Genetic and epigenetic alterations in the tumour,tumour margins,and normal buccal mucosa of patients with oral cancer

Despite adequate surgical resection, oral squamous cell carcinoma (OSCC) shows a high rate of recurrence and metastasis, which could be explained by the presence of molecular alterations in seemingly normal tumour margins and the entire oral mucosa. The aims of this study were (1) to assess the presence of gene amplification (c-Myc and HER2) and promoter methylation (p14 and p16) in the tumours, tumour margins, and unaffected oral mucosa of 40 OSCC patients, and (2) to evaluate the possibility of using these alterations as prognostic markers. c-Myc and HER2 genes were quantified by means of real-time PCR (qPCR), and p14 and p16 methylation status was determined by methylation-specific PCR (MSP PCR). All tissues examined exhibited molecular alterations in various proportions. Tumour tissues, as expected, showed the highest prevalence of alterations, while oral mucosa showed the lowest. Multiple alterations (co-alterations) in tumours and tumour margins were significantly more frequent than in unaffected oral mucosa (P < 0.001 and P = 0.027, respectively). HER2 amplification in margin tissue (P < 0.001) and swabs (P = 0.013), as well as the existence of three co-alterations in margins (P = 0.001) and macroscopically unaffected oral mucosa (P < 0.001) were correlated with shorter disease-specific survival.     

Warthin’s tumour in oral and maxillofacial regions: an 18-year retrospective study of 1084 cases in an eastern-Chinese population

There is little information in the English-language literature regarding Warthin’s tumour (WT) in the eastern-Chinese population. A large retrospective study (1084 primary tumours over a period of 18 years) was carried out to investigate the clinicopathological features (patients’ gender, age and tumour location) of these tumours in this population. A total of 994 (91.7%) patients were male and 90 (8.3%) were female, with a male/female ratio of 11:1. The mean age was 56.48 years (range 20–89 years), with a peak incidence in the fifth to seventh decade (82.1%). The favorite primary site of the tumour was the parotid gland (n = 1055), followed by intra-/peri-parotid lymph nodes (n = 13), upper neck (n = 10), submandibular gland (n = 4) and upper lip (n = 1). Multifocal WTs arose in 9.5% (103 patients) of cases whereas bilateral multifocal WTs were found in 0.65% (seven patients). In 24 (2.2%) patients, WT were found to coexist with other different types of neoplasm synchronously. The most common subtype of metaplasia was the squamous metaplasia (166/250, 66.4%). The usual treatment measure is (bilateral) superficial parotidectomy and the patients should be followed long term, in view of possible metachronous WT, even after prolonged time intervals.     

EGFR amplification and expression in oral squamous cell carcinoma in young adults

The aim of this study was to investigate epidermal growth factor receptor (EGFR) gene alterations in two groups of patients with oral squamous cell carcinoma (OSCC) (a test group of subjects aged ≤40 years and a control group of subjects aged ≥50 years) and to associate the results with EGFR immunostaining, clinicopathological features, and the prognosis. Sixty cases of OSCC were selected (test group, n = 21; control group, n = 39). The tissue microarray technique was applied to ensure the uniformity of results. Gene amplification was analyzed by fluorescence in situ hybridization (FISH), and immunohistochemical staining for EGFR was analyzed using an automated imaging system. EGFR amplification was higher in the test group than in the control group (P = 0.018) and was associated with advanced clinical stage (P = 0.013), regardless of age. Patients with EGFR overexpression had worse survival rates, as did patients who had T3–T4 tumours and positive margins. EGFR overexpression has a negative impact on disease progression. Despite the higher amplification of EGFR in young adults, it does not significantly impact the survival rates of affected patients.     

Primary epithelial salivary gland tumours in children and adolescents

Primary epithelial tumours of the salivary glands are very rare in paediatric patients. The aim of this study was to evaluate the clinical course, treatment, and outcomes of these uncommon neoplasms based on the authors’ experience and the recent literature. The medical charts of 12 female patients and seven male patients with primary epithelial salivary gland tumours were reviewed. All were under 19 years of age and underwent surgical treatment between 1994 and 2016. The results of this group of paediatric patients were compared with those of 621 adult patients. The two most common tumours in the paediatric patients were pleomorphic adenoma and mucoepidermoid carcinoma (89.4%; P = 0.004). The incidence of facial nerve palsy following surgery of the parotid tumours was similar in the two groups (P = 1.000). The most common primary cancer in the paediatric group was mucoepidermoid carcinoma (77.8%), while in the adult group, adenoid cystic carcinoma was most common (P < 0.001). The paediatric group had only low-grade cancers in early stages (P < 0.001), with an overall 5-year survival rate of 100%. These results show that the incidence of malignant salivary gland tumours is higher in paediatric patients than in adult patients. This should be taken into account during diagnosis and therapy.     

