Current Strategies for Treatment of Mandibular Fractures With Plate Osteosynthesis: A European Prospective Study.

PURPOSE: The training and preferences of surgeons influence the type of surgical treatment for mandibular fractures. This multicentre prospective study analyzed the current treatment strategies and outcomes for mandibular fractures with open reduction and internal fixation (ORIF). MATERIAL AND METHODS: This prospective study included patients aged ≥16 years who underwent ORIF for mandibular fractures in 12 European maxillofacial centers. Age, sex, pretrauma dental status, fracture cause, site and type, associated facial fractures, surgical approach, plate number and thickness (≤1.4 or ≥1.5 mm), duration of postoperative maxillomandibular fixation, occlusal and infective complications at 6 weeks and 3 months, and revision surgeries were recorded. RESULTS: Between May 1, 2021 and April 30, 2022, 425 patients (194 single, 182 double, and 49 triple mandibular fractures) underwent ORIF for 1 or more fractures. Rigid osteosynthesis was performed for 74% of fractures and was significantly associated with displaced ( P =0.01) and comminuted ( P =0.03) fractures and with the number of nonsurgically treated fracture sites ( P =0.002). The angle was the only site associated with nonrigid osteosynthesis ( P <0.001). Malocclusions (5.6%) and infective complications (5.4%) were not associated with osteosynthesis type. CONCLUSION: Rigid osteosynthesis was the most frequently performed treatment at all fracture sites, except the mandibular angle, and was significantly associated with displaced and comminuted fractures and the number of nonsurgically treated fracture sites. No significant differences were observed regarding postoperative malocclusion or infections among osteosynthesis types.

Open reduction and internal fixation of paediatric maxillozygomatic complex fractures: An 11-year multicentric retrospective study.

BACKGROUND/AIM: Paediatric maxillozygomatic complex (MZC) fractures are uncommon, and there is a scarcity of data regarding their surgical treatment. The aim of this study was to analyse choices and outcomes of open reduction and internal fixation (ORIF) for MZC fractures among 14 maxillofacial centers around the world. MATERIALS AND METHODS: This multicentric retrospective observational study included patients ≤16 years of age with quadripod MZC fractures treated with ORIF from January 2011 and December 2022. The following data were collected: age, gender, dentition stage (deciduous, mixed, and permanent), cause of injury, type of fracture, surgical approach, site of osteosynthesis (infraorbital rim, zygomaticomaxillary buttress, frontozygomatic, and zygomaticotemporal sutures), material (titanium or resorbable) and number of plates used, and outcome. The minimum follow-up was 6 months. Statistical analyses were performed with Fisher's exact test or chi-squared test, as appropriate. RESULTS: Sixty-four patients (mean age, 12.3 years) with quadripod MZC fractures were included. Seventy-two percent of patients received a single-point fixation. The zygomaticomaxillary buttress was the most common site for fixation, both in single-point and two-point fixation schemes, especially in combination with the frontozygomatic suture. Increasing age was associated with a higher rate of plate removal (p < .001). Postoperative complications included 5 (7.8%) cases of wound infections, 2 (3.1%) infraorbital paraesthesia, 1 (1.6%) ectropion. Residual facial asymmetry was found in 5 (7.8%) patients and was not associated with the type of fixation (p > .05). CONCLUSIONS: This study highlights the possibility of using ORIF, even with a single point of fixation, for the treatment of displaced quadripod MZC fractures in the paediatric population. The zygomaticomaxillary buttress was the preferred site of fixation and allowed for adequate stabilization with no external scars and a low risk of tooth damage. Future prospective studies with long-term follow-up are needed to establish definitive surgical protocols and clarify the surgical decision-making.

Methylation of Immune Gene Promoters in Oral and Oropharyngeal Cancer.

The proportion of oral and oropharyngeal squamous cell carcinoma (OOSCC) that can be attributed to human papillomavirus (HPV) infection is growing nowadays. A potential factor indicating the occurrence of HPV-positive OSCC is a change in the degree of methylation of gene promoters that play a key role in the immune response. In this study, we investigated the difference in the methylation of EDARADD, GBP4, HAVCR2, HLA DPB1, IL12RB1, MARCO, and SIGLEC12 gene promoters in samples of healthy oral mucosa versus samples of oral and oropharyngeal cancer. The presence of HPV infection in samples was examined earlier. To determine the difference in methylation of those gene promotors, isolated and bisulfite-modified DNA was analysed by the methylation-specific PCR method. The investigated gene promoters were found to be more hypomethylated in the oral and oropharyngeal cancer samples in comparison to normal tissue. The proportion of unmethylated gene promoters was similar in HPV-positive and HPV-negative cancers, although the data should be confirmed on a larger set of samples. To conclude, in samples of healthy oral mucosa, the investigated gene promoters were found to be methylated in a high percentage (73.3% to 100%), while in oral and oropharyngeal cancer samples, they were methylated in a low percentage (11.1% to 37%), regardless of HPV infection.

