OBJECTIVE: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the benefits and harms of secondary CRS and chemotherapy in comparison to chemotherapy alone for women with platinum-sensitive recurrent epithelial ovarian cancer.

CD8+ T cells are the primary mediators of anticancer immunity, and modulation of the CD8+ T cell response has been a central focus of immunotherapy to treat cancer. When CD8+ T cells specifically recognize antigenic peptides presented by the MHC-I on tumor cells, they become activated and kill the tumor cells. However, one pivotal mechanism through which tumor cells evade immune surveillance is to reduce their antigen presentation. To identify novel immunotherapeutic targets, we specifically focused on the role of MAL2 in immune evasion in endometrial cancer (EC) and the underlying mechanism. MAL2 was overexpressed in EC tissues and cells and its transcription was enhanced by RAD21. Knockdown of MAL2 or RAD21 inhibited malignant behavior and immune evasion of EC cells by repressing MHC-I expression and the cytotoxic effects of CD8+ cells. Conversely, MAL2 promoted immune evasion of EC cells and tumor growth in mice in the presence of RAD21 knockdown. These results indicate that RAD21 activation of MAL2 inhibits antigen processing and presentation of MHC-I, thereby inducing immune evasion of EC cells. We further suggest that RAD21 and MAL2 may serve as novel targets for EC immunotherapy.

UNASSIGNED: The aim of our study was to assess overall survival and cancer-specific survival in endometrial cancer patients with type 2 diabetes mellitus (T2DM) using metformin.
UNASSIGNED: Patients with endometrial cancer and T2DM during 2000-2012 period were identified from the Lithuanian Cancer Registry and the National Health Insurance Fund database. Cancer-specific and overall survival were primary outcomes.
UNASSIGNED: In our study we included 6287 women with endometrial cancer out of whom 664 were diagnosed with T2DM (598 metformin users and 66 never users). During follow-up (mean follow-up time was 8.97 years), no differences in risk of endometrial cancer specific mortality was observed in diabetic patients treated with metformin (Hazard Ratio (HR) 0.87, 95% Confidence Interval (CI) 0.70-1.07). Overall mortality in the diabetic metformin ever users\' group was significantly higher compared with the non-diabetic endometrial cancer women (HR 1.17, 95% CI 1.03-1.32) and in the group of metformin never users with T2DM (HR 1.42, 95% CI 1.07-1.87).
UNASSIGNED: Our study results suggest no beneficial impact on overall and cancer-specific survival in endometrial cancer patients who were treated with metformin as part of their diabetes treatment.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s40200-023-01358-3.

Integration of the human papillomavirus (HPV) genome into the cellular genome is a key event that leads to constitutive expression of viral oncoprotein E6/E7 and drives the progression of cervical cancer. However, HPV integration patterns differ on a case-by-case basis among related malignancies. Next-generation sequencing technologies still face challenges for interrogating HPV integration sites. In this study, utilizing Nanopore long-read sequencing, we identified 452 and 108 potential integration sites from the cervical cancer cell lines (CaSki and HeLa) and five tissue samples, respectively. Based on long Nanopore chimeric reads, we were able to analyze the methylation status of the HPV long control region (LCR), which controls oncogene E6/E7 expression, and to identify transcriptionally-active integrants among the numerous integrants. As a proof of concept, we identified an active HPV integrant in between RUNX2 and CLIC5 on chromosome 6 in the CaSki cell line, which was supported by ATAC-seq, H3K27Ac ChIP-seq, and RNA-seq analysis. Knockout of the active HPV integrant, by the CRISPR/Cas9 system, dramatically crippled cell proliferation and induced cell senescence. In conclusion, identifying transcriptionally-active HPV integrants with Nanopore sequencing can provide viable targets for gene therapy against HPV-associated cancers.

Cervical cancer, along with other sexual and reproductive health and rights (SRHR) conditions, poses a significant burden in the Kingdom of Saudi Arabia (KSA). Despite the availability of effective preventive methods such as vaccinations, particularly against the Human Papillomavirus (HPV), awareness about such preventive methods and HPV vaccination remains alarmingly low in the KSA, even with governmental effort and support. While many women are aware of the risks, the uptake of the HPV vaccine remains below 10% (7.6%) at the country level. This highlights the urgent need for Knowledge, Attitude, and Practice (KAP) at the community level to raise awareness, dispel misconceptions, and empower women to embrace vaccinations. Additionally, there is a need to revitalize the cancer registry system to better track and monitor cervical cancer cases. This short communication aims to map these barriers while identifying opportunities for impactful research. Drawing from the scientific literature, government reports, and expert insights, we highlight the challenges surrounding the tackling of HPV. By exploring diverse sources of knowledge, this paper not only highlights current obstacles but also proposes actionable solutions for future interventions.

HPV16 is responsible for approximately 60% and 90% of global HPV-induced cervical and oropharyngeal cancers, respectively. HPV16 intratype variants have been identified by HPV genome sequencing and classified into four phylogenetic lineages (A-D). Our understanding of HPV16 variants mostly derives from epidemiological studies on cervical cancer (CC) in which HPV16 B, C, and D lineages (previously named \"non-European\" variants) were mainly associated with high-grade cervical lesions and cancer. Although a predominance of HPV16 lineage A (previously named \"European variants\") has been observed in head and neck squamous cell carcinoma (HNSCC), epidemiological and in vitro biological studies are still limited for this tumor site. Next Generation Sequencing (NGS) of the entire HPV genome has deepened our knowledge of the prevalence and distribution of HPV variants in CC and HNSCC. Research on cervical cancer has shown that certain HPV16 sublineages, such as D2, D3, A3, and A4, are associated with an increased risk of cervical cancer, and sublineages A4, D2, and D3 are linked to a higher risk of developing adenocarcinomas. Additionally, lineage C and sublineages D2 or D3 of HPV16 show an elevated risk of developing premalignant cervical lesions. However, it is still crucial to conduct large-scale studies on HPV16 variants in different HPV-related tumor sites to deeply evaluate their association with disease development and outcomes. This review discusses the current knowledge and updates on HPV16 phylogenetic variants distribution in HPV-driven anogenital and head and neck cancers.