Prognostic value of lymph node count from selective neck dissection in oral squamous cell carcinoma

Unlike the levels of anatomical exploration, there is no consensus on the extent of lymph node dissection, or lymph node count (LNC), during selective neck dissection (SND). The aim of this study was to validate the prognostic impact of LNC on survival and to determine an optimal LNC cut-off value for SND. A retrospective investigation identified 78 patients with a diagnosis of oral squamous cell carcinoma (OSCC) who underwent SND (levels I–III or levels I–IV). LNC and clinicopathological variables were analyzed for any association with survival in Cox proportional hazards models. Based on the receiver operating characteristic curve, a cut-off value of 19 lymph nodes was found to predict overall survival (OS) (area under the curve 0.732, sensitivity 67.8%, specificity 75.0%; P = 0.026) and disease-specific survival (DSS) (area under the curve 0.762, sensitivity 68.1%, specificity 77.8%; P = 0.011). On Cox regression, LNC (≥19 vs. <19) was the only independent predictor of OS (hazard ratio 5.29, 95% confidence interval 1.39–20.05; P = 0.014) and DSS (hazard ratio 6.76, 95% confidence interval 1.40–32.77; P = 0.018). Similar results were obtained in the pathologically lymph node-negative subgroup (n = 66). Based on the study findings, SND should include 19 or more lymph nodes for a survival benefit.     

Comparison of retroauricular and small transcervical approaches for endoscopic-assisted selective neck dissection: a cadaveric study

Advances in endoscopic-assisted neck surgery have allowed surgeons to conceal the scars via various approaches. However, studies comparing the approaches are still rare. The aim of this study was to comparatively analyze the feasibility and oncological outcomes of the retroauricular approach (RA) and the small transcervical approach (STC) for endoscopic-assisted selective neck dissection (EASND). Five fresh cadavers were recruited. EASND was performed via RA on one side and via STC on the contralateral side of each of the cadavers. The duration of the procedure was subdivided into preparation and EASND, and was recorded during the operation. The preserved vital structures were inspected by another surgeon after the cadaver dissection. The total number of lymph nodes retrieved was assessed by a pathologist. There was no significant difference in lymph node count between the RA group (mean 21, range 9–38) and the STC group (mean 23, range 7–34) (P > 0.05). The operation time was significantly longer in the RA group than in the STC group (preparation, P = 0.042; EASND, P = 0.043). In terms of surgical feasibility, STC can be chosen as the approach of choice for EASND. In spite of a long learning curve, RA might be an alternative option in particular cases to minimize scarring.     

Perioperative evaluation of glycaemic status in neck dissection: a retrospective analysis at a single hospital centre

Diabetes mellitus is generally considered a risk factor for impaired wound healing. This study aimed to evaluate the glycaemic status of patients undergoing neck dissection and describe its impact on postoperative outcomes, especially wound healing. A retrospective analysis was performed of the preoperative, intraoperative, and postoperative glycaemic data obtained from the medical charts of 60 adult patients who had undergone 64 neck dissections. Nine of the 64 procedures were performed in diabetic patients (14.1%). The average glucose values were: preoperative 5.99 ± 1.25 mmol/l, intraoperative 8.90 ± 2.62 mmol/l, and postoperative 10.01 ± 2.49 mmol/l. All registered preoperative hyperglycaemia cases (eight cases) were diabetic. Postoperative insulin therapy was done in 14 procedures (21.9%). Wound healing complications were found in five patients (7.8%); there was no wound infection. There was no association of wound healing complications with preoperative diabetic status (P = 1.000), preoperative glucose control (P = 1.000), preoperative (P = 0.469), intraoperative (P = 0.248), and postoperative (P = 0.158) glucose values, or with postoperative glucose control (P = 0.577). These data do not support the association of stress-induced hyperglycaemia or diabetes mellitus with postoperative wound healing problems in neck dissection.     

Can radiological examination of mandibular bone invasion accurately predict the need for mandibular resection in oral squamous cell carcinoma?

