The interplay between HPV, other Sexually Transmissible Infections and genital microbiome on cervical microenvironment (MicroCervixHPV study).

Background: The importance of Cervicovaginal Microbiota in protecting against infections (such as HPV) is already well established, namely through Lactobacillus spp., as well as the mechanism through which HPV leads to Cervical Neoplasia. However, it is not possible to classify HPV as a complete carcinogen. Thus, the importance of exploring Cervicovaginal dysbiosis with the intention of deciphering this interaction with HPV, takes on greater relevance. The main objectives of this study were: 1) Comparison of the MCV composition of women with or without HPV and women with ASCUS or LSIL; 2) Characterization of cytokines present in the vaginal microenvironment; 3) Evaluation of the blood count ratios as prognostic systemic inflammatory biomarkers; 4) Correlation between MCV, HPV serotypes and cytokines. Methods: This was a retrospective, observational, multicenter, cross-sectional study. CVM analysis was performed by isolation RNA and sequencing on a NGS platform. Cytokine concentrations of CVM were obtained through Multiplex platform. Statistical analysis was performed in SPSS v 26.0. An α of 0.05 was considered statistically significant. Results: Highlighting the core of the study, CVM types of CST I and CST IV were found to influence the emergence of cervical lesions. Neutrophil-to-Lymphocyte ratio was found to impact the prognosis of ASCUS. Within CVM, Lactobacillus prevent the growth of other CST IV species, while the latter express symbiotic relationships with each other and show affinity for specific HPV serotypes. At last, RANTES chemokine is significantly elevated in cervicovaginal infections. Conclusion: The importance of using vaginal cytokine profiles and CVM is highlighted in the hypothesis of prevention of Cervical Neoplasia development, as well as in its use as a prognostic biomarker. Taken together, these insights are one step closer to personalized medicine.

An Unexpected and Unpredictable Emergence of Muscle-Invasive Bladder Cancer in a Patient Successfully Treated With Nivolumab for Small-Cell Bladder Cancer.

Small-cell bladder cancer (SCBC) is a rare subtype of bladder cancer with aggressive behavior and poor prognosis. Here, we report the case of a 50-year-old man who presented with hematuria for one month. A computed tomography scan showed an exophytic lesion on the right posterolateral wall of the bladder and a single liver metastasis with a 14 mm diameter. Transurethral resection of the bladder tumor was performed, and postoperative examination of the specimen showed muscle-invasive SCBC. Initially, the patient was treated with neoadjuvant chemotherapy. Rapid clinical and imaging deterioration was observed after the premature end of cisplatin and etoposide therapy. Second-line therapy with nivolumab demonstrated systemic and local complete response. However, the patient was further diagnosed with unpredictable and unexpected urothelial muscle-invasive bladder cancer. After 76 months of regular follow-up, imaging workup did not demonstrate SCBC recurrence or urothelial bladder cancer progression. This report highlights this disease's rarity and severity and no typical or even pathognomonic clinical and radiological presentation. Therefore, histopathology and immunohistochemistry findings play a key role in diagnosis. Immunotherapy has opened a new window in cancer treatment and maybe SCBC patients can benefit from it.