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Concomitant Analysis of Salivary Tumor Markers--A New Diagnostic Tool for Oral Cancer
Abstract
Oral squamous cell carcinoma (OSCC) is a common human malignancy. Circulatory epithelial tumor markers were previously investigated in the serum of OSCC patients but almost never in their saliva, in spite of the fact that there is a direct contact between the saliva and the oral cancer lesion. The purpose of the current study was to examine tumor markers in the saliva of OSCC patients.
We measured the concentrations of the six most studied epithelial serum circulatory tumor markers in the saliva of OSCC (tongue) patients.
Significant increases (of 400%) in salivary concentrations of Cyfra 21-1, tissue polypeptide antigen, and CA125 were shown. Salivary concentrations of CA19-9, SCC, and carcinoembryonic antigen were increased without statistical significance. A concurrent analysis of the three significantly increased markers revealed sensitivity, specificity, and negative and positive predictive values of 71%, 75%, 71%, and 75%, respectively.
The increase reported in salivary tumor markers may be used as a diagnostic tool, especially when a concurrent analysis for significantly increased markers is done. Salivary testing is noninvasive, making it an attractive, effective alternative to serum testing, and the possibility of developing home testing kits would further facilitate it as a diagnostic aid, enabling patients to monitor their own health at home and is important for those who live far from their treatment centers and especially for those at risk of developing OSCC.
... Saliva testing for these genetic changes may help in disease diagnosis and surveillance [27][28][29][30]. Salivary proteins have been the subject of several studies looking into potential diagnostic indicators for OC [31][32][33][34]. ...
... Three tumor markers, including the cytokeratin 19 fragment Cyfra21-1, the cancer antigen 125, and the tissue polypeptide antigen, were reported to be considerably enhanced in the saliva of OSCC patients. The results were equivalent in terms of diagnostic value when these markers were measured in the sera of OSCC patients when they were aggregated [32]. The amount of p53 autoantibody in saliva was also shown to be connected with its serum levels in OSCC, suggesting that salivary analysis of the p53 antibody may offer a specific method for identifying a subgroup of OSCC with p53 problems [33]. ...
... Accordingly, several biomarkers-such as tissue polypeptide antigen [TPA], cytokeratin-19 fragment [Cyfra21e1], and cancer antigen 125 [CA 125]-were four times more prevalent in OC patients [32]. The protein salivary biomarkers can be characterized separately or together to assist in the early identification of OSCC. ...
Early detection is crucial for the treatment and prognosis of oral cancer, a potentially lethal condition. Tumor markers are abnormal biological byproducts produced by malignant cells that may be found and analyzed in a variety of bodily fluids, including saliva. Early detection and appropriate treatment can increase cure rates to 80–90% and considerably improve quality of life by reducing the need for costly, incapacitating medicines. Salivary diagnostics has drawn the interest of many researchers and has been proven to be an effective tool for both medication monitoring and the diagnosis of several systemic diseases. Since researchers are now searching for biomarkers in saliva, an accessible bodily fluid, for noninvasive diagnosis of oral cancer, measuring tumor markers in saliva is an interesting alternative to blood testing for early identification, post-treatment monitoring, and monitoring high-risk lesions. New molecular markers for oral cancer detection, treatment, and prognosis have been found as a result of developments in the fields of molecular biology and salivary proteomics. The numerous salivary tumor biomarkers and how they relate to oral cancer and pre-cancer are covered in this article. We are optimistic that salivary protein biomarkers may one day be discovered for the clinical detection of oral cancer because of the rapid advancement of proteomic technology.
... Mean salivary LDH levels were higher in males in comparison to females in oral leukoplakia, OSCC, and healthy controls. Salivary LDH levels are consistently higher in oral precancer and cancer [81][82][83][84][85][86][87][88][89][90][91][92]. ...
... Salivary CEA and CA-50 levels were substantially greater in malignant tumors than in benign tumors and healthy people. CA125 was significantly increased by 400% [87]. Negri et al. reported a 145% rise in salivary CEA levels in OSCC patients [88]. ...
OSCC (Oral Squamous Cell Carcinoma) is a major health challenge in many parts of the world. It occurs most commonly in males and is associated with tobacco, pan, or areca nut consumption. One of the major challenges associated with the management of OSCC is late diagnosis. As a result, the treatment required is more aggressive, expensive, and has poor prognostic value. On the other hand, early diagnosis of OSCC can be life-saving with less aggressive treatment and a better prognosis.
A diagnostic method for early diagnosis of OSCC is greatly needed. A lot of research efforts have been made to identify biomarkers that can act as tools to classify the tumor status of the patient. Various biological fluids and tissues have been explored for such studies. Saliva appears to be the most attractive biological sample with many potential advantages over other matrices such as blood or tissue. Saliva as a diagnostic fluid has the advantage of ample availability, being non-invasive and being in the vicinity of the tumor, and having a less complex composition. Our paper provides an updated review of the state of the art of research in the area of salivary biomarkers for oral squamous cell carcinoma. The paper gives an account of methods for saliva collection, followed by a brief description of various protein biomarkers discovered to date, along with their status quo.
... [1,13,16] In our study, intra-group and pair-wise comparisons between different grades showed a significant rise in mean serum and salivary values between all grades except between well-differentiated and moderate differentiated OSCC (P-value 0.12). These observations were in accordance with Doweck et al. [19] and Rewa Malhotra et al. [1] but contradicting with Zhong et al. [15] and Rafael Nagler et al. [20] The cognition for the above might be with the fact that with increasing grade, the differentiation process will be compromised, so more immature, hyper-proliferative, and atypical cells will emerge. They tend to retain and express increased amounts of CK19 and show accelerated spillage of CYFRA 21-1 into extra-cellular spaces. ...
... This variation was often because of different biochemical techniques used to estimate the marker concentration and the difference in methods used to determine the cut-off values. [1,4,13,15,20] Both serum (86.26) and saliva (88.75) had almost proximate AUC, suggesting the undistinguishable diagnostic potency, but saliva is easily accessible, painless, quick, and economic to both the patient and the diagnostician. [4,13] We have also found that salivary values are 3-fold higher than those of serum, proving saliva to be the best screening tool compared to serum. ...
Background:
Cytokeratins are the largest sub-group of intermediate filaments and represent the most abundant proteins in epithelial cells. CYFRA 21-1 (human cytokeratin fragment antigen 21-1) is a soluble fragment of cytokeratin 19 known to increase in various malignancies.
Aim:
The present study is aimed to estimate salivary and serum levels of CYFRA 21-1 in oral squamous cell carcinoma (OSCC) patients and to compare them with healthy controls.
Settings and design:
A prospective, case-control study.
Material and methods:
This study included a total of 80 subjects, comprising 40 OSCC patients and 40 healthy controls. Saliva and blood samples were collected from the study population, and serum and salivary CYFRA 21-1 levels were measured by enzyme-linked immunosorbent assay.
Statistical analysis used:
The statistical tests applied were independent t-test, ANOVA test for comparison, and Post hoc test for correlation. A P value of < 0.05 was considered statistically significant.
Results:
A statistically significant increase in salivary and serum CYFRA 21-1 levels was observed between OSCC and control groups and with an increase in the pathological tumour node metastasis stage and histopathological grade of OSCC. On correlating salivary and serum CYFRA 21-1 values, there were 3-fold higher salivary levels than serum.
Conclusion:
CYFRA 21-1 can be suggested as a tumour marker that can be used for the early diagnosis of the OSCC. Further prospective studies with a larger sample size and advanced techniques recommended before CYFRA 21-1 can be recommended for routine clinical use.
... Tumour necrosis factor-alpha and salivary transferrin have also been identified as possible biomarkers for OC diagnosis because of the direct interaction between saliva and OC lesions. On the other hand, salivary soluble CD44 Ag can be used as a biomarker for head and neck squamous cell carcinoma [65], whereas OSCC-related salivary biomarkers include Cyfra 21-1 [66,67], tissue polypeptide Ag, cancer Ag 125 [66], and salivary zinc finger protein 510 peptide [68]. Saliva has recently been proved to be a useful diagnostic tool for diseases including human immunodeficiency virus (HIV) and hepatitis A, B, and C, in which immunologic markers such as IgG and microbics play a vital role. ...
... Tumour necrosis factor-alpha and salivary transferrin have also been identified as possible biomarkers for OC diagnosis because of the direct interaction between saliva and OC lesions. On the other hand, salivary soluble CD44 Ag can be used as a biomarker for head and neck squamous cell carcinoma [65], whereas OSCC-related salivary biomarkers include Cyfra 21-1 [66,67], tissue polypeptide Ag, cancer Ag 125 [66], and salivary zinc finger protein 510 peptide [68]. Saliva has recently been proved to be a useful diagnostic tool for diseases including human immunodeficiency virus (HIV) and hepatitis A, B, and C, in which immunologic markers such as IgG and microbics play a vital role. ...
Oral cancer is a serious concern to people all over the world because of its high mortality rate and metastatic spread to other areas of the body. Despite recent advancements in biomedical research, OC detection at an early stage remains a challenge and is complex and inaccurate with conventional diagnostics procedures. It is critical to study innovative approaches that can enable a faster, easier, non-invasive, and more precise diagnosis of OC in order to increase the survival rate of patients. In this paper, we conducted a review on how biosensors might be an excellent tool for detecting OC. This review covers the strategies that use different biosensors to target various types of biomarkers and focuses on biosensors that function at the molecular level viz. DNA biosensors, RNA biosensors, and protein biosensors. In addition, we reviewed non-invasive electrochemical methods, optical methods, and nano biosensors to analyze the OC biomarkers present in body fluids such as saliva and serum. As a result, this review sheds light on the development of ground-breaking biosensors for the early detection and diagnosis of OC.
... Amongst these biomarkers, CYFRA 21-1 is the prominent biomarker for identifying oral cancer in saliva [16]. It is a cytokeratin fragment, proteinaceous in nature (40 kDa) and found in higher concentrations, around 17.46 ng/mL, in the saliva of OCSc patients compared to 3.27 ng/mL in saliva of healthy person [3,17]. The detection of oral cancer biomarkers IL-6, IL-8, CD59, and CYFRA 21-1 [18][19][20][21] in saliva has been done by different techniques like electrochemical impedance spectroscopy (EIS), differential pulse voltammetry (DPV), optical, fluorescence, and amperometry [22][23][24][25][26]. Nonetheless, the problems associated with these techniques are lower sensitivity, slow response, challenges related to real-time detection, and batch fabrication, thus lacked uniformity among the devices [2,27]. ...
... Cytokeratin fragment 21-1 (CYFRA 21-1) CYFRA 21-1, also known as human cytokeratin fragment 21-1, is a soluble fragment derived from cytokeratin-19. It is known to be overexpressed in tissue, serum, and saliva of patients with OSCC [24][25][26][27]. Pre-operative levels of CYFRA 21-1 in the serum have shown promising potential as a biomarker for stratifying the risk associated with OSCC. ...
Proteomic and transcriptomic biomarkers have become valuable tools for the early detection and diagnosis of OSCC. The human saliva proteome, which was previously thought to contain a limited number of proteins, has now been found to consist of over 2000 proteins
... It is a 40 kDa molecule encoded by KRT19 gene. In saliva of oral cancer patients, it is secreted in higher concentration (17.46 71.46 ng mL À 1 ) (Nagler et al., 2006;Rajkumar et al., 2015). ...
Background:
Transcranial magnetic stimulation (TMS) can aid in alleviating clinical symptoms in Parkinson's disease (PD). To better understand the neural mechanism of the intervention, neuroimaging modalities have been used to assess the effects of rTMS.
Objective:
To study the changes in cortical connectivity and motor performance with rTMS at supplementary motor area (SMA) in PD using clinical assessment tools and task-based functional MRI.
Methodology:
3000 pulses at 5Hz TMS were delivered at the left SMA once a week for a total of 8 consecutive weeks in 4 sham sessions (week 1 to 4) and 4 real sessions (week 5 to week 8) in 16 subjects with PD. The outcomes were assessed with UPDRS, PDQ 39 and task-based fMRI at baseline, after sham sessions at week 4, and after real sessions at week 8. Visuo-spatial functional MRI task along with T1 weighted scans (at 3 Tesla) were used to evaluate the effects of rTMS intervention. Multivariate pattern analysis (MVPA) was used to analyse task-based fMRI using Conn toolbox.
Results:
Improvements (p<0.05) were observed in UPDRS II, III, Mobility and ADL of PDQ39 after real sessions of rTMS. MVPA of task-based connectivity revealed clusters of activation in right hemispheric precentral area, superior frontal gyrus, middle frontal gyrus, thalamus and cerebellum (cluster threshold pFDR=0.001).
Conclusions:
Weekly rTMS sessions at SMA incurred clinical motor benefits as revealed by an improvement in clinical scales and dexterity performance. These benefits could be attributed to changes in connectivity remote brain regions in the motor network.
... In dentistry, special needle-based devices could be very useful and beneficial, because oral carcinoma is often oral squamous cell cancer and is very difficult to detect in the early stages, being asymptomatic [30,33]. These special devices can detect elevated levels of biomarkers, such as Cyfra 21-1, TPA, CA-125 antigen, MMP-9 and TNF-α [37,38]. ...
