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Published in: BMC Infectious Diseases 1/2016

Open Access 01-12-2015 | Research article

Genital Epstein Barr Virus is associated with higher prevalence and persistence of anal human papillomavirus in HIV-infected men on antiretroviral therapy

Authors: Sara Gianella, Christine C. Ginocchio, Eric S. Daar, Michael P. Dube, Sheldon R. Morris

Published in: BMC Infectious Diseases | Issue 1/2016

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Abstract

Background

Epstein Barr virus (EBV) and human papillomavirus (HPV) can co-exist in pharyngeal and cervical malignancies. However, the natural history and factors associated with persistent HPV infection among HIV-infected men who have sex with men (MSM) are unclear.

Methods

131 HIV-infected MSM were followed for 48 weeks and screened for multiple co-infections, including seminal EBV DNA and high risk (HR)-HPV messenger RNA (mRNA) at several sites (semen, anal, pharynx). Primary analysis tested if seminal EBV shedding was associated with increased prevalence of HR-HPV at baseline using univariate tests and multivariable logistic regression. In participants with detectable anal HR-HPV at baseline, we tested if presence of seminal EBV shedding at baseline was also predictive of reduced HR-HPV clearance by log-rank test (over 48 weeks of follow-up).

Results

Baseline prevalence of HR-HPV was: anal 44 % (N = 54/121); pharynx 3.8 % (N = 5/131); semen 7.1 % (N = 7/98). Seminal EBV shedding was present in 28 % of participants and was associated with more than double the prevalence of detectable anal HR-HPV mRNA (71.4 % for EBV shedders versus 33.3 % for non-shedders, p < 0.01). In participants with detectable anal HR-HPV at baseline, we found increased persistence of HR-HPV over 48 weeks of follow-up (measured as time to first negative HR-HPV test in the EBV shedding group (p < 0.01).

