Background
The objective of this study was to characterise the incidence and prognostic correlation of perineural invasion (PNI) in oral squamous cell carcinoma and determine whether nerve growth ...factor and its receptor tyrosine Kinase A expression could be used as biological markers for PNI.
Methods
A retrospective review of pathology reports of 430 patients with oral squamous cell carcinoma who were treated from 1992 to 2014 in Tayside, Scotland, was carried out. The expression of nerve growth factor and tyrosine kinase A was assessed with immunohistochemistry in 132 tissue sections of oral squamous cell carcinoma.
Results
Perineural invasion was identified in 17.4% of oral squamous cell carcinomas. High expression of nerve growth factor and tyrosine kinase A was seen in 84% and 92% of oral squamous cell carcinoma, respectively. Tumours with PNI expressed nerve growth factor and tyrosine kinase A with a greater frequency than tumours without PNI. PNI and high expression of nerve growth factor were significantly associated with pain. PNI was significantly associated with stage IV tumours and poor disease‐specific survival.
Conclusions
A higher level of expression of nerve growth factor and tyrosine kinase A may predict PNI and therefore may be considered as biological markers for PNI in oral squamous cell carcinoma. PNI and nerve growth factor overexpression may contribute to the pain generation in oral cancer patients. PNI and nerve growth factor expression can predict the aggressiveness and prognosis of oral squamous cell carcinoma patients.
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CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Learning suturing skills is an important area of the undergraduate curriculum and ideally requires realistic and anatomically accurate surgical training models to prepare students for treating ...patients. Little is currently understood regarding which model might be perceived by students to be the best or which might most effectively facilitate their learning. The aim of this study was to compare four teaching models: a tabletop silicon dental model, a restricted access tabletop model, a traditional phantom head mounted model, and a Thiel cadaver. Student preferences were explored for each of the models. Following lecture and video-based teaching 67 fourth-year students attended a practical suturing teaching session followed by the second session more focused on the experience of cutting and suturing mucoperiosteal flaps. Forty-six students (67%) gave online anonymous feedback on the first session. The majority (95%) felt prepared to place a simple interrupted suture on a patient, and 88% felt confident to do so. Twenty-eight students (40%) provided feedback on the second session with 82% agreeing that they were prepared to cut a mucoperiosteal flap and 48% felt confident to do this for a patient. The cadaver model was rated as the best of the four models for both suturing and mucoperiosteal flap skills. These results support its use for teaching students to suturing and surgical skills. However, despite this teaching student-rated confidence to cut and suture flaps for a patient remains poor.
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CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
Oral cavity and oropharyngeal cancers are frequently described as part of a group of oral cancers or head and neck cancer. Treatment of oral cavity cancer is generally surgery followed by ...radiotherapy, whereas oropharyngeal cancers, which are more likely to be advanced at the time of diagnosis, are managed with radiotherapy or chemoradiation. Surgery for oral cancers can be disfiguring and both surgery and radiotherapy have significant functional side effects, notably impaired ability to eat, drink and talk. The development of new chemotherapy agents, new combinations of agents and changes in the relative timing of surgery, radiotherapy, and chemotherapy treatments may potentially bring about increases in both survival and quality of life for this group of patients.
Objectives
To determine whether chemotherapy, in addition to radiotherapy and/or surgery for oral cavity and oropharyngeal cancer results in improved survival, disease free survival, progression free survival, locoregional control and reduced recurrence of disease. To determine which regimen and time of administration (induction, concomitant or adjuvant) is associated with better outcomes.
Search methods
Electronic searches of the Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE, EMBASE, AMED were undertaken on 1st December 2010. Reference lists of recent reviews and included studies were also searched to identify further trials.
Selection criteria
Randomised controlled trials where more than 50% of participants had primary tumours in the oral cavity or oropharynx, and which compared the addition of chemotherapy to other treatments such as radiotherapy and/or surgery, or compared two or more chemotherapy regimens or modes of administration, were included.
Data collection and analysis
Eighty‐nine trials which met the inclusion criteria were assessed for risk of bias and data were extracted by two or more review authors. The primary outcome was total mortality. Trial authors were contacted for additional information or for clarification.