Taurine, a non-proteogenic amino acid and commonly used nutritional supplement, can protect various tissues from degeneration associated with the action of the DNA-damaging chemotherapeutic agent cisplatin. Whether and how taurine protects human ovarian cancer (OC) cells from DNA damage caused by cisplatin is not well understood. We found that OC ascites-derived cells contained significantly more intracellular taurine than cell culture-modeled OC. In culture, elevation of intracellular taurine concentration to OC ascites-cell-associated levels suppressed proliferation of various OC cell lines and patient-derived organoids, reduced glycolysis, and induced cell protection from cisplatin. Taurine cell protection was associated with decreased DNA damage in response to cisplatin. A combination of RNA sequencing, reverse-phase protein arrays, live-cell microscopy, flow cytometry, and biochemical validation experiments provided evidence for taurine-mediated induction of mutant or wild-type p53 binding to DNA, activation of p53 effectors involved in negative regulation of the cell cycle (p21), and glycolysis (TIGAR). Paradoxically, taurine\'s suppression of cell proliferation was associated with activation of pro-mitogenic signal transduction including ERK, mTOR, and increased mRNA expression of major DNA damage-sensing molecules such as DNAPK, ATM and ATR. While inhibition of ERK or p53 did not interfere with taurine\'s ability to protect cells from cisplatin, suppression of mTOR with Torin2, a clinically relevant inhibitor that also targets DNAPK and ATM/ATR, broke taurine\'s cell protection. Our studies implicate that elevation of intracellular taurine could suppress cell growth and metabolism, and activate cell protective mechanisms involving mTOR and DNA damage-sensing signal transducti.

BACKGROUND: The endometrium remains a difficult tissue for the analysis of microbiota, mainly due to the low bacterial presence and the sampling procedures. Among its pathologies, endometrial cancer has not yet been completely investigated for its relationship with microbiota composition. In this work, we report on possible correlations between endometrial microbiota dysbiosis and endometrial cancer.
METHODS: Women with endometrial cancer at various stages of tumor progression were enrolled together with women with a benign polymyomatous uterus as the control. Analyses were performed using biopsies collected at two specific endometrial sites during the surgery. This study adopted two approaches: the absolute quantification of the bacterial load, using droplet digital PCR (ddPCR), and the analysis of the bacterial composition, using a deep metabarcoding NGS procedure.
RESULTS: ddPCR provided the first-ever assessment of the absolute quantification of bacterial DNA in the endometrium, confirming a generally low microbial abundance. Metabarcoding analysis revealed a different microbiota distribution in the two endometrial sites, regardless of pathology, accompanied by an overall higher prevalence of pathogenic bacterial genera in cancerous tissues.
CONCLUSIONS: These results pave the way for future studies aimed at identifying potential biomarkers and gaining a deeper understanding of the role of bacteria associated with tumors.

Radical trachelectomy allows for fertility preservation in patients with early cervical cancer not qualifying as \"low-risk\" as defined by ConCerv. This study reports on the 10-year surgical, oncological, and obstetrical experience of patients treated by radical abdominal trachelectomy at an Austrian tertiary care center. A retrospective chart analysis and telephone survey of all patients with FIGO stage IA2-IB2 (2018) cervical cancer treated by radical abdominal trachelectomy and pelvic lymphadenectomy between 2013 and 2022 were performed. Radical abdominal trachelectomy was attempted in 29 patients, of whom 3 patients underwent neoadjuvant chemotherapy. Three cases, including one after neoadjuvant therapy, required conversion to radical hysterectomy due to positive margins; four cases had positive lymph nodes following surgical staging and were referred to primary chemo-radiotherapy. Twenty-two (75.9%) successful abdominal radical trachelectomies preserving fertility were performed. According to final histopathology, 79.3% of tumors would not have met the \"low-risk\"-criteria. At a median follow-up of 64.5 (25.5-104.0) months, no recurrence was observed. Eight (36.4%) patients attempted to conceive, with a live birth rate of 62.5%. Radical abdominal trachelectomy appears oncologically safe in early-stage cervical cancers that do not fulfill the \"low-risk\"-criteria. Strict preoperative selection of patients who might qualify for more conservative surgical approaches is strongly recommended.

Cervical cancer represents a global health issue as it is mostly encountered in women of reproductive age, while at the same time, survival outcomes seem to have remained constant during the last two decades. The need to implement fertility-sparing strategies as well as to decrease the morbidity that accompanies radical treatment has been extensively studied. During the last decade, several randomized clinical trials have been released, resulting in significant advances in the surgical treatment of early-stage disease. At the same time, evidence about the surgical treatment of advanced-stage disease as well as recurrent disease has gradually appeared and seems to be promising, thus leading the point forward towards personalized medicine that will remove the surgical barriers that seem concrete in our era. Nevertheless, the discrepancies in perioperative morbidity and survival outcomes that were observed among published studies raise several questions. In the present article, we chose to review the gray fields in the surgical treatment of early-stage and advanced-stage cervical cancer. Studies that are based on strong evidence that support current clinical practice are compared to smaller cohorts that present novel data that may form the basis for future research, and issues that remain poorly explored are discussed in an effort to help establish a consensus for future research development.