In this work, we aim to address several strategies to improve transdermal drug delivery, such as iontophoresis, sonophoresis, electroporation and micron. We also propose a review of some transdermal patches and their applications in medicine. TDDs (transdermal patches with delayed active substances) are multilayered pharmaceutical preparations that may contain one or more active substances, of which, systemic absorption is achieved through intact skin. The paper also presents new approaches to the controlled release of drugs: niosomes, microemulsions, transfersomes, ethosomes, but also hybrid approaches nanoemulsions and microns. The novelty of this review lies in the presentation of strategies to improve the transdermal administration of drugs, combined with their applications in medicine, in light of pharmaceutical technological developments.
... Our study aimed to determine the impact of tooth eruption and uncontrolled changes that occur during the first months of life on salivary metabolomic analysis of healthy infants and children. This information could impact studies in different areas such as dentistry, medicine, nutrition, development, and physiology, and it could influence the full assessment and monitoring of different types of diseases, both oral and systemic [49,50]. ...
The present study aims to identify the salivary metabolic profile of healthy infants and young children, and to correlate this with age, salivary gland maturation, and dentition. Forty-eight children were selected after clinical evaluation in which all intraoral structures were examined. Total unstimulated saliva was collected, and salivary metabolites were analyzed by 1H Nuclear Magnetic Resonance (NMR) at 25 °C. Partial least squares discriminant analysis (PLS-DA), orthogonal PLS-DA (O-PLS-DA), and univariate analysis were used, adopting a 95% confidence interval. The study showed a distinct salivary metabolomic profile related to age and developmental phase. The saliva of children in the pre-eruption teeth period showed a different metabolite profile than that of children after the eruption. However, more evident changes were observed in the saliva profile of children older than 30 months. Alanine, choline, ethanol, lactate, and sugar region were found in higher levels in the saliva of patients before 30 months old. Acetate, N-acetyl sugar, butyrate, caproate, creatinine, leucine, phenylalanine, propionate, valine, succinate, and valerate were found to be more abundant in the saliva of children after 30 months old. The saliva profile is a result of changes in age and dental eruption, and these findings can be useful for monitoring the physiological changes that occur in infancy.
... Various treatment modalities like targeted therapy, radiotherapy, surgery, and chemotherapy are given for treatment still the prognosis of OSCC is still poor because of the characteristics that it invades and cause recurrence [14][15] . Saliva satisfies the need for an accessible, affordable, and non-invasive test for the diagnosis, prognosis and follow-up of oral cancer patients after treatment [16] . This review was conducted with the aim of evaluating the role of miRNA as salivary biomarker reported in OSCC and OPMD with objective to find its role, advantages and disadvantages. ...
... Oral cancer refers to all malignancies arising from the lips, the oral cavity, and pharynx and it affects more than 481,000 new patients worldwide. 24 The 90% of oral cancers are oral squamous cell carcinoma.(OSCC) An increasing number of systemic diseases and conditions, amongst them oral cancer, have been shown to be reflected diagnostically in saliva. ...
... It was shown that antibodies specific for interleukin (IL)-6 and tumor protein P53 may be potential salivary biomarkers and that IL-6, IL-8, vascular endothelial growth factor, IL-1β, and tumor necrosis factor-alpha (TNF-α) also participate in the initial process of OSCC [38]. Nagler et al. [39] reported a fourfold increase in three known salivary markers in patients with OSCC, namely, cancer antigen 125 (CA125), cytokeratin 19 fragment (Cyfra 21-1), and tissue polypeptide antigen despite without statistical significance. The combination of these circulatory epithelial tumor markers with the salivary concentration of carcinoembryonic antigen enhanced the clinical prediction of OSCC development. ...
Oral squamous cell carcinoma (OSCC), one of the most common types of cancers worldwide, is diagnosed mainly through tissue biopsy. However, owing to the tumor heterogeneity and other drawbacks, such as the invasiveness of the biopsy procedure and high cost and limited usefulness of longitudinal surveillance, there has been a focus on adopting more rapid, economical, and noninvasive screening methods. Examples of these include liquid biopsy, optical detection systems, oral brush cytology, microfluidic detection, and artificial intelligence auxiliary diagnosis, which have their own strengths and weaknesses. Extensive research is being performed on various liquid biopsy biomarkers, including novel microbiome components, noncoding RNAs, extracellular vesicles, and circulating tumor DNA. The majority of these elements have demonstrated encouraging clinical outcomes in early OSCC detection. This review summarizes the screening methods for OSCC with a focus on providing new guiding strategies for the diagnosis of the disease.
... So far, more than 100 potential Oral squamous cell carcinoma (OSCC) salivary biomarkers have been reported in the literature, based mainly on comparing the levels found in OSCC patients to the levels found in non-OSCC normal controls [2]. Most categories of Potential salivary biomarkers for oral cancer detection are: Non-organic compound (Na, Ca, F, and Mg) [6], peptid (Defensin-1) [7], proteins (IL-1, IL-6, IL-8, TNFα, Endothelin-1,...) [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22], DNAs (P53 gene codon 63,…) [23][24], mRNAs (IL-1β, H3F3A,…) [25], Oxidative stress-related molecules (Glutathione, Peroxidase,…) [26], Glucocorticoid (Cortisol) [27], Meta-bolomics (Lactic acid, Valine,….) [28], Glycosylation related molecules (Sialic acid, α-L-fucosidase) [29][30]. ...
Aim: This article aims to provide a brief overview of various salivary biomarkers and their importance in early detection of oral cancer. Background: The tumor markers are playing an important role in cancer detection and management. The cancer biomarker is produced either by the tumor itself or by other tissues, and consider as molecular signature indicating the physiologic and pathologic changes in a particular tissue or cell during the development of cancer. The direct contact between the saliva and the oral cancer lesions makes the salivary biomarkers the best sensitive and specific test for primairy screening method in diagnosis, staging and follow-up of oral cancer. Materials and Methods: Studies were conducted by searching for reviews in salivary biomarkers of oral malignancy in the past 5 years in Google Scholar, Medline, and PubMed. The references were also crosschecked for the relation of salivary biomarkers and oral cancer. Articles were identified and subjected to qualitative and quantitative analyses. Review Results: More than 100 potential Oral squamous cell carcinoma (OSCC) salivary biomarkers have been reported in the literature. The proteomics analysis of saliva proteins is significance for early diagnosis of Oral squamous cell carcinoma (OSCC). Saliva contains reliable amounts of cells, mainly exfoliated from the oral cancer, which can provide early diagnosis and detection of oral malignancy. Conclusion: The goal of cancer screening is to detect tumor at an early stage, when treatment is most likely to be successful. Salivary biomarkers will help to differentiate patients who clinically have no detectable disease but are potential candidates for oral cancer.
... According to the data from western studies the commonly affected site is lateral border of tongue and most lethal being the base of tongue . 1 Pathogenesis involves mutation in oncogenes and tumor suppressor genes as a result of constant contact with the carcinogenic agents present in synthetic products having tobacco. They are responsible for mucosal alterations and development of premalignant and malignant lesions in oral cavity. 2 Squamous cell carcinoma is a prevalent condition in south Asia due to abundant use of carcinogenic elements present in pan and tobacco. ...
Objective: The aim of this study was to evaluate the spread and proportion of oral squamous cell carcinoma in oral lesions. Methods: Patient’s biopsies were collected from january2017 till July2017 from histopathology lab in public health care institute. Two types of specimens either submitted for diagnosis or post-operative analysis of the lesion were reported. The data of oral tissue biopsies was analyzed and cases were sorted on the basis of benign and malignant lesions. The incidence of cancer and benign lesions was reported as; gender, age and site. Results: Moderately differentiated histological subtype of oral squamous cell was found to be most prevailing in the middle age male population and the etiology and site were found to have the direct association. Conclusion: Our study reveals that male patients are more affected with the disease and the age group ranges from young to middle age individuals. The alteration in lifestyle, awareness and strict laws against the consumption of carcinogenic agents is necessary to address the problem. Keywords: Squamous Cell Carcinoma, Benign Lesion, Malignant Lesions, Biopsies
... For example, Nagler R and colleagues (2006) performed a case-control study to evaluate the salivary concentration of CA-125. Interestingly, the researchers observed a significant increase (400%) in the CA-125 levels in the OSCC group compared to the control group [188]. Similarly, Balan JJ and collaborators (2012) found that the mean salivary concentration of CA-125 in OSCC patients and the controls was 320.25 U/mL and 33.14 U/mL, respectively [189]. ...
Oral cancer is one of the most common malignancies worldwide, accounting for 2% of all cases annually and 1.8% of all cancer deaths. To date, tissue biopsy and histopathological analyses are the gold standard methods for the diagnosis of oral cancers. However, oral cancer is generally diagnosed at advanced stages with a consequent poor 5-year survival (~50%) due to limited screening programs and inefficient physical examination strategies. To address these limitations, liquid biopsy is recently emerging as a novel minimally invasive tool for the early identification of tumors as well as for the evaluation of tumor heterogeneity and prognosis of patients. Several studies have demonstrated that liquid biopsy in oral cancer could be useful for the detection of circulating biomarkers including circulating tumor DNA (ctDNA), microRNAs (miRNAs), proteins, and exosomes, thus improving diagnostic strategies and paving the way to personalized medicine. However, the application of liquid biopsy in oral cancer is still limited and further studies are needed to better clarify its clinical impact. The present manuscript aims to provide an updated overview of the potential use of liquid biopsy as an additional tool for the management of oral lesions by describing the available methodologies and the most promising biomarkers.
... In malignant epithelial cells activated protease increases degradation of cytokeratin; this results in release of large amounts of cytokeratin fragments in the blood making it an important biomarker in carcinomas [13][14][15] This marker is recognized by two monoclonal antibodies against fragments of CK 19. The epitopes of the two antibodies were determined to be within helix 2B of the rod domain of CK19, the epitope sequences lie within the amino acid sequence 311-335 for the cancer antibody Ks19.1 and within 346-367 for the detector BM 19.21. ...
Introduction: Oral squamous cell carcinoma recognized as the most frequently occurring malignant tumour of oral cavity with an incidence rate of 14.9 100,000. However in India and other Asian countries, there is a parti people which is being attributed to the influence of region specific epidemiological factors, especially heavy use of tobacco and betel quid chewing. challenge for medical professionals with the five year survival rate being 30% is an attractive diagnostic fluid because saliva collection is noninvasive as compared to the collection of blood plasma analyses. Our aim was in oral premalignant lesion patients as a biomarker for early detection of OSCC. collected from a total of 62 patients of both OSCC and premalignant oral lesions along with their respective biopsies. Salivary levels of CYFRA 21 were correlated with the histological diagn CYFRA 21-1 levels of healthy controls. carcinoma. Histologically and clinically results were found to be correlat the groups showed an increasing trend ranging from lowest value in the control group to higher in the premalignant group and the highest value in OSCC patients, the difference was significant amongst all three gro Operating Characteristic) curve analysis of CYFRA 21 good test results.
... Whole saliva can act as an excellent auxiliary tool in such cases as the mode of sampling is noninvasive, and cost-effective and further saliva can be easily transported and stored. Concomitant increase (400%) in the levels of CA-125 and CYFRA 21-1 protein markers in saliva of patients with OSCC has been reported previously (Nagler et al., 2006). It was observed that the values of CYFRA 21-1 were $3 folds higher in premalignant cases as compared to the healthy individuals (Rajkumar et al., 2015). ...
Globally, oral cancer kills an estimated 150,000 individuals per year, with 300,000 new cases being diagnosed annually. The high incidence rate of oral cancer among the South‐Asian and American populations is majorly due to overuse of tobacco, alcohol, and poor dental hygiene. Additionally, socio‐economic issues and lack of general awareness delay the primary screening of the disease. The availability of early screening techniques for oral cancer can help in carving out a niche for accurate disease prognosis and also its prevention. However, conventional diagnostic approaches and therapeutics are still far from optimal. Thus, enhancing the analytical performance of diagnostic platforms in terms of specificity and precision can help in understanding the disease progression paradigm. Fabrication of efficient nanoprobes that are sensitive, noninvasive, cost‐effective, and less labor‐intensive can reduce the global cancer burden. Recent advances in optical, electrochemical, and spectroscopy‐based nano biosensors that employ noble and superparamagnetic nanoparticles, have been proven to be extremely efficient. Further, these sensitive nanoprobes can also be employed for predicting disease relapse after chemotherapy, when the majority of the biomarker load is eliminated. Herein, we provide the readers with a brief summary of conventional and new‐age oral cancer detection techniques. A comprehensive understanding of the inherent challenges associated with conventional oral cancer detection techniques is discussed. We also elaborate on how nanoparticles have shown tremendous promise and effectiveness in radically transforming the approach toward oral cancer detection.
This article is categorized under: Diagnostic Tools > Biosensing
Diagnostic Tools > Diagnostic Nanodevices
Diagnostic Tools > In Vitro Nanoparticle‐Based Sensing
... The usefulness of saliva as a biological marker has been substantiated by various studies. 16,17 The diagnosis value of saliva in oral diseases and cancers is well established. The readily availability, non-invasiveness makes saliva the best option. ...
