Ultrasensitive detection of tumor-specific mutations in saliva of patients with oral cavity squamous cell carcinoma.

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 next-generation 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.

Improvement of oral cancer screening quality and reach: The promise of artificial intelligence.

Oral cancer is easily detectable by physical (self) examination. However, many cases of oral cancer are detected late, which causes unnecessary morbidity and mortality. Screening of high-risk populations seems beneficial, but these populations are commonly located in regions with limited access to health care. The advent of information technology and its modern derivative artificial intelligence (AI) promises to improve oral cancer screening but to date, few efforts have been made to apply these techniques and relatively little research has been conducted to retrieve meaningful information from AI data. In this paper, we discuss the promise of AI to improve the quality and reach of oral cancer screening and its potential effect on improving mortality and unequal access to health care around the world.

Lymph node level ratio: Are we relying too much on numbers?

The lymph node level ratio appears to be a continuation of nodal yield and nodal density, two prognostic metrics already in use. A retrospective analysis conducted in the current study showed that a value of fewer than 4 lymph nodes/level is linked to a lower overall and disease-specific survival. This letter aims to review the reasoning behind the use of node level ratios and nodal yields as quality and prognostic indicators, and to explore possible factors that could affect these.

Role of Imaging in Predicting the Deep Surgical Margin in Gingivobuccal Complex Cancers: A Pilot Study.

Cancers arising from the gingivobuccal complex are one of the most common types of cancer in the oral cavity and are associated with poor prognosis. Among the various prognostic factors, positive surgical margin is the most important one that can be controlled by the operating surgeon. The deep surgical margins for buccal mucosa cancers is normally assessed by palpating the skin for induration and skin pinchability. The present study evaluates the role of imaging in assessing the deep surgical margin and its efficacy for skin preservation in buccal mucosa/ gingivobuccal carcinomas. The patients of gingivobuccal complex squamous cell carcinomas after histopathological confirmation were selected for the study. In imaging, the distance between the base of the tumour and skin (epidermis) of the cheek was measured by a senior radiologist preoperatively. The frozen section findings were confirmed by histopathological examination and the depth of invasion of the tumour was measured and the clearance of the deep surgical margin was confirmed. The correlation between imaging, skin pinch test and histopathological examination of the specimen was assessed. The sensitivity and specificity of imaging to predict the skin preservation (deep surgical margin more than 5 mm) is 100% and 75% respectively compared to sensitivity and specificity of skin pinch test of 82.6% and 50% respectively. Imaging is an effective tool in predicting the skin preservation and skin excision compared to skin pinch test. Compared to the skin pinch test, imaging appears to be a useful tool for advising surgeons on skin preservation vs excision.

Upper oral cavity tumors: Is the risk of nodal metastasis different?

The state of the clinically evident cervical lymph nodes at the time of diagnosis is one of the most important factors impacting long-term survival. While squamous cell carcinomas (SCC) of the hard palate and maxillary alveolus are uncommon in comparison to other primary sites, there is a scarcity of published data on the effective management of the neck nodes for malignancies of these specific subsites. In such circumstances, an intraoperative frozen section or Sentinel node biopsy would aid in the optimal therapy of the neck.

The Impact and Prognostic Significance of Extra-Nodal Extension in Clinically N0 Oral Cancer: A Prospective Clinical Study.

Oral cavity squamous cell carcinoma (OCSCC) demonstrates a high propensity to metastasize to regional lymph nodes. Despite technological and scientific advances, identification of pathological adverse features preoperatively remains elusive. This study intended to identify the true occurrence of extra-nodal extension (ENE) in clinically and radiologically N0 OCSCC patients and to investigate its impact and prognostic significance. A prospective, single-centre, non-randomized study was conducted at a tertiary cancer centre in South India to include all untreated operable patients of OCSCC without clinical, radiological, or cytological evidence of nodal metastasis (cN0). All the patients underwent tumor resection surgery with neck dissection and received adjuvant therapy when indicated. Patients were followed up and neck dissection specimens were histopathologically analyzed. The primary outcome was to assess the presence of ENE in cN0 OCSCC patients and its extent. The secondary outcomes were 2-year disease-free survival (DFS) and tumor characteristics. A total of 237 patients with operable OCSCC were evaluated. Out of these, 80 patients who were clinically and radiologically N0 were included in the study and they underwent tumor resection surgery and neck dissection. The final histopathological evaluation revealed that 21.25% of patients (n = 17) had metastatic neck disease and 7.5% of patients (n = 6) had ENE, and all were reported as microscopic ENE. Within the node-positive group, the 2-year DFS for patients with and without ENE were 50% and 90.9%, respectively (p = 0.0362). The results suggest that ENE remains a strong predictor of adverse outcomes, recurrence, and survival in oral cancer patients.

Decoding the influence of the immune system and immunotherapy targets on carcinomas: A hidden prism in oral cancer therapy.

