Qinyong Hu

Ovarian cancer disease burden decreased in the United States from 1975 to 2018: A joinpoint and age-period-cohort analysis

Ovarian cancer (OC) is the leading cause of gynecological cancer-related deaths in the United States. The purpose of this study was to evaluate long-term trends in OC incidence and incidence-based mortality rates (IBM) in the U.S. from 1975 to 2018 and to assess the effects of age, period, and cohort factors on OC incidence and mortality using an age-period-cohort model. We obtained data from the U.S. OC incidence/mortality data from the Surveillance, Epidemiology, and End Results database from 1975 to 2018. Joinpoint regression analysis was used to determine long-term trends and transitions, and an age-period-cohort model was used to quantify the effects of age, period, and cohort parameters on incidence and mortality. In addition, 1990 to 2019 U.S. OC data obtained from the Global Burden of Disease study served as a potential validation set. Between 1975 and 2018, 80,622 new cases of OC and 60,218 deaths from OC were reported in the U.S. The average annual percent change for OC incidence was −1.33 (95% CI: −1.64 to −1.02, P < .001), with a significant decrease in incidence at a rate of 7.80% (95% CI: −11.52 to −3.92) per year from to 2015–2018. IBM reached its peak for the U.S. population in 1994, with an age-standardized mortality rate of 6.38 (per 100,000 people). IBM rose first, peaked in 1986, and then declined at a rate of 0.39% (95% CI: −0.66 to −0.12) and 2.48% (95% CI: −3.09 to −1.85) per year from to 1986–2007 and 2007–2018, respectively. In addition, age-period-cohort model analysis showed the highest risk of OC incidence in 1980 to 1984 and the highest risk of OC death in 1985–1989. This study reported a significant decline in OC morbidity and mortality in the U.S. since 1986. In addition, this study analyzed the changes in trends in OC incidence and mortality by race/ethnicity in the U.S. Monitoring trends in OC incidence and mortality by race/ethnicity can help in the development of targeted prevention and treatment measures.

Tumor Core‐Edge Divergence in T‐Cell Exhaustion and Clonal Expansion in HPV‐Related Cervical Squamous Cell Carcinoma Unveiled by Simultaneous Single‐Cell RNA and TCR Sequencing

ABSTRACT Tumor spatial architecture significantly influences immune responses, but the impact of regional variations on T cell exhaustion and clonality in human papillomavirus (HPV)‐related cervical squamous cell carcinoma (CESC) remains poorly understood. Using single‐cell RNA sequencing (scRNA‐seq, n  = 13) and TCR sequencing (scTCR‐seq, n  = 9), this study profiled T cells from paired tumor core and edge samples of patients with CESC. This was supplemented by bulk RNA‐seq data ( n  = 41), TCGA datasets from three cancer types (CESC, head and neck squamous cell carcinoma, and lung squamous cell carcinoma), and scRNA‐seq data from colorectal cancer for broader validation. We found that CD8 + T cells, natural killer T (NKT) cells, and γδ T cells in the tumor core exhibited higher inhibitory and cytotoxicity scores, while CD4 + T cells showed increased regulatory T (Treg) and cytotoxic features in the tumor core. Bulk RNA‐seq data confirmed elevated inhibitory and cytotoxic scores in the tumor core relative to the edge. Additionally, four subsets of exhausted CD8 + T cells (CD8 + Tex) were identified, including a stress‐associated subset characterized by heat shock protein (HSP) family gene expression, which was validated by immunofluorescence and inversely correlated with survival in patients with CESC undergoing radiotherapy. TCR analysis revealed clonal expansion and reduced clonal diversity in the tumor core. Notably, CD8 + Teff‐CD160 cells displayed substantial clonal sharing across regions and were associated with a favorable prognosis. Overall, our findings highlight distinct T cell states between the tumor core and edge in HPV‐related CESC, offering insights into prognostic biomarkers and potential therapeutic targets.