Oral cancer is the 16th most common cancer worldwide. It commonly arises from painless white or red plaques within the oral cavity. Clinical outcome is highly related to the stage when diagnosed. However, early diagnosis is complex owing to the impracticality of biopsying every potentially premalignant intraoral lesion. Therefore, there is a need to develop a non-invasive cost-effective diagnostic technique to differentiate non-malignant and early-stage malignant lesions. Optical spectroscopy may provide an appropriate solution to facilitate early detection of these lesions. It has many advantages over traditional approaches including cost, speed, objectivity, sensitivity, painlessness, and ease-of use in clinical setting for real-time diagnosis. This review consists of a comprehensive overview of optical spectroscopy for oral cancer diagnosis, epidemiology, and recent improvements in this field for diagnostic purposes. It summarizes major developments in label-free optical spectroscopy, including Raman, fluorescence, and diffuse reflectance spectroscopy during recent years. Among the wide range of optical techniques available, we chose these three for this review because they have the ability to provide biochemical information and show great potential for real-time deep-tissue point-based in vivo analysis. This review also highlights the importance of saliva-based potential biomarkers for non-invasive early-stage diagnosis. It concludes with the discussion on the scope of development and future demands from a clinical point of view.

Aims: Perineural invasion (PNI) is associated with survival in oral cavity squamous cell carcinoma (OCSCC). There is evidence to suggest that PNI location and extent may be of additional significance. The primary aim of this study was to evaluate the prognostic ability of PNI, including location and extent, in early‐stage OCSCC.Methods and results: This was a retrospective study, with the main cohort comprising of 129 patients with pT1/T2 pN0/Nx TNM8 OCSCC. Slides were re‐reviewed in cases reported as having PNI to classify location as intratumoural (IT) and/or extratumoural (ET) and extent as unifocal (UF) or multifocal (MF). Univariate and multivariate analysis assessing impact of pathological features on survival outcomes was performed. On multivariate analysis, IT PNI was significantly associated with locoregional recurrence‐free survival (LRS) [odds ratio = 5.69, 95% confidence interval (CI) = 1.50–21.63, P = 0.01]. Disease‐specific survival (DSS) and overall survival (OS) were non‐significant. In comparison, ET PNI was predictive of LRS (odds ratio = 20.57, 95% CI = 3.48–121.73, P = 0.001), DSS (odds ratio = 40.47, 95% CI = 5.17–316.96, P = 0.0004) and OS (odds ratio = 11.92, 95% CI = 2.18–65.22, P = 0.004). Multifocal PNI was significant on univariate analysis for all three outcome parameters evaluated, but these findings were not maintained on multivariate assessment.Conclusions: Extratumoural PNI is strongly predictive of survival outcomes, including OS, in early‐stage OCSCC. These findings support the reporting of PNI location as a mandatory data element. The impact of PNI extent requires further study.

Background: There is an ongoing need to identify pathologic prognosticators in early-stage oral cavity squamous cell carcinoma (OCSCC) to aid selection of patients who may benefit from adjuvant treatment. The objective of this study was to evaluate the prognostic ability of worst pattern of invasion-5 (WPOI-5) defined by the presence of satellite nodules, extratumoural perineural invasion (PNI) and/or extratumoural lymphovascular space invasion (LVI) in low-stage, node negative OCSCC. Methods: This was a retrospective study of 160 patients with T1/T2N0 tumours staged using TNM7 treated surgically. Histology of the primary tumour was re-reviewed as appropriate to assess for the presence of WPOI-5 parameters. Univariate and multivariate analysis assessing impact of pathological features on survival outcomes was performed. Results: On univariate analysis, WPOI-5 and its 3 constituent components of satellite nodules, extratumoural PNI and extratumoural LVI were all significantly associated with disease-specific survival (DSS) and overall survival (OS). On multivariate analysis, satellite nodules (odds ratio 6.61, 95% CI 2.83–15.44, p < 0.0001) and extratumoural LVI (odds ratio 9.97, 95% CI 2.19–45.35, p = 0.003) were independently associated with OS. Postoperative radiotherapy (odds ratio 0.40, 95% CI 0.19–0.87, p = 0.02) and non-tongue subsite (odds ratio 3.03, 95% CI 1.70–5.39, p = 0.0002) were also significantly associated with OS on multivariate analysis. Conclusion: Satellite nodules and extratumoural LVI correlated significantly with survival outcomes in our early-stage OSCC cohort. Further study is required to investigate the benefit of adjuvant treatment in these cases and to ascertain if WPOI-5 parameters including satellite nodules should be mandatory reporting data elements.

Objective: Lymph nodal yield (LNY) is increasingly used in oral squamous cell carcinoma (OSCC) research as a prognostic factor and quality metric but remain to be validated across independent OSCC cohorts. Study design: Retrospective cohort study. Setting: Primary OSCC patients (n = 1080) who underwent a neck dissection, collected from three sites: Brescia, Cork, and Heidelberg. Methods: The accuracy of LNY in predicting 3‐ and 5‐year mortality was evaluated using the area under the ROC curve (AUC). Binomial regression models, adjusted for LNY and various confounders, were used to cross‐validate predictive performance across independent cohorts. A model estimating the population‐average treatment effect of LNY was used to estimate the effect of what would have been observed if the OSCC patients had been randomly assigned to have specific ranges of LNYs removed, irrespective of their individual characteristics. Mean LNY was estimated between the three cohorts. Results: ROC curve analysis demonstrated that LNY did not improve prognostic accuracy in predicting 3‐ and 5‐year mortality risks. Cross‐validation across independent cohorts showed that adding LNY to the binomial regression models did not improve predictive accuracy. Using the LNY range of 33 to 44 as a reference, the average treatment effect model found no significant difference in the 3‐year risk of death across LNY groups (LNY: 2‐17, 17‐25, 25‐33, and 44‐119) for pN‐positive patients. Conclusion: We found no improvement in the prognostic accuracy for mortality when considering LNY in different settings. Substantial inter‐center variability and lack of consistent survival benefit challenge the use of LNY as a prognostic or surgical quality metric.