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

Abstract

BackgroundEpstein 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.Methods131 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).ResultsBaseline 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).ConclusionsSeminal 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.

Prevalence and anatomical sites of human papillomavirus, Epstein-Barr virus and herpes simplex virus infections in men who have sex with men, Khon Kaen, Thailand

“…HPV was also the most common virus found in anal swabs (44%), followed by semen (7.1%) and pharyngeal swabs (3.8%) in American MSM [ 35 ], consistent with our finding that HPV infection was more frequent in the anorectum than in the urethra and oropharynx.…”

“…In the urethral site, EBV was found in 30.7% of asymptomatic American MSM; notably, EBV prevalence (72.7%) was significantly associated with HIV shedding in semen [ 34 ], corresponding to our finding as shown in Table 2 . EBV infection of the urethra ranged from 28 to 30.7% among American MSM [ 34 , 35 ]. Meanwhile, EBV infection of the urethra of American and Spanish men was ranged from 0.4–45% [ 36 ].…”

“…In addition, HIV infection not only increases susceptibility to persistent HPV but also increases the risk of acquisition of new HPV infections [ 53 ]. Similarity, EBV shedding was significantly associated with persistent HPV infection among HIV-infected MSM in the USA [ 35 ]. Our finding demonstrated that the presence of HPV in the anorectum was significantly associated with HIV infection in MSM (Table 2 ).…”

“…(such as a self-report or community based). The strength of our study is that 1) we used swab sample in urethra because this can increase sensitivity of Neisseria gonorrhea detection compared with urine sample [ 24 ] whereas many previous studies performed EBV, HPV and HSV detection in MSM semen [ 35 , 36 ]; additionally the cell samples can indicate true infection at each anatomical site instead of movement of EBV infected B cells to each sites; and 2) all participants recruited in our study are collected cell samples from all anatomical sites to compare each participants that can reduce the error of data. However, there was a limitation in our study including self-reporting MSM that may provide invalid answers such as HIV status [ 54 ].…”

Genital human papillomavirus infections

“…Latent infection with Epstein-Barr Virus (EBV) can act as a carcinogenic co-factor. Presence of EBV co-infection is associated with a five-fold higher risk of integration of concurrent hr-HPV into the human genome which is an important step in the progression to invasive carcinoma (43).…”