Introducing a novel highly prognostic grading scheme based on tumor budding and cell nest size for squamous cell carcinoma of the uterine cervix

Objective:

Recently, it has been shown for several squamous cell carcinoma tumor entities that a grading approach incorporating the factors budding activity and cell nest size strongly outperforms conventional grading algorithms with respect to its prognostic value. Here, we tested this novel approach in two completely independent cohorts of cervical squamous cell carcinoma.

Material:

In order to improve morphology based grading, we determined budding activity and cell nest size as well as several other morphological factors in a test cohort (n = 125) and a completely independent validation cohort (n = 122) of cervical squamous cell carcinoma. Parameters were correlated with outcome and clinical factors.

Results:

As in several other squamous cell carcinoma entities, small cell nest size and high budding activity in cervical squamous cell carcinoma predicted a dismal patient prognosis (p < 0.001 for overall, disease-specific and disease-free survival) in our test cohort. A grading algorithm incorporating these two parameters was a stage independent prognosticator in the test cohort. Hazard ratio (HR) of this novel grading algorithm for OS was 2.3 for G2 and 5.1 for G3 tumors when compared to G1 neoplasms (p = 0.010). In the validation cohort HR for OS was 3.0 for G2 and 7.2 for G3 tumors (p = 0.012).

Conclusion:

Comparable to esophageal, lung and oral squamous cell carcinoma, in cervical carcinoma a grading algorithm incorporating cell nest size and budding activity had strong independent prognostic impact. We suggest this grading algorithm as an additional morphology based parameter in the routine diagnostic assessment for this tumor entity.