Genital Epstein Barr Virus is associated with higher prevalence and persistence of anal human papillomavirus in HIV-infected men on antiretroviral therapy.
ABSTRACT: 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.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).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).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.
Project description:<h4>Background</h4>Few studies focused on longitudinal modifications over time of high-risk HPV (HR-HPV) at anal and oral sites in HIV+ men who have sex with men (MSM).<h4>Methods</h4>We described patterns and longitudinal changes of HR-HPV detection and the prevalence of HR-HPV covered by the nonavalent HPV vaccine (vax-HPV) at oral and anal sites in 165 HIV+ MSM followed in an Italian hospital. The samples were collected at baseline and after 24?months (follow-up). The presence of HPV was investigated with Inno-LiPA HPV Genotyping Extra II.<h4>Results</h4>Median age was 44?years (IQR 36-53), median CD4+ cell count at nadir was 312 cells/mm<sup>3</sup> (IQR 187-450). A total of 120 subjects (72.7%) were receiving successful antiretroviral therapy (ART). At baseline and follow-up, the frequency of HR-HPV was significantly higher in the anal site (65.4% vs 9.4 and 62.4% vs 6.8%, respectively). Only 2.9% of subjects were persistently HR-HPV negative at both sites. All oral HR-HPV were single at baseline vs 54.6% at baseline at the anal site (p?=?0.005), and all oral HR-HPV were single at follow-up vs 54.4% at anal site at follow-up (p?=?0.002). The lowest rate of concordance between the oral and anal results was found for HR-HPV detection; almost all HR-HPV positive results at both anal and oral sites had different HR-HPV.The most frequent HR-HPV in anal swabs at baseline and follow-up were HPV-16 and HPV-52.At follow-up at anal site, 37.5% of patients had different HR-HPV genotypes respect to baseline, 28.8% of subjects with 1 HR-HPV at baseline had an increased number of HR-HPV, and patients on ART showed a lower frequency of confirmed anal HR-HPV detection than untreated patients (p?=?0.03) over time. Additionally,54.6 and 50.5% of patients had only HR-vax-HPV at anal site at baseline and follow-up, respectively; 15.2% had only HR-vax-HPV at baseline and follow-up.<h4>Conclusions</h4>We believe that it is important testing multiple sites over time in HIV-positive MSM. ART seems to protect men from anal HR-HPV confirmed detection. Vaccination programmes could reduce the number of HR-HPV genotypes at anal site and the risk of the first HR-HPV acquisition at the oral site.
Project description:BACKGROUND:High-risk (HR) human papillomavirus (HPV) infection remains a great concern in relation to African men who have sex with men (MSM), especially those infected with HIV. The prevalence of HR-HPV and associated risk factors was estimated in a cross-sectional observational study covering MSM living in Bangui, Central African Republic. METHODS:MSM receiving care at the Centre National de Référence des Infections Sexuellement Transmissibles et de la Thérapie Antirétrovirale, Bangui, were included. HIV serostatus and socio-demographic and behavioral characteristics were collected. HPV DNA was detected and genotyped on anal swabs using Anyplex™ II HPV28 test (Seegene, South Korea), and HSV DNA by in-house real-time PCR. Logistic regression analyses were used to determine risk factors associated with HPV outcomes. RESULTS:42 MSM (mean age, 23.2 years; range, 14-39) including 69.1% HIV-1-positive and 30.9% HIV-negative were prospectively enrolled. The prevalence of anal HPV was 69.1%, including 82.7% of HR-HPV which were multiple in 52.0%. The most prevalent genotypes were HPV-35, HPV-58, HPV-59 and HPV-31. While, HPV-16 and HPV-18 were present in a minority of samples. Multiple HR-HPV infection was more frequent in HIV-positive MSM (41.4%) with 2.7 genotypes per anal samples than in HIV-negative (7.7%) with 1.5 genotypes per anal samples. HPV types included in the prophylactic Gardasil-9® vaccine were detected in 68.9% of specimens and HPV-58 was the most frequently detected. MSM infected by HPV-16 and HPV-18 were all infected by HIV-1. Few anal swabs (11.9%) contained HSV-2 DNA without relationship with HPV detection. Condomless receptive anal intercourse was the main risk factor to being infected with any type of HPV and condomless insertive anal intercourse was significantly less associated with HPV contamination than receptive anal intercourse (Odd ratio = 0.02). CONCLUSION:MSM in Bangui are at-risk of HIV and HR-HPV anal infections. The unusual distribution of HPV-35 as predominant HPV suggests possible geographic specificities in the molecular epidemiology of HR-HPV in sub-Saharan Africa. Scaling up prevention strategies against HPV infection and related cancers adapted for MSM in Africa should be prioritized. Innovative interventions should be conceived for the MSM population living in Bangui.
