The Science

Do MRI structured reports with FIGO classifications of leiomyomas contain adequate information for clinical decision making?

Abstract Objective To evaluate if structured reports (SR) of pelvic magnetic resonance imaging (MRI) scans using the PALM‐COEIN FIGO (the International Federation of Gynecology & Obstetrics) uterine leiomyomas classification (SR‐FIGO) contain adequate information for clinical decision making compared with narrative reports (NR). Methods Three reporting templates for pelvic MRI scans were compared: NR, SR without the PALM‐COEIN FIGO classification of leiomyomas, and SR‐FIGO, for presence of 19 key‐features (KF) deemed relevant for leiomyoma management. Kruskal‐Wallis test was used to evaluate KF distribution across the report types. One gynecologist and one gynecologist‐in‐training evaluated the reports and MRI scans to assess the presence of sufficient information to decide on: (1) treatment type (observation/medical treatment/surgery/uterine artery embolization); (2) surgical approach (hysteroscopic/laparoscopic/robotic/open); (3) surgery type (myomectomy/hysterectomy); (4) necessity to review MRI scans; and (5) time spent reviewing MRI scans. The responses of the gynecologist and gynecologist‐in‐training to points 1 to 5 among report types were compared using χ 2 test. Results Twenty NR, 20 SR, and 20 SR‐FIGO were reviewed. The number of KF was significantly different among reports ( P  < 0.001): SR‐FIGO had the highest number of KF, followed by SR, and NR. In pairwise comparison, significant differences were observed between NR and SR ( P  = 0.001) and between NR and SR‐FIGO ( P  = 0.001), but not between SR and SR‐FIGO ( P  = 0.063). There were significant differences in answers to question 1 between the gynecologist and gynecologist‐in‐training for SR ( P  = 0.007) and SR‐FIGO ( P  = 0.024), with the gynecologist deeming SR and SR‐FIGO to provide enough information for treatment decisions more commonly than the gynecologist‐in‐training. Conclusion Although this investigation revealed that SR offers a greater wealth of information in contrast to NR, additional investigation is required to ascertain whether the integration of the PALM‐COEIN FIGO classification in SR enhances the clinical decision making capacity of gynecologists.

The effect of high-risk HPV E6/E7 mRNA on the efficacy of topical photodynamic therapy with 5-aminolevulinic acid for cervical high-grade squamous intraepithelial lesions

E6 and E7 high-risk human papillomavirus (HR-HPV) oncoproteins are closely associated with the initiation and progression of cervical cancer (CC) and pre-cancerous lesions. Cervical high-grade squamous intraepithelial lesions (HSIL), as pre-cancerous lesions, have a 5% chance of progressing to invasive cancer. Topical 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a novel non-invasive targeted therapy for intraepithelial lesions. Herein, we analyzed the effect of HR-HPV E6/E7 mRNA on ALA-PDT for cervical HSIL. A retrospective analysis of 148 HR-HPV-positive patients diagnosed with cervical HSIL and receiving ALA-PDT was carried out. ALA-PDT was performed with 20% ALA thermosensitive gel, and irradiation at wavelength of 635 nm and density of 80-100 J/cm At the 6-month follow up, the complete remission (CR) rate of patients' lesions was 86.5% (128/148), whereas the total HPV clearance rate was 72.3% (107/148). It was evident that positive E6/E7 mRNA before treatment had a significant effect on HPV clearance rate (66.3% VS 81.4%, P = 0.045) and CR rate (80.9% VS 94.9%, P = 0.015). The E6/E7 mRNA associated with HPV16/18 and HPV16/18 combined with other HR-HPV (HPV16/18 and other HR-HPV) affected HPV clearance (P = 0.035) and lesions CR (P = 0.039), respectively. Moreover, persistently positive E6/E7 mRNA after treatment was closely associated with poor efficacy (HPV clearance rate: P = 0.000, CR rate: P = 0.000). Throughout the follow up period, two cases recurred but none of the patients progressed. This study has shown that ALA-PDT is an effective, safe, and alternative treatment for cervical HSIL, especially for the patients of childbearing age. However, its efficacy is relatively poor in patients with persistently positive E6/E7 mRNA before and after treatment, who are relatively insensitive to ALA-PDT.

Bit1 promotes the progression of gastric cancer by facilitating epithelial–mesenchymal transition and alleviating apoptosis

Wealth-related inequalities of women’s cervical cancer screening in 11 Sub-Saharan African countries: evidence from a pooled decomposition analysis

Cervical cancer is a preventable disease and ranks as the fourth most common cancer, as well as a major cause of cancer deaths among women globally. Despite initiatives by the World Health Organization to reduce cervical cancer incidence through vaccination, screening, and treatment, significant inequalities in healthcare access persist, particularly in low-income regions where economic and infrastructural barriers hinder access to screening services. Therefore, this study aimed to examine wealth-related inequalities in cervical cancer screening among women in Sub-Saharan African countries. The study analyzed 138,605 weighted samples of reproductive-aged women from DHS data spanning 2015 to 2023 across SSA countries. To assess socioeconomic-related inequality in cervical cancer screening uptake, the Erreygers normalized concentration index and its concentration curve were utilized. Additionally, a decomposition analysis was conducted to identify factors contributing to this inequality. The weighted Erreygers normalized concentration index was 0.25 with a standard error of 0.0078 (P value < 0.0001), indicating a statistically significant pro-rich distribution of wealth-related inequalities in cervical cancer screening uptake among reproductive-aged women. The decomposition analysis identified media exposure (20%), wealth index (15.58%), educational status (6.23%), and place of residence (2.18%) significantly contribute to screening inequalities. To address cervical cancer screening disparities in SSA, targeted strategies such as awareness campaigns for low-income groups, free screening services, mobile units in rural areas, and health literacy programs are recommended. Training community health workers and policy advocacy are also crucial. Comprehensive interventions should enhance media outreach, health education, and healthcare accessibility in both urban and rural areas to ensure equitable screening rates.