Aim: To detect CA-125 level in saliva of oral cancer patients. Methodology: A total of fifty-six SCC patients and thirty healthy subjects were selected. A non-stimulated whole saliva (5cc) was collected and evaluated for CA-125 level ELISA. Results: A higher salivary CA 125 level (514.2±132.6 U/mL) was observed in poorly differentiated SCC followed by moderately differentiated (340.6±80.2 U/mL) and minimum values was observed in well differentiated SCC (236.2±76.2 U/mL). The mean± SD CA-125 level in group I patients was 428.5± 110.2 U/mL and in group II was 132.4± 58.6 U/mL. Higher salivary CA 125 level (520.5±168.4 U/mL) was observed in stage IV and minimum in stage I (165.2±46.2 U/mL) which was statistically significant (P< 0.05). Conclusion: Patients with poorly differentiated SCC, cases of buccal mucosa and stage IV exhibited higher values of salivary CA-125 level as compared to healthy control.
... In addition, salivary proteomic analysis identified elevated levels of salivary proteins compared to normal counterparts. These salivary biomarkers were able to distinguish cancer from benign diseases with high sensitivity and specificity [80,81]. Cytological study of oral cells is also a non-invasive technique that has been harnessed into use for detection of disease progression and therapeutic monitoring. ...
Early identification and management of precancerous lesions at high risk of developing cancers is the most effective and economical way to reduce the incidence, mortality, and morbidity of cancers as well as minimizing treatment-related complications, including pain, impaired functions, and disfiguration. Reliable cancer-risk-predictive markers play an important role in enabling evidence-based decision making as well as providing mechanistic insight into the malignant conversion of precancerous lesions. The focus of this article is to review updates on markers that may predict the risk of oral premalignant lesions (OPLs) in developing into oral squamous cell carcinomas (OSCCs), which can logically be discovered only by prospective or retrospective longitudinal studies that analyze pre-progression OPL samples with long-term follow-up outcomes. These risk-predictive markers are different from those that prognosticate the survival outcome of cancers after they have been diagnosed and treated, or those that differentiate between different lesion types and stages. Up-to-date knowledge on cancer-risk-predictive markers discovered by longitudinally followed studies will be reviewed. The goal of this endeavor is to use this information as a starting point to address some key challenges limiting our progress in this area in the hope of achieving effective translation of research discoveries into new clinical interventions.
... Dysplastic group also display reduced intensity values than the normal but not as significant as SCC group. Reduction of Raman peaks may be due to increase in concentration of saliva samples in diseased groups (SCC and dysplasia) [35]. It was also noticed during the study that diseased groups have higher concentration of saliva than the control group. ...
Head and neck cancer detection using fluorescence spectroscopy from human saliva is reported here. This study has been conducted on squamous cell carcinoma (SCC), and dysplastic (precancer) and control (normal) groups using an in-house developed compact set-up. Fluorescence set-up consists of a 375-nm laser diode and optical components. Spectral bands of flavin adenine dinucleotide (FAD), porphyrins, and Raman are observed in the spectral range of 400 to 800 nm. Presence of FAD and porphyrin bands in human saliva is confirmed by the liquid phantoms of FAD and porphyrin. Significant differences in fluorescence intensities among all the three groups are observed. Three spectral ranges from 455 to 600, 605 to 770, and 400 to 800 nm are selected for each group and area values under each spectral range are computed. To differentiate among the groups, receiver operating characteristic (ROC) analysis is employed on the area values. ROC differentiates among the groups with accuracies of 98%, 92.85%, and 81.13% respectively in the spectral ranges of 400 to 800 nm. However, in other two spectral ranges (455 to 600 and 605 to 770 nm), low accuracy values are found. Obtained accuracy values indicate that selection of human saliva for head and neck cancer detection may be a good alternative.
... This finding was consistent with previous studies that reported higher salivary CYFRA21-1 values in oral cancer compared to healthy controls. 18,28,[32][33][34] Likewise, other studies declared that salivary CYFRA21-1 was significantly higher in the PML group compared to healthy controls but still significantly lower than that of OSCC. 18,34 Surprisingly, Awasthi 34 mentioned that the mean salivary level of CYFRA21-1 in the PML group was 5.9 (±2.4) and in the OSCC group was 17.5 (±15.5) which is much higher than that reported in the present study. ...
Abstract
Aim and objective: To identify the specificity and sensitivity of CYFRA21-1 in differentiating between oral malignancy and oral potentially
malignant lesions (PML) and to be able to early diagnose malignant changes in oral lesions.
Materials and methods: It was a prospective pilot study. Twenty-eight participants were collected in a convenience series and divided into three
groups. Group I: 12 patients suffering from PML. Group II: eight patients with oral squamous cell carcinoma (OSCC). Group III: eight participants
with no oral lesions. Serum and salivary CYFRA21-1 levels were measured using enzyme-linked immunosorbent assay and correlated with the
histopathological examination to confirm the diagnosis.
Results: The OSCC group showed the highest levels of both salivary and serum CYFRA21-1 followed by the group of PML than the control group.
The differences in means were statistically significant. At a cutoff value of 0.4 ng/mL, salivary CYFRA21-1 showed 87.5% sensitivity and 100%
specificity in differentiating PML from OSCC, with 95% accuracy. Serum CYFRA21-1, at a cutoff value of 1.03 ng/mL showed 100% sensitivity,
specificity, and accuracy.
Conclusion: Serum and salivary CYFRA21-1 could be considered promising biomarkers for the diagnosis of oral malignancy and could help
detect early malignant changes in PML, especially oral lichen planus and leukoplakia.
Keywords: CYFRA21-1, Diagnostic accuracy study, Oral cancer, Potentially malignant lesions, Saliva.
World Journal of Dentistry (2021): 10.5005/jp-journals-10015-1825
... Several salivary tumor markers are found to be significantly increased in the saliva of oral cancer patients [5,6] such as 8-OHdG and MDA biomarkers. ...
Objective
There are inconclusive data connecting single-nucleotide polymorphisms (SNPs) of TNF-α (rs361525) and TNF-β (rs909253) to potential malignant oral disorder (PMOD) such as lichen planus and oral fibrosis. Here, we have investigated the risk of oral squamous cell carcinoma as well as oral pre-cancerous lesions in North Indian population with the polymorphism of the TNFα/ β genes.Material and methodsA total 500 patients with oral pre-cancer and OSCC and 500 healthy volunteers were genotypes for the TNF-α (-238) G/A (rs361525) and TNF-β (252) A/G (rs909253) gene polymorphism. Genotypes were identified by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP). Genotype frequencies were evaluated by Chi-square test.ResultsCompared to the GG genotype, the GA genotype of TNF-α (G238A) polymorphism (rs361525) has been found to significantly increase the risk of oral disease (OR = 1.99) and especially the risk of lichen planus and OSCC (OR = 2.805 and 5.790, respectively). Similarly, the risk of oral disease was also more in the heterozygote (AG) than the common allele homozygote (AA) of TNF-β (A252G) polymorphism (rs909253) (OR = 1.483).Conclusion
We conclude that the SNPs rs361525 and rs909253 were significantly associated with oral pre-cancer and OSCC.
... Other studies have identified additional proteomic salivary biomarkers potentially useful in detecting OSCC [13]. In a comparison of sera with saliva in patients with OSCC, three tumor markers: specifically Cyfra 21-1, tissue polypeptide antigen (TPA), and a cancer antigen CA125 were found to be significantly more elevated in the saliva of diseased subjects [14]. And results of an additional study suggest that five salivary proteins (M2BP, MRP14, profilin, CD59, and catalase) can discriminate oral cancer with 90% accuracy [15]. ...
... Recently, various biomarkers were postulated, as they can be used in the diagnosis of peri-implantitis 35 ; however, studies reporting candidate biomarkers for peri-implantitis are as yet limited and have significant deficiencies, such as being unverified in different patient populations and having low sensitivity and specificity. 35,36 Therefore, novel specific molecular markers need to be identified to prevent or limit the progression of the disease in peri-implantitis patients. ...
Purpose:
Peri-implantitis, a potentially progressive disease that occurs in patients with dental implants, is more aggressive than periodontal lesions, which makes the prevention of peri-implantitis an important priority. Due to problems in the early detection of peri-implantitis, there is an urgent need for discovering novel biologic molecules with the ability of early diagnosis. The goal of this study was to profile the microRNA content of saliva samples collected from patients with titanium-aluminum-vanadium alloy dental implants who experienced peri-implantitis and to find potential diagnostic markers for detection of this disease.
Materials and methods:
The microRNA expression profiles of eight saliva samples (four collected from patients with peri-implantitis, four collected from patients who have successful implants) were investigated, and the deregulation of select microRNAs was further confirmed using quantitative polymerase chain reaction.
Results:
The expressions of 179 microRNAs were found as deregulated in the saliva of peri-implantitis patients in comparison to controls. Then, downregulation of miR-4484 was confirmed in the saliva of peri-implantitis patients in a larger validation cohort. Also, 40% of non-peri-implantitis patients and 78% of peri-implantitis patients had significantly decreased miR-4484 expression in saliva samples collected after 4 to 6 months subsequent to implant placement compared with samples collected before implant placement.
Conclusion:
Considering these findings, microRNA content of saliva might be proposed as a plausible source for the early diagnosis of peri-implantitis, where miR-4484 might serve as an encouraging early diagnostic biomarker.
The aim of this study was to evaluate the effects of two forms of tobacco smoking, cigarettes and water pipe smoking (WPS), on the expression of a panel of salivary proteins in healthy adults. Three groups of age and gender-matched participants were enrolled in the study: never-smokers, cigarette smokers and WPS (N = 55 per group). Expression of epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), endothelin and transferrin in unstimulated whole saliva was estimated using enzyme-linked immunosorbent assays. Statistical analysis consisted of one-way ANOVA and Tukey’s post hoc tests, in addition to bioinformatics analysis. VEGF expression was the least in WPS (51.1 ± 14.5 pg/ml) compared to both controls (150.1 ± 13.8 pg/ml) and cigarette smokers (93 ± 9.9 pg/ml), with a significant difference in WPS (p < 0.001) and cigarette smokers (p < 0.01) compared to controls. Furthermore, transferrin showed the weakest expression in the WPS group (1238 ± 261.4 pg/ml) compared to controls (2205.6 ± 298.6 pg/ml) (p = 0.05) and cigarette smokers (1805.4 ± 244 pg/ml). Neither EGF nor endothelin expression showed any statistical difference between the groups (p > 0.05). Gene–gene interaction network demonstrated that FLT1, TFRC, KDR, VEGFB and PGF genes had the highest potential for interaction with the studied proteins. Further functional annotations on the identified markers in the interaction network were performed to identify HIF-1 pathways among the most relevant pathways. In conclusion, smoking habits alter the expression of salivary VEGF and transferrin, which may correspond to early sub-clinical changes in the oral mucosa. The clinical relevance of these salivary changes requires further research.
With the growing number of cancers, new assistive tools are required to obtain extensive molecular profiles of patients to help identify the disease. Early diagnosis of cancer is based on the analysis of relevant biomarkers, which can be used to monitor the population in order to identify the disease until it can be determined using standard methods and is not clinically manifest. One of the potential markers of cancer is heat shock proteins that act as molecular chaperones. Changes in heat shock proteins expression can serve as an important diagnostic marker of the cell’s response to damage. The paper presents a brief overview of the prevalence of oncological diseases in the world, the need of early oncological diagnostics development, as well as the prospects for the use of heat shock proteins in making an oncological diagnosis.
The precise identification of Alzheimer's disease and other prevalent neurodegenerative diseases remains a difficult issue that requires the development of early detection of the disease and inexpensive biomarkers that can replace the present cerebrospinal fluid and imaging biomarkers. Blood biomarkers, such as amyloid and neurofilament light, have been emphasized as an important and practical tool in a testing or examination procedure thanks to advancements in ultra‐sensitive detection techniques. Although saliva is not currently being researched for neurodegenerative diseases, it is an important source of biomarkers that can be used for the identification of diseases and has some advantages over other biofluids. While this may be true for most people, getting saliva from elderly people presents some significant challenges. In this overview, we will first discuss how saliva is created and how aging‐related illnesses may affect the amount and kind of saliva produced. The findings support the use of salivary amyloid protein, tau species, and novel biomarkers in the diagnosis of Alzheimer's disease.
