Objective – To explore the somatic and immunologic landscape of cervical primary vs metastatic tumors for differential sensitivity of metastatic cervical sites and potential therapeutic implications.

Methods – 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 intra-tumor abundance. Immune cell percentages, tumor mutational burden (TUMOR MUTATIONAL BURDEN), and tumor neoantigen burden (TUMOR NEOANTIGEN BURDEN) were compared across tumor sites. Chi-squared/Fischer’s exact tests or Kruskal-Wallis tests were used to assess statistical significance.

Results – The median cohort age was 52 years (IQR 42, 60). High tumor mutational burden (≥ 10 mut/Mb) was seen in 9.6% (9% primary, 0% lung, 17% liver, 17% lymph node, p=0.7) of patients. High MSI was noted in 1.5% (p=0.7) of patients. PD-L1 status was positive in 78% (76% primary, 88% lung, 71% liver, and 80% lymph node, p=0.8) of patients. Median tumor neoantigen burden was 1.71 (IQR 0.98, 3.20). Liver lesions had the lowest percentage of B cells (p=0.001) and a higher percentage of macrophages (p=0.053) versus other sites. There was a trend towards lower percentages of CD4 cells (p=0.053) and NK cells (p=0.090) in lymph nodes versus other sites. PIK3CA was the most common pathogenic somatic alteration, but not statistically different across sites (q=0.9).

Conclusions – 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.

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