The Rapidly Evolving Landscape of Human Epidermal Growth Factor Receptor 2 (HER2) Testing in Endometrial Carcinoma and Other Gynecologic Malignancies

Context.— Trastuzumab in combination with standard chemotherapy has been included in the guideline recommendations for human epidermal growth factor receptor 2 (HER2)–positive advanced-stage and recurrent endometrial carcinomas since 2019. A novel antibody drug conjugate, trastuzumab deruxtecan, gained tumor agnostic approval for HER2-positive metastatic solid tumors, including endometrial, ovarian, and cervical cancer, in 2024. Objective.— To provide a detailed overview of HER2 protein expression, gene amplification, and mutation in gynecologic malignancies in light of the newly available anti-HER2 therapies. Tumor-specific HER2 testing and scoring algorithms are discussed, including the implications of the DESTINY-PanTumor02 trial results and the significance of the HER2-low tumor category. Data Sources.— Review of the literature and personal experience of the author. Conclusions.— The clinical indications and demand for HER2 testing in gynecologic malignancies beyond endometrial cancer are expanding. It is essential for practicing pathologists to stay up to date on the latest clinical developments and use evidence-based HER2 testing and scoring criteria.

Analysis of the progression of cervical cancer in a low-and-middle-income country: From pre-malignancy to invasive disease

To better understand cervical cancer progression, we analyzed RNA from 262 biopsies from women referred for colposcopy. We determined the HPV type and analyzed the expression of 51 genes. HPV31 was significantly more prevalent in precancer than stage 1 cancer and invasive cancer (p < 0.0001), and HPV16 increased in invasive disease (p < 0.0001). CCNE1, MELTF, and ULBP2 were significantly increased in HPV16-positive compared to HPV31 precancers, while NECTIN2 and HLA-E expression decreased. Markers of the innate immune system, DNA repair genes, and cell cycle genes are significantly increased during cancer progression (p = 0.0001). In contrast, the TP53 and RB1 tumor suppressor gene expression is significantly decreased in cancer cells. The T cell markers CD28 and FLT3LG expression decreased in cancer while FOXP3, IDO1, and ULBP2 expression increased. There is a significantly higher survival rate in individuals with increased expression of CD28 (p = 0.0005), FOXP3 (p = 0.0002), IDO1 (p = 0.038), FLT3LG (p = 0.026), APOBEC3B (p = 0.0011), and RUNX3 (p = 0.019), and a significantly lower survival rate in individuals with increased expression of ULBP2 (p = 0.035). These results will help us elucidate the molecular factors influencing the progression of cervical precancer to cancer. Understanding the risk of progression of specific HPV types and sublineages may aid in the triage of positive patients, and better knowledge of the immune response may aid in developing and applying immunotherapies.

Significance of HPV status on tumor response and treatment outcomes in endocervical adenocarcinoma treated with definitive chemoradiotherapy: a retrospective study

We aimed to compare tumor response and treatment outcomes between human papillomavirus (HPV)-associated (HPVA) and HPV-independent (HPVI) endocervical adenocarcinomas (ADCs) treated with definitive concurrent chemoradiotherapy (CCRT) and to identify prognostic factors. We conducted a retrospective review of 40 patients with endocervical ADCs treated with definitive CCRT (stages I-IVA) between 2011 and 2022. Based on pathological review the cases were categorized as HPVA or HPVI ADCs. Statistical analyses were performed to compare the characteristics, complete response (CR) rates, and survival outcomes. Of 40 patients, 22 (55.0%) had HPVA and 18 (45.0%) had HPVI ADCs. HPVI patients had significantly higher rates of parametrial invasion (94.4% vs. 45.5%, p=0.001). CR was achieved in 57.5% of patients and was significantly more common in the HPVA group (81.8% vs. 27.8%, p=0.001). Patients with HPVI had higher recurrence rates (88.9% vs. 50.0%, p=0.016) and lower 3-year progression-free survival (PFS, 16.7% vs. 49.8%, p=0.001), distant metastasis-free survival (DMFS, 38.1% vs. 80.8%, p=0.001), and overall survival (OS, 42.3% vs. 90.7%, p=0.002) rates. HPVA remained a significant factor for PFS (hazard ratio [HR]=3.44; 95% confidence interval [CI]=1.09-10.81; p=0.035) and OS rates (HR=6.83; 95% CI=1.17-39.80; p=0.033) in multivariate analysis. HPVI ADC was associated with a lower response to definitive CCRT and worse prognosis than HPVA ADC. These findings suggest the need for tailored treatment strategies based on the HPV status.