In recent decades, understanding tumorigenesis and the complex interaction between the host and the immune system has been the pillar for significant advances in anticancer therapy. Conventional anticancer therapy (e.g., cut, burn, and cytotoxic drugs) involves multiple targeting of tumor cells. However, the tumor tissue microenvironment can present a dysregulated, stimulating, or subverted immune response which, in turn, reveals pro-tumor activities favoring tumor expansion and progression. Recently, new potential targets have been identified based on immunomodulatory therapies, which are crafted to re-establish the host anti-tumoral immune response. Clinicians should fully understand the intricate interactions between carcinogens, the tumor milieu, the immune system, and traditional anticancer therapies in order to progress and to overcome the refractory/recurrent challenges and morbidity of the disease. Thus, in this article, we highlight the complex milieu of the oral cancer immune response, pointing out potential therapeutic immunotargets for oral squamous cell carcinomas. The impact of traditional anticancer therapy on the immune system is also outlined.

The spiral ladder technique of facial nerve trunk identification during parotidectomy: A convenient roadmap for the beginners.

The intricate relationship between the facial nerve and the parotid gland makes the surgeries involving the gland challenging. Though several landmarks have been described to locate the nerve trunk, variations do exist due to the physical and racial characteristics of an individual. The spiral ladder technique described here uses multiple landmarks that appear in a stepwise manner as a beginner proceeds through the surgery as a road map to the nerve trunk. This simple adoption of a cluster of existing landmarks increases the certainty factor. This method may help beginners and in turn, reduce the chances of iatrogenic facial nerve injuries.

Oral cancer in India, a growing problem: Is limiting the exposure to avoidable risk factors the only way to reduce the disease burden?

Cancer represents an uncontrolled growth of cells that invade and cause damage to the adjacent tissues. Globally oral cancer ranks as the sixth most common type of cancer. As compared to the west, the problem of oral cancer is significantly higher in India. The spectrum of oral diseases is formed with oral cancer at one extreme and potentially malignant disorders (PMDs) at the other extreme. Screening programs for the early detection and prevention of oral cancer indicate that visual examination as a part of a population-based screening program reduces the mortality rate of oral cancer in high-risk individuals. Tobacco and alcohol consumption remains the main factors for oral cancer and education of the population about the ill effects of tobacco and alcohol consumption is necessary at a broader scale.

Swallowing: A delayed milestone post-surgery in tongue cancers.

Functional rehabilitation remains an important factor in the post-operative period following tongue cancer surgeries. Patients undergoing surgery for tongue cancers require intense rehabilitation in order to restore their swallowing function, and improve their nutritional status and quality of life. Various swallowing scales like the Functional Oral Intake Scale (FOIS), Performance status scale in head and neck cancer (PSSHNC) and 100 ml water swallow test are used to assess functionality in these patients. These aid in timely assessment and early intervention for better rehabilitation, in turn improving quality of life. Nasogastric tube (NG) or percutaneous endoscopic gastrostomy (PEG) aids in providing adequate nutrition in the immediate post-operative period and during adjuvant therapy to overcome radiation-induced dysphagia.

Does SLNB substitute END in the future with the sole advantage of preventing shoulder morbidity?

SLNB has emerged as a rational proposition in the management of early-stage oral cancer and has mixed responses within the oncological community. It is high time for the clinicians to look into the fact that, when a patient post-surgery has a regional recurrence within 6 months, it could be reasonable to believe that a tumor seed which was earlier an isolated tumor cell (ITC) or in the form of a micro-metastasis (MM) would have led to this. SLNB has the potential to become a standard of care in the future owing to the development and utility of better evaluation tools to pick nodal metastasis. It is not an overemphasizing statement to say that SLNB could become a standard recommendation in the near future, however, it still looks like a distant dream considering its logistical and technological limitations.

The impact of positive resection margins on survival requires further study?

Squamous cell carcinoma of oral cavity is usually treated by surgery followed by adjuvant treatment. In most standard cancer institutions, margin analysis is a key barometer for measuring the quality of surgical resection. Many studies reported that positive margins have at least a 50% reduction in the overall survival. The contributing factors that could improve surgical outcomes have to be explored. Patterns of outcomes in patients with positive margins can be understood better by analyzing the subsites involved. In the past, positive margins have been associated with a poor prognosis. A detailed analysis of the NCDB and other larger databases would aid in revising our practices to optimize oncological outcomes.

Prognostic Significance of Vocal Cord Mobility after Laryngeal Preservation Protocols in Locally Advanced Laryngopharyngeal Cancers: A Retrospective Analysis.

In the present study, we look at the prognostic implications of the recovery of vocal cord mobility after treatment in T3 laryngeal and hypopharyngeal cancers with fixed vocal cords. Patients with T3 laryngeal and hypopharyngeal carcinoma were considered for the study. All patients were treated with standard laryngeal preservation protocols as per treatment guidelines. Recovery of vocal cord functions was assessed with serial flexible laryngoscopic evaluation. Recovery of vocal cord mobility was compared with oncological outcomes. Twenty seven patients were available for final analysis. Cases, where vocal cords remained fixed or continued to have restricted mobility on follow up, were categorised as "unfavourable" and those with complete recovery of function as compared to pre treatment FOL as "Favourable". Thirteen (48%) patients did not regain complete mobility of vocal cords. Six patients from the 'unfavourable' group (46%) developed recurrence, whereas only one patient from the 'favourable' group (7%) had a recurrence (p = 0.03). The findings of the present study suggest that failure to regain complete vocal cord mobility after CTRT is a poor prognostic factor in T3 laryngeal and hypopharyngeal cancers.