Peri-implantitis develops in 43.3% of implant patients, which affects tissues around the implant that may ultimately cause implant loss if not treated properly. Due to difficulties in detecting peri-implantitis in its early phases, implant failures are constantly on the rise. Therefore, new specific molecular markers need to be identified to prevent or limit disease progression in peri-implantitis patients. We investigated levels of CXCL9, CXCL12, and CXCL14 in saliva samples of 45 patients with commercially pure grade 4/5 Titanium–Aluminum–Vanadium implants. We analyzed the correlation of the chemokine levels using Pearson’s Correlation test and investigated their power to discriminate peri-implantitis vs. non-peri-implantitis patients using receiver operating characteristic analysis. Our in silico investigation revealed CXCL9, CXCL12, and CXCL14 as predicted targets of miR-4484, which has been demonstrated as a powerful biomarker candidate for early detection of peri-implantitis in our previous study. We measured high CXCL9 and low CXCL14 levels in the saliva of peri-implantitis patients. We also reported that the CXCL14 level showed a significant positive correlation with miR-4484. Besides, CXCL14 together with miR-4484 in saliva differentiated peri-implantitis patients from non-peri-implantitis individuals with 100% success. We offer differential expressions of CXCL14 and miR-4484 in the saliva of patients with peri-implantitis as potential salivary biomarkers for early detection of this disease.
This study addresses the limited non-invasive tools for Oral Cavity Squamous Cell Carcinoma (OSCC) survival prediction by identifying Computed Tomography (CT)-based biomarkers to improve prognosis prediction. A retrospective analysis was conducted on data from 149 OSCC patients, including CT radiomics and clinical information. An ensemble approach involving correlation analysis, score screening, and the Sparse-L1 algorithm was used to select functional features, which were then used to build Cox Proportional Hazards models (CPH). Our CPH achieved a 0.70 concordance index in testing. The model identified two CT-based radiomics features, Gradient-Neighboring-Gray-Tone-Difference-Matrix-Strength (GNS) and normalized-Wavelet-LLL-Gray-Level-Dependence-Matrix-Large-Dependence-High-Gray-Level-Emphasis (HLE), as well as stage and alcohol usage, as survival biomarkers. The GNS group with values above 14 showed a hazard ratio of 0.12 and a 3-year survival rate of about 90%. Conversely, the GNS group with values less than or equal to 14 had a 49% survival rate. For normalized HLE, the high-end group (HLE > − 0.415) had a hazard ratio of 2.41, resulting in a 3-year survival rate of 70%, while the low-end group (HLE ≤ − 0.415) had a 36% survival rate. These findings contribute to our knowledge of how radiomics can be used to predict the outcome so that treatment plans can be tailored for patients people with OSCC to improve their survival.
Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the oral mucosa. Currently, the diagnosis of oral cancer is based on clinical examination and histopathological analysis. Numerous potential biomarkers have been suggested for oral cancer diagnosis, but the results are contradictory. A great achievement could be identification of biomarkers that indicate the early stage and progression of OSCC. Saliva is an easy to obtain biological fluid containing specific molecules for various pathologies. Some reliable saliva molecules described as oral biomarkers for OSCC are cytokines. A number of studies have shown that higher levels of the proinflammatory and proangiogenic cytokines, like IL-8, IL-6 and TNF-α in saliva could be used for early diagnosis of OSCC. Other studies have shown that the levels of some immunosuppressive cytokines (IL-4, IL-10, IL-13 and IL-1RA) are elevated in saliva in OSCC patients compared to controls. The importance of the immunoregulatory molecules as markers for OSCC is debated. Further studies are needed to identify clinically relevant biomarkers for screening and early detection of oral cancer.
Background:
Salivary gland cancer is a rare disease, and approximately 20% of tumors in the salivary glands are malignant. Reliable biomarkers may have a role in monitoring salivary gland cancer.
Aim:
To review the current literature on the role of biomarkers in liquid biopsies and saliva samples in the monitoring of salivary gland cancer.
Materials and method:
This study systematically reviewed the literature on studies detecting salivary gland cancer by biomarkers in liquid biopsies and saliva samples by systematically searching PubMed and Embase between 1 January 2013 and 7 March 2023.
Results:
Five studies covering 64 malignant cases of salivary gland cancer were included, which considered inflammatory biomarkers or markers of genetic material in either blood or saliva. In saliva, there were demonstrated elevations of CA-19-9 in malignant cases, and elevations of miRNA in malignant and benign cases. In blood, there were demonstrated elevations of IL-33 in malignant and benign cases, elevations of ctDNA in malignant cases, and elevations of CTC in malignant cases.
Conclusion and significance:
The studies indicate that there is potential in the detection method. The studies detecting genetic material by liquid biopsies showed the most promising results. At present, there is still progression to be made before the method can be implemented for diagnostic use.
Human saliva is incredibly a versatile organic fluid. Its collection is easy and non-invasive. The biomarkers present in the saliva prove themselves to be of diagnostic and prognostic importance for oral diseases like, periodontitis, oral lichen planus and oral leukoplakia. These biomarkers include growth factors, enzymes and interleukins. They also help in diagnosis of these diseases and for evaluation of risk of malignancy, monitoring of disease and the response to provided treatment. However, more research are required to discover biomarkers and verification of their diagnostic and prognostic role in context with oral diseases is needed. This article review a complete and thorough assessment of importance of saliva as a diagnostic device for the potential diagnosis of oral and systemic disease.
Over the current years, there seems to be an investigation into various nanomaterials for their use in biomedical diagnostics thereby providing a fast-evolving field in healthcare biosensing for its use. The birth of nanomaterials has delivered versatility to the sensing or biosensing platforms that even might permit movement during various detecting mechanisms. The prospect of a mixture of multiple nanomaterials has allowed its exploitation due to the synergistic novel and additive properties for developing the sensor platform. Moreover, there seems to be a great interest in using them for biosensors, especially for their application in biomedical areas. Thus, the combination of various nanostructure materials has given rise to biosensors connected with its biomedical applications, such as cancer biomarkers detection such as cytokeratin fragment-21-1 (Cyfra-21-1), interleukin (IL-8); Vitamin D3 biomarker detection, and so on. These biosensors provide several benefits in various aspects that are suitable for their use in biomedical fields, offering flexible devices, permitting biomedical investigation with high sensitivity, outstanding selectivity, and rapidness. This chapter provides the details of nano-biosensors, published in recent years for the detection of Vitamin D3 and cancer biomarkers that would give the understanding of the prospects of biosensors. Besides, this chapter also highlights the use of carbon quantum dots for its application in bioimaging. Thus, the most recent advancements described in this chapter grasp a remarkable potential for its nanomaterials application in early detection and bioimaging applications.KeywordsNanomaterialsElectrochemical biosensorsFunctionalizationBioimagingCancer biomarkersVitamin D3
The point-of-care test of tumor markers in saliva with high specificity and sensitivity for early diagnosis of oral cancer is of great interest and significance, but remaining a daunting challenge due to the low concentration of such biomarkers in oral fluid. Herein, a turn-off biosensor based on opal photonic crystal (OPC) enhanced upconversion fluorescence is proposed to detect the carcinoembryonic antigen (CEA) in saliva by applying fluorescence resonance energy transfer sensing strategy. Hydrophilic PEI ligands are modified on upconversion nanoparticles to enhance the sensitivity of biosensor by promoting sufficient contact between saliva and detection region. As a substrate for the biosensor, OPC can also provide a local-field effect for greatly enhanced upconversion fluorescence by coupling the stop band and excitation light, and a 66-fold amplification of the upconversion fluorescence signal was obtained. For the CEA detection in spiked saliva, such sensors showed a favorable linear relationship at 0.1-2.5 ng mL-1 and more than 2.5 ng mL-1, respectively. The limit of detection was down to 0.1 ng mL-1. Moreover, by monitoring real saliva, the effective discrepancy between patients and healthy people was confirmed, indicating remarkable practical application value in clinical early diagnosis and home-based self-monitoring of tumors.
Oral cancer is a malignant tumor that threatens the health of individuals on a global scale. Currently available clinical treatment methods, including surgery, radiotherapy, and chemotherapy, significantly impact the quality of life of patients with systemic side effects. In the treatment of oral cancer, local and efficient delivery of antineoplastic drugs or other substances (like photosensitizers) to improve the therapy effect is a potential way to optimize oral cancer treatments. As an emerging drug delivery system in recent years, microneedles (MNs) can be used for local drug delivery, offering the advantages of high efficiency, convenience, and noninvasiveness. This review briefly introduces the structures and characteristics of various types of MNs and summarizes MN preparation methods. An overview of the current research application of MNs in different cancer treatments is provided. Overall, MNs, as a means of transporting substances, demonstrate great potential in oral cancer treatments, and their promising future applications and perspectives of MNs are outlined in this review.
Background:
Biomarkers are emerging, advanced diagnostic tools for the assessment of periodontal disease progression. Omentin-1 is an anti-inflammatory adipocytokine, which has been observed and studied in the saliva of periodontitis patients. Non-surgical periodontal therapy (NSPT) is considered a vital part of periodontal disease treatment.
Objectives:
The study aimed to evaluate the interventional effect of NSPT on the levels of salivary omentin1 in healthy (H) and chronic periodontitis (CP) patients.
Material and methods:
A total of 60 participants were selected and equally divided into 2 groups (group A: H participants, group B: CP patients). After obtaining verbal and written consent, whole unstimulated saliva was collected from all participants and analyzed for omentin-1 levels using enzyme-linked immunosorbent assay (ELISA).
Results:
Mean salivary omentin-1 levels were elevated and found to be significantly higher in group A (95.80 ±26.65) compared to group B (61.97 ±24.53). In group B, there was a substantial rise in omentin1 levels from baseline to the 6th week of follow-up (p < 0.001). Thus, NSPT had a positive influence on salivary omentin-1 levels in the treatment group.
Conclusions:
Salivary omentin-1 levels may serve as diagnostic and prognostic indicators of periodontal disease progression, and may be used to assess therapeutic outcomes in periodontitis patients.
The study emphasizes the application of gold nanorods (GNRs) with different aspect ratios (ARs) for the development of multiplex assay for oral cancer detection. The tunable optical properties of the GNRs that rely on the geometrical alterations of the nanostructure and the corresponding change in the refractive indices of the local environment form the basis of the label-free biosensing mechanism. In the present work, two GNRs with AR 2.1 and AR 3.9 exhibiting LSPR at 620 and 775 nm were used for sensing oral cancer biomarkers (Cyfra 21-1 and CA-125). Clinically relevant salivary concentrations of CYFRA 21-1 and CA-125 were taken into consideration for designing the assay range. Herein, the antibodies against Cyfra 21-1 and CA-125 have been employed as biospecific probes to functionalize the GNRs with different ARs. Molecular interactions that induce a spectral shift of distinct plasmon band maxima facilitated quantitative assessment of the target analyte. The GNR bioprobe employed for sensing Cyfra 21-1 had a wide linear detection range of 0.496-48.4 ng mL-1 with a detection limit as low as 0.84 ng mL-1 and for CA-125 the detection range was 5-320 U mL-1 with a detection limit of 1.6 U mL-1. The individual GNR bioprobe also showed high specificity against several interferents. For multiplexed biosensing, the plasmon spectra of the GNR bioprobe mixture showed distinct responses upon binding of single and dual targets in the sample mixture and/or artificial saliva. The quantitative data from the developed method are of high clinical significance that can aid in the understanding of clinicopathological advancements in oral cancer at an early stage. This simple yet novel nanosized optical transducer technology can be further converted into miniaturized biochips and can be deployed in clinics as a nanoparticle-based point-of-care diagnostic adjunct.
Aim: To present a rare clinical case of X-linked retinoschisis, confirmed clinically, electrophysiologically and genetically.
Material and methods: A 12-year-old boy underwent detailed ophthalmic examination including fundus photography, full-field, multifocal and pattern electroretinography, visual field testing, optical coherence tomography, which established the clinical diagnosis, confirmed also genetically.
Results: The clinical findings included a slight loss of vision, central and paracentral scotomas, a characteristic spoke-wheel pattern appearance of the macula in fundoscopy and the pathognomic appearance of splitting of the retinal layers in the macula with foveal schisis with cystic spaces on OCT. Reduced cone and rod ERG responds were detected with the characteristic decreasing of b-ware near the isoelectric line. The genetic analysis found that the patient was hemizygous for the missense mutation c.598G>A (p.Arg200Cys) of RS1 gene, coming from his asymptomatic mother.
Conclusion: The comprehensive clinical, electrophysiological and genetic testing of patients with rare hereditary retinal dystrophies is essential for the correct diagnosis and the choice of therapeutic approach.
Liquid biopsy technologies have seen a significant improvement in the last decade, offering the possibility of reliable analysis and diagnosis from several biological fluids. The use of these technologies can overcome the limits of standard clinical methods, related to invasiveness and poor patient compliance. Along with this there are now mature examples of lab-on-chips (LOC) which are available and could be an emerging and breakthrough technology for the present and near-future clinical demands that provide sample treatment, reagent addition and analysis in a sample-in/answer-out approach. The possibility of combining non-invasive liquid biopsy and LOC technologies could greatly assist in the current need for minimizing exposure and transmission risks. The recent and ongoing pandemic outbreak of SARS-CoV-2, indeed, has heavily influenced all aspects of life worldwide. Ordinary tasks have been forced to switch from “in presence” to “distanced”, limiting the possibilities for a large number of activities in all fields of life outside of the home. Unfortunately, one of the settings in which physical distancing has assumed noteworthy consequences is the screening, diagnosis and follow-up of diseases.