Therapeutic management of PI3Kα inhibitor-induced hyperglycemia with a novel glucokinase activator: Advancing the Frontier of PI3Kα inhibitor therapy

The phosphatidylinositol 3-kinase (PI3K) signaling pathway is a pivotal target in cancer treatment, driving substantial investigation into PI3K inhibitors (PI3Ki). However, the common on-target adverse effect of hyperglycemia presents a substantial challenge to their clinical application. There is an urgent need to discover an anti-hyperglycemic agent that maintains the efficacy of PI3Ki. We conducted a comprehensive study to explore the interaction between exogenous hyperinsulinemia and PI3Ki in SKOV3 and OVCAR3 ovarian cancer cell lines. We used Western blotting, CCK-8, and EdU assays to determine the effect of this interaction on cell proliferation. In addition, we evaluated the anti-hyperglycemic effects of dorzagliatin in a PI3Ki-induced hyperglycemic mice model. Cell line-derived xenograft (CDX) models were employed to evaluate the in vivo tumor growth inhibitory effects of combining dorzagliatin with PI3Ki. Western blot analysis demonstrated that insulin activated the AKT/INSR/mTOR pathway, reversing PI3Ki-induced p-AKT inhibition. Insulin also attenuated the anti-proliferative effects of PI3Ki. In the hyperglycemic mouse model, dorzagliatin significantly reduced blood glucose levels compared to controls. The combination therapy group (Dorzagliatin + PI3Ki) in CDX models showed a marked reduction in tumor volume. Dorzagliatin not only mitigated hyperglycemia but also enhanced the anti-tumor effects of PI3Ki. A clinical trial (NCT06117566) in cervical cancer patients supported these findings, showing that dorzagliatin stabilized blood glucose levels, facilitated body weight recovery, and achieved a confirmed partial response (PR). Dorzagliatin shows promise for managing PI3Ki-associated hyperglycemia, thereby enhancing its therapeutic efficacy. The activation of liver glycogen kinase and insulin regulation may be key mechanisms underlying its therapeutic benefits.

Role of Epigallocatechin Gallate in Selected Malignant Neoplasms in Women

Tea is a significant source of flavonoids in the diet. Due to different production processes, the amount of bioactive compounds in unfermented (green) and (semi-)fermented tea differs. Importantly, green tea has a similar composition of phenolic compounds to fresh, unprocessed tea leaves. It consists primarily of monomeric flavan-3-ols, known as catechins, of which epigallocatechin gallate (EGCG) is the most abundant. Thanks to its antioxidant, antiproliferative, and antiangiogenic properties, EGCG has attracted the scientific community’s attention to its potential use in preventing and/or combating cancer. In this review article, we summarize the literature reports found in the Google Scholar and PubMed databases on the anticancer effect of EGCG on selected malignant neoplasms in women, i.e., breast, cervical, endometrial, and ovarian cancers, which have been published over the last two decades. It needs to be emphasized that EGCG concentrations reported as effective against cancer cells are typically higher than those found in plasma after polyphenol administration. Moreover, the low bioavailability and absorption of EGCG appear to be the main reasons for the differences in the effects between in vitro and in vivo studies. In this context, we also decided to look at possible solutions to these problems, consisting of combining the polyphenol with other bioactive components or using nanotechnology. Despite the promising results of the studies conducted so far, mainly in vitro and on animal models, there is no doubt that further, broad-based activities are necessary to unequivocally assess the potential use of EGCG in oncological treatment to combat cancer in women.

Self‐collected vaginal HPV samples for long‐term non‐attendees in the Swedish organized cervical cancer screening program

AbstractIntroductionMost cervical cancer cases in Sweden are diagnosed among women who have failed to attend screening. The objective of this study was to analyze the effectiveness of offering vaginal HPV (human papillomavirus) self‐samples to long‐term non‐attendees as a routine in this screening program, in which non‐attendees had already been the targets of several interventions.Material and MethodsRegister data from the organized cervical screening program were used in this population‐based study. From January 2016 to December 2019, 33 881 high‐risk (hr‐) HPV self‐sample kits were sent to the homes of long‐term screening non‐attendees (≥7 years without a registered screening test), aged between 29 and 64 years, in Region Västra Götaland, Sweden. All samples returned to the laboratory were analyzed with the Cobas HPV DNA assay (Roche) for HPV16, HPV18, and for 12 other hr‐HPV types. HPV‐positive women were referred for colposcopy. Compliance and results of follow‐up were assessed 12 months after HPV analysis. Descriptive statistics, trend analysis, and risk ratios were used to compare outcomes across groups.ResultsThe median age of invited women was 49 years; 35% had not been screened before. The response rate was 19.4% (6582/33881). The HPV prevalence was 12.0% (788/6582), and 80.2% of HPV‐positive women attended follow‐up. Women with no previous cervical sample had a lower response rate: 15.7% (RR (Risk ratio) 0.73 (95% CI (Confidence interval) 0.70–0.77)). They also had lower attendance in follow‐up when HPV‐positive (71.6% RR 0.86 (CI 0.78–0.94)), compared with women who had previous samples. The proportions of high‐grade histopathology (HSIL+) among followed‐up women were 31.3% for HPV16, 15.2% for HPV18, and 8.8% for HPVnon‐16/18. Nine cervical cancer cases were found among 6582 women, corresponding to a rate of 137 cases per 100,000 women.ConclusionsVaginal HPV self‐samples increased cervical screening attendance by almost one‐fifth among non‐attendees who had previously resisted several invitations and interventions. Biopsied women positive for HPV16 or HPV18 had a high prevalence of HSIL or cervical cancer, which strongly supports direct referral to colposcopy. Long‐term non‐attendees have an exceptionally high risk of cervical cancer and should receive special attention.