COVID-19 associated mucormycosis (CAM) in India: a formidable challenge.

Together with the ongoing serious COVID-19 second wave in India, a serious fungal infection, mucormycosis has been increasingly found in COVID-19-recovered patients. Colloquially known as 'black fungus', mucormycosis commonly causes necrosis in the head and neck including the nose, paranasal sinuses, orbits, and facial bones, with possible intracranial spread. The disease causes high morbidity and mortality given that it progresses rapidly and diagnosis is often delayed. Given the sheer magnitude of the outbreak, the Indian Health Ministry has advised all states to declare mucormycosis an epidemic. Typically, the disease has been found to be linked to COVID-19 infections caused by the B.1.617.2 (Delta) variant, which has spread rapidly throughout the country. This variant has already become a cause for global concern, having spread to at least 40 countries, including the USA and UK. We present the findings of a study conducted on COVID-19 associated mucormycosis (CAM) patients, and discuss the associated risk factors to raise awareness for OMFS colleagues.

Selective embolization of lingual artery in transoral robotic surgery for the management of recurrent base of tongue carcinomas.

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.

Multidimensional Mutational Profiling of the Indian HNSCC Sub-Population Provides IRAK1, a Novel Driver Gene and Potential Druggable Target.

Head and neck squamous cell carcinomas (HNSCC) include heterogeneous group of tumors, classified according to their anatomical site. It is the sixth most prevalent cancer globally. Among South Asian countries, India accounts for 40% of HNC malignancies with significant morbidity and mortality. In the present study, we have performed exome sequencing and analysis of 51 Head and Neck squamous cell carcinoma samples. Besides known mutations in the oncogenes and tumour suppressors, we have identified novel gene signatures differentiating buccal, alveolar, and tongue cancers. Around 50% of the patients showed mutation in tumour suppressor genes TP53 and TP63. Apart from the known mutations, we report novel mutations in the genes AKT1, SPECC1, and LRP1B, which are linked with tumour progression and patient survival. A highly curated process was developed to identify survival signatures. 36 survival-related genes were identified based on the correlation of functional impact of variants identified using exome-seq with gene expression from transcriptome data (GEPIA database) and survival. An independent LASSO regression analysis was also performed. Survival signatures common to both the methods led to identification of 4 dead and 3 alive gene signatures, the accuracy of which was confirmed by performing a ROC analysis (AUC=0.79 and 0.91, respectively). Also, machine learning-based driver gene prediction tool resulted in the identification of IRAK1 as the driver (p-value = 9.7 e-08) and also as an actionable mutation. Modelling of the IRAK1 mutation showed a decrease in its binding to known IRAK1 inhibitors.

Electronic cigarette use amongst youth: A threat to public health?

Electronic cigarettes is an unregulated commercially available nicotine dispensing tool. E-cigarettes contains nicotine which is a highly toxic chemical that can adversely affect any organ and is also potentially carcinogenic. Nicotine is the route to addiction and industry is using this drug to help people not forget tobacco. If not for nicotine these cigarettes will be useless. Thus it is just another way of keeping nicotine in blood to maintain cigarette smoking habits among existing customers and new way to attract young customers using technology to lure young minds, while serving purpose to deliver nicotine.

Periodontitis and oral Cancer-A striking link.

Oral squamous cell carcinoma (OSCC) has become a major public health problem in the worldwide for its increasing incidence and mortality, especially in younger trends. Risk factors for OSCC apart from alcohol and tobacco use, include poor oral hygiene, inflammation caused by inadequately fitting dentures and other rough teeth surfaces, poor nutrition and some chronic infections caused by fungi, bacteria or viruses. Several studies have also found that the risk of developing OSCC may increase with periodontal disease (PD). In addition to reduce harm caused by tobacco, alcohol and betel quid it seems prudent to take measures to improve oral hygiene in periodontally compromised patients to minimize OSCC risks. This further intensifies the need for oral health education programs and large cohurt studies to edify individuals about the importance of regular oral health maintenance and routine dental care towards the prevention of oral diseases including OSCC.

Molecular landscape of salivary gland cancers.

Accurate diagnosis of salivary gland tumors can be challenging because of the many diagnostic entities, the sometimes extensive morphologic overlap, and the rarity of most tumor types. The current understanding of molecular rearrangements in salivary gland tumor pathology, emphasizes the prospects for exploiting molecular alterations in salivary gland tumors for diagnosis and targeted therapy. As new targeted therapies emerge, it will become increasingly vital to incorporate appropriate molecular testing into the pathologic evaluation of salivary gland cancers.