In this review, we analyse biological fluids that are easily collected without the intervention of specialized personnel and the possibility that they may be used -or not-for innovative diagnostic assays. We consider their advantages and limitations, mainly due to stability and storage and their integration into Point-of-Care diagnostics, demonstrating that technologies in some cases are mature enough to meet current clinical needs.
Cancer is the second most common cause of death worldwide. Early cancer detection can lead to a better prognosis of the patients. Conventional diagnostic methods are invasive, labor-intensive, and expensive, thereby making the detection process quite cumbersome. Therefore, there is an urgent need to develop noninvasive, rapid, and highly accurate tests for the screening, early detection, and prognosis of cancer. Further, saliva serves as a “mirror of the present health of an individual.” Biochemically, saliva is the mixture of electrolytes, peptides, proteins, DNA, coding and noncoding RNAs, exosomes, and microbiota. Numerous candidate molecules have been identified in the saliva as potential cancer biomarkers. Here, we review emerging technologies being used for the detection of various analytes such as mRNAs, microRNAs, metabolites, and microbiota in the saliva of cancer patients. Next, we describe various types of detection systems and progress towards the development of point-of-care biosensor devices for salivary biomarkers. Finally, we discuss challenges in the field of cancer salivary biomarkers.
Nanotechnology in Cancer Management: Precise Diagnostics toward Personalized Health Care provides a well-focused and comprehensive overview of technologies involved in early stage cancer diagnostics via the detection of various cancer biomarkers, both in-vitro and in-vivo. The book briefly describes the advancement in cancer biomarker research relating to cancer diagnostics, covering fundamental aspects of various techniques, especially transduction methodologies, such as electrochemical, optical, magnetic, etc. In addition, it describes approaches on how to make options cost-effective, scalable for clinical application, and user-friendly. Advancements in technology related to device miniaturization, performance improvement and point-of-care applications round out discussions.
Rapid innovations in nanotechnology have allowed for the successful combination of many detection methods for cancer prognosis and diagnosis. The detection and analysis of cancer biomarkers are being investigated to develop reliable, cost-effective, powerful detection, and monitoring strategies for cancer risk indication, early detection, tumor classification, and recurrence. Surface-enhanced Raman spectroscopy (SERS) is one of the detection systems that has significantly improved the diagnostic approach for rapid trace-level cancer biomarker analysis because of its multiplexing capability, high sensitivity, high specificity, and barcoding effect. More efficient and convenient SERS-detecting systems have been realized due to the advancement in fabrication technology which has miniaturized the devices by combining well-designed assays/channels and SERS substrates. These immunoassays are being explored to find huge application toward healthcare application like early tumor cell detection, tumor cell imaging, intercellular interrogation of tissue, drug-delivery monitoring, etc. We further discuss the state-of-the-art technologies to highlight the significant advancement in cancer research diagnostics using Raman-based systems.
In this chapter, we discuss about electrochemical techniques, their working principle, and application in detection of cancer. The different cancer biomarkers and their role in clinical monitoring, prognosis and recurrence possibilities in cancer has been discussed to understand the importance of these biomarkers. Further, the role of nanomaterials for fabrication of efficient electrochemical biosensor has been discussed. Different detection strategies employed for cancer detection and to study the effect of drug on cancer cell has been also listed with suitable examples.
Head and neck cancer (HNC) is among the most common cancers in the world. The delayed diagnosis of HNC is a major cause of the increasing mortality rate. Thus, in recent years, there has been an increased interest in finding a source for early diagnosis of HNC. The limitations of using tissue biopsies have increased consideration for liquid biopsies. Liquid biopsies analyze circulating tumor-derived material called tumor circulome, which includes circulating tumor cells, circulating tumor DNA, and exosomes. This chapter discusses the potential role of exosomes, among others, in the early diagnosis of HNC. Exosomes have a potential role as an early diagnostic marker as they contain protein components consistent with the cell type of its origin and also contain miRNAs, which are used as diagnostic biomarkers for several cancers. Among the several sources of liquid biopsy, the advantages and shortcomings of saliva have been discussed in detail in this chapter due to its ready availability, which makes it beneficial for the non-invasive diagnosis of HNC.
Head and neck cancer (HNC) is one of the most common types of cancers accounting for 5% of total cancer cases worldwide. The proportion of HNC among malignancies is of much higher prominence in some world regions (e.g., up to 30% in Indo-Asia) as 70% of these cancers are induced by lifestyle habits. Risk factors have been identified such as alcohol, tobacco, smoking, and viral infections (e.g., HPV and EBV). While HNC is often curable when detected early, most patients present with late-stage cancer with regional nodal metastases, and up to 10% of them have distal metastases at the time of the first diagnosis. To date, no national screening programs for HNC have been implemented in the general population nor in high-risk groups. Timely and ultra-sensitive detection is also essential in patients with late-stage HNC to monitor disease recurrence and to assure locoregional control with an overall survival benefit. This chapter provides an overview of technologies that, along with appropriate biomarkers, are poised to revolutionize the early detection of HNC in the coming years.
Herein, we report results of the studies relating to the fabrication of yttria-doped zirconia-reduced graphene oxide nanocomposite (nYZR) based biosensing platform for detection of salivary CYFRA-21-1 biomarker. The nYZR nanocomposite was synthesized hydrothermally and amine-functionalized using 3-aminopropyl triethoxysilane (APTES). This functionalized nanocomposite (APTES/nYZR) was electrophoretically deposited (45 V; 3 min) onto pre-hydrolyzed indium tin oxide (ITO) coated glass substrate (APTES/nYZR/ITO) followed by biofunctionalization via covalent immobilization of the anti-CYFRA-21-1 antibodies (anti-CYFRA-21-1/APTES/nYZR/ITO). The synthesized nanomaterial and the fabricated electrodes were characterized to investigate crystal structure, morphology and electrochemical properties via X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, cyclic voltammetry, differential pulse voltammetry and electrochemical impedance spectroscopy. The fabricated biosensing electrode (BSA/anti-CYFRA-21-1/APTES/nYZR/ITO) has operating shelf life of 56 days and can be used to detect salivary CYFRA-21-1 biomarker concentration as low as 7.2 pg mL⁻¹ with wide linear detection range of 0.01-50 ng mL⁻¹. This work opens new opportunities to explore the electrochemical behavior of nanostructured yttria stabilized zirconia (YSZ) and its composites at room temperature and its utility in developing biosensors and other electrochemical devices.
BACKGROUND
Head and neck cancers, among the 10 most frequent cancers in the world, are common in regions with a high prevalence of tobacco and alcohol habits. They account for one-fourth of male and one-tenth of female cancers in India. The authors report and discuss the survival from these cancers in Mumbai (Bombay), India.METHODS
Follow-up information on 6311 head and neck cancer patients registered in the Bombay Population-Based Cancer Registry for the period 1987–1991 was obtained by a variety of methods, including matching with death certificates from the Bombay vital statistics registration system, postal/telephone enquiries, home visits, and scrutiny of medical records. The survival for each case was determined as the duration between the date of incidence and the date of death or date of loss to follow-up or the closing date of the study (December 31, 1996). Cumulative observed and relative survival were calculated by the Hakulinen method. For comparison of results with other populations, age-standardized relative survival (ASRS) was calculated by directly standardizing age specific relative survival to the specific age distributions of the estimated global incidence of major cancers in 1985. The log rank test was used in univariate analysis to identify the potentially important prognostic variables. The variables showing statistical significance in univariate analysis were introduced stepwise into a Cox regression model to identify the independent predictors of survival.RESULTSThe 5-year relative survival rates were 74.5% for the lip, 42.7% for the anterior tongue, 25.5% for the posterior tongue, 45.1% for the mouth, 29.7% for the oropharynx, 38.7% for the nasopharynx, 29.1% for the hypopharynx, and 41.2% for the larynx. Age, marital status, religion, and site and clinical extent of disease emerged as independent predictors of survival. Age specific 5-year relative survival declined with advancing age. Single patients had a 20% excess risk of death compared with married patients. Those with cancers of the lip, mouth, nasopharynx, and larynx had a better prognosis than those with cancer at other sites. Those with regional spread of disease experienced a threefold increased risk of death, and those with distant metastasis experienced a sixfold excess risk. Less than one-fourth of cancers were localized in the organ of origin at diagnosis; 5-year survival for localized cancers ranged from 52.9% to 80.2% depending on the subsite.CONCLUSIONS
There were significant variations in survival from cancer at individual sites within the head and neck region. Comparison with other populations revealed variations that seemed to be related to differences in detection and treatment. Tobacco and alcohol control measures and early detection linked with treatment are important measures to reduce mortality from head and neck cancer. Cancer 2000;89:437–44. © 2000 American Cancer Society.
The aim of this study was to evaluate the cytotoxic effects of Cigarette Smoke on the human peripheral blood lymphocytes in the presence of stimulated or non-stimulated saliva in an in vitro model.
Ten healthy volunteers in the age range of 21 to 29 were selected and samples of peripheral blood lymphocytes and saliva (whole and stimulated saliva) collected . Peripheral blood lymphocytes suspensions (PBS) were taken and exposed to 6 different media. Samples were collected from all media at both 20 and 80 minute time points. The survival rates of PBL were then determined at both 20 and 80 minute time points.
The cell survival rates following exposure to cigarette smoke (CS) in the presence of PBS supplemented with whole or stimulated saliva were significantly lower at 80 minutes when compared with the 20 minute rates (P<0.05).
Tobacco effects were significantly increased in the presence of saliva especially stimulated saliva.
Five tumor markers (CEA, Ferritin, CA-50, TPA and SCC) were assayed in 54 patients with ear, nose and throat (ENT) cancers in early and advanced stages. The specificity of these markers always exceeded 95%. Their sensitivity ranged from 13 to 43%, and reached 72% as a combination of all five markers.
No distinction was found between early and advanced stage of illness. These markers seem to have no distinct function in ENT oncological diagnosis and follow-up because objective data is easily available even in early tumors.
The gastrointestinal cancer-associated antigen (GICA) is recognised by a monoclonal antibody in both serum and tissues of patients with neoplasm of the GI tract. This study compared the serum and saliva values of carcinoembryonic antigen (CEA) and GICA in 19 healthy subjects, 43 patients with benign oral cavity lesions and 26 with histologically confirmed squamous-cell carcinomas. Serum CEA levels were much the same in all three groups, whereas salivary values were significantly higher (p less than 0.001) in both patient groups than in the controls. Serum GICA gave the opposite result: lower in carcinoma than in controls (p less than 0.001) and benign lesions (N.S.), while salivary GICA was significantly lower in carcinoma than in both the other two groups (p less than 0.001). The meaning of this difference between the values for the two antigens is discussed.
The incidence of and mortality from squamous cell carcinoma (SCC) of the tongue have increased during the recent decades in the Western world. Much effort has been made to predict tumour behaviour, but we still lack specific prognostic indicators. The aim of our study was to evaluate the relative importance of the known demographic, clinical and histological factors in a homogeneous population-based group of patients with SCC of the mobile tongue. The demographic and clinical factors were reviewed retrospectively from primary and tertiary care patient files. Histological prognostic factors were determined from pre-treatment biopsies. The TNM stage was found to be the most important prognostic factor. In particular, local spread outside the tongue rather than spread to regional lymph nodes was related to poor prognosis. Several demographic and histopathological factors were closely related to TNM stage. When the cases were divided into stage I-II carcinomas and stage III-IV carcinomas, it appeared that the patient's older age (> 65 years), a high malignancy score and an absence of overexpressed p53 protein were associated with a poorer prognosis in stage I-II carcinomas. Such cases may require more aggressive treatment. Among patients with stage III-IV carcinomas, heavy use of alcohol was significantly associated with a poor disease-specific survival time.
To evaluate the impact of comorbidities, symptoms, and patients' characteristics on the 5-year overall survival of patients who underwent surgery for cancer of the oral tongue or floor of the mouth and to improve the survival estimates by the creation of a new staging system.
A cohort of 110 patients with squamous cell carcinoma of the oral tongue or floor of the mouth, who were admitted to a tertiary cancer hospital from January 1, 1990, to December 31, 1994, and who underwent surgery was studied. Multivariate analysis distinguished that patients' characteristics, symptoms, and comorbidities have a significant impact on 5-year overall survival. This functional severity index combined with the TNM stage created the extended clinical severity staging system.
The 5-year overall survival was 33.4%. Survival by TNM cancer stage was 64.6% (stage I), 67.5% (stage II), 28.9% (stage III), and 13.1% (stage IV) (chi(2) = 22.88, P<.001). When patients were categorized according to the extended clinical severity staging system, survival was as follows: 74.0% (stage 1), 47.1% (stage 2), 28.6% (stage 3), and 8.4% (stage 4) (chi(2) = 38.67, P<.001).
Clinical variables have a prognostic impact on oral cancer that is surgically treated, and the consistency of results confirms that survival estimates can be improved by the addition of these elements to the TNM classification, creating a more powerful and precise system in the determination of a prognosis.
Approximately 1 woman in every 10 will develop breast cancer in her lifetime. It has been shown that screening for breast cancer can reduce breast cancer mortality. The use of a saliva-based test could prove to be very useful in post-operative and/or adjunctive therapy management of breast cancer patients.