Main results
There is evidence of a small increase in overall survival associated with induction chemotherapy compared to locoregional treatment alone (25 trials), hazard ratio (HR) of mortality 0.92 (95% confidence interval (CI) 0.84 to 1.00, P = 0.06). Post‐surgery adjuvant chemotherapy is associated with improved overall survival compared to surgery ± radiotherapy alone (10 trials), HR of mortality 0.88 (95% CI 0.79 to 0.99, P = 0.03), and there is some evidence that this improvement may be greater with concomitant adjuvant chemoradiotherapy (4 trials), HR of mortality 0.84 (95% CI 0.72 to 0.98, P = 0.03). In patients with unresectable tumours, there is evidence that concomitant or alternating chemoradiotherapy is associated with improved survival compared to radiotherapy alone (26 trials), HR of mortality 0.78 (95% CI 0.73 to 0.83, P < 0.00001). These findings are confirmed by sensitivity analyses based on studies assessed at low risk of bias. There is insufficient evidence to identify which agent(s) and/or regimen(s) are the most effective. The additional toxicity attributable to chemotherapy in the combined regimens remains unquantified.
Authors' conclusions
Chemotherapy, in addition to radiotherapy and surgery, is associated with improved overall survival in patients with oral cavity and oropharyngeal cancers. Induction chemotherapy may prolong survival by 8 to 20% and adjuvant concomitant chemoradiotherapy may prolong survival by up to 16%. In patients with unresectable tumours, concomitant or alternating chemoradiotherapy may prolong survival by 10 to 22%. There is insufficient evidence as to which agent or regimen is most effective and the additional toxicity associated with chemotherapy given in addition to radiotherapy and/or surgery cannot be quantified.
Surgery is an important part of the management of oral cavity cancer with regard to both the removal of the primary tumour and removal of lymph nodes in the neck. Surgery is less frequently used in ...oropharyngeal cancer. Surgery alone may be treatment for early stage disease or surgery may be used in combination with radiotherapy, chemotherapy and immunotherapy/biotherapy. There is variation in the recommended timing and extent of surgery in the overall treatment regimens of people with these cancers.
To determine which surgical treatment modalities for oral cavity and oropharyngeal cancers result in increased overall survival, disease free survival, progression free survival and reduced recurrence.
The following electronic databases were searched: the Cochrane Oral Health Group Trials Register (to 17 February 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1), MEDLINE via OVID (1950 to 17 February 2011) and EMBASE via OVID (1980 to 17 February 2011). There were no restrictions regarding language or date of publication.
Randomised controlled trials where more than 50% of participants had primary tumours of the oral cavity or oropharynx, and which compared two or more surgical treatment modalities or surgery versus other treatment modalities.
Data extraction and assessment of risk of bias was undertaken independently by two or more review authors. Study authors were contacted for additional information as required. Adverse events data were collected from published trials.
Seven trials (n = 669; 667 with cancers of the oral cavity) satisfied the inclusion criteria, but none were assessed as low risk of bias. Trials were grouped into three main comparisons. Four trials compared elective neck dissection (ND) with therapeutic neck dissection in patients with oral cavity cancer and clinically negative neck nodes, but differences in type of surgery and duration of follow-up made meta-analysis inappropriate. Three of these trials reported overall and disease free survival. One trial showed a benefit for elective supraomohyoid neck dissection compared to therapeutic ND in overall and disease free survival. Two trials found no difference between elective radical ND and therapeutic ND for the outcomes of overall survival and disease free survival. All four trials found reduced locoregional recurrence following elective ND.A further two trials compared elective radical ND with elective selective ND and found no difference in overall survival, disease free survival or recurrence. The final trial compared surgery plus radiotherapy to radiotherapy alone but data were unreliable because the trial stopped early and there were multiple protocol violations.None of the trials reported quality of life as an outcome. Two trials, evaluating different comparisons reported adverse effects of treatment.
Seven included trials evaluated neck dissection surgery in patients with oral cavity cancers. The review found weak evidence that elective neck dissection of clinically negative neck nodes at the time of removal of the primary tumour results in reduced locoregional recurrence, but there is insufficient evidence to conclude that elective neck dissection increases overall survival or disease free survival compared to therapeutic neck dissection. There is very weak evidence from one trial that elective supraomohyoid neck dissection may be associated with increased overall and disease free survival. There is no evidence that radical neck dissection increases overall survival compared to conservative neck dissection surgery. Reporting of adverse events in all trials was poor and it was not possible to compare the quality of life of patients undergoing different surgeries.
