The Epidemiology of Anal Human Papillomavirus (HPV) in HIV-Positive and HIV-Negative Women and Men: A Ten-Year Retrospective Observational Study in Rome (Italy).

Human papillomaviruses (HPVs) commonly infect the anogenital mucosa; most infections are transient, but a fraction of those caused by high-risk (HR) types persist and may lead to anogenital cancer. The epidemiology of HPV genotypes in anal infections in groups at different risk for anal cancer has not been well described in Italy. This retrospective study reports the results of HPV DNA testing and complete genotyping performed on anal swabs from 691 female and male patients attending proctology clinics in Rome during 2012-2021; one-third had repeated testing. Cumulative HPV positivity in 1212 anal swabs was approximately 60%, was not age related, and showed an increasing trend over the study period. HPV rates differed significantly by sex and HIV status: HIV-negative women had the lowest (43.6%) and HIV-positive men the highest (83.5%) HPV prevalence. HIV-positive men had more oncogenic HPV genotypes detected, more multiple infections, and the highest frequency of persistent infections. Two-thirds of all infections were vaccine-preventable. This study found that anal HPV infection rates are still elevated and even increasing in groups at low and high risk of developing anal cancer. Prevention programs need to be improved to reduce rates of anal infection in young women and men.

International Anal Neoplasia Society's consensus guidelines for anal cancer screening.

The International Anal Neoplasia Society (IANS) developed consensus guidelines to inform anal cancer screening use among various high-risk groups. Anal cancer incidence estimates by age among risk groups provided the basis to identify risk thresholds to recommend screening. Guided by risk thresholds, screening initiation at age 35 years was recommended for men who have sex with men (MSM) and transgender women (TW) with HIV. For other people with HIV and MSM and TW not with HIV, screening initiation at age 45 years was recommended. For solid organ transplant recipients, screening initiation beginning from 10 years post-transplant was recommended. For persons with a history of vulvar precancer or cancer, screening initiation was recommended starting within 1 year of diagnosis of vulvar precancer or cancer. Persons aged ≥45 years with a history of cervical/vaginal HSIL or cancer, perianal warts, persistent (>1 year) cervical HPV16, or autoimmune conditions could be considered for screening with shared decision-making, provided there is adequate capacity to perform diagnostic procedures (high-resolution anoscopy [HRA]). Anal cytology, high-risk (hr) human papillomavirus (HPV) testing (including genotyping for HPV16), and hrHPV-cytology co-testing are different strategies currently used for anal cancer screening that show acceptable performance. Thresholds for referral for HRA or follow-up screening tests are delineated. These recommendations from IANS provide the basis to inform management of abnormal screening results, considering currently available screening tools. These guidelines provide a pivotal foundation to help generate consensus among providers and inform the introduction and implementation of risk-targeted screening for anal cancer prevention.

HPV Vaccination after Primary Treatment of HPV-Related Disease across Different Organ Sites: A Multidisciplinary Comprehensive Review and Meta-Analysis.

OBJECTIVE: To assess evidence on the efficacy of adjuvant human papillomavirus (HPV) vaccination in patients treated for HPV-related disease across different susceptible organ sites. METHODS: A systematic review was conducted to identify studies addressing the efficacy of adjuvant HPV vaccination on reducing the risk of recurrence of HPV-related preinvasive diseases. Results were reported as mean differences or pooled odds ratios (OR) with 95% confidence intervals (95% CI). RESULTS: Sixteen studies were identified for the final analysis. Overall, 21,472 patients with cervical dysplasia were included: 4132 (19.2%) received the peri-operative HPV vaccine, while 17,340 (80.8%) underwent surgical treatment alone. The recurrences of CIN 1+ (OR 0.45, 95% CI 0.27 to 0.73; p = 0.001), CIN 2+ (OR 0.33, 95% CI 0.20 to 0.52; p < 0.0001), and CIN 3 (OR 0.28, 95% CI 0.13 to 0.59; p = 0.0009) were lower in the vaccinated than in unvaccinated group. Similarly, adjuvant vaccination reduced the risk of developing anal intraepithelial neoplasia (p = 0.005) and recurrent respiratory papillomatosis (p = 0.004). No differences in anogenital warts and vulvar intraepithelial neoplasia recurrence rate were observed comparing vaccinated and unvaccinated individuals. CONCLUSIONS: Adjuvant HPV vaccination is associated with a reduced risk of CIN recurrence, although there are limited data regarding its role in other HPV-related diseases. Further research is warranted to shed more light on the role of HPV vaccination as adjuvant therapy after primary treatment.

Clinical Effects of Oral Bacteriotherapy on Anal HPV Infection and Related Dysplasia in HIV-Positive MSM: Results from the "HPVinHIV" Trial.

