TRMTyler R. McKinnish
Papers(2)
Trends in Cervical an…Chemoradiation Reprog…
Collaborators(10)
Varintra E. LanderYize LiAna Carolina Paschoal…Andrew HoustonBrian T. EdelsonClifford G. RobinsonDavid G. DeNardoDhaval P. BhattDonghua HuEliwaza Naomi S. Msen…
Institutions(1)
Taylor Family Institu…

Papers

Trends in Cervical and Anal Cancer Incidence and Mortality in the United States

Objectives This article describe trends in the incidence and mortality of cervical (CC) and anal (AC) cancers by race and neighborhood socioeconomic status. Methods The Surveillance, Epidemiology, and End Results (SEER) database was used to construct a cohort of CC and AC cases from 2006 to 2018. Incidence rates and survival were calculated by race and neighborhood socioeconomic status (nSES). Annual percent change (APC) in incidence was calculated using linear regression, and 5-year overall survival (OS) by the Kaplan-Meier method. Results Of the cases, 33,487 CC and 16,018 AC cases were identified. Women of low nSES were nearly 4 times more likely to be diagnosed with cervical cancer than those of high nSES. Cervical cancer incidence declined marginally in all groups except for low nSES women who are White (APC 0.0). Women who are Black had lower 5-year OS than their nSES counterparts of other races (most notably for Black women of low nSES 53% vs White 63%). Similarly, the low nSES AC cohort contained nearly 3 times the number of diagnoses as the high nSES cohort. AC incidence increased most in women who are White (APC 1.8 and 2.2 for low and high nSES) and men who are Black and low nSES (APC 3.3). Five-year OS was lowest for men who are Asian American and Pacific Islander (40% and 50% for low and high nSES, respectively). Conclusions These data suggest a strong correlation between nSES, race, and their interaction on the incidence and survival trends of HPV-related disease and highlight inconsistent effects between cervical and anal cancers.

Chemoradiation Reprograms Tumor Cells and the Immune Microenvironment in Cervical Cancer

Abstract Despite advances in screening and prevention, cervical cancer remains a leading cause of cancer-related deaths worldwide, underscoring the need for better treatments. In this study, we conducted a multicohort longitudinal study of human cervical tumors and the tumor microenvironment during chemoradiotherapy (CRT) and integrated RNA sequencing and single-cell transcriptomics to define the cellular and molecular programs shaping cell interactions and how CRT alters them. The analysis identified multiple therapeutic targets in CRT-resistant tumors, notably including MDM2, a key mediator of radiation responses in tumor and immune cells. MDM2 inhibition enhanced the effects of radiotherapy in human papillomavirus (HPV)–positive, TP53 wild-type cervical cancer cells; improved radiation response; and reshaped the immune landscape in preclinical models. These findings highlight the potential of combining MDM2 inhibition with CRT to overcome resistance and improve patient outcomes. The insights into therapy-induced changes in tumor and immune compartments could guide improved strategies against treatment-resistant HPV-positive cancers. Significance: Mapping of the impact of chemoradiation on cellular interactions in cervical cancer reveals how treatment reshapes the tumor microenvironment and highlights targets for developing future immunotherapeutic approaches. See related commentary by Klopp, p. 1540

2Papers
31Collaborators