BackgroundTislelizumab is an anti-programmed cell death 1 (PD-1) monoclonal antibody engineered to minimize binding to Fcγ receptors. It has been used to treat several solid tumors. However, its efficacy and toxicity, and the predictive and prognostic value of baseline hematological parameters in patients with recurrent or metastatic cervical cancer (R/M CC) receiving tislelizumab remain unclear.MethodsWe reviewed 115 patients treated for R/M CC with tislelizumab from March 2020 to June 2022 in our institute. The antitumor activity of tislelizumab was assessed using RECIST v1.1. Associations between the baseline hematological parameters and efficacy of tislelizumab in these patients were analyzed.ResultsWith a median follow-up of 11.3 months (range, 2.2–28.7), the overall response rate was 39.1% (95% CI, 30.1–48.2) and the disease control rate was 77.4% (95% CI, 69.6–85.2). The median progression-free survival (PFS) was 19.6 months (95% CI, 10.7 to not reached). The median overall survival (OS) was not reached. Treatment-related adverse events (TRAEs) of any grade occurred in 81.7% of the patients and only 7.0% of the patients experienced grade 3 or 4 TRAEs. Univariate and multivariate regression analyses showed that the level of pretreatment serum C-reactive protein (CRP) was an independent risk factor for the response (complete or partial response) to tislelizumab and the PFS of R/M CC patients treated with tislelizumab (P = 0.0001 and P = 0.002, respectively). R/M CC patients with elevated baseline CRP levels had a short PFS (P = 0.0005). Additionally, the CRP-to-albumin ratio (CAR) was an independent risk factor for the PFS and OS of R/M CC patients treated with tislelizumab (P = 0.001 and P = 0.031, respectively). R/M CC patients with an elevated baseline CAR had short PFS and OS (P < 0.0001 and P = 0.0323, respectively).ConclusionsTislelizumab showed promising antitumor activity and tolerable toxicity in patients with R/M CC. The baseline serum CRP levels and CAR showed potential for predicting the efficacy of tislelizumab and the prognosis of R/M CC patients receiving tislelizumab.

N6-methyladenosine (m6A) is a highly abundant RNA modification in eukaryotic cells.Methyltransferase-like 3 (METTL3), a major protein in the m6A methyltransferase complex, plays important roles in many malignancies, but its role in cervical cancer metastasis remains uncertain. Here, we found that METTL3 was significantly upregulated in cervical cancer tissue, and its upregulation was associated with a poor prognosis in cervical cancer patients. Knockdown of METTL3 significantly reduced cervical cancer cell migration and invasion. Conversely, METTL3 overexpression markedly promoted cervical cancer cell metastasis in vitro and in vivo. Furthermore, METTL3 mediated the m6A modification of cathepsin L (CTSL) mRNA at the 5′-UTR, and the m6A reader protein insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) bound to the m6A sites and enhanced CTSL mRNA stability. Our results indicated that METTL3 enhanced CTSL mRNA stability through an m6A-IGF2BP2-dependent mechanism, thereby promoting cervical cancer cell metastasis. These findings provide insights into a novel m6A modification pattern involved in cervical cancer development.

Background: The systemic immune-inflammation index (SII) has been identified as a predictor of chemotherapy efficacy for a variety of cancers, and we aimed to determine its ability to predict the response to chemotherapy and its long-term prognosis for patients with cervical squamous cell carcinoma (CSCC) who have underwent platinum-based neoadjuvant chemotherapy (NACT).Methods: The date from 210 patients (133 in the training cohort and 77 in the validation cohort) with CSCC who received NACT were analyzed retrospectively. The association between SII and the pathological complete response (pCR) was determined using Pearson’s chi-square test, receiver operating characteristic (ROC) curve, and Logistic regression analysis. The Kaplan-Meier method and Cox proportional regression model were used to assess the relationship between SII and progression-free survival (PFS) or overall survival (OS).Results: The calculated optimal SII cutoff values for pCR and survival were 568.7051 and 600.5683, respectively, and patients were divided into two groups: a low SII group (≤568.7051 or ≤600.5683) and a high SII group (>568.7051 or >600.5683). A high SII was associated significantly with a lower pCR. Further analysis determined that SII was a more efficient predictor of pCR than the prognostic nutritional index, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio. Upon multivariate logistic analysis, SII proved to be an independent risk factor to predict the pCR of patients with CSCC. Kaplan-Meier analysis demonstrated that PFS and OS rates were significantly higher in the low-SII group compared with those in the high-SII group. Additional multivariate analysis indicated that the SII is an independent prognostic factor for patients with CSCC treated with NACT.Conclusion: The results confirmed that the pre-treatment SII is not only an independent predictor of pCR but also an independent prognostic factor of CSCC patients treated with platinum based NACT.