The following study was undertaken to establish the possible usefulness of the salivary protein product of the oncogene c-erbB-2 in following patients diagnosed with carcinoma of the breast. Included in this study were 25 patients with a mean age of 54 years with varying histological diagnoses and stages of carcinoma of the breast. ELISA assays for c-erbB-2 and CA 15-3 were performed on serum and stimulated whole saliva samples collected on all patients prior to any adjunct therapy or surgery and sequentially during therapy.
The results of the GLM analyses using marker concentration as the dependent variable and treatment regimen and the serial assessments as independent variables yielded a significant overall model for both the serum (P < 0.007) and salivary (P < 0.017) c-erbB-2 markers. The model for serum c-erbB-2, however, exhibited a significant difference for treatment regimen (P < 0.001) with the chemotherapy and radiation treatment regimen being significantly different (P < 0.001) from the other treatment therapies. Time (serial assessments) was not significant. The model for the salivary c-erbB-2 marker was reversed. Treatment regimen was not significant for this model; however, time (serial assessments) was significant (P < 0.002). The serum and salivary CA 15-3 marker models yielded no significant results. Paired t-test analyses indicated that only the salivary c-erbB-2 concentrations exhibited a significant difference between the pre- and post-therapy values (t = 4.245, P < 0.0001). Additionally, salivary c-erbB-2 displayed greater percent reductions across all therapies as compared to the other markers.
This preliminary study appears to indicate that c-erbB-2 protein expression in saliva may be a very useful diagnostic tool for measuring patient response to chemotherapy and/or surgical treatment of their disease.
Objectives: To evaluate the impact of comorbidities, symptoms, and patients' characteristics on the 5-year overall survival of patients who underwent surgery for cancer of the oral tongue or floor of the mouth and to improve the survival estimates by the creation of a new staging system. Patients and Methods: A cohort of 110 patients with squamous cell carcinoma of the oral tongue or floor of the mouth, who were admitted to a tertiary cancer hospital from January 1, 1990, to December 31, 1994, and who underwent surgery was studied. Multivariate analysis distinguished that patients' characteristics, symptoms, and comorbidities have a significant impact on 5-year overall survival. This functional severity index combined with the TNM stage created the extended clinical severity staging system. Results: The 5-year overall survival was 33.4%. Survival by TNM cancer stage was 64.6% (stage I), 67.5% (stage II), 28.9% (stage: III), and 13.1% (stage IV) (chi(2)=22.88, P<.001). When patients were categorized according to the extended clinical severity staging system, survival was as follows: 74.0% (stage 1), 47.1% (stage 2), 28.6% (stage 3), and 8.4% (stage 4) (chi(2)=38.67, P<.001). Conclusion: Clinical variables have a prognostic impact on oral cancer that is surgically treated, and the consistency of results confirms that survival estimates can be improved by the addition of these elements to the TNM classification, creating a more powerful and precise system in the determination of a prognosis.
In einer prospektiven Studie zur Validierung von Tumormarkerbestimmungen wurden bei 139 Patienten mit Kopf-Hals-Karzinomen prätherapeutisch bis zu fünf Serumtiter des SCC- (squamous cell Carcinoma) -Antigens bestimmt. Werte von über 2 ng/ml gelten als pathologisch. Zwischenergebnisse wurden bereits publiziert (1). Die abschließende Auswertung der Studie zeigt, dass in insgesamt 53% der Fälle pathologische Initialwerte gefunden wurden. Hohe Serumtiter fanden sich häufiger bei großen Primärtumoren (60% positive Befunde bei T4-Tumoren) und hoch differenzierten Karzinomen. In einem Drittel der Fälle mit Mehrfachbestimmungen schwankte der Titerwert bereits vor Einleitung der Therapie um mindestens 1 ng/ml. Das Sensitivitäts-Spezifitätsdiagramm weist bei einer Spezifität von 85% eine Sensitivität von 40% aus, womit das SCC-Antigen als Tumormarker bei der Initialdiagnostik von Kopf-Hals-Karzinomen nicht geeignet erscheint.
Summary
The serum - SCC antigen levels of patients with head and neck tumors were studied prospectively to determine their value in the initial diagnosis of head-and neck-cancer patients. Serum concentrations above 2 ng/ml are considered abnormal. Preliminary results of the study after a 12-month period have been reported elsewhere (1). The final results of the study show an increased percentage (53%) of pathologic findings, mostly due to the increasing number of advanced stage tumors. High serum levels were found in 60% of the T4-tumors (Fig. 4a). Well differentiated carcinomas seem to be associated with the antigen more frequently than poorly differentiated tumors (Fig. 5). SCC antigen levels were examined as many as five times before the start of treatment (85 patients), and in one-third of those cases the differences between the serum levels exceeded 1 ng/ml. As far as 85% specifity is concerned, the ROC-curve shows a sensitivity of only 40% (Fig. 2) which, in addition to the fact that the antigen was most frequently found in cases of advanced tumors, indicates that the usefulness of the SCC antigen as a tumor marker for head and neck cancer must still be regarded as low.
BACKGROUND
Mucosal oral squamous cell carcinoma (SCC) accounts for 3–5% of all reported cancers, with a 5-year survival rate of approximately 50%. Unfortunately, current detection means are of no value in diagnosing lesions early enough for cure, especially when they recur after resection. Postoperative radiotherapy and/or covering the resection site with reconstructive flaps (regional or free vascularized) often makes early diagnosis an impossible task.METHODS
The authors examined the detection and treatment monitoring capacity of two relatively new tumor markers in the serum of SCC patients, comparing their levels with those in patients with other oral/perioral malignancies or benign oral tumors and with disease free, posttreatment SCC patients and healthy controls.RESULTSValues of sensitivity, specificity, and positive and negative prediction for Cyfra 21-1 were 96%, 87%, 93%, and 53%, respectively, whereas those for tissue polypeptide specific antigen (TPS) were 69%, 87%, 93%, and 54%, respectively. Approximately 2–3 weeks after resection of the SCC lesion, Cyfra 21-1 and TPS levels were reduced by 47% (P ≤ 0.003) and 36% (P ≤ 0.041), respectively. Cyfra 21-1 levels in SCC patients were significantly greater than those of healthy patients by 73% (P ≤ 0.0001), patients with benign tumors by 74% (P ≤ 0.0003), and patients in disease remission by 66% (P ≤ 0.0002). Similarly, the TPS levels of SCC patients were significantly greater than those of healthy patients by 59% (P ≤ 0.0005), patients with benign tumors by 55% (P ≤ 0.0001), and patients in disease remission by 59% (P ≤ 0.0001). In two patients, a second, new SCC lesion was diagnosed within the follow-up period, with increased tumor markers noted concomitantly with the diagnosis.CONCLUSIONS
The accumulated data point to the suitability of the clinical usage of these two markers, especially Cyfra 21-1, in the early detection of oral SCC lesions (primary, recurrent, or secondary) as well as for treatment monitoring. These results may open new avenues for the diagnosis and follow-up of these patients and hopefully improve their treatment outcome. Cancer 1999;85:1018–25. © 1999 American Cancer Society.
Background. Cancers of the upper aerodigestive tract constitute approximately 4% of all malignancies. These include cancer of the lip, tongue, major salivary glands, gums and adjacent oral cavity tissues, floor of the mouth, tonsils, oropharynx, nasopharynx, hypopharynx and other oral regions, nasal cavity, accessory sinuses, middle ear, and larynx.Methods. The histologically diagnosed cancers of the upper aerodigestive tract reported to the Surveillance, Epidemiology, and End Results program of the National Cancer Institute in 1973-1987 were tabulated by histologic type, sex, age, and racial group, and according to quinquennium (1973-1977, 1978-1982, 1983-1987). Frequencies, age-specific incidence rates, median age, and extent of spread at diagnosis, stage, and survival were examined.Results. Cancer of the upper aerodigestive tract represented 3.5% of all microscopically proven malignant neoplasms. Except for salivary glands, gums, nasopharynx, and nasal cavity and accessory sinuses, epidermoid carcinomas accounted for greater than 95% of the cancers. For all aerodigestive sites combined, there was a 2-to-1 male-to-female ratio (greater for laryngeal cancer, which was approximately 5 to 1). Incidence in black males was often twice the levels recorded in white males, whereas rates for black and white females tended to be close. The 5-year relative survival was approximately 50% (90% for lip and 65% for larynx), was somewhat better for whites than for blacks, and did not improve significantly over the 15 years studied. Salivary gland adenocarcinoma carried a survival of approximately 80%.Conclusions. Because many of the cancers of the upper aerodigestive tract are caused by alcohol and tobacco use, the potential for prevention is considerable. Cancer 1995;75:147-53.
Biochemical Markers (alpha-1-acid glycoprotein, ferritin, transferrin) and tumor associated markers (TPA, CEA, SCC-antigen) are described. Concerning the screening of oral carcinoma, the use of tumor markers is to be considered with criticism. The SCC-antigen seems to be the most useful for detection of recurrence in the follow-up. But no tumor marker can replace exact physical and ultrasound examinations.
An increased squamous cell carcinoma antigen (SCC) value was found in 33.3% of the patients with carcinomas of the oral cavity. In those patients in whom the tumor recurred, this percentage increased to 75%. Although elevated in 43.4% of the tumor patients, CEA values failed to drop after treatment like the SCC antigens did. Nor was there, in contrast to the SCC antigens, any evident correlation with tumor volume. Thus, pathologic CEA values must be attributed to non-tumor specific concomitant diseases. Ca 19-9, Ca 125 and Ca 15-3 exhibited poor sensitivity. According to the results of our studies the only valid tumor markers are SCC antigens, particularly for monitoring treatment.
The serum--SCC antigen levels of patients with head and neck tumors were studied prospectively to determine their value in the initial diagnosis of head- and neck-cancer patients. Serum concentrations above 2 ng/ml are considered abnormal. Preliminary results of the study after a 12-month period have been reported elsewhere (1). The final results of the study show an increased percentage (53%) of pathologic findings, mostly due to the increasing number of advanced stage tumors. High serum levels were found in 60% of the T4-tumors (Fig. 4a). Well differentiated carcinomas seem to be associated with the antigen more frequently than poorly differentiated tumors (Fig. 5). SCC antigen levels were examined as many as five times before the start of treatment (85 patients), and in one-third of those cases the differences between the serum levels exceeded 1 ng/ml. As far as 85% specificity is concerned, the ROC-curve shows a sensitivity of only 40% (Fig. 2) which, in addition to the fact that the antigen was most frequently found in cases of advanced tumors, indicates that the usefulness of the SCC antigen as a tumor marker for head and neck cancer must still be regarded as low.
The serum concentration of squamous-cell-carcinoma antigen (SCC) and carcinoembryonic antigen (CEA) in 51 patients with squamous cell carcinoma of the oral cavity were compared to those of 53 patients with non-malignant disorders of the head and neck. The sensitivity found for SCC was only 24%, but was much higher than for CEA. SCC could be a valuable tool in follow-up monitoring of patients treated for squamous cell carcinomas of the oral cavity.
In the last few years serum CA 19-9 has been shown to be a highly sensitive marker of pancreatic adenocarcinoma. This study assesses the value of serum CA 19-9 assay in the postsurgical follow-up of patients undergoing pancreatic cancer resection. In 14 patients with cancer in the head of the pancreas and abnormal preoperative serum CA 19-9 values (greater than 40 U/ml), a pancreatoduodenectomy was performed. In all patients the CA 19-9 antigen was immunohistochemically demonstrated on the removed tumoral tissue. Postoperative serum CA 19-9 concentrations were serially measured 15 days after surgery and then every other month. Serum CA 19-9 scores returned to the normal range only in 7 (50%) of the resected patients. All patients with a normal postoperative value and none of those with a persistently elevated one survived longer than 7 months. Early postoperative serum CA 19-9 assay was superior to perioperative staging of the tumor as a prognostic index. All of the seven patients with postoperative normal values exhibited a subsequent increase within 16 months. In all cases the elevation of CA 19-9 occurred at least 2 months before ultrasound (US) could detect local recurrences of hepatic metastasis. Our data indicate that a normal early postoperative CA 19-9 score is a relatively favourable prognostic index in patients who undergo radical surgery for pancreatic cancer and that the CA 19-9 test can be used, as an early marker of recurrence, in monitoring these patients.
The murine monoclonal antibody OC 125 reacts with an antigen (CA 125) common to most nonmucinous epithelial ovarian carcinomas. An assay has been developed to detect CA 125 in serum. By this assay, only 1 per cent of 888 apparently healthy persons and 6 per cent of 143 patients with nonmalignant disease had serum CA 125 levels above 35 U per milliliter. In contrast, 83 of 101 patients (82 per cent) with surgically demonstrated ovarian carcinoma had elevated levels of antigen. In 38 patients with epithelial ovarian carcinoma monitored on 2 to 18 occasions during 2 to 60 months, antigen levels ranged from less than 1 to more than 8000 U per milliliter. Rising or falling levels of CA 125 correlated with progression or regression of disease in 42 of 45 instances (93 per cent). Determination of CA 125 levels may aid in monitoring the response to treatment in patients with epithelial ovarian cancer.
