Background: Individually personalized reconstructive microsurgery is more and more universally recognized and applied as a one-time, part of a few, or even the only highly effective treatment of patients with locally advanced midface cancer. Among the increasing number of publications focused on this field, most present different reconstructive techniques used for a single patient (case reports), and fewer papers evaluate a group including more than 100 patients. Methods: A dataset of 119 locally advanced midface cancers in stage T₃ or T₄ was used to analyze whether there is any correlation between clinical factors, resection defect parameters, and the free flaps chosen for reconstruction. Results: In general, the 5-year OS was 95% and 77% for the DFS, which inversely correlated with the increasing Cordeiro’s type of resective defects. Local recurrence occurred in 23% of cases. Taxonomic dendrograms allow the selection of four (A–D) different case clusters. Cluster B, which characterizes a tumor size of 8–18 cm², Cordeiro type IIIA, and an uncertain radicalism of resection, has the worst prognosis with a very high (89%) risk of local recurrence. On the contrary, the most favorable was found in cluster C, characterized by Cordeiro type IIA, a tumor size of 8 cm², and negative resective margins, because it has a very low (6%) risk of local recurrence. Conclusions: The results of the present analysis have led to design algorithms for midface resection and reconstruction. However, these should not be considered obligatory but rather as a useful general guideline.

Background/Objectives: Head and neck squamous cell carcinoma (HNSCC) ranks sixth in the world in terms of incidence. Small proline-rich proteins (SPRRs) are precursors of the keratinocyte envelope and act as substrates of transglutaminase. A change in SPRR expression is characteristic in a few types of cancer. Our aim was to determine the concentration of SPRR1A and SPRR2A in tumours samples obtained from 61 patients with HNSCC (OSCC, OPSCC, LSCC, HPSCC, NCSCC, and SSCC). Also, we aimed to determine the relationship between protein concentration and other clinical and/or demographic variables. Methods: An ELISA test was used to determine the concentrations of SPRR in the tumour tissue homogenates. Results: In margin samples, we found a statistically significant association between SPRR1A levels and nodal status (N) and between SPRR1A levels in tumours and margins with G2 histological grade. When we analysed the effect of tobacco and alcohol habits, we found a statistically significant difference between the SPRR1A and SPRR2A amount in smokers and non-smokers in margin samples. Also, we found a statistically significant difference between the SPRR1A and SPRR2A levels in tumour and margin samples obtained from patients that either abstain and occasionally or regularly consume alcohol. Furthermore, we found in tumour and margin samples from patients with concomitant diseases an association between SPRR1A and SPRR2A levels. Our results showed altered concentrations of SPRR1A at margins, depending on HPV status. Conclusions: These results suggest that differences in SPRR proteins are determined by disease status and unhealthy behaviours, which, in a wider perspective, can influence carcinogenesis.