One of the most prevalent forms of oral cancer is oral squamous cell carcinoma (OSCC), a major cause of morbidity and mortality worldwide. Following a definite oral cancer diagnosis, OSCC is typically treated with a multidisciplinary approach including surgery, chemotherapy, and radiation. In contrast, conventional chemotherapy medicines may be ineffective and have a range of side effects. Many techniques have been proved and authorized for treatment and diagnostics of different types of oral cancer, while others are currently being investigated in clinical trials. This book chapter is aimed to explain the current preclinical status of nano-based techniques to successfully diagnose and treat OSCC. This book chapter would also emphasize recent theranostics approaches utilized to cure OSCC. Nanotechnology also improved cancer biomarker detection, making them faster and more sensitive. To overcome these constraints and improve in situ drug delivery, various nanoparticles have been employed as innovation drivers.
Oral cancers form one of the most common malignancies seen worldwide, with a steady increase in number over time. Surgery with the addition of adjuvant therapy forms the cornerstone of therapeutic management for these cancers. Despite excellent surgical management, loco-regional recurrences have always been of concern. This has expanded the role of radiotherapy, with concomitant therapies, allowing to establish an effective management protocol. Over the last two decades, there have been huge strides taken towards understanding these specific aspects and providing insight into the most fruitful application of radiotherapy in these patients. In this chapter, we have presented the oncologists perspective to dealing with the non-surgical aspects of oral cancer management. We have elaborated on the chronological order with which radiotherapy has evolved and provided the contemporary aspects of decision making, essential for current practice. The evidence-based approach will address all components of radiotherapy workflow from basic understanding of patient’s anatomy, planning & evaluation during therapy to the outcomes & toxicity profiles to be expected in day-to-day clinics. Established guidelines have been incorporated into the graphical representations to ensure scenario-based understanding. Future perspectives, essential for identifying the possible direction of therapy & potential improvements in outcomes, have also been addressed.
One of the most common types of cancer is head and neck cancer. Head and neck cancers are the sixth most common cancer worldwide and the most common cancer in developing countries. Oral cancer, which is a subset of head and neck cancers, refers to any cancerous growth in the oral cavity. Risk factors for oral cancer include age, malnutrition, genetic factors, family history, X-rays, papilloma virus, alcohol, smoking, tobacco, which three last are the strongest risk factors. The destructive link between tobacco products and human cancers stems from a powerful combination of two factors - nicotine and carcinogens. The highest incidence of tobacco related oral cancer is seen in low and middle income countries. The chance of curing oral cancers increases if they are diagnosed and treated early. At least three-quarters of all oral cancers can be prevented by quitting smoking and drinking alcohol. Screening programs can be valuable in patients from high-risk groups (smokers and alcoholics) or in patients with a previous diagnosis of cancer outside the head and neck.
Fine needle aspiration cytology is an important diagnostic tool in cytopathology. There are many challenges and pitfalls encountered in intraoral salivary gland cytopathology as tumours of these glands show morphological diversity and overlapping features. There are often variable solid-cystic components, metaplastic or necrotic changes, fibrosis, hyalinisation and haemorrhage accounting for heterogeneity of these tumours. The tumour profile of intraoral salivary gland is quite different from the major salivary glands and needs special attention. A low-grade malignant tumour may sometimes mimic a benign neoplasm or a non-neoplastic lesion resulting in a false negative diagnosis. Moreover, misinterpretation and failure to recognize subtle morphological and architectural patterns of cells also pose diagnostic challenges. In this chapter, we intend to highlight the key cytopathological features of intraoral salivary gland tumours and tumour-like lesions with emphasis to overcome diagnostic challenges and pitfalls to avoid misdiagnosis which will aid in planning further management and treatment.