Comparative effectiveness of paclitaxel versus cyclophosphamide in platinum-based adjuvant treatment of high-risk early-stage epithelial ovarian cancer: an Asian population study

Findings from a qualitative analysis: Social media influencers of color as trusted messengers of HPV vaccination messages

Background Despite HPV vaccination reducing the prevalence of cervical cancer by 90%, vaccination rates remain lower among communities of color due to vaccine hesitancy and mistrust in traditional public health messengers. The emergence of social media influencers, a newer kind of messenger, presents a unique opportunity to share immunization messages in new ways with a variety of communities. This paper reviews the qualitative findings from a study aimed at assessing influencers’ perceptions of and approaches to sharing messaging about the HPV vaccine. Methods Guided by several theories (Theory of Planned Behavior, Narrative Theory, and Opinion Leader Theory), the study team designed an intervention-based study consisting of qualitative interviews and social media influencer-designed and disseminated messaging. We worked closely with an influencer marketing firm to recruit 10 influencers of color who had children aged 9-14 – to write about the vaccine with their followers. Influencers used a provided factsheet to draft social media posts about vaccinating their children against HPV. Influencers were interviewed about their post and posts and interview transcripts were analyzed for key themes. Results Most influencers were hesitant to talk about vaccinations for fear of backlash. Most committed to writing, however, because they were compelled to support important health topics. All used the power of storytelling to convey the messages and highlighted their personal journeys of vaccine decision making. Influencers also highlighted the struggles of parenting and talked emotionally about how making decisions about this vaccine prompted feelings about their child growing up. Influencers also believed that they could help people make the decision to vaccinate. Conclusions The findings from this study elucidates the emotional context within which parents are being asked to vaccinate their children and thus, how personal the decision to vaccinate is. Most influencers noted that they had received a doctor’s recommendation but were taking the time to do their own research. Insights from this study can help inform current and future public health communication programs aimed at supporting immunization efforts. It also can provide lessons for other health topics.

Implementing High-Risk Human Papillomavirus Self-Sampling for Cervical Cancer Screening in Ghana: A Study (CarciSCAN) Protocol

Background: The World Health Organization (WHO) aims to eliminate cervical cancer by 2030 through a global strategy, centred on high-risk Human papillomavirus (hrHPV)-based screening and treatment. Implementing these strategies in low-resource settings remains challenging, due to barriers associated with limited healthcare infrastructure and patient awareness. Self-sampling for hrHPV has shown higher acceptability and similar diagnostic accuracy compared to clinician-taken samples. This study proposes a protocol to evaluate the clinical efficacy of a cervical cancer screening program utilising hrHPV self-sampling in Ghana. Methods and Analysis: 1000 non-pregnant women aged 30-65 years will be invited to self-collect hrHPV samples. Those testing hrHPV positive will undergo visual inspection with acetic acid. Those diagnosed with high-grade squamous intraepithelial lesions will be offered ablation. In any case where there is a suspicion of invasion, or equivocal diagnosis, biopsies will be taken. Follow-up for women who are test positive for hrHPV and/or undergo treatment, will involve hrHPV self-sampling after 6 months. HrHPV-negative women will rescreen after 3 years. Biopsies will be taken where immediate treatment is not suitable, and women with confirmed or suspected invasive cervical carcinoma will be referred for surgical and/or oncological care. The primary outcome will be the proportion of women successfully screened, defined as the proportion of women with a valid HPV test result out of those invited to attend cervical screening. Secondary outcomes include screening uptake, disease detection rate, hrHPV genotype prevalence, treatment acceptance rate, successful treatment response, missed disease during treatment, number lost to follow-up, and disease recurrence. Discussion: In low-resource settings, hrHPV self-sampling offers an accessible method to increase screening uptake. This study will inform strategies for broader implementation of cervical cancer screening and contribute to achieving the WHO’s goal of elimination by 2030. Trial Registration: Ethical approval for this study was obtained from the Kintampo Health Research Centre Institutional Ethics Committee (IEC), Bono East, Ghana, West Africa, on 24 May 2024 (IEC IRB Registration No. 0004854; Study ID: KHRCIEC/2024-03).

A multimodal deep learning model for cervical pre-cancers and cancers prediction: Development and internal validation study

The current cervical cancer screening and diagnosis have limitations due to their subjectivity and lack of reproducibility. We describe the development of a deep learning (DL)-based diagnostic risk prediction model and evaluate its potential for clinical impact. We developed and internally validated a DL model which accommodates both clinical data and colposcopy images in predicting the patients CIN2+ status using a retrospective cohort of 6356 cases of LEEP-conization/cone-biopsy (gold-standard diagnosis) following an abnormal screening result. The overall performance, discrimination, and calibration of the model were compared to expert clinician's colposcopic impression. The potential for clinical impact was assessed with rate of unnecessary conizations that could be avoided by using our model. The model combining clinical history and colposcopy images demonstrated superior performance prediction of CIN2+(AUC-ROC = 95.3 %, accuracy = 90.8 %, PPV = 94.1 %, NPV = 87.9 %) and better calibration compared to models that used image or clinical history data alone and outperformed clinician's colposcopic impressions. Moreover, if a decision threshold of 10 % is applied to the predicted probability from this model to recommend conization, up to 35 % of conizations could be avoided without missing any true CIN2+ cases. We present a novel DL model to predict cervical neoplasia with potential for reducing unnecessary conization. External validation studies are warranted for assessing generalizability.