Project description:Little is known about the epidemiology on human papillomavirus (HPV) infection among HIV-infected men in Korea. The objective of this study was to determine the prevalence, genotype distribution and risk factors associated with anal HPV infection among HIV-infected men in Korea.A single-center cross-sectional study was conducted with HIV-infected men in Korea. Participants completed a detailed sexual behavior risk factor questionnaire. Anal samples were collected for cytology and HPV genotyping. Factors associated with anal HPV infection were assessed using multivariable logistic regression, stratifying by sexual behaviour.A total of 201 HIV-infected men were included in the study: 133 were from men who have sex with men (MSM) and 68 from men who have sex with women (MSW). Any anal HPV infection was detected in 82.7% of HIV-infected MSM and in 51.5% of HIV- infected MSW (P < 0.001). High-risk HPV (HR-HPV) prevalence was higher among MSM (47.4%) than MSW (25.0%; P = 0.002). The HR-HPV types identified most frequently were HPV 16 (11%), HPV 18 (9.9%), and HPV 58 (5%) in MSM, and HPV 58(11%) and HPV 16 (8.9%) in MSW. Prevalence of any HPV types in 9-valent vaccine types was higher among MSM than MSW (47.4% vs 22.1%. P = 0.001). Abnormal anal cytology was more commonly detected in MSM than MSW (42.9% vs.19.1%, P < 0.001). In HIV-infected MSM, higher number of lifetime male sex partners was significantly associated with any anal HPV infection, but age was a significant risk factor associated with anal HR-HPV infection.Anal HPV infection was highly prevalent in HIV-infected MSM in Korea, and also commonly found in HIV-infected MSW. In HIV-infected MSM, the significant risk factor for being infected with any HPV infection was lifetime number of male sexual partners, and with anal oncogenic HPV infection was age.
Project description:Prevalence estimates of anal high-risk human papillomavirus (HR-HPV) are needed in sub-Saharan Africa where HIV is endemic. This study evaluated anal HR-HPV in Nigeria among HIV-positive and HIV-negative men who have sex with men (MSM) for future immunization recommendations.We conducted a cross-sectional study to compare the prevalence of anal HR-HPV infections between 64 HIV-negative and 90 HIV-positive MSM. Multivariate Poisson regression analyses were used to examine demographic and behavioral risk factors associated with any HR-HPV infections.The median age of the 154 participants was 25 years (interquartile range, 22-28 years; range, 16-38 years), and the median age at initiation of anal sex with another man was 16 years (interquartile range, 13-18 years; range, 7-29 years). The prevalence of anal HR-HPV was higher among HIV-positive than HIV-negative MSM (91.1% vs. 40.6%, P < 0.001). In the multivariate analysis, HIV infection (adjusted prevalence ratio [aPR], 2.02; 95% confidence interval [CI], 1.49-2.72), 10 years or more since anal sexual debut (aPR, 1.26; 95% CI, 1.07-1.49), and concurrent relationships with men (aPR, 1.32; 95% CI, 1.04-1.67) were associated with increased anal HR-HPV prevalence.Anal HR-HPV infection is high for young Nigerian MSM, and rates are amplified in those coinfected with HIV. Providing universal coverage as well as catch-up immunization for young MSM may be an effective anal cancer prevention strategy in Nigeria.