Early stage oral cavity squamous cell carcinoma (OCSCC) has a significant risk of subclinical nodal metastases, which is the strongest independent prognostic factor for regional recurrence and survival. However current preoperative imaging modalities are unable to identify patients with micrometastases, and an observation strategy has been associated with inferior outcomes when compared to an elective neck dissection. Sentinel lymph node biopsy provides a safe and accurate staging procedure to select the patients who benefit from an elective neck dissection, while avoiding unnecessary surgery in the patients who are node negative. There is recent Level II evidence demonstrating equivalent oncological outcomes when compared with elective neck dissection. However, a multidisciplinary approach is required including reliable mapping of the sentinel lymph node, precise surgical technique and comprehensive histopathological analysis to ensure accurate results are obtained.
Oral Cancer is one of the most common malignancies of the head and neck region. Despite technological advancements and improvements in Oral cancer diagnosis and treatment modalities, the 5-year survival rate remains low and is associated with poor prognosis and high mortality rate especially when detected at a later stage. The empirical therapy followed for the treatment of oral cancer includes surgery, radiotherapy and chemotherapy. The treatments are not equally efficacious for all patients, are associated with side effects and poor prognosis. The need of the hour is early diagnosis and tailored treatment therapies for individual patients. With the advent of immunotherapy, the cancer treatment has moved toward personalised precision medicine which tailors’ treatments to each individual. Personalised precision medicine incorporates, molecular profiling of tumours with OMICS technology, biomarkers and companion diagnostics to build databases of patients and devise tailor made treatment approaches for individual patients. This article discusses the role of precision medicine in OSCC prevention, detection, and management by reviewing our understanding of OC from both genetic and OMICS perspectives.
Ameloblastoma is a locally aggressive odontogenic tumour (OT) that arises from odontogenic epithelium without neoplastic involvement of odontogenic ectomesenchyme. It is the commonest OT in developing countries, especially in Africa, and, hence, a clinically significant lesion among Africans. It has been suggested that the biologic behaviour of ameloblastoma in black Africans is different from the other populations. The high incidence of ameloblastoma in Africans warrants further evidence-based research.
Salivary microRNAs (miRNAs) could potentially serve as biomarkers for the diagnosis and prognosis of various types of oral cancer but the significance of it is yet to be fully elucidated. This article reports our study results on the role of salivary miRNAs and their potential use as biomarkers in head and neck cancer (HNC) diagnosis with an emphasis on oral cancers (OC). Supernatant saliva samples from 24 subjects, including 12 OC patients and 12 healthy individuals as a control group, were initially profiled using next generation sequencing (NGS). A novel miR-7703 was further validated in 160 samples collected from OC patients (n = 80) and controls (n = 80) by quantitative real-time polymerase chain reaction (qRT-PCR) assays. Data analysis revealed that 373 miRNA expressions were significantly decreased and 265 miRNA expressions were significantly increased in patients with OC (p ≤ 0.05). Of the 638 miRNA, twenty-seven were non-redundant miRNAs associated with OC (p ≤ 0.0001). Validation of the novel miR-7703 showed a significant increase in the OC group when compared to the control group. Most importantly, this pattern of increased expression was also positively correlated with tumour stage, lymph node metastasis status, and clinical stage. This study identified twenty-seven non-redundant, differentially expressed miRNAs associated with OC. These signatures include a number of novel miRNAs as well as those that have been previously reported in either oral or other cancers. However, miR-7703 is a previously uncharacterised miRNA with the potential to be a significant biomarker for the diagnosis of OC.