Head and Neck Cancer Patients' Survival According to HPV Status, miRNA Profiling, and Tumour Features-A Cohort Study.

Head and neck cancers (HNC) are a heterogeneous group of tumours mainly associated with tobacco and alcohol use and human papillomavirus (HPV). Over 90% of all HNC are squamous cell carcinomas (HNSCC). Sample material from patients diagnosed with primary HNSCC (n = 76) treated with surgery as primary treatment at a single centre were assessed for HPV genotype, miR-9-5p, miR-21-3p, miR-29a-3p and miR-100-5p expression levels. Clinical and pathological data were collected from medical records. Patients were enrolled between 2015 and 2019 and followed-up until November 2022. Overall survival, disease-specific survival and disease-free survival were assessed and correlated with clinical, pathological, and molecular data. Kaplan-Meier and Cox proportional hazard regression was used to assess different risk factors. In the study, male gender, HPV-negative HNSCC (76.3%) mostly located in the oral region (78.9%) predominated. Most patients had stage IV cancer (47.4%), and the overall survival rate was 50%. HPV was found not to affect survival, indicating that in this population, classic risk factors predominate. The presence of both perineural and angioinvasion was strongly associated with survival in all analyses. Of all miRNAs assessed, only upregulation of miR-21 was consistently shown to be an independent predictor of poor prognosis and may thus serve as a prognostic biomarker in HNSCC.

Manual versus rigid intraoperative maxillo-mandibular fixation in the surgical management of mandibular fractures: A European prospective analysis.

PURPOSE: Intraoperative stabilisation of bony fragments with maxillo-mandibular fixation (MMF) is an essential step in the surgical treatment of mandibular fractures that are treated with open reduction and internal fixation (ORIF). The MMF can be performed with or without wire-based methods, rigid or manual MMF, respectively. The aim of this study was to compare the use of manual versus rigid MMF, in terms of occlusal outcomes and infective complications. MATERIALS AND METHODS: This multi-centric prospective study involved 12 European maxillofacial centres and included adult patients (age ≥16 years) with mandibular fractures treated with ORIF. The following data were collected: age, gender, pre-trauma dental status (dentate or partially dentate), cause of injury, fracture site, associated facial fractures, surgical approach, modality of intraoperative MMF (manual or rigid), outcome (minor/major malocclusions and infective complications) and revision surgeries. The main outcome was malocclusion at 6 weeks after surgery. RESULTS: Between May 1, 2021 and April 30, 2022, 319 patients-257 males and 62 females (median age, 28 years)-with mandibular fractures (185 single, 116 double and 18 triple fractures) were hospitalised and treated with ORIF. Intraoperative MMF was performed manually on 112 (35%) patients and with rigid MMF on 207 (65%) patients. The study variables did not differ significantly between the two groups, except for age. Minor occlusion disturbances were observed in 4 (3.6%) patients in the manual MMF group and in 10 (4.8%) patients in the rigid MMF group (p > .05). In the rigid MMF group, only one case of major malocclusion required a revision surgery. Infective complications involved 3.6% and 5.8% of patients in the manual and rigid MMF group, respectively (p > .05). CONCLUSION: Intraoperative MMF was performed manually in nearly one third of the patients, with wide variability among the centres and no difference observed in terms of number, site and displacement of fractures. No significant difference was found in terms of postoperative malocclusion among patients treated with manual or rigid MMF. This suggests that both techniques were equally effective in providing intraoperative MMF.

Sialocele of Submandibular Gland, an Unreported Complication of Bilateral Sagittal Split Osteotomy.

ABSTRACT: Bilateral sagittal split osteotomy is a routine procedure with predictable and well-known complications. The authors report a thitherto unreported complication of bilateral sagittal split osteotomy presenting as a postoperative sialocele of submandibular salivary gland tissue in the floor of the mouth. The sialocele was probably caused by overinstrumentation and injury to sublingual salivary tissues or Wharton's duct during bicortical drilling or screw fixation. This iatrogenic sialocele was managed conservatively with multiple aspiration and compression dressings. Although rare and unreported so far this complication may be included in the preoperative consent process.

