Hanmei Lou

Integrated Proteomics and Metabolomics Profiling Unveils Biomarkers and Immune Characteristics for Pelvic Lymph Node Metastasis in Cervical Cancer

Pelvic lymph node metastasis (PLNM) significantly affects the prognosis of cervical cancer (CC). However, current imaging examinations and serum squamous cell carcinoma antigen (SCCA) testing are inadequate for assessing the pelvic lymph node status in CC. To identify accurate noninvasive biomarkers for diagnosing PLNM and minimizing unnecessary postoperative lymphadenectomy and its associated complications, we performed a comprehensive proteomic and metabolomic analysis of plasma from 124 patients with CC, along with a proteomic analysis of 60 paired tissue samples. Through machine learning methods, we identified potential plasma biomarkers (TTR, MASP2, APOD, and 7α-hydroxy-cholestene-3-one) and constructed a diagnostic model. In the validation cohort, the diagnostic model combined with SCCA exhibited a higher sensitivity (72.4%) than SCCA (64.3%) and imaging examination (14.3%). The plasma protein biomarkers were consistently validated in paired tissue samples. Additionally, immune infiltration analysis demonstrated that CD4 and CD8 T cells were highly infiltrated in the PLNM group, suggesting a potentially enhanced response to immunotherapy. Here, we established a biomarker panel for PLNM and highlighted the altered immune characteristics associated with PLNM, offering valuable insights for the development of immunotherapy strategies for patients with PLNM.

Monitoring circulating cell-free HPV DNA in metastatic or recurrent cervical cancer: clinical significance and treatment implications

Background:Monitoring circulating HPV cell-free DNA (cfDNA) offers a minimally invasive method for surveillance in HPV-associated cancers, particularly cervical cancer. However, the role of dynamic HPV cfDNA monitoring in guiding clinical treatment decisions for recurrent or metastatic cervical cancer remains underexplored.Methods:In this prospective pilot observational study, levels of HPV cfDNA in serum samples from 28 patients with recurrent or metastatic HPV-positive cervical cancer were measured via digital droplet polymerase chain reaction. Results for HPV cfDNA levels were matched to clinical outcomes and to serum levels of squamous cell carcinoma antigen (SCC-Ag) to assess the clinical potential of HPV cfDNA as a tumor marker.Results:HPV cfDNA was detected in all 28 patients. Notably, median baseline HPV cfDNA levels varied according to the metastatic pattern observed in individual patients (p=0.019). All participants exhibited changes in HPV cfDNA levels over a median monitoring period of 2 months (range 0.3–16.9 months) prior to evaluations for treatment response or disease progression. Among 26 patients initially diagnosed with squamous cell cervical cancer, the positivity rate was 100% for HPV cfDNA and 69.2% for SCC-Ag (p=0.004, 95% confidence interval (CI), 0–0.391). Among 20 patients longitudinally monitored for squamous cell cervical cancer, the concordance with changes in disease status was 90% for HPV cfDNA and 50% for SCC-Ag (p=0.014, 95% CI, 0.022–0.621).Conclusions:Our study demonstrates that HPV cfDNA is a promising tumor marker for monitoring of recurrent or metastatic HPV-positive cervical cancer.Funding:This work was supported by the Key R&D Program of Zhejiang (2022C04001), the Zhejiang Province Medicine and Health Science and Technology Program (2020KY454), the Zhejiang Science and Technology Department Public Welfare Project (LGF22H160075).

Deficiency of the UBE2C/F264 Axis Underlies Intrinsic Radioresistance in Cervical Carcinoma

Intrinsic radiotherapy resistance remains a persistent challenge to the treatment of cervical cancer (CC), as the underlying mechanisms remain largely elusive. In this study, proteomic profiling was combined with

Efficacy and safety of cisplatin combined with paclitaxel concurrent radiotherapy in patients with locally advanced cervical squamous cell carcinoma

