BACKGROUND: Human papillomavirus (HPV)-related biomarkers have shown good cross-sectional performance for anal precancer detection in human immunodeficiency virus-positive (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. METHODS: We enrolled 363 HIV+ MSM between 2009-2010, 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. RESULTS: 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-positive, followed by those testing dual stain-positive. Those testing HR-HPV- or dual stain-negative had the lowest 2- and 5-year risks of HSIL/AIN2+. CONCLUSIONS: HPV-related biomarkers provide long-term risk stratification for anal precancers. HR-HPV- and dual stain-negativity 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. Published by Oxford University Press for the Infectious Diseases Society of America 2018.
BACKGROUND:Human papillomavirus (HPV)-related biomarkers have shown good cross-sectional performance for anal precancer detection in human immunodeficiency virus-positive (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. METHODS: We enrolled 363 HIV+ MSM between 2009-2010, 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. RESULTS: 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-positive, followed by those testing dual stain-positive. Those testing HR-HPV- or dual stain-negative had the lowest 2- and 5-year risks of HSIL/AIN2+. CONCLUSIONS:HPV-related biomarkers provide long-term risk stratification for anal precancers. HR-HPV- and dual stain-negativity 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. Published by Oxford University Press for the Infectious Diseases Society of America 2018.
Authors: Warner K Huh; Kevin A Ault; David Chelmow; Diane D Davey; Robert A Goulart; Francisco A Garcia; Walter K Kinney; L Stewart Massad; Edward J Mayeaux; Debbie Saslow; Mark Schiffman; Nicolas Wentzensen; Herschel W Lawson; Mark H Einstein Journal: J Low Genit Tract Dis Date: 2015-04 Impact factor: 1.925
Authors: Teresa M Darragh; Diane Tokugawa; Philip E Castle; Stephen Follansbee; Sylvia Borgonovo; Brandon J LaMere; Lauren Schwartz; Julia C Gage; Barbara Fetterman; Thomas Lorey; Nicolas Wentzensen Journal: Cancer Cytopathol Date: 2012-07-18 Impact factor: 5.284
Authors: Nicolas Wentzensen; L Stewart Massad; Edward J Mayeaux; Michelle J Khan; Alan G Waxman; Mark H Einstein; Christine Conageski; Mark H Schiffman; Michael A Gold; Barbara S Apgar; David Chelmow; Kim K Choma; Teresa M Darragh; Julia C Gage; Francisco A R Garcia; Richard S Guido; Jose A Jeronimo; Angela Liu; Cara A Mathews; Martha M Mitchell; Anna-Barbara Moscicki; Akiva P Novetsky; Theognosia Papasozomenos; Rebecca B Perkins; Michelle I Silver; Katie M Smith; Elizabeth A Stier; Candice A Tedeschi; Claudia L Werner; Warner K Huh Journal: J Low Genit Tract Dis Date: 2017-10 Impact factor: 1.925
Authors: Michael J Silverberg; Bryan Lau; Amy C Justice; Eric Engels; M John Gill; James J Goedert; Gregory D Kirk; Gypsyamber D'Souza; Ronald J Bosch; John T Brooks; Sonia Napravnik; Nancy A Hessol; Lisa P Jacobson; Mari M Kitahata; Marina B Klein; Richard D Moore; Benigno Rodriguez; Sean B Rourke; Michael S Saag; Timothy R Sterling; Kelly A Gebo; Natasha Press; Jeffrey N Martin; Robert Dubrow Journal: Clin Infect Dis Date: 2012-01-30 Impact factor: 9.079
Authors: Diane Solomon; Diane Davey; Robert Kurman; Ann Moriarty; Dennis O'Connor; Marianne Prey; Stephen Raab; Mark Sherman; David Wilbur; Thomas Wright; Nancy Young Journal: JAMA Date: 2002-04-24 Impact factor: 56.272
Authors: Philip E Castle; Stephen Follansbee; Sylvia Borgonovo; Diane Tokugawa; Lauren M Schwartz; Thomas S Lorey; Brandon LaMere; Julia C Gage; Barbara Fetterman; Teresa M Darragh; Ana Cecilia Rodriguez; Nicolas Wentzensen Journal: Cancer Epidemiol Biomarkers Prev Date: 2012-11-15 Impact factor: 4.254
Authors: Julia C Gage; Mark Schiffman; Hormuzd A Katki; Philip E Castle; Barbara Fetterman; Nicolas Wentzensen; Nancy E Poitras; Thomas Lorey; Li C Cheung; Walter K Kinney Journal: J Natl Cancer Inst Date: 2014-07-18 Impact factor: 13.506
Authors: Nicolas Wentzensen; Stephen Follansbee; Sylvia Borgonovo; Diane Tokugawa; Vikrant V Sahasrabuddhe; Jie Chen; Thomas S Lorey; Julia C Gage; Barbara Fetterman; Sean Boyle; Mark Sadorra; Scott Dahai Tang; Teresa M Darragh; Philip E Castle Journal: J Clin Microbiol Date: 2014-06-04 Impact factor: 5.948
Authors: Kalyani Sonawane; Yueh-Yun Lin; Haluk Damgacioglu; Yenan Zhu; Maria E Fernandez; Jane R Montealegre; Cecilia Ganduglia Cazaban; Ruosha Li; David R Lairson; Ying Lin; Anna R Giuliano; Ashish A Deshmukh Journal: JAMA Netw Open Date: 2021-09-01
Authors: Alan G Nyitray; Vanessa Schick; Michael D Swartz; Anna R Giuliano; Maria E Fernandez; Ashish A Deshmukh; Timothy J Ridolfi; Christopher Ajala; Bridgett Brzezinski; Micaela Sandoval; Belinda Nedjai; Jennifer S Smith; Elizabeth Y Chiao Journal: BMJ Open Date: 2021-06-29 Impact factor: 2.692