Emerging roles of exosomes in diagnosis, prognosis, and therapeutic potential in ovarian cancer: a comprehensive review

Ovarian cancer is a leading cause of cancer-related deaths in women, and the development of chemoresistance remains a major challenge during and after its treatment. Exosomes, small extracellular vesicles involved in intercellular communication, have emerged as potential biomarkers and therapeutic targets in ovarian cancer. This review summarizes the current literature on differences in exosomal protein/gene expression between chemosensitive and chemoresistant ovarian cancer, and the effects of exosomal modifications on chemotherapeutic response. Clinical studies have identified alterations in several exosomal components from ovarian cancer tissues and serum samples arising as a consequence of chemosensitivity, which indicates their potential usefulness as potential biomarkers for predicting the development of chemoresistance. Interventional investigations from in vitro and in vivo studies demonstrated that modulation of specific exosomal components can influence ovarian cancer cell phenotypes and individual responses to chemotherapy. Exosomal delivery of chemotherapeutic agents, such as cisplatin, has presented as a potential targeted drug delivery strategy for overcoming chemoresistance in preclinical models. In summary, this review highlights the potential for exosomal proteins and genes to be useful biomarkers for predicting chemotherapy response and being therapeutic targets for overcoming chemoresistance in ovarian cancer. However, future research is still needed to validate these findings and explore the clinical utility of exosomal biomarkers and therapeutics in ovarian cancer management. In addition, understanding the molecular mechanisms underlying exosome-mediated chemoresistance may provide valuable insights for the development of personalized therapeutic strategies, improving outcomes for patients with ovarian cancer.

Knowledge, attitudes and practices of women regarding breast and cervical cancer screening: a qualitative study in India

In this study, we aimed to understand the factors that influence the use of breast and cervical cancer screening services in India. Purposive sampling was applied - and 64 participants with different characteristics based on their literacy, screening status, and rural or urban setting were classified into eight groups. The Knowledge, Attitudes and Practices (KAP) framework was used to conduct focus group discussions with each group. Data was analysed using directed content analysis. Regarding knowledge, our findings indicated that women who had previously undergone screening had some knowledge about the causes, risk factors, and symptoms of breast and cervical cancer. Most women were unaware of the screening procedure types and their costs, eligibility criteria, and frequency. None were aware of the link between cervical cancer and the human papillomavirus (HPV) infection. Regarding attitudes, all participants expressed that screening would be beneficial;when questioned if they would undergo screening without symptoms or physicians recommendations their opinions varied. The influence of their spouses or male children influenced their decision to undergo screening. Regarding practices, participants were unaware of and even overestimated the actual costs of screening services. They agreed that they would require subsidisation or fixed pricing from the government to undergo screening.

The Use of APC/C Antagonists to Promote Mitotic Catastrophe in Cancer Cells

Prospects of GPR68 in combined chemo-immunotherapy of tumors

Endometrial carcinomas – Challenges and updates on selected topics

Endometrial carcinoma comprises a heterogeneous group of tumors with distinct histologic, immunophenotypic, and molecular profiles that have important diagnostic and clinical implications. This review focuses on selected subtypes of endometrial carcinomas with the most update. Endometrial serous carcinoma, though representing ∼10 % of endometrial cancers, accounts for a disproportionate number of endometrial cancer deaths; its early forms - serous endometrial intraepithelial carcinoma and superficial serous carcinoma, collectively termed minimal uterine serous carcinoma (MUSC) - predominantly arise in an endometrial polyp and demonstrate a paradoxically high rate of extrauterine spread despite minimal tumor volume, mandating comprehensive staging. Corded and hyalinized endometrioid carcinoma (CHEC) and pilomatrix-like high-grade endometrial carcinoma (PiMHEC) are CTNNB1/β-catenin-driven variants of endometrioid carcinoma with biphasic or basaloid morphology that may mimic carcinosarcoma, serous, or squamous carcinoma and show variable, sometimes aggressive behavior. Mesonephric-like adenocarcinoma (MLA) is an ER/PR-negative, KRAS-mutated carcinoma with mesonephric-type morphology, frequent deep myometrial and lymphovascular invasion, and a predilection for pulmonary metastasis. Primary endometrial squamous cell carcinoma (PESCC) and endometrial gastric (gastrointestinal)-type mucinous carcinoma (EmGA) are exceptionally rare entities that require stringent exclusion of cervical or metastatic primaries and are typically associated with p53-abnormal and/or gastrointestinal-type molecular signatures and poor outcomes. Across these variants, integration of morphology with immunohistochemistry and molecular testing (including p53, MMR status, POLE) is essential for accurate classification and risk stratification. HER2 overexpression and/or amplification occurs in 25-30 % endometrial serous carcinoma and HER2 testing has become a standard biomarker for selecting patients with recurrent or advanced disease for trastuzumab, and more recently trastuzumab-deruxtecan therapy.