BACKGROUND: Anal HPV infection, anal dysplasia and, ultimately, anal cancer are particularly common in HIV-infected men who have sex with men. Treatment of anal dysplasia, aiming to prevent evolution to squamous cell carcinoma of the anus, is currently limited to direct ablation and/or application of topical therapy. The aim of the present study is to investigate the effect of oral bacteriotherapy (Vivomixx® in EU, Visbiome® in USA) on anal HPV infection and HPV-related dysplasia of the anal canal in HIV-infected men who have sex with men. METHODS: In this randomized, placebo-controlled, quadruple-blinded trial (NCT04099433), HIV-positive men who have sex with men with anal HPV infection and HPV-related dysplasia were randomized to receive oral bacteriotherapy or placebo for 6 months. Anal HPV test, anal cytology and high resolution anoscopy with biopsies of anal lesions were performed at baseline and at the end of the study. Safety and tolerability of oral bacteriotherapy were also evaluated. Interim analysis results were presented. RESULTS: 20 participants concluded the study procedures to date. No serious adverse events were reported. In respect to participants randomized to placebo, individuals in the experimental arm showed higher rate of anal dysplasia regression (p = 0.002), lower rate of onset of new anal dysplasia (p = 0.023) and lower rates of worsening of persistent lesions (p = 0.004). Clearance of anal HPV infection was more frequently observed in the bacteriotherapy group (p = 0.067). CONCLUSION: Being an interim analysis, we limit ourselves to report the preliminary results of the current study. We refer the conclusions relating to the possible effectiveness of the intervention to the analysis of the definitive data.

Physical Activity and HIV: Effects on Fitness Status, Metabolism, Inflammation and Immune-Activation.

Several studies evidenced that a sedentary lifestyle is related with higher levels of systemic inflammation and highlighted that physical activity can trigger anti-inflammatory effects. To evaluate the impact of self-prescribed physical activity on fitness status, metabolism, inflammation and immune-activation in people living with HIV, an interim analysis of the results of the clinical trial PRIMO (NCT03392805) was performed. Patients enrolled were divided in 2 groups on the basis of self-prescribed physical activity: a physically active group (self-prescribed physical activity) and a sedentary group. Physical fitness was evaluated by sport medicine specialists and related to nutritional status, anthropometric variables, adipokines levels (adiponectin, leptin, resistin), peripheral immune-activation (CD38, HLA-DR on CD4 and CD8), and plasma inflammatory markers (IL-6 and TNF-α). The physically active group had a better profile in anthropometric measures and aerobic fitness but did not show lower levels of immune-activation compared to sedentary group. Also serum IL-6, TNF-α, and adipokines levels showed no statistical differences. On the basis of these data, a regular self-organized physical activity seems useful to improve cardio-respiratory fitness, but unable to control HIV-related immune-activation.

Clearance of human papillomavirus related anal condylomas after oral and endorectal multistrain probiotic supplementation in an HIV positive male: A case report.

INTRODUCTION: Here we present the case of a 56-year-old human immunodeficiency virus (HIV)-infected man with multiple anal condylomas and positivity for human papilloma virus (HPV) 18 on anal brushing. Biopsies of the anal mucosa led to the diagnosis of Bowen's disease and a subsequent pelvic magnetic resonance imaging (MRI) scan evidenced multiple reactive lymphoadenopathies and large intra-anal condylomas. The patient was treated with a complete excision of Bowen's lesion and with a 4 months course of supplementation with a high concentration multistrain probiotic formulation administered orally and by rectal instillation with the purpose to reduce local inflammation and to enhance local mucosal immunity. CONCLUSION: An MRI performed at the end of the supplementation period evidenced the clearance of the anal condylomas previously described and no evidence of residual lymphadenopathies. Trials are therefore required to confirm this therapeutic possibility and for a better understanding of the mechanisms by which this specific probiotic formulation interacts with local epithelium when administered by the anal route.

Dominant enrichment of phenotypically activated CD38(+) HLA-DR(+) CD8(+) T cells, rather than CD38(+) HLA-DR(+) CD4(+) T cells, in HIV/HCV coinfected patients on antiretroviral therapy.

HIV infection may enhance immune-activation, while little is known regarding the role of HCV infection. This study investigates the impact of HCV in HIV coinfected patients with undetectable viraemia under HAART on the levels of peripheral T cell's immune-activation. We determined T lymphocytes subsets to characterize immune-activation defined as CD38 and/or HLA-DR expression in chronic monoinfected HCV, HIV, and HIV/HCV coinfected subjects. One hundred and fifty six patients were divided into three groups: (i) 77 HIV+ patients; (ii) 50 HCV+ patients; and (iii) 29 coinfected HIV/HCV patients. The level of CD4(+) was significantly higher in HCV+ than in HIV+ or in coinfected HIV/HCV subjects. The frequencies of CD4(+) CD38(+) /HLA-DR(-) , CD4(+) CD38(-) /HLA-DR(+) and CD4(+) CD38(+) /HLA-DR(+) in HIV+ patients were comparable to those measured in coinfected patients, but statistically higher than those observed in HCV+ subjects. The percentage of CD8(+) was comparable in HIV-1+ patients and coinfected HIV/HCV but the results obtained in both groups were significantly higher compared to the results obtained in HCV patients. The level of CD8(+) CD38(+) /HLA-DR(-) showed values lower in HIV+ patients than in that monoinfected HCV and coinfected HIV/HCV patients. The frequencies of CD8(+) CD38(-) /HLA-DR(+) were higher in HIV+ patients compared to HCV+ and coinfected HIV/HCV patients. HIV/HCV coinfected group showed highest levels of CD8(+) CD38(+) /HLA-DR(+) . HIV plays a pivotal role to determine the immune activation in the host. The role of HCV needs of further investigations but our data show that HCV mainly influences the immune-activation of the pool of CD8, but also probably plays a supporting additive effect on CD4 immune-activation. J. Med. Virol. 88:1347-1356, 2016. © 2016 Wiley Periodicals, Inc.