The Effects of Dextran on Postoperative Thrombosis and Hemodilution in Microvascular Head and Neck Reconstruction.

BACKGROUND: Free tissue transfer is an integral part of reconstructive head and neck surgery today. Although increased experience and refinements in techniques have minimized flap loss, pharmacological agents have been used to prevent thrombus formation and flap failures, despite their questionable effectiveness. The aim of this study is to investigate the use of dextran 40 in thrombosis prophylaxis, as well as its effects on blood coagulability and flap survival. METHODS: This is a retrospective analysis of 176 free flaps performed at University Hospital Dubrava, Zagreb, Croatia, during a 4-year period. A comparison was made between 2 patient groups, based on their respective postoperative prophylaxis protocols. All patients were treated with low-molecular-weight heparin as deep vein thrombosis prevention, until patient mobilization. Group 1 was on dextran 40 protocol, whereas group 2 did not receive additional treatment. Primary outcome of the study was determined as flap loss rate, whereas secondary outcome was evaluated as the rate of thrombosis or hemorrhage. The hemodilution potential of dextran 40 was examined through blood count laboratory values. RESULTS: Total flap survival rate was 90.34%. There were 16 free flap losses and 1 partial loss overall. Anastomoses were re-explored in a total of 27 cases, of which 17 were salvaged. There were 29 events of hemorrhage or arterial or venous thrombosis: 17 in group 1 and 12 in group 2. A sum of 26 incidences of other postoperative complications was recorded, 13 in each group. Hemodilution status showed a statistically significant reduction in erythrocyte count and hemoglobin and hematocrit levels in the group receiving dextran 40, on postoperative days 1 and 3, but no such effect was observed on postoperative platelet count. CONCLUSIONS: Although dextran 40 has been shown to have a valuable effect on hemodilution, which is beneficial in microsurgery, it did not demonstrate better outcomes in terms of flap survival. Because it can cause serious systemic complications, it is better not to administer it routinely. However, its important influence on reduction in erythrocyte count and hemoglobin and hematocrit levels should be further investigated.

Rigid Fiber-Optic Device Intubation in a Child With Temporomandibular Joint Ankylosis.

The authors present a case of rigid fiber-optic device intubation in an 8-year-old boy with posttraumatic temporomandibular joint ankylosis. For this intention, a 5 mm diameter Bonfils fiberscope was used. Such practice has never been described before in pediatric patients with temporomandibular joint ankylosis. The procedure was successful and without complications. Therefore, the authors conclude that this method represents a useful alternative in difficult airway management in children with limited mouth opening.

DNA Methylome Distinguishes Head and Neck Cancer from Potentially Malignant Oral Lesions and Healthy Oral Mucosa.

There is a strong need to find new, good biomarkers of head and neck squamous cell carcinoma (HNSCC) because of the bad prognoses and high mortality rates. The aim of this study was to identify the potential biomarkers in HNSCC that have differences in their DNA methylome and potentially premalignant oral lesions, in comparison to healthy oral mucosa. In this study, 32 oral samples were tested: nine healthy oral mucosae, 13 HNSCC, and 10 oral lesions for DNA methylation by the Infinium MethylationEPIC BeadChip. Our findings showed that a panel of genes significantly hypermethylated in their promoters or specific sites in HNSCC samples in comparison to healthy oral samples, which are mainly oncogenes, receptor, and transcription factor genes, or genes included in cell cycle, transformation, apoptosis, and autophagy. A group of hypomethylated genes in HNSCC, in comparison to healthy oral mucosa, are mainly involved in the host immune response and transcriptional regulation. The results also showed significant differences in gene methylation between HNSCC and potentially premalignant oral lesions, as well as differently methylated genes that discriminate between oral lesions and healthy mucosa. The given methylation panels point to novel potential biomarkers for early diagnostics of HNSCC, as well as potentially premalignant oral lesions.

Management of maxillofacial trauma in the elderly: A European multicenter study.