Low-grade appendiceal mucinous neoplasm: A case report

BACKGROUND Low-grade appendiceal mucinous neoplasms are papillary or flat mucinous tumors with low-grade cytologic atypia. They are the most frequent source of pseudomyxoma peritonei. They can be easily misdiagnosed, due to unspecific symptoms, with acute appendicitis, retroperitoneal tumors or adnexal mass. Cases of huge appendiceal mucinous neoplasms are even more extremely rare. CASE SUMMARY We report a 54-year-old patient who presented with a 10-month history of constant dull distension accompanied by nausea. A surgical procedure of total hysterectomy, bilateral adnexectomy, appendectomy, greater omentectomy and right hemicolectomy was performed as a result of the findings on ultrasound, computed tomography scan and magnetic resonance imaging. Diagnosis was made after the pathological examination, which revealed low-grade appendiceal mucinous neoplasm. The patient received hyperthermic intraperitoneal chemotherapy with cisplatin and was discharged from the hospital. CONCLUSION Low-grade appendiceal mucinous adenomas are rare tumors that are easily misdiagnosed, and a more thorough clinical workup is required to make a definitive diagnosis.

Advances in the Prevention of Cervical Cancer by Anti‐Human Papillomavirus Agents

ABSTRACTBackgroundCervical cancer remains a major global health threat for women, primarily driven by human papillomavirus (HPV) infection. While HPV vaccination serves as the cornerstone of prevention, disparities in vaccine accessibility persist across low‐income countries. Secondary prevention through screening faces challenges in public engagement, often leading to late‐stage diagnoses. Recent advancements in novel anti‐HPV drugs offer expanded opportunities for cervical cancer management.AimThis review examines emerging anti‐HPV therapeutics to provide insights into innovative strategies for cervical cancer prevention and treatment.MethodsWe conducted a systematic analysis of published studies investigating anti‐HPV agents, focusing on their molecular mechanisms and clinical efficacy in cervical cancer prevention.Results &amp; ConclusionsMultiple promising anti‐HPV agents have been identified, including 3‐hydroxyphthalic anhydride‐modified bovine β‐lactoglobulin (3HP‐β‐LG), carrageenan, defensins, and 25‐hydroxycholesterol (25HC). These compounds exert antiviral effects through distinct mechanisms: 3HP‐β‐LG competitively inhibits viral attachment, carrageenan blocks HPV entry via heparan sulfate mimicry, defensins inhibit the dissociation of viral capsid, and 25HC activates cholesterol‐mediated antiviral pathways. They have demonstrated strong inhibitory effects on HPV infection, making them novel therapeutic candidates for the prevention and treatment of cervical cancer.

Screening and identification analysis of core markers for leukemia and cervical cancer: Calmodulin 3 as a core target

Leukemia is a type of malignant tumor affecting hematopoietic system. Cervical cancer is a malignant tumor of female reproductive tract. The relationship between Calmodulin 3 (CALM3) and leukemia, cervical cancer remains unclear. Leukemia dataset GSE26294 and cervical cancer dataset GSE173097 profiles were downloaded from gene expression omnibus. Principal component analysis, differentially expressed genes (DEGs) screening, weighted gene co-expression network analysis (WGCNA), functional enrichment analysis, gene set enrichment analysis, immune infiltration analysis, protein–protein interaction network construction and analysis, survival analysis were performed. Gene expression heatmaps were plotted. Comparative Toxicogenomics Database (CTD) was used to find diseases most related to core genes. 77 DEGs were identified. According to gene ontology, in biological process category, they were mainly enriched in cell proliferation, immune response, and apoptotic process. In cellular component category, they were mainly enriched in nucleus and Golgi apparatus. In molecular function category, they were mainly enriched in DNA binding, protein binding, transcription factor activity. In Kyoto encyclopedia of gene and genome analysis, they were mainly enriched in cell adhesion molecules, Wnt signaling pathway, cAMP signaling pathway, cGMP-PKG signaling pathway, and basal cell carcinoma. The soft-threshold power in WGCNA was set to 1, generating 6 modules. Finally identifying 3 core genes (CALM3, secreted frizzled-related protein 4, plasminogen). CTD analysis revealed that core genes were related to leukemia, coagulation disorders, vaginal tumors, cervical tumors, autoimmune diseases, and inflammation. CALM3 is lowly expressed in leukemia samples and highly expressed in cervical cancer samples.

A rare case of numerous parasitic myomas after laparoscopic myomectomy

AbstractParasitic myoma is a relatively rare disease in which one or more leiomyomas form outside the uterus; however, the detailed causes are unknown. Few sporadic reports are available, and per our research, the maximum number of parasitic myomas reported to date was 26, and almost all cases were treated by surgical resection. We report a rare case of numerous parasitic myomas in the abdominal cavity, possibly including an intrathoracic lesion, which could not be resected completely. The patient was a 42‐year‐old, gravid 2, para 0, artificially aborted 2, and not yet menopausal woman. She had undergone laparoscopic myomectomy at a different hospital 6 years prior. Laparoscopically, numerous hard white masses, ranging from 1 mm to approximately 55 mm in size, were found in the abdominal cavity. The masses were particularly numerous in the omentum and mesentery but were also found on the diaphragm, abdominal peritoneum, and intestinal surface. The patient was pathologically diagnosed with multiple benign leiomyomas. On computed tomography, a similar nodule was observed in the right lower lobe of the lung. Despite using in‐bag morcellation, as in this case, numerous parasitic myomas occurred, suggesting that greater caution should be exercised when explaining laparoscopic myomectomy to patients.

