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Gene expression profiling reveals biological pathways responsible for phenotypic heterogeneity between UK and Sri Lankan oral squamous cell carcinomas

Saeed AA, Sims AH, Prime SS, Paterson I, Murray PG, Lopes VR

Oral Oncol, 2015 Mar;51(3):237-46.
PMID: 25560800 DOI: 10.1016/j.oraloncology.2014.12.004

It is well recognized that oral squamous cell carcinoma (OSCC) cases from Asia that are associated with betel quid chewing are phenotypically distinct to those from Western countries that are predominantly caused by smoking/drinking, but the molecular basis of these differences are largely unknown. The aim of this study is to examine gene expression, related carcinogenic pathways and molecular processes that might be responsible for the phenotypic heterogeneity of OSCC between UK and Sri Lankan population groups.
Genomic DNA copy number alterations from precursor oral lesions to oral squamous cell carcinoma

Salahshourifar I, Vincent-Chong VK, Kallarakkal TG, Zain RB

Oral Oncol, 2014 May;50(5):404-12.
PMID: 24613650 DOI: 10.1016/j.oraloncology.2014.02.005

Oral cancer is a multifactorial disease in which both environmental and genetic factors contribute to the aetiopathogenesis. Oral cancer is the sixth most common cancer worldwide with a higher incidence among Melanesian and South Asian countries. More than 90% of oral cancers are oral squamous cell carcinoma (OSCC). The present study aimed to determine common genomic copy number alterations (CNAs) and their frequency by including 12 studies that have been conducted on OSCCs using array comparative genomic hybridization (aCGH). In addition, we reviewed the literature dealing with CNAs that drive oral precursor lesions to the invasive tumors. Results showed a sequential accumulation of genetic changes from oral precursor lesions to invasive tumors. With the disease progression, accumulation of genetic changes increases in terms of frequency, type and size of the abnormalities, even on different regions of the same chromosome. Gains in 3q (36.5%), 5p (23%), 7p (21%), 8q (47%), 11q (45%), 20q (31%) and losses in 3p (37%), 8p (18%), 9p (10%) and 18q (11%) were the most common observations among those studies. However, losses are less frequent than gains but it appears that they might be the primary clonal events in causing oral cancer.
Novel MDM2 splice variants identified from oral squamous cell carcinoma

Sam KK, Gan CP, Yee PS, Chong CE, Lim KP, Karen-Ng LP, et al.

Oral Oncol, 2012 Nov;48(11):1128-35.
PMID: 22705356 DOI: 10.1016/j.oraloncology.2012.05.016

The presence of a variety of MDM2 splice variants has been reported in a range of different tumor types and is associated with poor patient prognosis. Furthermore, several MDM2 variants have been shown to have oncogenic properties. Despite this, MDM2 splice variants have not been comprehensively characterized in oral squamous cell carcinoma (OSCC).
Validity of the FACT-H&N (v 4.0) among Malaysian oral cancer patients

Doss JG, Thomson WM, Drummond BK, Raja Latifah RJ

Oral Oncol, 2011 Jul;47(7):648-52.
PMID: 21602094 DOI: 10.1016/j.oraloncology.2011.04.023

To assess the cross-sectional construct validity of the Malay-translated and cross-culturally adapted FACT-H&N (v 4.0) for discriminative use in a sample of Malaysian oral cancer patients. A cross-sectional study of adults newly diagnosed with oral cancer. HRQOL data were collected using the FACT-H&N (v 4.0), a global question and a supplementary set of eight questions ('MAQ') obtained earlier in pilot work. Of the 76 participants (61.8% female; 23.7% younger than 50), most (96.1%) had oral squamous cell carcinoma; two-thirds were in Stages III or IV. At baseline, patients' mean FACT summary (FACT-G, FACT-H&N, FACT-H&N TOI, and FHNSI) and subscale (pwb, swb, ewb, fwb, and hnsc) scores were towards the higher end of the range. Equal proportions (36.8%) rated their overall HRQOL as 'good' or 'average'; fewer than one-quarter rated it as 'poor', and only two as 'very good'. All six FACT summary and most subscales had moderate-to-good internal consistency. For all summary scales, those with 'very poor/poor' self-rated HRQOL differed significantly from the 'good/very good' group. All FACT summary scales correlated strongly (r>0.75). Summary scales showed convergent validity (r>0.90) but little discriminant validity. The discriminant validity of the FHNSI improved with the addition of the MAQ. The FACT-H&N summary scales and most subscales demonstrated acceptable cross-sectional construct validity, reliability and discriminative ability, and thus appear appropriate for further use among Malaysian oral cancer patients.
Microsatellite instability and loss of heterozygosity in oral squamous cell carcinoma in Malaysian population

Ashazila MJ, Kannan TP, Venkatesh RN, Hoh BP

Oral Oncol, 2011 May;47(5):358-64.
PMID: 21450513 DOI: 10.1016/j.oraloncology.2011.03.005