Suturing is an essential skill in dentistry and not one easily acquired. The COVID-19 pandemic prompted a change to the use of Thiel cadavers and online resources with the aim of improving skill ...acquisition using the best model available. This study investigated the utility of the Thiel cadaver for teaching suturing skills and the potential impact of the lockdown. Fifty-seven year 4 students attended a teaching session. Student views on this teaching were explored via a questionnaire survey and qualitative data collected from a focus group. Data were analysed using an inductive approach. The response rate was 53% (30 students) for the questionnaire with 9 students participating in the focus group. Independent feedback was provided by two members of the teaching staff. Online video resources were very well received by the students with 97% agreeing that it was useful preparation. Ninety percent (90%) thought that the cadaveric model was suitable for this teaching and realistic. Positive emergent themes from the focus group centred on the use of the cadaveric model and the positive and relaxed teaching and learning environment. Staff perceived this model as superior to previously used models. There were no reported negative pandemic impacts and the cadaver model was well received.
The detrimental impact of the COVID-19 pandemic on dental education prompted the Scottish Government to fund an additional year to the dental course to ensure that the students had the necessary ...clinical experience. The aim of the study was to better understand the final year student perceptions of this extension on their oral surgery experience at the University of Dundee.
This mixed methods study consisted of an anonymous online questionnaire and a focus group.
Forty-one students (69.3%) completed the questionnaire and ten students participated in the focus group. Thirty-six (88.8%) students agreed that the oral surgery teaching provided sufficient knowledge to undertake independent practice. All of the students felt confident to carry out an extraction, and the majority of them (
= 40, 95%) felt confident to remove a retained root, however, their confidence with surgery was lower.
The extension gave the students sufficient experience in oral surgery to gain confidence in clinical skills and an appropriate level of knowledge in preparation for the next phase of their career. Most of the students agreed that the extension was necessary and beneficial. This cohort graduated with more oral surgery experience than any of the students did in the previous 4 years from Dundee and with experience that was comparable with the students at other schools in the pre-COVID-19 era.
Background/Aim
Machine learning analyses of cancer outcomes for oral cancer remain sparse compared to other types of cancer like breast or lung. The purpose of the present study was to compare the ...performance of machine learning algorithms in the prediction of global, recurrence‐free five‐year survival in oral cancer patients based on clinical and histopathological data.
Methods
Data were gathered retrospectively from 416 patients with oral squamous cell carcinoma. The data set was divided into training and test data set (75:25 split). Training performance of five machine learning algorithms (Logistic regression, K‐nearest neighbours, Naïve Bayes, Decision tree and Random forest classifiers) for prediction was assessed by k‐fold cross‐validation. Variables used in the machine learning models were age, sex, pain symptoms, grade of lesion, lymphovascular invasion, extracapsular extension, perineural invasion, bone invasion and type of treatment. Variable importance was assessed and model performance on the testing data was assessed using receiver operating characteristic curves, accuracy, sensitivity, specificity and F1 score.
Results
The best performing model was the Decision tree classifier, followed by the Logistic Regression model (accuracy 76% and 60%, respectively). The Naïve Bayes model did not display any predictive value with 0% specificity.
Conclusions
Machine learning presents a promising and accessible toolset for improving prediction of oral cancer outcomes. Our findings add to a growing body of evidence that Decision tree models are useful in models in predicting OSCC outcomes. We would advise that future similar studies explore a variety of machine learning models including Logistic regression to help evaluate model performance.
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CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Objectives
The aims of this study were to investigate the role of nerve growth factor on perineural invasion in oral and salivary gland tumour cell lines and whether there is an involvement of ...PI3K/Akt pathway.
Materials and Methods
Four cell lines were investigated: HSG and TYS (salivary gland tumours), SAS‐H1 (oral squamous cell carcinoma) and HaCaT (human skin keratinocyte). Initially, Boyden chamber assay was done to examine the effect of different concentration of nerve growth factor on cell migration. Western blot/ immunofluorescence techniques were used to investigate the phosphorylation status of the Akt pathway within the cells in response to nerve growth factor. The effect of this growth factor and the addition of an Akt inhibitor on cell morphology and migration were also examined using scatter/scratch assays.
Results
Nerve growth factor triggered the PI3K/Akt pathway in oral and salivary tumour cells and induced oral and salivary tumour cell scattering and migration. Inhibitor assays confirmed that oral and salivary gland tumour cell scattering and migration is Akt dependent.
Conclusions
Nerve growth factor can stimulate scattering and migration in cells derived from oral and salivary gland tumours, thereby potentially enhancing perineural invasion. Phosphorylated Akt controls cancer cell migration and scattering. Blocking the Akt pathway may inhibit cell migration and therefore perineural invasion and metastasis.