Bone invasion by oral squamous cell carcinoma necessitates jaw resection, with preoperative imaging ideally able to guide the resection. A retrospective review of 109 patients with oral squamous cell carcinoma who underwent mandibular resection was performed. Eighty-three had preoperative computed tomography (CT) imaging and 72 underwent magnetic resonance imaging (MRI). The presence of bone invasion on imaging was compared to histopathology. Bone invasion was detected in 44 of 109 resection specimens (40.4%) and was identified on CT in 31 of 83 cases (37.4%) and on MRI in 35 of 72 cases (48.6%). The sensitivity and specificity of CT for detecting bone invasion was 69.0% and 79.6%, respectively, while for MRI was 87.1% and 80.5%, respectively. Histological detection of bone invasion was associated with greater disease-specific mortality (P = 0.002), as was MRI detection of bone invasion (P = 0.027). CT detection was not significant (P = 0.240). Negative prediction of bone invasion was 95% accurate for both modalities in clinically non-invaded mandibles. Survival was reduced in patients who underwent marginal mandibular resection when bone invasion was detected histologically (33.3% vs. 70.5%, P = 0.277) and with CT, although this was not statistically significant. More data are required to determine whether more aggressive resection is warranted when bone invasion is detected preoperatively.     

Selective versus comprehensive neck dissection in the treatment of patients with a pathologically node-positive neck with or without microscopic extracapsular spread in oral squamous cell carcinoma

The objective of this study was to compare the prognosis and complications between selective neck dissection (SND) and comprehensive neck dissection (CND) for patients with a pathologically node-positive neck in squamous cell carcinoma of the tongue and the floor of the mouth. This was a retrospective cohort study. There was no significant difference between the SND group and the CND group in 3-year neck control rate (86.2% vs. 85.9%, P = 0.797) or disease-specific survival (DSS) rate (64.6% vs. 61.9%, P = 0.646). Further analyses of the respective 3-year DSS rates in the SND and CND subgroups were as follows: pN1 without extracapsular spread (ECS), 67.7% vs. 72.2%, P = 0.851; pN2b without ECS, 64.7% vs. 68.8%, P = 0.797; and pN+ with ECS, 57.1% vs. 60.0%, P = 0.939. Of note, there were significantly fewer complications in the SND group compared with the CND group (7.3% vs. 20.0%, P = 0.032). Multivariate analysis showed that the modality of neck treatment, pN+ status, and microscopic ECS did not serve as independent prognostic factors. SND plus adjuvant radiotherapy is a management strategy of high efficiency and minor morbidity for selected oral cancer patients with a pN+ neck with or without microscopic ECS.     

Evaluation of DNA methylation in matched oral swab and tissue specimens from Chinese patients with oral squamous cell carcinoma

The DNA methylation statuses of the paired box 1 (PAX1) and zinc finger protein 582 (ZNF582) genes have shown promise in the detection of oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the ability of PAX1 and ZNF582 methylation to distinguish OSCC and the adjacent normal tissue among cancer patients. This study included 67 patients with OSCC. The methylation levels of these two genes were analysed in tissue specimens (lesion site and adjacent normal site) and in oral swabs (lesion site and contralateral normal site). Levels of DNA methylation were higher at lesion sites than at the corresponding normal sites. According to receiver operating characteristics curve analysis, the area under the curve for PAX1 and ZNF582 methylation ranged from 0.73 to 0.82. No significant difference was observed between tissue specimens and oral swabs (PAX1, P =  0.41; ZNF582, P = 0.28). For the oral swab, PAX1 methylation was more pronounced in bone invasion (Z = 1.988, P =  0.047), and ZNF582 methylation was more pronounced in early-stage (Z = 2.354, P =  0.02) and well-differentiated tumours (Z = 3.731, P =  0.0002). Hypermethylated PAX1 and ZNF582 are effective biomarkers to distinguish lesion sites and corresponding normal sites in tissue specimens and oral swabs from OSCC patients.     