Serum carcinoembryonic antigen (CEA) and salivary CEA levels were determined for 18 patients with squamous oral carcinoma, 12 patients with oral leukoplakia, and 14 healthy volunteers. The determination of the CEA-serum levels has no diagnostic significance. Salivary CEA levels are not correlated with CEA-serum values, with cigarette consumption and clinical stage. Salivary CEA determination provides no additional information for the primary diagnosis. Serial determinations may have adjunctive value in monitoring oral cancer.
Prognostic parameters of patients with stomach and colorectal cancer, which could be established within a few days during hospitalization of patients for primary treatment, were characterized and compared in a clinical investigation with observed postoperative survival. Statistical analysis was based on data from a long-term follow-up study of 563 colorectal and 390 stomach cancer patients registered since 1974. The potential prognostic parameters included resectability, tumor extension, and preoperative serum CEA levels. Statistical examination revealed that each of the parameters was associated with highly significant differences in survival of the patients. Combinations of clinical parameters with distinct ranges of preoperative serum CEA levels gave additional valuable prognostic information, thus facilitating the management of patients for adjuvant postoperative treatment.
Serum levels of six tumor markers (carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCCA), immunosuppressive acidic protein (IAP), alpha-fetoprotein (AFP), ferritin (FER), and carbohydrate antigen 19-9 (CA 19-9)) were simultaneously measured in 29 patients with primary squamous cell carcinoma (SCC) of the oral cavity to determine their significance. The positive rates were 34.5% for CEA, 41.4% for SCCA, 51.7% for IAP, 0% for AFP, 10.3% for FER, and 6.9% for CA 19-9 in patients with oral SCC. Therefore, CEA, SCCA, and IAP levels, of which the positive rates were significantly different (P < 0.01) from those of control patients without oral cancer, were considered to be of diagnostic value. The sensitivity (69.0%) and accuracy (90.3%) of the combination assay with these three tumor markers proved to be higher than those obtained with individual markers. A combination assay with CEA, SCCA, and IAP could be useful for the screening of patients with oral cancer.
Serum prolactin and tissue polypeptide specific antigen (TPS) were assayed pretherapeutically and sequentially thereafter in 20 male patients with advanced (stages III and IV) tongue cancer. The markers were correlated with disease stage, histologic grade and an attempt was also made to compare the predictive value of these markers and two year survival. Prolactin and TPS levels were significantly higher at diagnosis when compared to controls (a = 0.005). Prolactin and TPS levels did not correlate with stage and histologic grade of the tumor. We found that the positive predictive value for prolactin and TPS was 100% and 75% respectively. The two year survival of patients with prolactin > 15.0 ng/ml was 7.88 +/- 1.48 months, compared to 16.98 +/- 1.47 months of those with prolactin less than 15.0 ng/ml (P < 0.001), whereas such a trend was not observed for TPS. This analysis showed an excellent correlation between serial serum prolactin changes and the response to treatment or progression of disease in patients with advanced tongue carcinoma.
Cancers of the upper aerodigestive tract constitute approximately 4% of all malignancies. These include cancer of the lip, tongue, major salivary glands, gums and adjacent oral cavity tissues, floor of the mouth, tonsils, oropharynx, nasopharynx, hypopharynx and other oral regions, nasal cavity, accessory sinuses, middle ear, and larynx.
The histologically diagnosed cancers of the upper aerodigestive tract reported to the Surveillance, Epidemiology, and End Results program of the National Cancer Institute in 1973-1987 were tabulated by histologic type, sex, age, and racial group, and according to quinquennium (1973-1977, 1978-1982, 1983-1987). Frequencies, age-specific incidence rates, median age, and extent of spread at diagnosis, stage, and survival were examined.
Cancer of the upper aerodigestive tract represented 3.5% of all microscopically proven malignant neoplasms. Except for salivary glands, gums, nasopharynx, and nasal cavity and accessory sinuses, epidermoid carcinomas accounted for greater than 95% of the cancers. For all aerodigestive sites combined, there was a 2-to-1 male-to-female ratio (greater for laryngeal cancer, which was approximately 5 to 1). Incidence in black males was often twice the levels recorded in white males, whereas rates for black and white females tended to be close. The 5-year relative survival was approximately 50% (90% for lip and 65% for larynx), was somewhat better for whites than for blacks, and did not improve significantly over the 15 years studied. Salivary gland adenocarcinoma carried a survival of approximately 80%.
Because many of the cancers of the upper aerodigestive tract are caused by alcohol and tobacco use, the potential for prevention is considerable.
A retrospective study was performed on 52 advanced tongue cancer patients (stages III + IV) in order to assess the prognostic value of circulating prolactin, tissue polypeptide-specific antigen (TPS), insulin-like growth factor 1 (IGF-1) and epidermal growth factor (EGF). These markers were correlated with short-term prognosis (2 years). The advanced tongue cancer patients had significantly elevated levels of prolactin (p < 0.02), TPS (p < 0.05) and EGF (p < 0.01) and low levels of IGF-1 when compared to controls. The patients were grouped according to the commonly used cut-off levels of these markers. A significant difference in survival was observed only between two subgroups of prolactin (< 15.0 and > 15.0 ng/ml; p < 0.001). Hence, prolactin may provide an independent predictor of short-term prognosis in patients with advanced tongue cancer.
Tissue-polypeptide-specific antigen (TPS) from the human colon adenocarcinoma cell line WiDr was purified using the monoclonal antibody M3 as a probe. Upon SDS/polyacrylamide gradient gel electrophoresis, several TPS-positive bands were detected (corresponding to 13 kDa, 22 kDa and a doublet at 42 kDa). The 13-kDa moiety was purified about 30,000-fold by a 5-step protocol. The electro-phoretically homogeneous component was obtained in a 7% yield of the total TPS activity of the crude extract. N-terminal sequence analysis showed the presence of an N-terminally truncated molecule and identified the 13-kDa TPS component as a fragment of human cytokeratin 18, with a major from starting at position 284 of the parent molecule. Laser-desorption mass spectrometry showed the presence of one major component with a molecular mass corresponding to a C-terminal end close to position 396 (which gives 12776 Da for the form with non-truncated N-terminus). The M3 antibody was also used to screen a human prostate cDNA lambda gt11 library. Four identical phage clones were detected, each producing a fusion protein with beta-galactosidase and the M3-positive component. PCR amplification showed the presence of an approximately 1200-bp insert, and sequence analysis revealed it to contain a 996-nucleotide fragment corresponding to residues 103-429 of human cytokeratin 18 (plus a non-coding human desmin artifact fragment). Smaller fragments, engineered by PCR and expressed as fusion proteins using the pET3xc vector in Escherichia coli, showed that the M3 epitope is localized to cytokeratin 18, residues 322-340. Two other TPS-active monoclonal antibodies were localized to cytokeratin 18 with similar techniques, ascribing an epitope (to M21) to residues 414-429 and another (to M24) to residues 139-297. Combined, the results demonstrate that TPS reactivity is derived from specific epitopes of human cytokeratin 18.
This study evaluated use of a combination assay of tumor markers in the diagnosis of oral squamous cell carcinoma.
Serum levels of four tumor markers (carcinoembryonic antigen [CEA], squamous cell carcinoma antigen [SCCA], immunosuppressive acidic protein [IAP], and cytokeratin 19 fragment [Cyfra]) were simultaneously measured in 42 patients with oral squamous cell carcinoma (O-SCC) and in 12 patients with oral benign diseases.
The positive rates were 31.0% for CEA, 38.1% for SCCA, 52.4% for IAP, and 38.1% for Cyfra in patients with O-SCC. These rates were significantly different (P < .01) from those of control patients with oral benign diseases. The sensitivity (81.0%) and accuracy (77.8%) of the combination assay uses higher than that obtained with individual markers.
A combination assay with CEA, SCCA, IAP, and Cyfra may be useful for the screening of patients with suspected oral squamous cell carcinoma.
Facial trauma and head and neck oncologic patients are often destined for extensive reconstructive procedures with microvascular free flaps due to ablative injuries or postoperative defects. The integrity and competence of the vasculature in the head and neck recipient site must be imaged and evaluated preoperatively as an essential prerequisite for the success of the reconstructive transfer. In a prospective study of five patients, we compared conventional angiography, the traditional technique, with a new vascular imaging modality--spiral computed tomographic (CT) angiography. One patient suffered from an extensive, ablative facial trauma, and the other four had undergone mandibulectomy as part of their oncologic therapy. In contrast to conventional angiography, spiral CT angiography is a noninvasive imaging technique, which we found to be characterized by much shorter patient examination time, avoidance of selective cannulation with its attendant risks, improved perception of anatomy, and the ability to rotate the reconstructed images in any plane to obtain the best view of any vessel in question. Disadvantages of spiral CT angiography in imaging vessels include the need for relatively large amounts of contrast medium, great dependence on the skill and experience of the operator, and the need for optimizing the timing of the contrast bolus and the scan.
The aims of the study are three-dimensional analysis of mode and distance of local spread of oral tongue carcinoma.
The glossectomy specimens were examined in the coronal plane in 3 mm thickness section.
There were 50 glossectomy specimens. The maximum spread was 1.8 cm. Ninety-six percent of specimens had local spread within 1.2 cm. The distance of spread was not correlated with tumor size, including the diameter, depth, and volume. The incidence of local recurrence was 27% with positive histological margin. Perineural infiltration was the most important prognostic factor for local recurrence and survival.
A minimum of 1.5-cm surgical resection margin is recommended. A smaller margin is not recommended as it has significant risk of local recurrence. A maximum of 2-cm surgical resection margin is recommended; larger margins will increase the surgical morbidity without a significant advantage of local control.
CYFRA 21-1 (CYFRA) is a newly developed tumour marker which is useful in evaluating large cell lung carcinoma, especially the squamous cell type. The purpose of this study was to assess the clinical value of CYFRA for squamous cell carcinoma of the head and neck and compare the results with squamous cell carcinoma antigen (SCCA).
Serum levels of CYFRA were measured in 168 patients with a newly diagnosed head and neck squamous carcinoma. In addition, 77 patients without evidence of neoplasm were included as controls. At the same time, SCCA was also determined. The cut-off values of CYFRA and SCCA, determined at the 95th percentile of the standard Gaussian variate of controls, were 2.48 ng/ml and 1.49 ng/ml respectively. The diagnostic sensitivity of CYFRA was superior to that of SCCA, especially for nasopharyngeal carcinoma. The sensitivity of CYFRA for nasopharyngeal carcinoma was much higher (58.3%) than that of SCCA (15.5%). However, the sensitivity of CYFRA is not satisfactory in all types of squamous carcinoma. For oral cancer, the sensitivity is only 25.6%. CYFRA is a useful serum marker for patients with certain types of head and neck squamous carcinoma, such as nasopharyngeal carcinoma and hypopharyngeal carcinoma. In addition, CYFRA may be also useful in monitoring recurrence of certain types of SCCHN, which are sometimes difficult to detect.
The prognosis of oral cavity carcinoma is limited by recurrent disease or lymph node metastasis. Secondary to surgery and radiotherapy, anatomical structures are often severely changed and make early diagnosis of renewed tumour growth by clinical and radiological examination difficult. We studied the course of serum SCC-Ag, CEA, CA 19.9 and CA 125 in 121 patients with untreated squamous cell carcinoma of the head and neck (SCCHN) before and after therapy and evaluated their relevance for diagnosis and follow-up in oral cancer. CA 19.9 and CA 125 seemed to be useless for this tumour entity. CEA resembled more the alcohol consumption and smoking habits of the patients examined than their state of disease. Only SCC-Ag correlated with the tumour burden and represented the disease course. In the event of relapse, half the patients had an exponential increase in SCC-Ag, 1-2 months prior to diagnosis.
There are no reliable laboratory procedures to monitor intraoperative tumor antigen dispersal in patients with squamous cell carcinoma of the head and neck. This study evaluated the use of serologic parameters as perioperative indicators of systemic manifestations.
In 28 patients, serial measurements of different tumor markers (squamous cell carcinoma antigen, carcinoembryonic antigen, carbohydrate antigen 19.9, carcinoma antigen 125) were made preoperatively, intraoperatively, and postoperatively at short intervals to determine the influence of tumor ablation on the antigen concentration in the serum. A microparticle enzyme immunoassay was used for the serologic analysis.
Squamous cell carcinoma antigen showed elevated serum levels preoperatively, which increased intraoperatively and decreased significantly postoperatively. The serologic examinations in the control group and the other tumor markers showed no correlation with the clinical situation.
The results suggest that the titer of squamous cell carcinoma antigen in serum has a positive correlation with the tumor burden and the operative trauma in the case of surgery. These results support the value of intraoperative and postoperative serum antigen monitoring.
Mucosal oral squamous cell carcinoma (SCC) accounts for 3-5% of all reported cancers, with a 5-year survival rate of approximately 50%. Unfortunately, current detection means are of no value in diagnosing lesions early enough for cure, especially when they recur after resection. Postoperative radiotherapy and/or covering the resection site with reconstructive flaps (regional or free vascularized) often makes early diagnosis an impossible task.