BACKGROUND/AIMS: Management of maxillofacial trauma in the geriatric population poses a great challenge due to anatomical variations and medical comorbidities. The aim of this study was to analyze the management variables, timing, and outcomes of facial fractures in elderly patients (aged 70 years or more) at several European departments of oral and maxillofacial surgery. MATERIALS AND METHODS: This study was based on a systematic computer-assisted database that allowed the recording of data from all geriatric patients with facial fractures from the involved maxillofacial surgical units across Europe between 2013 and 2017. RESULTS: A total of 1334 patients were included in the study: 665 patients underwent closed or open surgical treatment. A significant association (P < .005) was found between the presence of concomitant injuries and a prolonged time between hospital admission and treatment. The absence of indications to treatment was associated with comorbidities and an older age (P < .000005). CONCLUSIONS: Elderly patients require specific attention and multidisciplinary collaboration in the diagnosis and sequencing of trauma treatment. A prudent attitude may be kept in selected cases, especially when severe comorbidities are associated and function is not impaired.

The "European Mandibular Angle" Research Project: The Epidemiologic Results From a Multicenter European Collaboration.

PURPOSE: The aim of this study was to analyze the demographic variables and causes and characteristics of mandibular angle fractures managed at several European departments of maxillofacial surgery. MATERIALS AND METHODS: This study was based on a multicenter systematic database that allowed the recording of data from all patients with mandibular angle fractures between January 1, 2013, and December 31, 2017. The following data were recorded: gender, age, etiology, side of angle fracture, associated mandibular fractures, presence of third molar, intermaxillary fixation, and osteosynthesis. RESULTS: The study included 1,162 patients (1,045 male and 117 female patients). A significant association was found between the presence of a third molar and the diagnosis of an isolated angle fracture (P < .0000005). Furthermore, assaults were associated with the presence of voluptuary habits (P < .00005), a younger mean age (P < .00000005), male gender (P < .00000005), and left-sided angle fractures (P < .00000005). CONCLUSIONS: Assaults and falls actually represent the most frequent causes of angle fractures. The presence of a third molar may let the force completely disperse during the determination of the angle fracture, finding a point of weakness.

Extended Karapandzic Flap Technique for Reconstruction of Lower Lip and Chin Defect.

PURPOSE: Near total defect of the lower lip adjacent to the chin remains a reconstructive challenge for surgeons in function and esthetics. The objective of this study was to present a modified extended Karapandzic technique for reconstruction of near total defects of the lower lip adjacent with the chin. MATERIALS AND METHODS: From 2000 to 2013, patients with lip cancer or oral cavity cancer who required subtotal lower lip and chin resection and subsequently underwent reconstruction with an extended Karapandzic flap were included in this retrospective study. Patient demographics, histopathology, tumor stage, localization, tumor extension, method of reconstruction, and postoperative complications were extracted from patients' documentation. RESULTS: Reconstruction of the lower lip and chin was performed in 21 patients using a combination of double local extended Karapandzic flaps with microvascular free flaps for intraoral and mandibular reconstruction. There was no flap necrosis; the main complications were fistula and exposure of the osteosynthesis plate. All lips were functional and the esthetic result was pleasing. All patients returned to a peroral diet, although a variable degree of microstomia was present. CONCLUSION: The extended Karapandzic flap technique provides superior results for esthetic and functional lip reconstruction and chin reconstruction compared with any other regional or free flap. Free flaps should be reserved for oral cavity and mandibular reconstruction, if needed.

Development of a Valid and Reliable Instrument for the Assessment of Quality of Life in Adolescents with Clefts - Detection of Potential Mental Health Issues.

BACKGROUND: The rehabilitation of patients with cleft deformities is very complex and unique, and managed by a team of professionals. Quality of life depends on the health, and represents an instrument that examines the disease impact and treatment modalities on the health, integrating an objective assessment of the health status and its subjective experience. Children with clefts are often teased by their peers, and that is the reason why they experience different kinds of psychological distress. Patients with non-syndromic clefts may develop depression and anxiety, hyperactivity, elevated risk of suicide and increased drug abuse in adolescence. SUBJECTS AND METHODS: Experienced members of a cleft palate team developed a specific questionnaire divided into 2 parts: the first contains the clinical profile of adolescents, and the second part contains questions regarding quality of life. This questionnaire was administered to 73 patients between June 2015 and June 2016, who matched these criteria during their control examinations at the University Hospital Dubrava. RESULTS: In general, the patient group showed significantly worse scores on majority of answers, specifying that their quality of life is worse compared to the control group. The principal component analysis revealed the presence of three components (factors). The interpretation of the three components was consistent with loadings indicating the component names: Component 1: The relationship with parents, success, society; Component 2: Appearance, and Component 3: Function. CONCLUSION: According to our results, we created a specific instrument - The Quality of Life in Adolescents with Cleft Assessment to assess aesthetic and functional results of treatment and quality of life of the operated adolescents with clefts. The adolescents in this study have no psychiatric disorders diagnosed in their medical charts, but results indicate that some of them need help in dealing with future life. Regarding these findings, it will be possible to intervene in the process of treatment and improve the overall outcome of therapy.