Radiogenic side effects are frequently seen in patients undergoing radiotherapy for head and neck tumors. Intensified dental and mucosal care reduce oral hygienic deficits. The aim of this study was the optimization of mouth hygiene using dexpanthenol rinsing solution applied with a dental waterjet system (DWS). 30 consecutive head and neck tumor patients (44–75 years) were analyzed, who received intensity-modulated radiation treatment (IMRT; total dose range: 54–66 Gy) with helical Tomotherapy HiArt II. The group under investigation (n = 10) additionally received a professional DWS using dexpanthenol mouthrinse (Bepanthen). The first control group received dexpanthenol mouthrinse alone. The second control group only performed the standardized mouth hygiene protocol. Grade of xerostomia, taste, dysphagia, thrush, and mucositis was evaluated on a daily basis. 29 of 30 patients completed radiation therapy. Change in taste occurred in all patients in all groups, however, with a delay in the study group. The occurrence of grade III stomatitis and Xerostomia grade II was significantly reduced in the study arm. No patient suffered from grade III xerostomia in the study arm versus four patients in the control groups. Dysphagia grade II was observed significantly less frequent in the study group (p = 0.0004). Thrush occurrence showed a delay in the study group. Our study underlines the importance of an intensified mouth hygiene during radiation therapy. The combination of dexpanthenol rinsing solution + DWS reduces the incidence of high-grade early side effects which often lead to a reduced quality of life and abortion of the treatment.
We sought to identify stably expressed genes in tumors of gingivo-buccal region and tongue from untreated as well as treated patients. The study was undertaken in view of the ambiguity with regards to the choice of reference genes for normalization of gene expression data from gingivo-buccal region and tongue. This aspect was also examined in tumors from treated patients since it could provide clues for such analyses in the assessment of treatment modalities in the future. Expression of ten candidate housekeeping genes, identified in array-based studies, was tested using TaqMan based semi-quantitative real-time PCR. Thirty-five buccal mucosa derived (18 from treated patients) and 15 tongue tumors (8 from treated patients) were studied. Most stable genes were identified based on the consensus between the results of the three methods, Comparative δCt, BestKeeper and NormFinder, used for data analysis. CHMP2A and VPS29 were identified as the most stably expressed genes suitable for normalization of data from buccal-mucosa tumors, whereas RPS13 and PSMB2 were indicated for similar specimens from treated patients. The same criteria identified stable expression of PSMB2 and PUM1 in tumors from tongue and OAZ1 and RPS13 for the post-treatment tongue tumors. We have identified stably expressed genes in common oral cancers which can be used for normalization of the gene expression data. Results also established differences in tumors arising at different sites of the oral cavity and highlighted further changes following exposure to therapy.
To investigate the association of Single Nucleotide Polymorphisms of DNA repair genes and patient-specific clinical characteristics with the risk of developing severe acute radiotoxicities and treatment response in Oropharyngeal Carcinoma. 179 cases of Oropharyngeal Carcinoma treated with 2-D radical radiotherapy were evaluated for acute radiotoxicity end-points viz; oral mucositis, dermatitis, dysphagia, and xerostomia; and the resultant requirement of nasogastric feeding tube, significant (> 10%) weight loss during treatment and treatment break(s). Eleven Single Nucleotide Polymorphisms of DNA repair genes were analyzed using Polymerase Chain Reaction and Restriction Fragment Length Polymorphism and correlated with the severity of these radiotoxicities (Common Toxicity Criteria for Adverse Events v4.0 grading) and the treatment response. Clinical parameters like age, Karnofsky Performance Status, smoking and tobacco chewing, etc. were also analysed in relation to the above. Homozygous AA genotype of XRCC1 (rs25487) (p = 0.024*, OR 2.629, 95% CI 1.136–6.087), Karnofsky Performance Status < 80 (p = 0.050*, OR 2.723, CI 1.000–7.418) and history of tobacco chewing (p = 0.030*, OR 2.615, 95% CI 1.099–6.222) were independent predictive factors for increased risk of severe (≥ grade 3) mucositis. Also, the presence of Homozygous AA genotype of XRCC1(rs25487) was significantly associated with poor response to radiotherapy in these patients (p = 0.014, OR 2.235, 95% CI 1.074–5.744). Our findings illustrate that patients with Homozygous AA genotype of XRCC1 (rs25487) and certain clinical characteristics are likely to develop severe acute mucositis after radiotherapy for Oropharyngeal Carcinoma and the presence of this polymorphism is also associated with poor response to treatment.