Project description:This study aimed to assess the prevalence of and associated risk factors for anal high-risk human papillomavirus (hr-HPV) infection among men who have sex with men (MSM) and transgender women (TGW) in Indonesia, Thailand, and Malaysia.This was baseline data from a prospective cohort study with clinic sites in Jakarta and Bali (Indonesia), Bangkok (Thailand), and Kuala Lumpur (Malaysia).MSM and TGW aged 18 years and older from Indonesia, Thailand, and Malaysia were enrolled. Demographic and behavioral characteristics were assessed, and anal samples were collected for HPV genotyping. Multivariate logistic regression models were used to assess risk factors for anal hr-HPV overall and among HIV-positive participants.A total of 392 participants were enrolled, and 48 were TGW. As many as 245 were HIV-positive, and 78.0% of the participants were on combination antiretroviral therapy (cART). Median CD4 count was 439?cells/mm and 68.2% had undetectable HIV-RNA. HIV-positive participants had significantly more hr-HPV compared to HIV-negative participants (76.6% vs 53.5%, P?<?.001). HPV-16 was the most common high-risk type (20%), whereas HPV-33, -39, and -58 were significantly more common among HIV-positive participants. HIV-positive participant significantly associated with anal hr-HPV infection compared with HIV-negative (OR: 2.87, 95% CI: 1.76-4.70, P ? .001), whereas among HIV-positive participants transgender identity had lower prevalence of hr-HPV infection (OR: 0.42, 95% CI: 0.19-0.91, P?=?.03).High-risk HPV infection was very common among MSM and TGW in South-East Asia. Overall, HIV-infection, regardless of cART use and immune status, significantly increased the risk, while among HIV-positive participants transgender identity seemed to decrease the risk of anal hr-HPV.
Project description:Recent studies in Puerto Rico have reported an increasing incidence of anal cancer in Puerto Rican men. The objective of this study was to determine the prevalence, genotype distribution and risk factors associated with anal HPV infection among men attending an STI clinic in Puerto Rico.We conducted a cross-sectional study among 205 men 18 years and older. A comprehensive survey was administered that included a demographic and a behavioral assessment. Separate logistic regression models were performed to determine factors associated with any, high-risk (HR), and multiple anal HPV infection.The mean age of the study sample was 38.0±13.5 years. The most common HR types were 58, 51 and 31. Overall, HR anal HPV infection was found in 53.5% of the participants. Multiple HPV types in the anal canal were found in 47.6% of the sample. A third (29.8%) of participants reported being men who had sex with men (MSM). MSM had a significantly higher prevalence of any, HR and multiple HPV infection (p-value<0.05). Separate multivariate logistic regression analyses showed that being MSM was associated with any (OR = 4.5; [95%CI: 1.9-10.7]), HR (OR = 3.4; [95%CI: 1.1-10.3) and multiple anal HPV infection (OR = 3.6; [95%CI: 1.5-9.1). HIV was marginally associated with multiple anal HPV infection in multivariate analysis (OR = 3.3; 95%CI = 1.0-11.0).Anal HPV is common among sexually active men attending this STI clinic, with higher likelihood of anal HPV infection among MSM.
Project description:Men who have sex with men (MSM) are at high risk of developing human papillomavirus (HPV)-related anal cancer. We compared HPV genotypes in anal tissues (Bx) and anal liquid-based cytology fluid (LBC) from HIV-positive and HIV-negative MSM.Bx (32 normal, 41 low-grade squamous intraepithelial lesions (LSIL) and 22 high-grade squamous intraepithelial lesions (HSIL)), along with LBC from the same visit, were selected from 61 HIV-positive and 34 HIV-negative MSM who enrolled into a prospective cohort in Bangkok, Thailand. HPV genotyping was performed on Bx and LBC.Any HPV and high-risk HPV (HR-HPV) prevalence were 63.2% and 60.0% in Bx and 71.6% and 62.1% in LBC, respectively. HIV-positive MSM had higher rates of HR-HPV genotypes detection (70.5% vs. 47.1%, p=0.03) in LBC than HIV-negative MSM. HPV16 (27%) was the most common HR-HPV found in HSIL tissue. In HIV-positive MSM, the frequency of HR-HPV detection increased with histopathologic grading in both Bx and LBC samples. HSIL was associated with the presence of any HR-HPV(OR 7.6 (95%CI 1.8-31.9); P=0.006) in LBC and in Bx((OR 5.6 (95%CI 1.4-22.7); P=0.02).Our data strongly support the integration of HR-HPV screening on LBC samples, along with HPV vaccination, into an anal cancer prevention program.