Health-related quality of life of parotid carcinoma patients—a comparative study with parotid adenoma patients and assessment of the influence of demographic,treatment, and pathological factors

The aim of this study was to compare the health-related quality of life (HRQoL) of patients treated for parotid carcinoma (PC) and parotid adenoma (PA). The impact of demographic, treatment, and pathological factors was analyzed within the PC group. The EORTC QLQ-C30 and QLQ-H&N35 questionnaires were completed by 45 PC patients and 46 PA patients. A number of HRQoL domains were significantly worse in the PC group than in the PA group: global health status, pain, insomnia, loss of appetite, mouth opening, swallowing problems, dry mouth, sticky saliva, problems with senses and speech, social eating, and cognitive functioning (P < 0.05). In the PC group, significantly worse scores were found for age >55 years, radical parotidectomy, neck dissection, radiotherapy, recurrence of the disease, pT3/T4 stage, pN+ status, and high-grade tumour (P < 0.05). Worse results were related to global health status, social contact, mouth opening, weight and appetite loss, physical, role, emotional, and social functioning, fatigue, speech problems, social eating, and financial difficulties. The study results demonstrate worse HRQoL in PC patients in comparison to PA patients. Older age, radical parotidectomy, neck dissection, radiotherapy, T3/T4 stage, pN+, high-grade tumours, and recurrence had a significant influence on HRQoL in PC patients.     

Clinicopathological and prognostic significance of preoperative serum epidermal growth factor levels in patients with oral squamous cell carcinoma

Epidermal growth factor (EGF) promotes tumourigenesis and tissue repair of epithelial and mesenchymal cells and has a role in chemotaxis, mitogenesis, cell motility, and cytoprotection. It also enhances the growth of cancers. EGF may therefore have a role in the initiation or promotion of oral carcinogenesis. The cases of 152 patients with oral squamous cell carcinoma whose preoperative serum EGF level was determined by enzyme-linked immunosorbent assay were analyzed retrospectively, along with those of 40 age- and sex-matched controls. Patients with higher levels of EGF were more likely to have neck lymph node metastasis (P = 0.026), advanced stage cancer (P = 0.04), and a worse survival status (P = 0.0019). Multivariate analysis using the Cox proportional hazards model indicated that the EGF level was an independent predictor of poor survival (hazard ratio 1.99, P = 0.018). Patients with higher preoperative serum EGF levels had significantly poorer cancer-specific survival by Kaplan–Meier analysis (P = 0.032). This study indicates that a higher preoperative serum EGF level is associated with neck lymph node metastasis, more advanced stage, and poor survival. EGF should be considered as a potential prognostic biomarker and a therapeutic target for patients with oral cancer.     

Prognostic factors in primary salivary gland mucoepidermoid carcinoma: an analysis of 376 cases in an Eastern Chinese population

Mucoepidermoid carcinoma (MEC) is an infrequent malignant neoplasm that originates most commonly in the salivary glands. The present study aimed to provide new information on prognostic factors in patients with salivary gland MEC. A retrospective analysis of the medical records of patients diagnosed with primary salivary gland MEC between 2003 and 2010 was conducted. The incidence of MEC in the minor salivary glands (62.2%) was almost twice that in the major salivary glands (37.8%). The most frequently affected sites were the parotid gland and palate. Lymph node metastasis was reported more frequently in male than female patients (P = 0.02), in high-grade than low/intermediate grade lesions (P < 0.001), and in lesions involving the submandibular gland (P < 0.001). The disease-free survival (DFS) at 5 years was 80.47%, with rates of 98.0%, 86.5%, and 38.5% for low-, intermediate-, and high-grade tumours, respectively. Among various clinicopathological factors, the only independent prognostic factor was histological grade (P < 0.001). Primary tumour site and histological grade are two important factors affecting cervical lymph node metastasis. Histological grade is the only independent factor affecting survival beyond tumor lymph node metastasis (TNM) staging in salivary gland MEC. Further advances in therapy are needed to improve the outcomes for patients with high-grade lesions.     

Prognostic value of elective neck dissection in adenoid cystic carcinoma of head and neck: a meta-analysis: A call for randomized trials and international consensus

Adenoid cystic carcinoma of head and neck (AdCCHN) is an uncommon salivary gland cancer characterized for infrequent neck metastases, and high rate of local and distant recurrence. The aim of this meta-analysis was to analyse the significance of elective neck dissection (END) in terms of overall survival (OS) in patients with AdCCHN. A systematic literature search and meta-analysis was performed. Endpoint assessed by this meta-analysis included 5-year OS (death from any cause). Statistical heterogeneity was assessed using the Cochrane Q test and I² statistic. A pooled odds ratio (OR) was reported with 95% confidence interval (CI). There were 1934 patients in the END arm and 3083 in the observation group. The pooled OR, calculated for END vs. observation, was 0.94. Patients receiving END had similar risk for death compared to observation cohort (P = 0.76). No significant difference in final outcome after patient stratification based on T stage was identified (OR for T1/T2 1.27, P = 0.39; OR for T3/T4 0.95, P = 0.90). Observation for cN0 neck is a reasonable option in AdCCHN. These findings suggest the need for prospective trials on indications and extent of END in AdCCHN.     