A Diagnostic Conundrum: Ectopic Nasal Ossification, Submucosal Alveolar Cleft, Absent Posterior Atlantal Arch, and Corpus Callosum Lipoma.

A 19-year-old woman was referred for nasal breathing and aesthetic concerns regarding her nose. A computed tomography scan revealed a massive osseous shield anterior to the piriform aperture. Furthermore, there was a submucosal median alveolar cleft, and the posterior arch of C1 was missing. The magnetic resonance imaging brain scan revealed a curvilinear lipoma of corpus callosum. The ectopic nasal bone was removed by open rhinoplast,y and nasal function and aesthetics were restored. The described features defy conventional clinical diagnosis and severity classifications and present a diagnostic conundrum somewhere between a mild form of frontonasal dysplasia, oculoauriculofrontonasal syndrome, and Pai syndrome.

Integrative analysis in head and neck cancer reveals distinct role of miRNome and methylome as tumour epigenetic drivers.

Head and neck cancer is the sixth most common malignancy worldwide, with the relatively low 5-year survival rate, mainly because it is diagnosed at a late stage. Infection with HPV is a well known aetiology, which affects the nature of these cancers and patients' survival. Besides, it is considered that the main driving force for this type of cancer could be epigenetics. In this study we aimed to find potential epigenetic biomarkers, by integrating miRNome, methylome, and transcriptome analyses. From the fresh head and neck cancer tissue samples, we chose a group for miRNome, methylome and transcriptome profiling, in comparison to adequate control samples. Bioinformatics analyses are performed in R v4.2.2. Count normalisation and group differential expression for mRNA and the previously obtained miRNA count data was performed with DESeq2 v1.36. Gene set enrichment analysis was performed and visualised using gProfiler2 v0.2.1 Identification of miRNA targets was performed by querying in miRTarBase using multiMiR v1.18.0. Annotation of CpG sites merging into islands was obtained from RnBeads.hg19 v1.28.0. package. For the integrative analysis we performed kmeans clustering using stats v4.2.2 package, using 8-12 clusters and nstart 100. We found that transcriptome analysis divides samples into cancers and controls clusters, with no relation to HPV status or cancer anatomical location. Differentially expressed genes (n = 2781) were predominantly associated with signalling pathways of tumour progression. We identified a cluster of genes under the control of the transcription factor E2F that are significantly underexpressed in cancer tissue, as well as T cell immunity genes and genes related to regulation of transcription. Among overexpressed genes in tumours we found those that belong to cell cycle regulation and vasculature. A small number of genes were found significantly differentially expressed in HPV-positive versus HPV-negative tumours (for example NEFH, ZFR2, TAF7L, ZNF541, and TYMS). In this comprehensive study on an overlapping set of samples where the integration of miRNome, methylome and transcriptome analysis were performed for head and neck cancer, we demonstrated that the majority of genes were associated exclusively with miRNome or methylome and, to a lesser extent, under the control of both epigenetic mechanisms.

Moderate SCRIB Expression Levels Correlate with Worse Prognosis in OPSCC Patients Regardless of HPV Status.

Head and neck cancers rank as the sixth most prevalent cancers globally. In addition to traditional risk factors such as smoking and alcohol use, human papillomavirus (HPV) infections are becoming a significant causative agent of head and neck cancers, particularly among Western populations. Although HPV offers a significant survival benefit, the search for better biomarkers is still ongoing. In the current study, our objective was to investigate whether the expression levels of three PDZ-domain-containing proteins (SCRIB, NHERF2, and DLG1), known HPV E6 cellular substrates, influence the survival of HNSCC patients treated by primary surgery (n = 48). Samples were derived from oropharyngeal and oral cancers, and HPV presence was confirmed by PCR and p16 staining. Clinical and follow-up information was obtained from the hospital database and the Croatian Cancer registry up to November 2023. Survival was evaluated using the Kaplan-Meier method and Cox proportional hazard regression. The results were corroborated through the reanalysis of a comparable subset of TCGA cancer patients (n = 391). In conclusion, of the three targets studied, only SCRIB levels were found to be an independent predictor of survival in the Cox regression analysis, along with tumor stage. Further studies in a more typical Western population setting are needed since smoking and alcohol consumption are still prominent in the Croatian population, while the strongest association between survival and SCRIB levels was seen in HPV-negative cases.

