Several studies on oral squamous cell carcinomas (OSCC) suggest that the cl
inical value of traditional histologic grading is limited both by poor repr
oducibility and by low prognostic impact. However. the prognostic potential
of a strictly quantitative and highly reproducible assessment of the tissu
e architecture in OSCC has not been evaluated. Using image analysis, in 193
cases of T1-2 (Stage I-II) OSCC we retrospectively investigated the progno
stic impact of two graph theory-derived structural features: the average De
launay Edge Length (DEL_av) and the average homogeneity of the Ulam Tree (E
LH_av). Both structural features were derived from subgraphs of the Voronoi
Diagram. The geometric centers of the cell nuclei were computed, generatin
g a two-dimensional swarm of point-like seeds from which graphs could be co
nstructed. The impact on survival of the computed values of ELH_av and DEL_
av was estimated by the method of Kaplan and Meier, with relapse-free survi
val and overall survival as end-points. The prognostic values of DE_av and
ELH_av as computed for the invasive front, the superficial part of the carc
inoma, the total carcinoma, and the normal-appearing oral mucosa were compa
red. For DEL_av, significant prognostic information was found in the invasi
ve front (p < 0.001). No significant prognostic information was found in su
perficial part of the carcinoma (p = 0.34), in the carcinoma as a whole (p
= 0.35), or in the normal-appearing mucosa (p = 0.27). For ELH_av, signific
ant prognostic information was found in the invasive front (p = 0.01) and,
surprisingly, in putatively normal mucosa (p = 0.03). No significant progno
stic information was found in superficial parts of the carcinoma (p = 0.34)
or in the total carcinoma (p = 0.11). In conclusion, strictly quantitative
assessment of tissue architecture in the invasive front of OSCC yields hig
hly prognostic information.