The action of anti-inflammatory agents in healthy temporomandibular joint synovial tissues is sex-dependent

This study evaluated the effects of dexamethasone, parecoxib, and glucosamine on cartilage thickness and cytokine levels in the temporomandibular joint (TMJ). Forty-eight rats (24 female, 24 male) were assigned to four treatments administered once daily for 7 days: control (saline intramuscularly), parecoxib (0.3 mg/kg intramuscularly), dexamethasone (0.1 mg/kg intramuscularly), and glucosamine (80 mg/kg orally). The thickness of TMJ cartilage and levels of four cytokines were measured. Median cartilage thickness was higher in males than in females in the control (253.2 vs. 240.4 μm, P = 0.0036), parecoxib (227.3 vs. 192.1 μm, P < 0.0001), and dexamethasone (227.1 vs. 170.5 μm, P = 0.017) groups, but was lower in males in the glucosamine group (214.5 vs. 239.6 μm, P = 0.0001). IL-1β was not detected. Median IL-1α levels differed between males and females in the parecoxib group (0.08 vs. 0.04 ng/ml, P = 0.0055), but not in the control (0.07 vs. 0.06 ng/ml), dexamethasone (0.06 vs. 0.04 ng/ml), or glucosamine (0.08 ng/ml vs. 0.06 ng/ml) groups (all P > 0.05). Only dexamethasone induced lower IL-6 levels in males than in females (median 4.6 vs. 2.1 ng/ml, P = 0.0044). Median TNF-α levels did not differ between males and females in the control (0.07 vs. 0.05 ng/ml) or parecoxib (0.07 vs. 0.05 ng/ml) groups (both P > 0.05), but dexamethasone (0.09 vs. 0.05 ng/ml, P = 0.0002) and glucosamine (0.09 vs. 0.07 ng/ml, P = 0.0259) induced higher TNF-α levels in females. Thus, the effects of the three treatments on the levels of cytokines and thickness of condylar cartilage were sex-dependent.     

Tuberculosis: the great imitator in the head and neck - our experience of 24 cases in 22 years

This retrospective study covered over two decades, during which an individual head and neck surgeon treated 24 patients with cervicofacial lymphadenitis that was related to both Mycobacterium tuberculosis complex (n = 17, made up of M tuberculosis (n = 16) and M bovis (n = 1)), and non-tuberculous mycobacteria. The seven cases of non-tuberculous mycobacteria were caused by M avium complex (n = 3), M malmoense (n = 3), and M kansaii (n = 1). By using a tailored management approach, at times selective combined surgical and antimycobacterial treatment, he achieved a success rate of 23/24 cases, with only one recurrence and no major complications. The results suggest that patients with tuberculosis confined to the head and neck rarely develop constitutional symptoms, so the absence of such symptoms may not exclude tuberculosis. There was also a good correlation between predictive variables (immune state, inflammatory markers on admission, causative mycobacterium, and the antimycobacterial regimen used) and time spent under follow-up at the head and neck outpatient clinic.     

Gland-sparing neck dissection: oncological and functional outcomes in oral cancer patients

This study was performed to evaluate the subjective and objective functional outcomes of patients who had undergone submandibular gland-sparing neck dissection. All data were obtained from patients treated in a single hospital. Seventy-seven patients who had undergone complete submandibular gland sparing (CSGS) were included in the study. Cancer prognosis items were recorded. The subjective outcomes included patient self-evaluation of mouth dryness and the evaluation of the presence of saliva secretion following the application of digital pressure. Saliva scintigraphy served as the objective test. Self-reported xerostomia was compared between the CSGS patients and a control group of patients who had undergone unilateral submandibular gland removal (USGR; n = 74). In the CSGS group, local recurrence occurred in 3.8% of the 80 cancer sites, and neck recurrence occurred in 5.9% of neck dissection sites. Regarding the subjective measurements, 7.0% of the CSGS patients reported xerostomia and 91.9% demonstrated saliva secretion by digital pressure. Scintigraphy revealed actively secreting glands, with 42.9% of them showing normal gland function; none of the patients had severe xerostomia. The relative risk of dry mouth was significantly higher in the USGR patients than in the CSGS patients (P < 0.001). Submandibular gland sparing during neck dissection was found to result in satisfactory saliva secretion, with a relatively small risk of local or neck recurrence.     