Epidemiology, etiopathogenesis, and management of MRONJ: A European multicenter study.

INTRODUCTION: The purpose of this European multicenter study was to describe the general characteristics and risk factors of MRONJ lesions as well as their clinical diagnosis and management at different European Oral and Maxillofacial Surgery centers, in order to minimize selections biases and provide information about the epidemiology, etiopathogenesis, and the current trends in the treatment of MRONJ across Europe. MATERIALS AND METHODS: The following data were registered for each patient: gender; age at MRONJ diagnosis; past medical history; indication for antiresorptive or antiangiogenic therapy; type of antiresorptive medication; local risk factor for MRONJ; MRONJ Stage; anatomic location and symptoms; treatment; surgical complications; recurrence. RESULTS: A total of 537 patients (375 females, 162 males) with MRONJ were included. Statistically significant associations were found between patients with metastatic bone disease and recurrences (P < 0.0005) and between advanced MRONJ stages (stages 2 and 3) and recurrences (P < 0.005). Statistically significant associations were also found between male gender and recurrences (P < 0.05), and between MRONJ maxillary sites and recurrences (P < 0.0000005). CONCLUSIONS: A longer mean duration of antiresorptive medications before MRONJ onset was observed in patients affected by osteoporosis, whereas a shorter mean duration was observed in all metastatic bone cancer patients, and in particular in those affected by prostate cancer with bone metastases or multiple myeloma. Surgery plays an important role for the management of MRONJ lesions.

Brown class III maxillectomy defects reconstruction with prefabricated titanium mesh and soft tissue free flap.

BACKGROUND: Midface reconstruction is one of the most challenging tasks for the reconstructive surgeon. We present a technique for the reconstruction of the midface after total maxillectomy with preservation of orbital contents. METHODS: Skeletal reconstruction is achieved with a preoperatively bent titanium sheet mesh on a universal skeletal model. The alveolar ridge, the anterior wall of the maxillary sinus, the zygomatic prominence, the lower orbital rim, and the orbital floor are reconstructed with a titanium mesh. A soft tissue free flap, preferably anterolateral thigh free flap, is harvested as well. A part of the flap is deepithelized and put in front of the mesh to prevent exposure, and the other part is used for palatal reconstruction. RESULTS: Four male and 1 female patients were reconstructed with titanium mesh. Four free flaps were raised: 3 anterolateral thigh and 1 latissimus dorsi. All free flaps survived. All patients received postoperative irradiation with 64 Gy. Median follow-up was 12 months; no major complications occurred. Mesh was exposed in only 1 case, which was managed successfully with resuspension of the heavy latissimus dorsi myocutaneous flap. Midface projection and height, globe position, ocular movements, and vision where satisfactory in all cases. CONCLUSIONS: Midface reconstruction with titanium mesh and soft tissue free flap is a reliable and safe method for functional and aesthetic reconstruction after maxillectomy.

HPV16 Impacts NHERF2 Expression in Oropharyngeal Cancers.

Infection with human papillomaviruses (HPVs), in particular with HPV type 16, is now considered to be a key risk factor for the development of a subset of oropharyngeal squamous cell carcinomas (OPSCC) that show different epidemiological, clinical, and prognostic characteristics from HPV-negative (HPV-) OPSCCs. So far, extensive research efforts aiming to distinguish these two distinct entities have not identified specific biomarkers, nor led to different therapies. Previous research has shown that HPV16 E6 oncoprotein binds NHERF2, inducing its proteasomal degradation, and consequently increasing cell proliferation; we therefore aimed to investigate how this might be reflected in human histological samples. We analyzed NHERF2 expression patterns in HPV16-positive (HPV16+) and HPV- OPSCC samples, to investigate any potential differences in NHERF2 pattern. Interestingly, we observed a statistically significant decrease in NHERF2 levels in HPV16+ and poorly differentiated HPV- OPSCCs, compared with healthy tissue. Furthermore, we observed a significant reduction in the percentage of NHERF2 immunoreactive cancer cells in HPV16+ tumors, compared with well and moderately differentiated HPV- OPSCCs, suggesting the importance of 16E6's targeting of NHERF2 in HPV-driven oncogenesis in the head and neck area.