Head and neck squamous cell carcinomas (HNSCCs) are the eighth most common cancers worldwide. While promising new therapies are emerging, cisplatin-based chemotherapy remains the gold standard for advanced HNSCCs, although most of the patients relapse due to the development of resistance. This review aims to condense the different mechanisms involved in the development of cisplatin resistance in HNSCCs and highlight future perspectives intended to overcome its related complications. Classical resistance mechanisms include drug import and export, DNA repair and oxidative stress control. Emerging research identified the prevalence of these mechanisms in populations of cancer stem cells (CSC), which are the cells mainly contributing to cisplatin resistance. The use of old and new CSC markers has enabled the identification of the characteristics within HNSCC CSCs predisposing them to treatment resistance, such as cell quiescence, increased self-renewal capacity, low reactive oxygen species levels or the acquisition of epithelial to mesenchymal transcriptional programs. In the present review, we will discuss how cell intrinsic and extrinsic cues alter the phenotype of CSCs and how they influence resistance to cisplatin treatment. In addition, we will assess how the stromal composition and the tumor microenvironment affect drug resistance and the acquisition of CSCs’ characteristics through a complex interplay between extracellular matrix content as well as immune and non-immune cell characteristics. Finally, we will describe how alterations in epigenetic modifiers or other signaling pathways can alter tumor behavior and cell plasticity to induce chemotherapy resistance. The data generated in recent years open up a wide range of promising strategies to optimize cisplatin therapy, with the potential to personalize HNSCC patient treatment strategies.

Maxillectomies cause malocclusion, masticatory disorders, swallowing disorders and poor nasolabial projection, with consequent esthetic and functional sequelae. Reconstruction can be achieved with conventional approaches, such as closure of the maxillary defect by microvascular free flap surgery or prosthetic obturation. Four patients with segmental maxillary defects that had been reconstructed with customized subperiosteal titanium maxillary implants (CSTMI) through virtual surgical planning (VSP), STL models and CAD/CAM titanium mesh were included. The smallest maxillary defect was 4.1 cm and the largest defect was 9.6 cm, with an average of 7.1 cm. The reconstructed maxillary vertical dimension ranged from 9.3 mm to 17.4 mm, with a mean of 13.17 mm. The transverse dimension of the maxilla at the crestal level was attempted to be reconstructed based on the pre-excision CT scan, and these measurements ranged from 6.5 mm in the premaxilla area to 14.6 mm at the posterior level. All patients were rehabilitated with a fixed prosthesis on subperiosteal implants with good esthetic and functional results. In conclusion, we believe that customized subperiosteal titanium maxillary implants (CSTMI) are a safe alternative for maxillary defects reconstruction, allowing for simultaneous dental rehabilitation while restoring midface projection. Nonetheless, prospective and randomized trials are required with long-term follow-up, to assess its long-term performance and safety.

Background: The American Joint Committee on Cancer (AJCC), in its 8th edition, introduces modifications to the previous TNM classification, incorporating tumour depth of invasion (DOI). The aim of this research is to analyse the prognosis (in terms of disease-free survival and overall survival) of clinical early stage (I and II) squamous cell carcinomas of the oral tongue according to the DOI levels established by the AJCC in its latest TNM classification to assess changes to the T category and global staging system and to evaluate the association between DOI and other histological risk factors. Methods: A retrospective longitudinal observational study of a series of cases was designed. All patients were treated with upfront surgery at our institution between 2010 and 2019. The variables of interest were defined and classified into four groups: demographic, clinical, histological and evolutive control. Univariate and multivariate analyses were carried out and survival functions were calculated using the Kaplan–Meier method. Statistical significance was established for p values below 0.05. Results: Sixty-one patients were included. The average follow-up time was 47.42 months. Fifteen patients presented a loco-regional relapse (24.59%) and five developed distant disease (8.19%). Twelve patients died (19.67%). Statistically significant differences were observed, with respect to disease-free survival (p = 0.043), but not with respect to overall survival (p = 0.139). A total of 49.1% of the sample upstaged their T category and 29.5% underwent modifications of their global stage. The analysis of the relationship between DOI with other histological variables showed a significant association with the presence of pathological cervical nodes (p = 0.012), perineural invasion (p = 0.004) and tumour differentiation grade (p = 0.034). Multivariate analysis showed association between depth of invasion and perineural invasion. Conclusions: Depth of invasion is a histological risk factor in early clinical stages of oral tongue squamous cell carcinoma. Depth of invasion impacts negatively on patient prognosis, is capable per se of modifying the T category and the global tumour staging, and is associated with the presence of cervical metastatic disease, perineural invasion and tumoural differentiation grade.

(1) Background: A decrease in operative time can not only improve patient outcomes through a reduction in the risk of developing complications but can also result in cost savings. The aim of this study is to determine whether there an intraoperative time gain can be achieved by using the preoperative virtual planning of mandibular reconstruction using a free fibula flap compared with freehand plate bending and osteotomies. (2) Methods: A retrospective comparative study was carried out in the Oral and Maxillofacial Department of La Paz University Hospital, Madrid, Spain. The study compared 18 patients in the CAD/CAM group with 19 patients in the conventional freehand group. A comparison was made between the total surgical time, the comorbidities, and the hospital stay. The resource consumption was estimated using a cost analysis. (3) Results: Although CAD/CAM was a statistically more expensive procedure in the perioperative phase, no significant differences were observed in total health care costs between the two groups. There was a non-significant trend towards an increase in complications with conventional reconstruction plates compared to patient-specific plates (PSI). (4) Conclusions: CAD/CAM technology and a 3D printed cutting guide offer a significantly shorter surgical time, which is associated with a reduction in hospital days, PACU days, and complications. The cost of CAD/CAM technology is comparable to that of the conventional freehand technique.

(1) Background: Healthcare-associated infections (HAIs) after head and neck free-flap reconstruction are a common postoperative complication. Risk factors for HAIs in this context and their consequences have not been adequately described. (2) Methods: Ongoing prospective multicentre study between 02/2019 and 12/2020. Demographic characteristics and outcomes were analysed, focusing on infections. (3) Results: Forty out of 65 patients (61.54%) suffered HAIs (surgical site infection: 52.18%, nosocomial pneumonia: 23.20%, bloodstream infection: 13% and urinary tract infection: 5.80%). Methicillin-resistant Staphylococcus aureus (MRSA) and resistant Pseudomonas aeruginosa, Klebsiella pneumoniae and Enterobacter cloacae were the most frequently implicated. The significant risk factors for infection were: previous radiotherapy (Odds ratio (OR): 5.42; 95% confidence interval (CI), 1.39–21.10), anaemia (OR: 8.00; 95% CI, 0.96–66.95), salvage surgery (eight out of eight patients), tracheostomy (OR: 2.86; 95% CI, 1.01–8.14), surgery duration (OR: 1.01; 95% CI, 1.00–1.02), microvascular reoperation <72 h (eight/eight) and flap loss (eight/eight). The major surgical complications were: a need to reoperate (OR: 6.89; 95% CI, 1.42–33.51), prolonged hospital admission (OR: 1.16; 95% CI, 1.06–1.27) and delay in the initiation of postoperative radiotherapy (OR: 9.07; 95% CI, 1.72–47.67). The sixth month mortality rate in patients with HAIs was 7.69% vs. 0% in patients without HAIs (p = 0.50). (4) Conclusions: HAIs were common after this type of surgery, many of them caused by resistant microorganisms. Some modifiable risk factors were identified. Infections played a role in cancer prognosis by delaying adjuvant therapy.