Elucidating the Molecular Mechanisms of Hederagenin-Regulated Mitophagy in Cervical Cancer SiHa Cells through an Integrative Approach Combining Proteomics and Advanced Network Association Algorithm

Hederagenin (Hed), a natural triterpenoid, exhibits antitumor potential in cervical cancer. The present study was designed to explore Hed's regulatory mechanisms on mitophagy in SiHa cervical cancer cells, employing tandem mass tag (TMT) proteomics and an advanced network association algorithm (NAA). Our findings revealed that Hed decreased SiHa cell viability, induced apoptosis, and altered mitochondrial membrane potential. Notably, Hed inhibited mitophagic flux under both normoxic and hypoxic conditions. Through TMT proteomics analysis and innovative NAA, we identified a close association between the HIF-1 signaling pathway and mitophagy. Network analysis further suggested that Hed acts on a target network centered on SRC, STAT3, AKT1, and HIF1A. Western blot analysis confirmed the expression and phosphorylation status of these targets in response to Hed. This study elucidates the molecular mechanisms underlying Hed's regulation of mitophagy in SiHa cells, offering novel insights and potential therapeutic targets for cervical cancer treatment.

Use and outcomes of hormonal therapy for advanced-stage, low-grade serous ovarian cancer.

To examine trends in the use of hormonal therapy for advanced-stage, low-grade serous ovarian carcinoma and to compare survival outcomes of patients who received traditional chemotherapy, hormonal therapy alone, or the combination of both. Women with stage II to IV low-grade serous ovarian cancer diagnosed between 2011 and 2020 were identified from the National Cancer Data Base. Patients undergoing primary surgery followed by adjuvant chemotherapy, hormonal therapy, or both were included. A multinomial logistic regression model was used to examine factors associated with treatment. Propensity score-weighted Cox proportional hazards models (via inverse probability of treatment weighting) were applied to compare overall survival across the treatment groups. Among 1532 women, 68.0% received chemotherapy alone, 12.3% received hormonal therapy alone, and 19.8% received combination therapy. Use of hormonal monotherapy increased from 0.8% in 2011 to 27.4% in 2020, and use of combination therapy increased from 0.8% to 32.6% (p 70 years) (p = .001) and those with Medicare insurance (p < .001), while combination therapy was more common in women with stage III to IV disease (p = .001). After applying propensity score weighing, 5-year survival was 76.6% (95% CI 73.2% to 79.7%) for chemotherapy alone, 85.5% (95% CI 66.1% to 94.3%) for hormonal therapy alone, and 75.8% (95% CI 59.7% to 86.2%) for combination therapy. Compared to chemotherapy alone, the HR for all-cause mortality was 0.74 (95% CI 0.46 to 1.19) for hormonal therapy alone and 0.88 (95% CI 0.63 to 1.24) for combination therapy. In advanced-stage low-grade serous ovarian cancer, the use of hormonal therapy increased substantially over time. Comparable survival outcomes across modalities suggest hormonal therapy may be a viable treatment option, particularly for patients who will not tolerate the side effects of cytotoxic chemotherapy.

Perceived Risk and HPV Vaccination Awareness Among Women in Rural and Underserved Communities in the State of Louisiana

Abstract Despite the availability of effective preventive measures, women in rural and underserved communities of Louisiana face health disparities regarding human papillomavirus infections. This study explores how perceived risk and socioeconomic factors, such as income, influence HPV vaccine awareness and attitudes toward HPV risk. A cross-sectional study was conducted among women in rural and underserved areas of Louisiana from November 2022 to December 2023. Participants were eligible to be included in the study if they were adult females aged 25 to 64 with no history of hysterectomy and no history of cervical cancer. We used convenience sampling through a mobile health unit that travels to rural and underserved areas of north and central Louisiana, offering cervical cancer screening. A total of 141 women participated in the study. Findings revealed significant gaps in HPV awareness and vaccination knowledge. Only 10.6% of participants considered themselves at risk for HPV. Higher HPV knowledge scores were positively associated with perceived HPV risk, increasing by approximately 20% per correct response. Approximately 40% of the participants were unaware of the existence of the HPV vaccine, 96.5% had never received the HPV vaccine, and 91.4% had never been offered it. Only 42% indicated that they would consider vaccination if offered. Addressing health disparities in rural Louisiana requires targeted interventions to improve healthcare access, education, and community engagement. Efforts to enhance education and awareness and foster community engagement should be prioritized.

