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Background: Anal cancer prevention has two critical points: the incidence rate is several fold higher for some groups, such as people living with human immunodeficiency virus (HIV) and men who have sex with men (MSM), and there is not a well-defined guideline for its screening. This systematic review evaluates the accuracy of DNA HRHPV (high-risk human papillomavirus), mRNA HPV, DNA HPV16 isolated and p16 staining biomarkers in anal canal smears for identifying anal intraepithelial neoplasia (AIN) 2 or 3, summarised as anal high-grade squamous intraepithelial lesions (aHSIL), and cancer. Methods: We searched the MEDLINE, Cochrane Library and Embase electronic databases as well as Grey literature to identify eligible papers published up to 31st July 2022. This systematic review and meta-analysis included observational studies comparing biomarker tests to histopathology after HRA (High-resolution Anoscopy) as a reference standard. We (ACM, TF) analysed studies in which patients of both sexes were screened for anal cancer using DNA HRHPV, mRNA HPV, DNA HPV16 and/or p16 biomarkers. The analysis was performed in pairs, for instance AIN2 or worse (AIN2+) vs. AIN1, HPV infection and normal (AIN1-). PROSPERO CRD42015024201. Findings: We included 21 studies with 7445 patients. DNA HR HPV showed a higher sensitivity 92.4% (95% CI 84.2-96.5), specificity 41.7% (95% CI 33.9-44.9) and AUC 0.67, followed by the mRNA HPV test, with a sensitivity 77.3% (95% CI 73.2%-80.9%), specificity 61.9% (95% CI 56.6-66.9) and AUC 0.78. DNA HPV16 showed higher specificity 71.7% (95% CI 55.3-83.8), followed by p16 test, 64.1% (95% CI 51.0-75.4); Sensitivity of DNA HPV16 was 53.3% (95% CI 35.4-70.3) and AUC 0.69, while p16 had a sensitivity of 68.8% (95% CI 47.9-84.1) and AUC 0.74. Subgroup analysis of MSM with HIV, with 13 studies and 5123 patients, showed similar accuracy, with a bit higher sensitivities and lower specificities. Considering the measure of the total between-study variability, mRNA HPV tests showed the smallest area of the 95% prediction ellipse, 6.0%, influenced by the low logit sensitivity, 0.011. All other groups of tests exceed 50% prediction ellipse area, which represent a high heterogeneity. Interpretation: Our findings suggested that DNA HR HPV can be a useful tool for screening for aHSIL and anal cancer if followed by biomarker with a higher specificity. As an isolated test, mRNA HPV had better performance. Funding: There was no funding source for this study.

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To map and assess evidence regarding use of the levonorgestrel-releasing intrauterine system (LNG-IUS) and its association with breast cancer, we conducted a systematic review and meta-analysis. A search strategy was developed using the terms "Levonorgestrel-releasing," "LNG-IUS," "intrauterine system," and "breast cancer. The electronic databases searched were MEDLINE, Embase, Cochrane Library, Latin American & Caribbean Health Sciences Literature, and Google Scholar for studies published until August 2020. We included observational studies: prospective or retrospective cohort, case-control, and cross-sectional. A total of 494 studies were identified, 294 studies were evaluated by title and abstract, and 262 were excluded because they did not meet the inclusion criteria. A total of 32 studies were read in full, and 24 were excluded. Thus, eight studies were included in the systematic review. The meta-analysis included four studies (two cohort and two case-control studies). Two subgroup analyses were performed for different study designs. The estimated relative risk for the two cohort studies (144,996 cases), with moderate-quality evidence, was 0.93 (95% confidence interval [CI], 0.840-1.03). The odds ratio estimated for the two case-control studies (5556 cases and 35987 controls), with moderate-quality evidence, was 1.07 (95% CI, 0.91-1.26). Evidence of an increased risk of breast cancer was not observed in levonorgestrel-releasing intrauterine system users.

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OBJECTIVE: This systematic review evaluates the accuracy of the mRNA HPV biomarker in cervical smears to identify cervical intraepithelial neoplasia (CIN) 2 or 3 and cervical cancer. DATA SOURCE: Eligible studies were identified by performing a search of electronic databases on Medline via Pubmed, Lilacs, Cochrane Library, Embase, and Grey literature for papers published between January 1990 and June 2018. STUDY ELIGIBILITY CRITERIA: As no randomized studies were identified, this review focuses on observational studies in which the mRNA HPV diagnostic test was compared to a histopathology reference standard. We analyzed studies that included women screened for cervical cancer using mRNA HPV. STUDY APPRAISAL AND SYNTHESIS METHODS: After screening, 61 studies including 29,674 patients met the inclusion criteria and were analyzed. Dichotomization was performed by defining CIN2 or worse (CIN2+) versus CIN1, HPV infection, and normal (CIN 1-). The analysis was discriminated by the following tests: Aptima, PreTect HPV Profeer, NucliSens EasyQ HPV, OncoTect, and Quantivirus. RESULTS: Analyzing by technique, Aptima, with 28 studies, exhibited superior performance, showing for the outcomes CIN2+ and CIN3+ an AUC of 0.88 (0.82-0.95) and 0.91 (0.84-0.99), a pooled sensitivity of 92.8% (95%CI 91.9-93.7) and 95.6% (95%CI 94.5-96.5), and a pooled specificity of 60.5% (95%CI 59.8-61.3) and 61.9% (95%CI 61.1-62.7), respectively. CONCLUSION: This study supports the current hypothesis that the mRNA HPV assay is an adequate tool for secondary cervical cancer screening.

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OBJECTIVE: A systematic review was performed to estimate the accuracy of human epididymis protein 4 (HE4) assay in the diagnosis of ovarian tumors. METHODS: A comprehensive search of the MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials, IBECS, BIOSIS, Web of Science, SCOPUS, congress abstracts, and Grey literature (Google scholar; British Library) from January 1990 to April 2013 was conducted. Studies that evaluated HE4 levels for the diagnosis of ovarian tumors and compared them with paraffin-embedded sections as the diagnostic standard were included. RESULTS: Forty-five studies were analyzed, which included 10,671 women and 3946 ovarian cancer cases. The pooled sensitivity for the diagnosis of borderline tumors or ovarian cancer was 78% (95% confidence interval, 77%-79%), and the specificity was 86% (95% confidence interval, 85%-87%). Summary receiver operating characteristic curves were constructed. For malignant and borderline ovarian tumors versus benign lesions, the area under the curve was 0.916. Besides the overall analysis, stratification was performed in premenopause and postmenopause, early and late stages, and for accuracy by enzyme-linked immunosorbent assay and chemiluminescence microparticle immuno assay. CONCLUSIONS: A HE4 level is a useful preoperative test for predicting the benign or malignant nature of pelvic masses.

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O advento da infecção pelo HIV tem gerado forte impacto social e, além do aspecto clínico, questões sociais e comportamentais são permanentemente trazidas à discussão. Estas têm influência decisiva sobre a incidência de novos casos e, conseqüentemente, são fundamentais para a definição de medidas de saúde pública. O atendimento oferecido às gestantes soropositivo deve abranger questões como planejamento familiar, prevenção de doenças e mesmo espaço para conversar sobre expectativas e qualidade de vida. Os estudos com mulheres soropositivo deixam claras as carências de informações e de planejamento familiar. A partir da sensibilização e informação dos profissionais de saúde, será possível orientá-las de forma mais precisa, proporcionando melhores condições de cuidado à sua saúde, de seus filhos e parceiros, além de diminuir a incidência de transmissão vertical.

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