-Year Prospective Evaluation of Cytology, Human Papillomavirus Testing, and Biomarkers for Detection of Anal Precancer in Human Immunodeficiency Virus\u2013Positive Men Who Have Sex With Men"],"prefix":"10.1093","volume":"69","author":[{"given":"Megan A","family":"Clarke","sequence":"first","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li C","family":"Cheung","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Lorey","sequence":"additional","affiliation":[{"name":"Kaiser Permanente The Permanente Medical Group Regional Laboratory, Berkeley"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brad","family":"Hare","sequence":"additional","affiliation":[{"name":"The Permanente Medical Group, San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Landy","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Tokugawa","sequence":"additional","affiliation":[{"name":"Kaiser Permanente The Permanente Medical Group Regional Laboratory, Berkeley"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia C","family":"Gage","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa M","family":"Darragh","sequence":"additional","affiliation":[{"name":"University of California, San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip E","family":"Castle","sequence":"additional","affiliation":[{"name":"Albert Einstein College of Medicine, Bronx, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Wentzensen","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,11,12]]},"reference":[{"key":"2019080101004170500_CIT0001","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21442","article-title":"Cancer statistics, 2018","volume":"68","author":"Siegel","year":"2018","journal-title":"CA Cancer J Clin"},{"key":"2019080101004170500_CIT0002","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1097\/QAI.0b013e31817aebfe","article-title":"Incidence and epidemiology of anal cancer in the multicenter AIDS cohort study","volume":"48","author":"D\u2019Souza","year":"2008","journal-title":"J Acquir Immune Defic Syndr"},{"key":"2019080101004170500_CIT0003","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1093\/cid\/cir1012","article-title":"Risk of anal cancer in HIV-infected and HIV-uninfected individuals in North America","volume":"54","author":"Silverberg","year":"2012","journal-title":"Clin Infect Dis"},{"key":"2019080101004170500_CIT0004","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/S1473-3099(17)30653-9","article-title":"Human papillomavirus types from infection to cancer in the anus, according to sex and HIV status: a systematic review and meta-analysis","volume":"18","author":"Lin","year":"2018","journal-title":"Lancet Infect Dis"},{"key":"2019080101004170500_CIT0005","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1086\/344057","article-title":"Natural history and clinical management of anal human papillomavirus disease in men and women infected with human immunodeficiency 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