The impact of antibiotics, proton pump inhibitors, H2-receptor antagonists, and steroids on survival in ovarian cancer patients receiving PARP inhibitor therapy

Antibiotics (ABX) have been linked to reduced survival in ovarian cancer (OC) when administered before or during platinum-based chemotherapy. This study evaluates the impact of ABX, proton pump inhibitors (PPI), H2-receptor antagonists (H2RA), and steroids on progression-free survival (PFS) in OC patients receiving poly-ADP-ribose polymerase inhibitors (PARPi). This retrospective study examined OC patients who used ABX, PPI, H2RA, or steroids before or during PARPi therapy. Demographics, clinicopathologic characteristics, and treatment outcomes were analyzed. Cox proportional hazards models assessed risk factors for PFS, and Kaplan-Meier analysis with log-rank testing evaluated survival differences based on ABX use. Among 237 patients treated with 269 PARPi regimens, most received PARPi in the recurrent setting (79.6 %). At the time of PARPi therapy, 21.6 % used ABX, 15.6 % PPI, 11.2 % H2RA, and 63.9 % steroids. Patients with HRP/unknown status had significantly worse median PFS than those with BRCA-mutated/HRD (6 vs. 11 months; p < 0.001). ABX use correlated with improved median PFS (10 vs. 7 months; p = 0.049) but lost significance in multivariate analysis. PPI, H2RA, and steroids had no impact on PFS. In this retrospective analysis, concurrent medications were not associated with worsened survival outcomes in OC patients receiving PARPi. Further, while ABX use during PARPi therapy was associated with improved survival this was not significant after adjusting for confounders.

ATP13A2 as a prognostic biomarker and its correlation with immune infiltration in cervical cancer: A retrospective study

Abstract While the oncogene ATP13A2 is reportedly involved in colorectal cancer, its role in cervical cancer (CC) has yet to be fully characterized. In this study, we investigated ATP13A2 as a potential prognostic biomarker of CC. To this end, we compared CC tissues with normal tissues to identify differentially expressed genes, identifying ATP13A2 as a potential marker of CC. Elevated ATP13A2 expression levels were identified in CC samples compared to noncancerous samples across various data sets, with further immunohistochemical validation. Functional enrichment analysis revealed that ATP13A2 plays an essential role in the CXCL12‐activated CXCR4 signalling pathway and chemotaxis regulation, which may alter immune infiltration. Notably, increased ATP13A2 levels were associated with poor overall survival. Furthermore, multiple clinical characteristics were significantly associated with ATP13A2 expression. Additionally, tumour bacterial infiltration was assessed using weighted co‐expression network analysis, revealing a relationship between ATP13A2 expression and bacteria in the CC tumour microenvironment. Our results suggest that ATP13A2 is a promising diagnostic and prognostic marker for CC. However, further large‐scale studies are needed to fully elucidate the mechanisms underlying the involvement of ATP13A2 in CC.

Technical, legal and ethical framework of cancer audit in cervical screening – Summary of best practices for organised programmes delineated through an expert group consultation

AbstractEfficient and well‐organised cervical screening programmes have significantly reduced both the incidence and mortality rates of cervical cancer in the population. For optimal performance, such programmes need to incorporate essential quality assurance measures. The International Agency for Research on Cancer (IARC/WHO) organised an expert consultation to delineate best practices in auditing cancers in a cervical screening programme, the legal and ethical frameworks governing such audits, and communicating audit outcomes. As a best practice, every programme should have a well‐documented policy and process framework for cancer audits. The TWGs agreed that the primary goal of programmatic cancer audits is to assess the programme's effectiveness in lowering cervical cancer incidence and minimising screening‐related risks. Using audit results, informed decisions can be made to enhance service delivery, including professional training, adopting improved screening tests, strengthening fail‐safe mechanisms, reducing delays, and minimising inequalities. Legal complexities in cervical screening stem from its inherent limitations and risks, and differentiating cases of negligence from inevitable and non‐negligent errors where an abnormality is not detected but actually exists is crucial. TWGs suggested that determining whether a screening error was serious enough to be categorised as negligent and/or to entitle the patient to compensation should reflect the inherent limitations of cervical screening. Data obtained while performing screening tests and subsequent diagnostic tests or treatments are sensitive and need to be safeguarded. The best practice document drafted through expert consultation will help cervical screening programmes standardise practices related to cancer audits and address associated legal and ethical issues.

Efficacy and safety of photodynamic therapy mediatied by 5-aminolevulinic acid for the treatment of cervical intraepithelial neoplasia 3(CIN 3): A single-center, prospective, cohort study

Cervical intraepithelial neoplasia grade 3(CIN 3) is a precancerous lesion condition with high progression rate and is advised to be treated immediately. Because traditional treatments have limited effects or complications, here we evaluated the efficacy and safety of topical 5-aminolevulinic acid (ALA)-based photodynamic therapy (PDT). This study consisted of 56 female patients diagnosed with CIN3. A 20 % 5-ALA jelly formation was topically applied to the cervix, followed by 635 nm PDT at 7-14 days intervals. Cytology, human papillomavirus (HPV) genotyping, colposcopy, and pathology were assessed after treatment. Among the 56 patients in our study, 26.8 % (15/56) patients had disease remission after just one course PDT, 69.6 % (39/56) patients had partial remission to CIN2, which suggested a response to the therapy and should be treated with more course. The total pathological regression rate was 89.3 %(50/56). Although6 patients did CKC finally, none of the pathology suggest cervical cancer and 2 of them were LSIL. The HPV clearance rate during the 6-month follow-up was 51.8 %. 4 patients had recurrent disease during the 2-year follow-up time point. The most common adverse event was increased vaginal discharge, other side effects include abdominal pain, vulvar pruritus, and vaginal bleeding. No severe adverse effect was observed during the treatment. ALA-PDT is a treatment option for CIN 3 which meet certain conditions, with the main goal to preserve the struction and founction of cervix.