Desmoplasia in cervical cancer is associated with a more aggressive tumor phenotype

In cancer of the uterine cervix, the role of desmoplasia, i.e., peritumoral stromal remodeling characterized by fibroblast activation and increased extracellular matrix deposition, is not established. We conducted a retrospective cohort study based on data from 438 patients who had undergone surgical treatment for cervical cancer as part of the prospective Leipzig Mesometrial Resection study between 1999 and 2021. Using non-parametric tests, Kaplan-Meier plotting, and Cox regression modeling, we calculated the prognostic impact of desmoplasia and its association with other risk factors. Desmoplasia was present in 80.6% of cases and was associated with a higher frequency of lymphovascular space involvement (76.5 vs. 56.5%, p < 0.001) and venous infiltration (14.4 vs. 2.4%, p < 0.001). Lymph node metastasis (23.0 vs. 11.8%, p < 0.05) and parametrial involvement (47.3 vs. 17.6%, p < 0.0001) were also more common in patients with desmoplasia. The presence of desmoplasia was associated with inferior overall (80.2% vs. 94.5% hazard ratio [HR] 3.8 [95% CI 1.4-10.4], p = 0.002) and recurrence-free survival (75.3% vs. 87.3%, HR 2.3 [95% CI 1.2-4.6], p = 0.008). In addition, desmoplasia was associated with significantly less peritumoral inflammation (rho - 0.43, p < 0.0001). In summary, we link desmoplasia to a more aggressive phenotype of cervical cancer, reduced peritumoral inflammation, and inferior survival.