Michael A. Thompson

Exploratory evaluation of the somatic and immunologic landscape of primary and metastatic cervical cancer to better inform future clinical trial development.

To explore the somatic and immunologic landscape of cervical primary versus metastatic tumors for differential sensitivity of metastatic cervical sites and potential therapeutic implications. Patients with sequenced squamous cell cervical cancer were selected from the Tempus Database (2016-2023). The cohort included 136 unmatched samples (73 primary, 63 metastatic sites). Pathogenic somatic mutations and gene expression patterns of immune cells were evaluated for relative intratumor abundance. Immune cell percentages, tumor mutational burden, and tumor neoantigen burden (tumor mutational burden) were compared across tumor sites. χ The median cohort age was 52 years (interquartile range; 42-60). High tumor mutational burden (≥ 10 mut/Mb) was seen in 9.6% (9% primary, 0% lung, 17% liver, 17% lymph node, p = .7) of patients. High microsatellite instability (MSI) was noted in 1.5% (p = .7) of patients. PD-L1 status was positive in 78% (76% primary, 88% lung, 71% liver, and 80% lymph node, p = .8) of patients. Median tumor neoantigen burden was 1.71 (interquartile range; 0.98-3.20). Liver lesions had the lowest percentage of B cells (p = .001) and a higher percentage of macrophages (p = .053) compared with other sites. There was a trend toward lower percentages of CD4 cells (p = .053) and natural killer cells (p = .090) in lymph nodes compared with other sites. PIK3CA was the most common pathogenic somatic alteration but not statistically different across sites (q = 0.9). Molecular and immune profiling of primary and metastatic lesions indicated that liver lesions had a less immunogenic microenvironment. Further interrogation of the molecular landscape across paired samples is needed to better inform the development and use of novel therapies.