Is there a correlation between arthroscopic findings and the clinical signs and symptoms of patients with internal derangement of the temporomandibular joint? A prospective study

The aim of this study was to evaluate the correlation between clinical signs and symptoms of patients with internal derangement of the temporomandibular joint (TMJ) and arthroscopic findings. The study included a sample of 67 patients who underwent TMJ arthroscopy. The variables evaluated were the arthroscopic findings of synovitis, chondromalacia, adhesion, and roofing. The Spearman correlation index was used to correlate these findings with the clinical signs and symptoms of internal derangement of the TMJ, namely maximum mouth opening, pain (visual analogue scale, VAS), and the Wilkes classification. The mean age of the population was 36.16 years, and 85% were female. There was a correlation between pain and synovitis (P = 0.0029, r = 0.3508), between mouth opening limitation and the amount of adhesion (P = 0.0004, r = ?0.4084), and between Wilkes classification and the presence of chondromalacia and disc displacement (P = 0.001, r = 0.374 and P = 0.0045, r = ?0.3357, respectively). No correlation was found between age and the presence of chondromalacia (P = 0.3444, r = 0.1147). Patients who had worse pain symptoms had more advanced stages of synovitis, and the increased presence of adhesions was associated with limitations in mouth opening. Furthermore, those with more advanced Wilkes stages had greater disc displacement and more severe stages of chondromalacia.     

Orbit,zygoma, and maxilla growth patterns in Crouzon syndrome

The facial malformations of Crouzon syndrome involve the entire cranio-orbito-zygomatic region. The detailed sequence of changes in orbit, zygoma, and maxilla over time, the mutual influence among these three anatomical structures, and their relationship with the cranial base were studied to determine the sequence and timing of deformity. Preoperative CT scans of 36 patients with Crouzon syndrome (mean age 10.84 ± 14.70 years; 14 male, 22 female) and CT scans of 54 control subjects (mean age 8.53 ± 13.22 years; 29 male, 25 female) were divided into five subgroups by age: 0–6 months, 6 months–2 years, 2–6 years, 6–18 years, and 18–62 years. Craniofacial morphometric cephalometrics were analyzed using Materialise software. Crouzon orbit anteroposterior length was shorter before 6 months (P = 0.021) and remained shorter into adulthood (P < 0.001). Globe projection was greater across all age subgroups (P < 0.001), reaching a peak at 6 months to 2 years (P < 0.001). The increased medial orbital width was the most remarkable and persistent secondary deformity (P < 0.001). The zygoma anterior protrusion was retruded before 6 months of age (P < 0.001), but then improved gradually. The width of maxilla was greater by 24% in the Crouzon cohort (P < 0.001), with a difference of 16% before 6 months (P = 0.024), and was developed earlier than the shortened anteroposterior length. Crouzon high and shallow orbital walls are distinctive. Maxillary widening developed before the malformation of sphenoid. The anteroposterior position of zygoma is likely a principal deformity, rather than a reflection of the intrinsic shape of the bone.Level of Evidence: II     

Evaluation of two-dimensional lateral cephalogram and three-dimensional cone beam computed tomography superimpositions: a comparative study

Superimposition of radiographic imaging is used to evaluate patient growth and the effects of surgical and/or orthodontic treatment. The purpose of this study was to compare the outcomes of superimposition between two-dimensional (2D) and three-dimensional (3D) superimpositions. 2D lateral cephalograms were generated from the initial and final cone beam computed tomography scans (CBCT) of 18 patients and superimposed. Both 3D CBCT and 2D CBCT generated lateral cephalograms were oriented to the Frankfort horizontal plane and superimposed according to the American Board of Orthodontics recommendations. Changes in landmark position were quantified from the resulting superimposition outcomes via linear measurements made with Dolphin software. Differences between the two methods were analyzed using paired t-tests. Measurements were repeated twice for 10 randomly selected scans to assess reliability by intra-class correlation coefficient (ICC) analysis. Intra-examiner reliability was high for all measurements (ICC > 0.84). Agreement between 2D and 3D superimposition outcomes, as measured by P-values, was low for ANS (P = 0.026), B-point (P < 0.001), ST Upper lip (P = 0.019), U1 tip (P = 0.010), and U1 apex (P = 0.026). 2D measurements were significantly higher than 3D measurements for ANS, B-point, ST Upper lip, U1 tip, and U1 apex. Findings indicated that both methods of superimposition (2D and 3D) are highly reliable. Statistical differences between 2D and 3D superimposition outcomes were below the threshold of clinical significance.