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CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
Oral cavity and oropharyngeal cancers are the most common cancers arising in the head and neck. Treatment of oral cavity cancer is generally surgery followed by radiotherapy, whereas ...oropharyngeal cancers, which are more likely to be advanced at the time of diagnosis, are managed with radiotherapy or chemoradiation. Surgery for oral cancers can be disfiguring and both surgery and radiotherapy have significant functional side effects. The development of new chemotherapy agents, new combinations of agents and changes in the relative timing of surgery, radiotherapy, and chemotherapy treatments may potentially bring about increases in both survival and quality of life for this group of patients. This review updates one last published in 2011.
Objectives
To determine whether chemotherapy, in addition to radiotherapy and/or surgery for oral cavity and oropharyngeal squamous cell carcinoma results in improved overall survival, improved disease‐free survival and/or improved locoregional control, when incorporated as either induction therapy given prior to locoregional treatment (i.e. radiotherapy or surgery), concurrent with radiotherapy or in the adjuvant (i.e. after locoregional treatment with radiotherapy or surgery) setting.
Search methods
An information specialist searched 4 bibliographic databases up to 15 September 2021 and used additional search methods to identify published, unpublished and ongoing studies.
Selection criteria
We included randomised controlled trials (RCTs) where more than 50% of participants had primary tumours in the oral cavity or oropharynx, and that evaluated the addition of chemotherapy to other treatments such as radiotherapy and/or surgery, or compared two or more chemotherapy regimens or modes of administration.
Data collection and analysis
For this update, we assessed the new included trials for their risk of bias and at least two authors extracted data from them. Our primary outcome was overall survival (time to death from any cause). Secondary outcomes were disease‐free survival (time to disease recurrence or death from any cause) and locoregional control (response to primary treatment).
We contacted trial authors for additional information or clarification when necessary.
Main results
We included 100 studies with 18,813 participants. None of the included trials were at low risk of bias.
For induction chemotherapy, we reported the results for contemporary regimens that will be of interest to clinicians and people being treated for oral cavity and oropharyngeal cancers. Overall, there is insufficient evidence to clearly demonstrate a survival benefit from induction chemotherapy with platinum plus 5‐fluorouracil prior to radiotherapy (hazard ratio (HR) for death 0.85, 95% confidence interval (CI) 0.70 to 1.04, P = 0.11; 7427 participants, 5 studies; moderate‐certainty evidence), prior to surgery (HR for death 1.06, 95% CI 0.71 to 1.60, P = 0.77; 198 participants, 1 study; low‐certainty evidence) or prior to concurrent chemoradiation (CRT) with cisplatin (HR for death 0.71, 95% CI 0.37 to 1.35, P = 0.30; 389 participants, 2 studies; low‐certainty evidence). There is insufficient evidence to support the use of an induction chemotherapy regimen with cisplatin plus 5‐fluorouracil plus docetaxel prior to CRT with cisplatin (HR for death 1.08, 95% CI 0.80 to 1.44, P = 0.63; 760 participants, 3 studies; low‐certainty evidence).
There is insufficient evidence to support the use of adjuvant chemotherapy over observation only following surgery (HR for death 0.95, 95% CI 0.73 to 1.22, P = 0.67; 353 participants, 5 studies; moderate‐certainty evidence). Among studies that compared post‐surgical adjuvant CRT, as compared to post‐surgical RT, adjuvant CRT showed a survival benefit (HR 0.84, 95% CI 0.72 to 0.98, P = 0.03; 1097 participants, 4 studies; moderate‐certainty evidence).
Primary treatment with CRT, as compared to radiotherapy alone, was associated with a reduction in the risk of death (HR for death 0.74, 95% CI 0.67 to 0.83, P < 0.00001; 2852 participants, 24 studies; moderate‐certainty evidence).
Authors' conclusions
The results of this review demonstrate that chemotherapy in the curative‐intent treatment of oral cavity and oropharyngeal cancers only seems to be of benefit when used in specific circumstances together with locoregional treatment. The evidence does not show a clear survival benefit from the use of induction chemotherapy prior to radiotherapy, surgery or CRT. Adjuvant CRT reduces the risk of death by 16%, as compared to radiotherapy alone. Concurrent chemoradiation as compared to radiation alone is associated with a greater than 20% improvement in overall survival; however, additional research is required to inform how the specific chemotherapy regimen may influence this benefit.
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