Conclusions

Seminal EBV shedding was associated with an increased risk of having detectable anal HR-HPV in a cohort of HIV-infected MSM on suppressive ART. Future studies should examine if co-infection with EBV and HR-HPV may act synergistically in pathogenesis of anal cancer in HIV-infected individuals.
Literature
1.
go back to reference de Pokomandy A, Rouleau D, Ghattas G, Vézina S, Coté P, Macleod J, et al. Prevalence, clearance, and incidence of anal human papillomavirus infection in HIV-infected men: the HIPVIRG cohort study. J Infect Dis. 2009;199(7):965–73.CrossRefPubMed de Pokomandy A, Rouleau D, Ghattas G, Vézina S, Coté P, Macleod J, et al. Prevalence, clearance, and incidence of anal human papillomavirus infection in HIV-infected men: the HIPVIRG cohort study. J Infect Dis. 2009;199(7):965–73.CrossRefPubMed
2.
go back to reference Nadarzynski T, Smith H, Richardson D, Jones CJ, Llewellyn CD. Human papillomavirus and vaccine-related perceptions among men who have sex with men: a systematic review. Sex Transm Infect. 2014;90(7):515–23.CrossRefPubMed Nadarzynski T, Smith H, Richardson D, Jones CJ, Llewellyn CD. Human papillomavirus and vaccine-related perceptions among men who have sex with men: a systematic review. Sex Transm Infect. 2014;90(7):515–23.CrossRefPubMed
3.
go back to reference Barroso 2nd LF, Wilkin T. Human papillomavirus vaccination in males: the state of the science. Curr Infect Dis Rep. 2011;13(2):175–81.CrossRefPubMed Barroso 2nd LF, Wilkin T. Human papillomavirus vaccination in males: the state of the science. Curr Infect Dis Rep. 2011;13(2):175–81.CrossRefPubMed
4.
go back to reference Sendagorta E, Herranz P, Guadalajara H, Bernardino JI, Viguer JM, Beato MJ, et al. Prevalence of abnormal anal cytology and high-grade squamous intraepithelial lesions among a cohort of HIV-infected men who have sex with men. Dis Colon Rectum. 2014;57(4):475–81.CrossRefPubMed Sendagorta E, Herranz P, Guadalajara H, Bernardino JI, Viguer JM, Beato MJ, et al. Prevalence of abnormal anal cytology and high-grade squamous intraepithelial lesions among a cohort of HIV-infected men who have sex with men. Dis Colon Rectum. 2014;57(4):475–81.CrossRefPubMed
5.
go back to reference Schim van der Loeff MF, Mooij SH, Richel O, de Vries HJ, Prins JM. HPV and anal cancer in HIV-infected individuals: a review. Curr HIV/AIDS Rep. 2014;11(3):250–62.CrossRefPubMed Schim van der Loeff MF, Mooij SH, Richel O, de Vries HJ, Prins JM. HPV and anal cancer in HIV-infected individuals: a review. Curr HIV/AIDS Rep. 2014;11(3):250–62.CrossRefPubMed
6.
go back to reference Palefsky JM, Holly EA, Efirdc JT, a Costa M, Jay N, Berry JM, et al. Anal intraepithelial neoplasia in the highly active antiretroviral therapy era among HIV-positive men who have sex with men. AIDS. 2005;19(13):1407–14. Palefsky JM, Holly EA, Efirdc JT, a Costa M, Jay N, Berry JM, et al. Anal intraepithelial neoplasia in the highly active antiretroviral therapy era among HIV-positive men who have sex with men. AIDS. 2005;19(13):1407–14.
7.
go back to reference Goldstone S, Palefsky JM, Giuliano AR, Moreira ED, Jr., Aranda C, Jessen H, et al. Prevalence of and risk factors for human papillomavirus (HPV) infection among HIV-seronegative men who have sex with men. J Infect Dis. 2011;203(1):66–74.PubMedCentralCrossRefPubMed Goldstone S, Palefsky JM, Giuliano AR, Moreira ED, Jr., Aranda C, Jessen H, et al. Prevalence of and risk factors for human papillomavirus (HPV) infection among HIV-seronegative men who have sex with men. J Infect Dis. 2011;203(1):66–74.PubMedCentralCrossRefPubMed
8.
go back to reference Moscicki AB. HPV-associated cancers: it’s not all about the cervix. Prev Med. 2011;53 Suppl 1:S3–4.CrossRefPubMed Moscicki AB. HPV-associated cancers: it’s not all about the cervix. Prev Med. 2011;53 Suppl 1:S3–4.CrossRefPubMed
9.
go back to reference Gianella S, Massanella M, Wertheim JO, Smith DM. The sordid affair between human herpesvirus and human immunodeficiency virus. J Infect Dis. 2015;212(6):845–52.CrossRefPubMed Gianella S, Massanella M, Wertheim JO, Smith DM. The sordid affair between human herpesvirus and human immunodeficiency virus. J Infect Dis. 2015;212(6):845–52.CrossRefPubMed
10.
