Gustavo A.R. Maciel

Self-sampling for HPV genotyping: a study of vaginal and urine collection in Brazilian women with high-grade lesions

In Brazil - a country of continental dimensions with marked socioeconomic disparities - the use of self-collected samples and first-void urine for cervical cancer screening may be particularly valuable. This study aimed to assess the acceptability of two self-sampling approaches - first-void urine collection and vaginal self-sampling - among women diagnosed with high-grade cervical lesions (CIN2+) referred to a tertiary care center. Additionally, the study evaluated the concordance of high-risk HPV (hrHPV) test results obtained from self-collected samples compared to those collected by a healthcare professional. This cross-sectional study included 100 women. Participants completed a structured questionnaire on clinical history, demographics, gynecological and obstetric background. Following an instructional video, they performed self-collection of urine and vaginal samples. All participants then underwent colposcopic examination for lesion assessment and therapeutic planning. HPV DNA testing was conducted, and agreement analysis was performed between sample types. Both urine and vaginal self-collection methods were reported as easy and comfortable. Instructions were considered easy or very easy by nearly all participants for all collection methods. Clinician-collected sampling was associated with higher embarrassment and discomfort. Agreement analysis showed excellent concordance for HPV 16 and other high-risk HPV types between self-collected, urine, and clinician-collected samples, with all comparisons reaching statistical significance. Urine and vaginal self-collection are feasible, acceptable, and reliable methods. Urine sampling was the preferred method in the present study. High concordance with clinician-collected samples confirms their clinical utility, and the positive response to instructional videos highlights the importance of educational support.

FOXO3a deregulation in uterine smooth muscle tumors

The present study aimed to investigate FOXO3a deregulation in Uterine Smooth Muscle Tumors (USMT) and its potential association with cancer development and prognosis. The authors analyzed gene and protein expression profiles of FOXO3a in 56 uterine Leiomyosarcomas (LMS), 119 leiomyomas (comprising conventional and unusual leiomyomas), and 20 Myometrium (MM) samples. The authors used techniques such as Immunohistochemistry (IHC), FISH/CISH, and qRT-PCR for the present analyses. Additionally, the authors conducted an in-silico analysis to understand the interaction network involving FOXO3a and its correlated genes. This investigation revealed distinct expression patterns of the FOXO3a gene and protein, including both normal and phosphorylated forms. Expression levels were notably elevated in LMS, and Unusual Leiomyomas (ULM) compared to conventional Leiomyomas (LM) and Myometrium (MM) samples. This upregulation was significantly associated with metastasis and Overall Survival (OS) in LMS patients. Intriguingly, FOXO3a deregulation did not seem to be influenced by EGF/HER-2 signaling, as there were minimal levels of EGF and VEGF expression detected, and HER-2 and EGFR were negative in the analyzed samples. In the examination of miRNAs, the authors observed upregulation of miR-96-5p and miR-155-5p, which are known negative regulators of FOXO3a, in LMS samples. Conversely, the tumor suppressor miR-let7c-5p was downregulated. In summary, the outcomes of the present study suggest that the imbalance in FOXO3a within Uterine Smooth Muscle Tumors might arise from both protein phosphorylation and miRNA activity. FOXO3a could emerge as a promising therapeutic target for individuals with Unusual Leiomyomas and Leiomyosarcomas (ULM and LMS), offering novel directions for treatment strategies.