Oral leukoplakia represents the most common oral potentially malignant disorder. While a number of risk factors have been identified, its aetiology remains incompletely understood, and prediction of disease progression, stability or regression, a significant challenge. While excision is often the recommended treatment to reduce the risk of malignancy, this is not always possible and ultimately numerous disease and patient characteristics impact on the decision to initiate treatment or recommend surveillance. At present, the coexistence and impact of chronic diseases in oral leukoplakia patients remains largely unexplored, yet has the potential to significantly impact on diagnosis, treatment decisions, treatment outcomes and prognosis. Exploration of comorbid conditions in oral leukoplakia may additionally lead to greater insight of risk factors and disease pathogenesis and potentially offer more opportunities for screening and early disease detection. The aim of this review is to stimulate discussion about the role of chronic diseases comorbidity in oral leukoplakia.
One strategy for treating cancer is to prevent metastatic spread. Matrix metalloproteinase are considered potential targets for cancer therapy because of their role in degrading the extracellular matrix and fostering tumor progression. In some cancer models, the small molecule 1,2,3,4,6-Penta-O-galloyl-β-d-glucose (PGG) exhibited inhibitory properties against matrix metalloproteinase (MMP) related metastatic activity. This study explored whether PPG may limit the potential for metastatic spread in oral squamous cell carcinoma.
Locally advanced or recurrent head and neck cancer can present both oncologic and reconstructive challenges. There are no current guidelines for reconstruction of multi-unit defects, yet reconstructive goals should serve the purpose of providing a safe healing environment for both adjuvant therapy and functional rehabilitation. In light of a younger head and neck cancer population, reconstructive methods aimed at preserving form and function over a long survivorship period are optimal.
Tumor growth is closely related to the development of an intrinsic vascular network. However, microvascular appearance was not regarding highly to pathological diagnosis, though clinical applicability of endoscopic narrow-bad imaging (NBI) is developed in the oral cavity. To analyze changes of intraepithelial papillary capillary loop (IPCLs) patterns as the utility for pathological diagnosis, comparative histomorphometric analysis of IPCLs among squamous cell hyperplasia, leukoplakia with low- or high-grade dysplasia, and oral squamous cell carcinoma (OSCC) had performed.
The role of tea or coffee on head and neck cancer (HNC) risk has not been consistent, especially in Asian populations. The aim of the study was to investigate whether tea or coffee is associated with HNC risks in a Chinese population.
Oral squamous cancers constitute a large proportion of head–neck malignancies in India. One subset of oral cancers includes lesions arising in the oral commissure and the mucosa around it. These are unique in their location and pattern of spread with even small lesions affecting oral competence, function, and cosmesis. This study was done to analyse such “pericommissural” cancers and to explore if they should be placed in a distinct subcategory of buccal cancers with different implications for management and prognostication.
Oral squamous cell carcinoma (OSCC)—a subset of head and neck cancer is the sixth most common cancer worldwide and leading disease in India. The genes involved in PI3 K/AKT (Phosphatidylinositol 3-kinase—Akt) pathway, such as PIK3CA (Phosphoinositide-3-kinase catalytic α) and PTEN (Phosphatase and tensin homologue) were found to be associated with OSCC. The present study was aimed to find the genetic association of various polymorphisms in intron 9 of the PIK3CA gene and intron 5 of PTEN gene with primary OSCC tumors.
The invasive tumor front (ITF) and pattern of invasion (POI) are significant prognosticators in head and neck cancer squamous cell carcinoma (HNSCC); this study evaluates the expression of CSC marker, CD44 at the ITF and their combined prognostic potential.
The true aggressive behavior of oral cavity BSCC compared to SCC has been debated, and the study of disturbances in cell cycle proteins may help understand the biological behavior in both variants. The aim of this study was to investigate the p53 and p16 status in 32 SCC and 16 BSCC of oral cavity.
