BACKGROUND: Oral cavity squamous cell carcinoma (OCSCC) is the most common head and neck malignancy. Although the survival rate of patients with advanced-stage disease remains approximately 20% to 60%, when detected at an early stage, the survival rate approaches 80%, posing a pressing need for a well validated profiling method to assess patients who have a high risk of developing OCSCC. Tumor DNA detection in saliva may provide a robust biomarker platform that overcomes the limitations of current diagnostic tests. However, there is no routine saliva-based screening method for patients with OCSCC. METHODS: The authors designed a custom nextgeneration sequencing panel with unique molecular identifiers that covers coding regions of 7 frequently mutated genes in OCSCC and applied it on DNA extracted from 121 treatment-naive OCSCC tumors and matched preoperative saliva specimens. RESULTS: By using stringent variant-calling criteria, mutations were detected in 106 tumors, consistent with a predicted detection rate ≥88%. Moreover, mutations identified in primary malignancies were also detected in 93% of saliva samples. To ensure that variants are not errors resulting in false-positive calls, a multistep analytical validation of this approach was performed: 1) re-sequencing of 46 saliva samples confirmed 88% of somatic variants; 2) no functionally relevant mutations were detected in saliva samples from 11 healthy individuals without a history of tobacco or alcohol; and 3) using a panel of 7 synthetic loci across 8 sequencing runs, it was confirmed that the platform developed is reproducible and provides sensitivity on par with droplet digital polymerase chain reaction. CONCLUSIONS: The current data highlight the feasibility of somatic mutation identification in driver genes in saliva collected at the time of OCSCC diagnosis.
6562 Background: Oral cavity squamous cell carcinoma (OCSCC) frequently presents as clinically advanced disease with poor prognosis. When diagnosed at early stages, survival rates approach 80%, underscoring the need for validated, cost-effective detection methods. OCSCC is driven by the serial acquisition of genetic alterations. Tumor-defining somatic mutations are attractive biomarkers and hence their presence in saliva may be associated with malignancy as shown in a few proof-of-concept studies, including our previous work. Based on this premise, we present a low-cost, accurate, next generation sequencing (NGS) test with high clinical utility aimed at detecting mutations in the saliva for early diagnosis and potential screening of OCSCC. Methods: We have designed a custom NGS panel that covers exons of 7 most frequently mutated genes in OSCC. This minimal gene set derived from the analysis from 3 public datasets, predicted incidence of at least one somatic aberration in 89% of patients. We recruited 91 treatment-naïve OCSCC patients and profiled DNA from tissue and matched pre-operative saliva using this test. We also tested DNA from 12 subjects with premalignant lesions with high-grade oral dysplasia and matched saliva. Results: Using stringent variant calling criteria, at least one somatic variant was detected in 88 (96%) of the 91 primary tumors. 90.9% of the matched saliva were concordant, with only a minor decrease in early stage disease. Tumor-specific mutations (≥5% AF) in driver genes were detected in 10 (83.3%) dysplastic lesions, suggesting that driving clonal events may occur early in disease development. Interestingly, in 3 matched saliva of the dysplastic samples, the same mutations were detected. To ensure a variant is not a false positive call, we performed a vigorous multistep analytical validation of this saliva-based test: (i) independent re-sequencing of 24 saliva confirmed 94% reproducibility; (ii) no functionally relevant variants were detected in saliva from 12 of 13 healthy subjects without history of tobacco and alcohol usage; (iii) reproducibility, sensitivity, and specificity were confirmed using a positive control with 7 loci at 0.25% AF across 8 independent saliva sequencing runs and a certified negative control and was found to be on par with droplet digital PCR. Conclusions: These data highlight the feasibility of saliva-based testing for early diagnosis of OCSCC and premalignant lesions.
Tumour metastasis is one of the leading cause of cancer-related mortality. Circulating tumour cells (CTCs) have been implicated in loco-regional and distant metastasis and its role is being extensively studied in various malignancies, including those from the head and neck region. The main challenge in understanding their significance lies in the rarity of these cells in the blood. However, newer technologies have attempted to overcome these pitfalls. This review explores the evolution of CTC research and other related areas, including its biological significance, sustainability within the circulating vascular environment and possible clinical implications.
Background: The incidence of oropharyngeal carcinoma has been on the rise in recent decades. About 30% of patients who undergo definitive chemoradiation as the initial treatment present with residual/recurrent disease. In such a situation, surgical salvage either in the form of traditional open surgery or transoral robotic surgery (TORS) remains a viable treatment option. However, the extensive vascular supply of the posterior tongue and tonsillar bed increases the risk of perioperative bleeding, which is a key concern. The article describes the technique of selective pre-operative embolization to reduce the risk of perioperative bleeding and enumerate its advantages in providing a bloodless field during surgery. Methods: Prospective study of 5 patients with recurrent or residual midline BOT tumours who underwent TORS after selective lingual artery embolization at our centre. Results and Conclusions: None of the patients had any major perioperative bleeding or post procedural complications. All the patients after TORS had their tongue vascularity preserved with adequate recovery of tongue functions. Selective embolization of the feeder vessels provides a favorable bloodless surgical field without affecting the vascular integrity of the remnant tongue. This added advantage helps restoring the normal oral phase of swallowing.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.