This study aimed to compare outcomes and adverse events of patients with locally advanced cervical cancer (LACC) undergoing concurrent chemoradiotherapy (CCRT) with cisplatin single-agent chemotherapy vs. CCRT with cisplatin combined with paclitaxel dual-agent therapy. The primary outcomes are overall survival (OS), progression-free survival (PFS), local recurrence (LR), distant metastasis (DM) and the occurrence of adverse events. This retrospective cohort study included patients with FIGO 2009 stage IB1-IVA cervical squamous cell carcinoma undergoing radical CCRT. Patients were divided into groups A and B, treatment outcomes were compared between the two groups after 1:1 proportional propensity score matching. Medical records of 1,203 patients were reviewed and 572 patients were finally included for propensity score matching. After propensity score matching, 121 pairs of patients were selected for analysis. The OS, PFS, LR and DM rates were 78.5% and 83.5% (p=0.417), 73.3% and 78.5% (p=0.312), 6.6% and 2.5% (p=0.123), 19% and 15.7% (p=0.497) for groups A and B, respectively. Further subgroup analysis according to stage and lymph node metastatic status showed no difference in survival between the two groups. The incidence of grade 3-4 acute haematological toxicities was different between the two groups (p<0.05). Cisplatin combined with paclitaxel CCRT couldn't improve the survival rates of patients with LACC. However, the hematological toxicity of combination chemotherapy is more severe but controllable. Cisplatin single-agent therapy remains the first choice for CCRT. Further prospective studies are indicated to provide evidence for the efficacy of cisplatin plus paclitaxel in dual-agent concurrent therapy.

Comparison of adenocarcinoma and adenosquamous carcinoma prognoses in Chinese patients with FIGO stage IB-IIA cervical cancer following radical surgery

Abstract Background To compare adenocarcinoma (AC) and adenosquamous carcinoma (ASC) prognoses in patients with FIGO stage IB–IIA cervical cancer who underwent radical hysterectomy. Methods We performed a retrospective analysis of 240 patients with AC and 130 patients with ASC. Kaplan–Meier curves, Cox regression models, and log-rank tests were used for statistical analysis. Results Patients with ASC had higher frequencies of lymphovascular space invasion (LVSI) and serum squamous cell carcinoma antigen (SCC-Ag) &gt; 5 ng/ml ( p  = 0.049 and p  = 0.013, respectively); moreover, they were much older ( P  = 0.029) than patients with AC. There were no clinically significant differences in overall survival (OS) between the groups. When stratified into three risk groups based on clinicopathological features, survival outcomes did not differ between patients with AC and those with ASC in any risk group. Multivariate analysis showed that lymph node metastasis (LNM) was an independent risk factor for recurrence-free survival (RFS) and OS in patients with AC and in patients with ASC. Carcinoembryonic antigen (CEA) &gt; 5 ng/ml and SCC-Ag &gt; 5 ng/ml were independent predictors of RFS and OS in patients with AC. In addition, among those stratified as intermediate-risk, patients with ASC who received concurrent chemoradiotherapy (CCRT) had significantly better RFS and OS ( P  = 0.036 and P  = 0.047, respectively). Conclusions We did not find evidence to suggest that AC and ASC subtypes of cervical cancer were associated with different survival outcomes. CCRT is beneficial for survival in intermediate-risk patients with ASC, but not in those with AC. Serum tumour markers can assist in evaluating prognosis and in providing additional information for patient-tailored therapy for cervical AC.

Cadonilimab Combined with Chemotherapy with or without Bevacizumab as First-Line Treatment in Recurrent or Metastatic Cervical Cancer (COMPASSION-13): A Phase 2 Study

Abstract Purpose: Immune checkpoint inhibitors (ICI) have been a potential treatment option for patients with cervical cancer in several clinical studies. We investigated the safety and efficacy of cadonilimab, a bispecific antibody targeting PD-1 and CTLA-4, plus standard therapy for the first-line treatment of R/M CC (recurrent and/or metastatic cervical cancer). Patients and Methods: Eligible patients were assigned to 3 cohorts: cohort A-15 (cadonilimab 15 mg/kg every 3 weeks (Q3W) plus chemotherapy), cohort A-10 (cadonilimb 10 mg/kg Q3W plus chemotherapy), and cohort B-10 (cadonilimab 10 mg/kg Q3W plus chemotherapy and bevacizumab). They received the corresponding treatments until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision. The primary objective was safety; the secondary endpoints included objective overall response (ORR), duration of response, disease control rate, progression-free survival, and overall survival. This study is registered with ClinicalTrials.gov (NCT04868708). Results: As of February 13, 2023, treatment-related adverse events (TRAE) occurred in 45 (100.0%) patients. Grade ≥3 TRAEs were reported in 33 (73.3%) patients. Immune-related adverse events (irAE) occurred in 29 (64.4%) patients and grade ≥3 irAEs were observed in 9 (20.0%) patients. Seven (15.6%) of 45 patients permanently discontinued cadonilimab treatment due to TRAEs. One death due to hemorrhagic shock occurred in cohort B-10. Among 44 patients who underwent at least one post-baseline tumor assessment, the ORR was 66.7% in cohort A-15, 68.8% in cohort A-10, 92.3% in cohort B-10, and 79.3% in cohorts A-10 and B-10 combined. Conclusions: Cadonilimab combined with standard therapy was acceptable, with encouraging antitumor activity in patients with R/M CC.