Yanhong Zhuo

Molecular and Immune Correlates of Response to First-Line De-escalated Chemotherapy plus Penpulimab and Anlotinib in Advanced Cervical Cancer

Abstract The standard of care for advanced cervical cancer includes chemotherapy, antiangiogenic, and/or immune checkpoint blockade regimens. Although effective, it leads to pleiotropic side effects. Deescalation chemotherapy together with immunotargeted therapies has been proven effective and less toxic in other cancers. In this study, we conducted a multicenter, single-arm, phase II study of first-line deescalated platinum-based chemotherapy plus anlotinib and penpulimab, followed by maintenance therapy solely with anlotinib and penpulimab in patients with PD-L1–positive, persistent, recurrent, or metastatic cervical cancer. Of 32 efficacy-evaluable patients, 30 (93.8%, 95% confidence interval, 79.2%–99.2%) had an investigator-confirmed objective response. Single-nucleus RNA sequencing implied enhanced chemotaxis and proliferative activity of tumor-infiltrating T cells, and activated germinal center B cells portended optimal treatment response. Patients with a high tertiary lymphoid structure-to-tumor area ratio exhibited better survival. Our findings lay the groundwork for the feasibility of first-line de-escalated chemotherapy plus anlotinib and penpulimab in patients with metastatic, persistent, or recurrent cervical cancer. Significance: We recruited 34 patients with advanced cervical cancer receiving two cycles of platinum-based chemotherapy plus anlotinib and penpulimab, followed by maintenance therapy solely with anlotinib and penpulimab, and showed safety and efficacy of this deescalation regimen. This work highlights the potential for personalized treatment strategies and feasibility of reduced-toxicity regimens.

Comprehensive clinical analysis of gastric-type endocervical adenocarcinoma: a real-world multicenter study

Gastric-type endocervical adenocarcinoma (G-EAC) is a rare malignancy, and its clinicopathological characteristics remain poorly defined. This study aimed to evaluate the real-world features, treatment patterns, and outcomes of patients with G-EAC. Clinical data from 124 patients diagnosed with G-EAC between 2012 and 2024 across four tertiary hospitals in China were retrospectively analyzed. Clinicopathological features, therapeutic approaches, and survival outcomes were assessed. Overall survival (OS) was the primary endpoint. Kaplan-Meier and Cox regression analyses were performed to identify prognostic factors. The median diagnostic age was 55 years (range, 33-82). At presentation, 62.1% of patients had invasion or metastasis, most commonly lymphovascular (47.6%). Surgery was performed in 81.5% of cases, and 84.7% received chemotherapy, primarily platinum-based (81.5%). Radiotherapy was administered to 69.4%. The 1-, 3-, and 5-year OS rates were 78.6%, 54.8%, and 46.1%, respectively. Older age (≥65 years; HR, 4.71; 95% CI, 1.52-14.58; G-EAC exhibits aggressive behavior and unfavorable prognosis, with a 5-year OS of 46.1%. Multimodal treatment, particularly surgery combined with chemotherapy, remains the cornerstone of management and may improve survival. Prospective multicenter studies are warranted to further define optimal therapeutic strategies for this rare entity.

Association between serum γ-Glutamyltransferase and the risk of cervical cancer: Evidence from the national health and nutrition examination survey

Background The principal cause of cervical cancer is sustained high-risk human papillomavirus (HPV) infection. However, some cases remain unrelated to HPV infections. Current HPV screening methods have difficulties identifying HPV-negative patients and implementing them in low-resource settings. Therefore, it is important to explore easily accessible and low-cost biomarkers to optimize the current cervical cancer screening strategies. Methods This cross-sectional study included 6998 women from the US National Health and Nutrition Examination Survey (NHANES), among whom 147 had self-reported cervical cancer. Serum γ – Glutamyltransferase (GGT) was employed as a continuous variable (naturally logarithmically transformed) and a categorical variable (≥50 U/L versus <50 U/L), and multivariate logistic regression models were utilized to progressively adjust for demographic features, sexual history, and clinical behaviors. The restricted cubic spline approach was adopted to further explore the dose-response relationship between GGT levels and cervical cancer to depict the potential nonlinear trends between them in a more elaborate manner. We also conducted subgroup and sensitivity analyses to ensure reliability of our results. This included multiple imputation of missing data and adjustment for crucial covariates, such as body mass index (BMI) and tobacco exposure, to comprehensively evaluate the impact of different factors on the outcomes. Ultimately, through mediation analysis, we probed the mediating function of tobacco exposure in the association between GGT levels and cervical cancer, aiming to obtain a more profound understanding of the underlying mechanisms of this health-related relationship. Results Serum GGT levels are positively correlated with cervical cancer risk. For each log unit increase in GGT levels, there was a 31% increased risk of cervical cancer (OR = 1.31, 95%CI: 1.01–1.70, P = 0.041) in the model adjusted for multiple risk factors. When the GGT level reached or exceeded 50 U/L, the risk increased by 76% (OR = 1.76, 95%CI: 1.04–2.98, P = 0.034). This tendency was consistent across several crucial subgroups, particularly among HPV-negative women (OR = 1.36, 95%CI: 1.01–1.84), suggesting that GGT may have some significance in different populations. The results of the sensitivity analyses demonstrated that the main findings remained robust, even when multiple imputations were employed to handle missing data. Nevertheless, the significant association between GGT and cervical cancer weakened when tobacco exposure was further adjusted, indicating that tobacco use might be involved. Mediation analysis further showed that the overall impact of GGT on cervical cancer was statistically significant (β = 0.0014; 95%CI: 0.0001–0.0020; P = 0.046), and approximately 18.15% of the impact was accounted for by tobacco exposure (ACME: β = 0.0003, 95%CI: 0.0001–0.0004, P < 0.001), suggesting a partial mediating role. Conclusion Elevated serum GGT levels are associated with a heightened risk of cervical cancer even in HPV-negative patients. Although this association is partly mediated by tobacco exposure, GGT may still play a role in cervical cancer via nontobacco routes. The potential application of GGT as an auxiliary biomarker requires further validation in prospective studies.