The authors examined the detection and treatment monitoring capacity of two relatively new tumor markers in the serum of SCC patients, comparing their levels with those in patients with other oral/perioral malignancies or benign oral tumors and with disease free, posttreatment SCC patients and healthy controls.
Values of sensitivity, specificity, and positive and negative prediction for Cyfra 21-1 were 96%, 87%, 93%, and 53%, respectively, whereas those for tissue polypeptide specific antigen (TPS) were 69%, 87%, 93%, and 54%, respectively. Approximately 2-3 weeks after resection of the SCC lesion, Cyfra 21-1 and TPS levels were reduced by 47% (P < or = 0.003) and 36% (P < or = 0.041), respectively. Cyfra 21-1 levels in SCC patients were significantly greater than those of healthy patients by 73% (P < or = 0.0001), patients with benign tumors by 74% (P < or = 0.0003), and patients in disease remission by 66% (P < or = 0.0002). Similarly, the TPS levels of SCC patients were significantly greater than those of healthy patients by 59% (P < or = 0.0005), patients with benign tumors by 55% (P < or = 0.0001), and patients in disease remission by 59% (P < or = 0.0001). In two patients, a second, new SCC lesion was diagnosed within the follow-up period, with increased tumor markers noted concomitantly with the diagnosis.
The accumulated data point to the suitability of the clinical usage of these two markers, especially Cyfra 21-1, in the early detection of oral SCC lesions (primary, recurrent, or secondary) as well as for treatment monitoring. These results may open new avenues for the diagnosis and follow-up of these patients and hopefully improve their treatment outcome.
Ninety-eight untreated patients with squamous cell carcinoma of the head and neck of different localizations (larynx 36, oral cavity 48, nasal cavity 14) were selected for a study to measure TPA, CEA, CA 19-9, CA125 pre- and post-therapy. Fifty healthy individuals and 42 patients with benign lesions were as normal and disease controls. The positive rates were 22.3%, 27.8%, 5.6% and 0% respectively in TPA, CEA, CA 19-9 and CA125 markers in laryngeal cancer patients. The positive rates of TPA level was higher with significant difference in advanced stage group than in early stage group; conversely, the positive rate of CEA levels were somewhat high in early stages of laryngeal cancer. Meanwhile, the positive rates were 25.0%, 18.8%, 14.6% and 4.2% individually in the same order in oral cancer patients. There was no relationship between the marker levels and progression of the oral cancer. The tumor markers were almost of no use in detecting nasal cancer. It also seemed there was no relationship between the various serum levels and the tumor or nodal burden in laryngeal and oral cancer. Only TPA level decreased significantly after therapy in patients with laryngeal and oral cancer who had originally elevated marker levels. Conclusively, only TPA and CEA markers are of some clinical use in the disease.
This study was designed to determine whether the incidence of squamous cell carcinoma of the oral tongue (SCCOT) in young adults has changed during the past 25 years and to determine prognostic factors for young adult patients (aged < 40 years) with SCCOT.
A retrospective review of young adults with SCCOT who sought treatment at the M. D. Anderson Cancer Center between 1973 and 1995 was undertaken.
The percentage of young adult SCCOT patients at M. D. Anderson increased from 4% in 1971 to 18% in 1993. T stage, N stage, perineural invasion, and lymphatic invasion were all associated with decreased survival. Patients who received a neck dissection as part of their primary treatment had a better chance of survival than patients who did not.
The incidence of SCCOT in the young adult population is increasing in the United States. Appropriate surgical management for young adults with SCCOT includes resection of the primary tumor along with a selective node dissection.
A population-based descriptive study was conducted to describe incidence and survival of cancer of the mobile tongue in Finland between 1953 and 1994. The study included 1504 patients, drawn from the Finnish Cancer Registry, with first primary mobile tongue cancer diagnosed between 1953 and 1994. Incidence and relative survival were determined. The age-standardized overall incidence rate was 0.6 per 100000 years in 1953-1994. At the time of diagnosis 78% of the patients had either localized or regional disease. The age-standardized incidence rate decreased after the mid-1960s, but increased in the 1990s. The 5-year relative survival rate increased gradually from 40% in 1953 1959 to 58% in 1988-1994. Disease stage at the time of the diagnosis strongly affected the survival rate. Survival increased especially in regional disease. Cancer of the mobile tongue is increasing in Finland, but survival has increased particularly in regional disease, probably because of improved treatment. Early diagnosis is emphasized for a good prognosis.
The mortality because of malicious tumours of the oral cavity, of the pharynx and of the larynx has considerably increased in the Federal Republic of Germany during the last two decades. The prognosis not only shows a high ratio of recidivations and formation of metastases, but also a typical field canceration. There is a high rate of incidence of multiple primary, resp. secondary tumours that may occur synchronously or metachronously. Up to now we have learnt only little about the mechanisms concerning the development of tumours and their spread on the cellular molecular level.
The subject of the present retrospective study was the analysis of patients suffering from an epithelioma of the oral cavity, the pharynx and the larynx and the following secondary carcinomatas. The control group were patients suffering from primary tumours of the same location and subsequent recidivation or metachronous metastasis. By determination of the degree of malignity and keratinisation of the DNA ploidy, of the immunohistological expression of p53 and the immunohistological proliferation marker MIB1 conclusions had to be drawn with regard to the biological behaviour of tumours.
The evaluation of the clinical parameters of the 122 patients on the whole revealed a clear increase of new disease as well as a shifting to the younger age within the last five years. Surprisingly, most common were secondary tumours in case of larynx carcinomatas. Patients suffering from secondary tumours show a bad prognosis, however, their maximum survival does not differ considerably from that of patients suffering from recidivations, resp. metastases. Because of the early diagnosis of the secondary carcinomatas the prognosis will depend on the primary carcinoma in most of the cases. The prognosis data indicate that independently from the fact whether there is a primary or a subsequent tumour, the therapy to be applied can only be a combined therapy consisting of operation and ray-therapy. The present examinations confirm reports with regard to disturbance of the p53 regulation that also play an important role in case of the head-neck area. The parallel analysis of MIB1 as a proliferation marker showed in case of the primary carcinomatas a correlation of positive p53-immunocolour with moderate and strong proliferation. Tumours in the hypopharynx and larynx showed a significantly smaller proliferation than that of the oral cavity and oropharynx. In case of the primary and secondary tumours the proliferation is more common in case of the G3-tumours.
The in total modest differences between the primary and secondary carcinoma with regard to the DNA-ploidy; the proliferation and the p53-expression presumably originate in their formation within the scope of a so-called field canceration. Because of the field canceration supposed for the mucous membranes of the upper aerodigestive tract, the check-ups of these patients performed in regular intervals must not be limited in any case to the area of the primary tumour. They will have to consider the entire visible area of the upper respiratory and esophageal tract.
One purpose of this study was to compare various biochemical and immunological parameters in blood and saliva that are routinely evaluated only in the blood for general medical requirements. Another purpose was to concomitantly compare these and other oral/salivary parameters differentially in whole, parotid, and submandibular and sublingual saliva to examine the source of those parameters and their specific concentrations.
Twelve healthy individuals (6 women, 6 men) were examined in the blood-saliva comparison study, and 30 healthy individuals (15 women, 15 men) were studied in the intersalivary comparison study.
On the basis of the results we obtained, we suggest a classification scheme using a whole saliva compositional profile as a diagnostic tool in the evaluation of systemic and/or local pathologies. This system may be used to analyze various components of saliva beyond those analyzed in this study, thereby increasing the clinician's ability to locate and assess specific pathologies. We also suggest that consideration be given to the use of compositional saliva analysis in the diagnosis of general medical conditions in which there is a high correlation between the salivary and blood concentrations of relevant components.
We think that saliva analysis is a useful, worthwhile diagnostic tool because saliva collection is noninvasive, easy, and inexpensive and may be performed by the patient with no need for the involvement of medical personnel, if so desired.
In the current study, we examined the clinical characteristics and survival probability rates of 116 patients treated for squamous cell carcinoma (SCC) of the tongue. In 55 randomly selected patients these data were correlated with the immunohistological analysis of the tumor and apoptosis-related markers, p53, Bcl-2, c-erbB-2 (Her-2/neu), and to the apoptosis rate assessment by the terminal dUTP nick-end-labeling (TUNEL) method. The overall 5-year survival probability was 55%, which might be the result of the low incidence of smoking and/or alcohol consumption among the patients (21%), the early diagnosis (65% at Stages I-II) and the low histological grades (91% good-moderate). Radiotherapeutic or surgical treatment of the neck did not alter the survival probability achieved by local surgery for Stage I patients, but significantly improved survival for Stage II patients. Independent tumor-related variables which significantly worsened the probability of survival were found. Concomitant non-oral cancer was found to be a poor variable for prognosis prediction. Positive staining of p53, TUNEL (apoptosis rate), c-erbB-2 and Bcl-2 was found in 60, 48, 18 and 15% of the lesions, respectively (P<0.0001). The possible biological significance of these markers in tongue SCC is discussed in relation to the current literature, and an independent role for TUNEL and p53 is suggested.
The purpose of this study was to analyze factors influencing outcome in patients who received postoperative irradiation for advanced squamous cell carcinoma of the oral cavity.
Between October 1964 and November 2000, 226 patients with 230 previously untreated primary invasive squamous cell carcinomas of the oral cavity were treated postoperatively with continuous-course external beam irradiation. All patients had a minimum follow-up of 2 years (analysis, November 2002). No patient was lost to follow-up.
The 5-year actuarial rates of locoregional control by pathologic American Joint Committee on Cancer stage were: stage I, 100%; stage II, 84%; stage III, 78%; and stage IV, 66%. Recurrence of cancer above the clavicles developed in 55 patients (24%). In multivariate analysis of locoregional control, positive margins, vascular invasion, perineural invasion, extracapsular extension, and T classification remained significant.
This article provides additional data defining relatively favorable and unfavorable groups of patients in the postoperative setting. Dose recommendations are re-examined and selectively increased for high-risk patients.
The elective dissection of cervical lymph nodes from patients with early oral tongue cancer and a clinically negative neck (T1/T2N0), remains an unsettled issue that continues to be investigated. This study examines clinical and histopathologic factors through univariate and multivariate analysis to correlate the risk of neck micrometastasis in patients with T1/T2N0 squamous cell carcinoma of the oral tongue.
The clinical files and histologic sections of tumor from 45 clinically determined N0 patients were retrospectively analyzed. The factors examined include degree of tumor cell differentiation, T1/T2 staging, presence of perineural invasion, presence of angiolymphatic invasion, type of invasion front, depth of muscle invasion, and tumor thickness.
Independent correlates of positive occult neck metastasis included greater tumor thickness ( P = 0.01), greater depth of muscle invasion ( P = 0.01), T2 stage ( P = 0.01), poorly differentiated tumors ( P = 0.007), infiltrating-type invasion front ( P = 0.03), presence of perineural invasion ( P = 0.001), and presence of angiolymphatic invasion ( P = 0.005). The final multivariate model for estimation of an increased probability of occult neck disease included greater tumor thickness, presence of perineural invasion, infiltrating-type invasion front, poorly differentiated tumors, and T2 stage.
The clinical and histopathologic factors studied herein permit greater selectivity and more informed decision-making than does presurgical evaluation, when addressing elective neck treatment for early N0 oral tongue cancer. The multivariate model derived from this study appears to be a more reliable method for determining the patients most likely to benefit from elective neck dissection.
Oral squamous cell carcinoma (SCC) is most induced by exposure of the oral epithelial cells to tobacco products such as cigarette smoke. This exposure always occurs in the presence of saliva and presumably is induced by free radicals. To explore the effects of CS on cells in the presence of saliva, we used peripheral blood lymphocytes (PBL) and exposed them to CS, alone or in the presence of saliva. We discovered that after 80min, exposure of the lymphocytes to CS alone resulted in a time-dependent cellular loss with a survival rate of 56%, while following lymphocyte exposure to CS in the presence of saliva, less than 15% of the cells survived. This was accompanied by concomitant accumulation of cellular protein carbonyls which could be protected by the exogenous addition of uric acid or glutathione, but not by the addition of ascorbate (Asc), N-acetyl-l-cystein (NAC) or desferal (DES). Exposure of the lymphocytes to aldehydes present in CS, such as acrolein and croton-aldehyde, also resulted in the elevation of protein carbonyls, which was ameliorated primarily by the addition of glutathione. However, lymphocyte exposure to acroline in the presence of saliva did not show the same synergism in cell death observed as when the lymphocytes were exposed to CS and saliva. Thus, we postulated the existence of another mechanism and examined the role of redox active iron as an additional explanation for this synergism. In fact, it was found that in the presence of saliva and ascorbate there was a marked decrease in the lymphocyte survival rate; this was reversed by the addition of the iron chelator desferal. In light of these results, a comprehensive mechanism for the induction of oral cancer by cigarette smoke is suggested, stressing the role of a pivotal player in the process leading to oral cancer which has never been previously considered in this regard - the saliva.
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