Project description:BACKGROUND:There are no HPV-based measures for managing anal cancer (AC) in HIV-infected (HIV+) men who have sex with men (MSM) because of the high positivity of high-risk (HR)-HPVs. As next-generation sequencing (NGS) is able to describe the composition of HPVs as percent (%) reads rather than positive vs negative results, we used NGS approach to detect HPVs in anal samples of HIV+ MSM to test its ability to differentiate those who are diagnosed with atypical squamous cells of unknown significance or greater (ASCUS+) from those who are free of such lesions and to understand the burden of HPV infections in relation to HPV vaccines. METHODS:Study included 81 HIV+ MSM characterized for demographics, patient-reported outcome measures, HIV related laboratory measures and anal cytology. We summarized NGS HPV data using % read cut points (>0%->30%) and tested the relationship between % reads of HR-HPVs and risk of ASCUS+ using logistic regression. RESULTS:Forty-six HPVs were detected at the >0% read cut point. The prevalence of any HR-HPVs varied from 100% to 40% with >0% to >30% reads while ?99% were infected with HR-HPVs included or not included in the 9 valent HPV vaccine at the >0% read cut point. MSM with >30% HR-HPV reads were 4.5 times more likely to be diagnosed with ASCUS+ compared to ?30% reads (P = .033). CONCLUSION:NGS-based approach is more accurate than PCR-based HPV testing for identifying HIV+ MSM at risk for developing AC. We raise the concern regarding the efficacy of current HPV vaccines for preventing AC in this high-risk population.
Project description:HIV-positive MSM are at increased risk of anal human papillomavirus (HPV) infection compared with men in the general population, and little is known about the natural history of anal HPV infection in this population. The objective of this study was to determine the incidence of and risk factors for anal type-specific HPV infection.Prospective cohort study.HIV-positive MSM were evaluated for anal HPV DNA, lifestyle factors, and sexual risk behaviors every 6 months for at least 2 years.The overall incidence rate of detectable type-specific anal HPV infection was 21.3 per 100 person-years [95% confidence interval (CI) 17.7-25.4] and was 13.3/100 person-years (10.5-16.6) for oncogenic HPV types. The most common incident infections were HPV 18 (3.7/100 person-years) and HPV 16 (3.5/100 person-years). An increased number of recent partners with whom the participant was the receptive partner [odds ratio (OR) 2.9 (1.6-5.1) 8+ partners vs. 0-1], an increased number of new partners in which the participant was the receptive partner [OR 1.03 (1.01-1.1) per partner], an increased number of new oral-anal contact partners in which the participant was the receptive partner [OR 1.1 (1.03-1.1) per partner], and the frequency of receptive anal intercourse [OR 1.1 (1.03-1.1) per act] all significantly increased the odds of incident HPV infection (P ? 0.05).HIV-positive MSM have a high incidence of oncogenic anal HPV infection. Recent receptive anal sexual behaviors, including receptive anal intercourse and receptive oral-anal contact, are the most important risk factors for incident anal HPV infection.
Project description:BACKGROUND:HIV-positive men who have sex with men (MSM) are at high risk of anal cancer compared with the general population. Human papillomavirus (HPV) infection, particularly HPV 16, is causally associated with anal cancer. However, the risk factors for anal HPV 16 infection are poorly understood. We determined the prevalence and risk factors for anal HPV 16 infection in a population of HIV-positive MSM, most of whom were being treated with antiretroviral therapy. DESIGN:Cross-sectional data from the baseline visit of a 4-year prospective cohort study. METHODS:Three hundred forty-eight HIV-positive MSM were recruited in San Francisco, and they received a detailed sexual behavior risk factor questionnaire. An anal swab was used to collect specimens for HPV type-specific DNA testing using L1 HPV DNA polymerase chain reaction. We used log-binomial multivariable models to determine the risk factors for anal HPV 16 infection. RESULTS:Ninety-two percent of HIV-positive MSM had at least 1 anal HPV type, 80% had at least 1 oncogenic HPV type, and 42% had HPV 16. Non-Hispanic white race and higher level of education were associated with a decreased risk of HPV 16 infection. A higher number of total male partners was associated with HPV 16 (relative risk: 1.6, 95% confidence interval 1.1 to 2.4, P = 0.01) for 201-1000 partners compared with 1-200. Injection drug use was independently associated with anal HPV 16 infection (relative risk: 1.5, 95% confidence interval 1.2 to 1.9, P = 0.003). CONCLUSIONS:The prevalence of anal HPV infection, including HPV 16, is high in HIV-positive MSM. HIV-positive MSM should be counseled about the risk associated with increased partners and injection drug use.