Objectives: The present study aimed to identify the predictive value of inflammatory indexes stratified according to human papillomavirus (HPV) infection status in women with FIGO 2018 stage IB∼IIA cervical cancer. We also explored the influences of HPV infection status on the survival of cervical cancer patients.Methods: We collected data for 583 women with stage IB∼IIA cervical cancer in Sun Yat-sen University Cancer Center between 2009 and 2017. The t-test, chi-squared (χ2) test and Fisher’s exact test were applied to compare the differences of inflammatory indexes and clinicopathological features between HPV-positive and HPV-negative groups. Univariate and multivariate analyses were used to identify clinicopathological factors that were associated with the prognosis of cervical cancer patients.Results: There were no differences in overall survival (OS) and progression-free survival (PFS) between HPV-positive and HPV-negative groups. In HPV-positive group, the maximum tumor size, neoadjuvant chemotherapy and the body mass index (BMI) correlated significantly with C-reactive protein/albumin ratio (CAR). The maximum tumor size and the prognostic nutritional index (PNI) correlated significantly with the platelet-lymphocyte ratio (PLR). The maximum tumor size, neoadjuvant chemotherapy and PLR correlated significantly with PNI. Univariate and multivariate analyses showed that the depth of tumor invasion (HR: 3.651, 95% CI: 1.464–9.103, p = 0.005; HR: 2.478, 95% CI: 1.218–5.043, p = 0.012) and CAR (HR: 5.201, 95% CI: 2.080–13.004, p < 0.0001; HR: 2.769, 95% CI: 1.406–5.455, p = 0.003) were independent predictors of poor OS and PFS. PNI was an independent protective factor of OS (HR: 0.341, 95% CI: 0.156–0.745, p = 0.007). PLR was an independent factor of PFS (HR: 1.991, 95% CI: 1.018–3.894, p = 0.044). In HPV-negative group, BMI correlated significantly with CAR. Only depth of invasion (HR: 9.192, 95% CI: 1.016–83.173, p = 0.048) was the independent predictor of poor OS, and no inflammation indexes were independent predictors of prognosis.Conclusion: In patients with HPV-positive cervical cancer, depth of invasion, PNI and CAR are independent factors of OS, and depth of invasion, PLR and CAR are independent factors for PFS. For patients with HPV-negative disease, no inflammation indexes had predictive value for prognosis. The predictive value of inflammation indexes on prognosis is more significant in patients with HPV-positive cervical cancer. Stratification of HPV infection status promotes a more precise clinical application of inflammation indexes, thus improving their accuracy and feasibility.

Objective To summarize the risk factors and emphasize the prognostic importance of the site of recurrent neuroendocrine cervical cancer (NECC). Methods We enrolled 88 patients who developed recurrence after radical surgery for pathological stage I–IVa primary NECC between January 2003 and 30 December 2020 and classified these cases into 7 groups based on the initial recurrence. The risk factors for post-recurrence survival (PRS) were analyzed by Kaplan–Meier and Cox regression methods. Results Among 88 NECC patients, nearly all patients (95.50%) experienced progression within 3 years. The time to progression was significantly longer in patients with lung recurrence than in patients without lung recurrence (p = 0.008). After the first recurrence, the median follow-up was 11.1 months (range 2.37–65.50 months), and the 5-year PRS was only 20.6%. The depth of invasion in the primary surgery, number of recurrent sites, abdominal organ recurrence were correlated with PRS by univariate analysis. Multivariate analyses revealed that the number of recurrent sites (p = 0.025) and abdominal organ recurrence (p = 0.031) were independent prognostic factors. Notably, the combination of immune checkpoint inhibitors and chemotherapy, with or without surgery, showed a 43.8% objective response rate in recurrent NECC. Conclusion Patients with abdominal organ recurrence need more sophisticated therapy. The combination of immune therapy and chemotherapy might be an opportunity for recurrent NECC.