go back to reference Gianella S, Morris SR, Anderson C, Spina CA, Vargas MV, Young JA, et al. Herpesviruses and HIV-1 drug resistance mutations influence the virologic and immunologic milieu of the male genital tract. AIDS. 2013;27(1):39–47.PubMedCentralCrossRefPubMed Gianella S, Morris SR, Anderson C, Spina CA, Vargas MV, Young JA, et al. Herpesviruses and HIV-1 drug resistance mutations influence the virologic and immunologic milieu of the male genital tract. AIDS. 2013;27(1):39–47.PubMedCentralCrossRefPubMed
11.
go back to reference Thompson S, Messick T, Schultz DC, Reichman M, Lieberman PM. Development of a high-throughput screen for inhibitors of Epstein-Barr virus EBNA1. J Biomol Screen. 2010;15(9):1107–15.PubMedCentralCrossRefPubMed Thompson S, Messick T, Schultz DC, Reichman M, Lieberman PM. Development of a high-throughput screen for inhibitors of Epstein-Barr virus EBNA1. J Biomol Screen. 2010;15(9):1107–15.PubMedCentralCrossRefPubMed
12.
go back to reference Khenchouche A, Sadouki N, Boudriche A, Houali K, Graba A, Ooka T, et al. Human papillomavirus and Epstein-Barr virus co-infection in cervical carcinoma in Algerian women. Virol J. 2013;10:340.PubMedCentralCrossRefPubMed Khenchouche A, Sadouki N, Boudriche A, Houali K, Graba A, Ooka T, et al. Human papillomavirus and Epstein-Barr virus co-infection in cervical carcinoma in Algerian women. Virol J. 2013;10:340.PubMedCentralCrossRefPubMed
13.
go back to reference Kahla S, Oueslati S, Achour M, Kochbati L, Chanoufi MB, Maalej M, et al. Correlation between ebv co-infection and HPV16 genome integrity in Tunisian cervical cancer patients. Braz J Microbiol. 2012;43(2):744–53.PubMedCentralCrossRefPubMed Kahla S, Oueslati S, Achour M, Kochbati L, Chanoufi MB, Maalej M, et al. Correlation between ebv co-infection and HPV16 genome integrity in Tunisian cervical cancer patients. Braz J Microbiol. 2012;43(2):744–53.PubMedCentralCrossRefPubMed
14.
go back to reference Szkaradkiewicz A, Wal M, Kuch A, Pieta P. Human papillomavirus (HPV) and Epstein-Barr virus (EBV) cervical infections in women with normal and abnormal cytology. Pol J Microbiol. 2004;53(2):95–9.PubMed Szkaradkiewicz A, Wal M, Kuch A, Pieta P. Human papillomavirus (HPV) and Epstein-Barr virus (EBV) cervical infections in women with normal and abnormal cytology. Pol J Microbiol. 2004;53(2):95–9.PubMed
15.
go back to reference Gianella S, Smith DM, Vargas MV, Little SJ, Richman DD, Daar ES, et al. Shedding of HIV and human herpesviruses in the semen of effectively treated HIV-1-infected men who have sex with men. Clin Infect Dis. 2013;57(3):441–7.PubMedCentralCrossRefPubMed Gianella S, Smith DM, Vargas MV, Little SJ, Richman DD, Daar ES, et al. Shedding of HIV and human herpesviruses in the semen of effectively treated HIV-1-infected men who have sex with men. Clin Infect Dis. 2013;57(3):441–7.PubMedCentralCrossRefPubMed
16.
go back to reference Gianella S, Smith DM, Daar E, Dube MP, Lisco A, Vanpouille C, et al. Genital Cytomegalovirus Replication predicts Syphilis Acquisition among HIV-1 infected Men who have Sex with Men. PLoS One. 2015; In Press. Gianella S, Smith DM, Daar E, Dube MP, Lisco A, Vanpouille C, et al. Genital Cytomegalovirus Replication predicts Syphilis Acquisition among HIV-1 infected Men who have Sex with Men. PLoS One. 2015; In Press.
17.
go back to reference Geskus RB, Gonzalez C, Torres M, Del Romero J, Viciana P, Masia M, et al. Incidence and clearance of anal high-risk human papillomavirus in HIV-positive MSM: estimates and risk factors. AIDS. 2015. Geskus RB, Gonzalez C, Torres M, Del Romero J, Viciana P, Masia M, et al. Incidence and clearance of anal high-risk human papillomavirus in HIV-positive MSM: estimates and risk factors. AIDS. 2015.
18.
go back to reference Phelan DF, Gange SJ, Ahdieh-Grant L, Mehta SH, Kirk GD, Shah K, et al. Determinants of newly detected human papillomavirus infection in HIV-infected and HIV-uninfected injection drug using women. Sex Transm Dis. 2009;36(3):149–56. Phelan DF, Gange SJ, Ahdieh-Grant L, Mehta SH, Kirk GD, Shah K, et al. Determinants of newly detected human papillomavirus infection in HIV-infected and HIV-uninfected injection drug using women. Sex Transm Dis. 2009;36(3):149–56.
Metadata
Title
Genital Epstein Barr Virus is associated with higher prevalence and persistence of anal human papillomavirus in HIV-infected men on antiretroviral therapy
Authors
Sara Gianella
Christine C. Ginocchio
Eric S. Daar
Michael P. Dube
Sheldon R. Morris
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2016
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-016-1356-y

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