Evidence of synergistic relationships between HIV and human papillomavirus (HPV): Systematic reviews and meta-analyses of longitudinal studies of HPV acquisition and clearance by HIV status, and of HIV acquisition by HPV status

Introduction: Observational studies suggest HIV and human papillomavirus (HPV) infections may have multiple interactions. We reviewed the strength of the evidence for the influence of HIV on HPV acquisition and clearance, and the influence of HPV on HIV acquisition. Methods: We performed meta-analytic systematic reviews of longitudinal studies of HPV incidence and clearance rate by HIV status (review 1) and of HIV incidence by HPV status (review 2). We pooled relative risk (RR) estimates across studies using random-effect models. I 2 statistics and subgroup analyses were used to quantify heterogeneity across estimates and explore the influence of participant and study characteristics including study quality. Publication bias was examined quantitatively with funnel plots and subgroup analysis, as well as qualitatively. Results and discussion: In review 1, 37 publications (25 independent studies) were included in the meta-analysis. HPV incidence (pooled RR=1.55, 95%CI 1.29-1.88; heterosexual males: pooled RR=1.95, 95%CI 1.62, 2.34; females: pooled RR=1.63, 95%CI 1.26-2.11; men who have sex with men: pooled RR=1.36, 95%CI 1.01-1.82) and high-risk HPV incidence (pooled RR=2.20, 95%CI 1.90-2.54) was approximately doubled among people living with HIV (PLHIV) whereas HPV clearance rate (pooled RR=0.53, 95%CI 0.42-0.67) was approximately halved. In review 2, 14 publications (11 independent studies) were included in the meta-analysis. HIV incidence was almost doubled (pooled RR=1.91, 95%CI 1.38-2.65) in the presence of prevalent HPV infection. There was more evidence of publication bias in review 2, and somewhat greater risk of confounding in studies included in review 1. There was some evidence that adjustment for key confounders strengthened the associations for review 2. Misclassification bias by HIV/HPV exposure status could also have biased estimates toward the null. Conclusions: These results provide evidence for synergistic HIV and HPV interactions of clinical and public health relevance. HPV vaccination may directly benefit PLHIV, and help control both HPV and HIV at the population level in high prevalence settings. Our estimates of association are useful for mathematical modelling. Although observational studies can never perfectly control for residual confounding, the evidence presented here lends further support for the presence of biological interactions between HIV and HPV that have a strong plausibility

Comparação das contagens das células de Langerhans de tecidos contendo carcinoma anal em doentes com e sem infecção pelo HIV Comparison of Langerhans cells counts from tissues containing anal carcinoma of patients with and without HIV infection

INTRODUÇÃO: As células de Langerhans (LC) são derivadas da medula óssea e constituem-se nas principais apresentadoras de antígeno da pele.conferindo desta forma, a resposta imune cutânea. Seu número está reduzido nos imunodeprimidos, incluindo na infecção pelo HIV, e a presença do tumor inibe sua migração, impedindo que os linfócitos T promovam regressão das células neoplásicas. OBJETIVO: Conhecer as diferenças entre as contagens de LC no tecido tumoral de doentes de carcinomas anais com e sem AIDS. MÉTODO: Avaliamos 24 doentes, sendo 14 com HIV e 10 outros sem HIV . O tratamento para o carcinoma foi semelhante nos dois grupos. Cortes retirados de blocos parafinados submetidos ao teste imunoistoquímico com anticorpo anti-CD68. Contamos as LC com método da histometria e os comparamos aos números obtidos com amostras previamente conhecidas de doentes sem doença infecciosa anorretal ou infecção pelo HIV. Revisamos também a evolução e as contagens séricas de linfócitos T CD4+ de doentes HIV-positivos. RESULTADOS: Observamos que o carcinoma anal foi mais freqüente em mulheres HIV-negativas e em homens HIV-positivos e que esses ultimos eram mais jovens. As LC foram menos numerosas nos doentes HIV-positivos e as maiores contagens estavam associadas com pior evolução. Os doentes HIV-positivos com os níveis mais baixos de linfócitos T CD4+ também tiveram as piores evoluções. CONCLUSÃO: Concluímos que as LC estavam diminuídas nos doentes HIV-positivos, portadores de carcinoma anal, quando comparados aos soronegativos.<br>Langerhans cells (LC) are bone marrow derived dendritic cells that represent the major antigen-presenting cells (APC) in the skin, thus representing an integral part of the cutaneous immune response. Immunossupression decreases their number, including HIV infection, and skin tumors products are sufficient to immobilize LC within the tumor, preventing their migration to lymph nodes. This reduces the number of T cells that infiltrate the tumor, preventing regression. OBJETIVE: Our proposal was to know what are the differences among LC counts comparing HIV-positive and -negative patients with anal carcinoma. METHOD: We evaluated 24 patients, 14 with HIV and 10 HIV-negative. Treatment for carcinoma was similar in both groups. Paraffin blocks containing biopsies were cut and stained with antibody anti-CD68. LC were counted in a histometrical way and number were compared to previous known specimens of HIV-negative patients without infectious anorectal diseases. We also studied cancer evolution and T CD4+ lymphocytes blood counts of HIV-positive patients. RESULTS: Statistics showed that anal carcinomas were more frequent in females HIV-negative and in seropositive males. HIV-positive patients were younger than seronegative ones. LC were decreased in seropositive patients and the most numerous counts were associated to worse prognosis. HIV-positive patients who had the most decreased T CD4+ counts had the worst prognosis, too. CONCLUSION: We conclude that LC were decreased in HIV-positive patients with anal carcinoma rather than in seronegative

Potential mechanisms of susceptibility to periodontitis in tobacco smokers

Tobacco smoking is probably the most important, controllable environmental risk factor in periodontitis. It results in changes in the vascular, inflammatory, immune and healing responses. The degree of exposure to tobacco smoking can be measured in pack years or by measuring serum cotinine and nicotine levels. In a previous paper we reported elevated levels of serum soluble intercellular adhesion molecule-1 (sICAM-1) in smokers, regardless of periodontal status. Elevated sICAM-1 has been found to be a risk marker for cardiovascular disease. In the present paper we report the short-term effects of an episode of smoking on blood how and levels of sICAM-1. Human volunteers included non-smokers, light smokers and heavy smokers. Relative blood flow was monitored in the gingivae and forehead skin using a laser Doppler flowmeter and serum levels of sICAM-1, cotinine and nicotine measured before during and up to 60 min following an episode of smoking. We could not provide evidence to support the theory that there is localized vasoconstriction within the gingival tissues. In contrast, there was a significant increase in blood flow in the forehead skin of light smokers which was not observed in non-smoking controls or in heavy smokers, suggesting a long-term tolerance in this latter group. The level of sICAM-1 remained unchanged during this episode, further suggesting a long-term effect. In a parallel group of subjects, we were able to demonstrate a direct significant correlation between sICAM and serum cotinine levels. These observations may be relevant to aetiological mechanisms in periodontitis and other smoking-associated diseases