Loss of heterozygosity (LOH) and microsatellite instability (MSI) have been documented as important events in oral squamous cell carcinoma (OSCC). Five microsatellite markers D3S192, D3S966, D3S647, D3S1228 and D3S659 were selected on chromosome 3p because of high frequency of alterations reported in head and neck squamous cell carcinoma and the involvement of von Hippel Lindau (VHL) at 3p25-26 and the fragile histidine triad (FHIT) at 3p14.2 genes proven in many tumour types. A total of 50 archival tissue samples of OSCC and corresponding normal samples were analyzed for LOH and MSI status. The overall LOH for the markers selected on 3p was 56 out of 189 informative cases (29.6%). The most frequent LOH was identified for the marker D3S966 which was 18/42 (42.8%) of informative cases suggesting the presence of putative tumour suppressor genes (TSGs) in this loci. In this study, high frequency of microsatellite instability was found in D3S966 which was 28.6% of informative cases; this reveals the possibility of mutations of MMR genes in this region. Frequent microsatellite alterations (MA) were observed in 3 markers D3S966 (71.4%), D3S1228 (56.7%) and D3S192 (41.0%). There was no significant association between LOH with gender, tumour stages and differentiation grades. However, there was a significant association between tumour stage and differentiation grades with MSI status in OSCC in Malaysian population with p values of 0.002 and 0.035, respectively. There was also a significant association between MA and differentiation grades (p=0.041).
Transcriptional profiling of oral squamous cell carcinoma using formalin-fixed paraffin-embedded samples

Saleh A, Zain RB, Hussaini H, Ng F, Tanavde V, Hamid S, et al.

Oral Oncol, 2010 May;46(5):379-86.
PMID: 20371203 DOI: 10.1016/j.oraloncology.2010.02.022

Despite the advances in cancer treatment, the 5-year survival rate for oral cancer has not changed significantly for the past 40 years and still remains among the worst of all anatomic sites. Gene expression microarrays have been used successfully in the identification of genetic alterations in cancer development, however, these have hitherto been limited by the need for specimens with good quality intact RNA. Here, we demonstrated the use of formalin-fixed paraffin-embedded tissues in microarray experiments to identify genes differentially expressed between cancerous and normal oral tissues. Forty-three tissue samples were macrodissected and gene expression analyses were conducted using the Illumina DASL assay. We report RNA yield of 2.4 and 0.8 microg/mm(3) from tumour and normal tissues, respectively and this correlated directly with the tissue volume used for RNA extraction. Using unsupervised hierarchical clustering, distinct gene expression profiles for tumour and normal samples could be generated, and differentially expressed genes could be identified. The majority of these genes were involved in regulation of apoptosis and cell cycle, metastasis and cell adhesion including BCL2A1, BIRC5, MMP1, MMP9 and ITGB4. Representative genes were further validated in independent samples suggesting that these genes may be directly associated with oral cancer development. The ability to conduct microarrays on formalin-fixed paraffin-embedded specimens represents a significant advancement that could open up avenues for finding genes that could be used as prognostication and predictive tools for cancer.
Posttraumatic growth: a novel concept in oral cavity cancer care?

Rajandram RK, Jenewein J, McGrath CP, Zwahlen RA

Oral Oncol, 2010 Nov;46(11):791-4.
PMID: 20850373 DOI: 10.1016/j.oraloncology.2010.08.010

Recently the importance of posttraumatic growth (PTG), a phenomenon of positive psychological growth beyond baseline values, has been discovered in the field of oncology. An evidence based review of the literature regarding PTG was performed, both to support its understanding and to consider its application within the research field of oral cavity (OC) cancer. A Pubmed, Medline, PsycINFO search from the earliest date until April 2010 was carried out. Full articles meeting the inclusion and exclusion criteria were reviewed. The search yielded 852 papers, 91 'potentially relevant papers' and 29 'effective papers', the latter of which formed the basis of this review. PTG was assessed in twenty-eight studies with the Posttraumatic Growth Inventory and in only one study with the Perceived Benefits Scale (PBS). PTG in cancer patients has been reported in five main domains (i) appreciation of life, (ii) relating to others, (iii) increased personal sense, (iv) sense of new possibilities and (v) positive spiritual change. Socio-demographic factors, stressor characteristics and coping strategies influence and predict the development PTG. In the past decade an increasing interest in the concept of PTG in the field of oncology has emerged. This evidence based review presents PTG to the research community in the field of OC cancer, appraises its modification capacity of the treatment outcome in other cancer research fields and hypothesizes its eventual benefit in the field of OC cancer research.
MDM2 SNP309 does not confer an increased risk to oral squamous cell carcinoma but may modulate the age of disease onset

Hamid S, Yang YH, Peng KN, Ismail SM, Zain RB, Lim KP, et al.

Oral Oncol, 2009 Jun;45(6):496-500.
PMID: 18804411 DOI: 10.1016/j.oraloncology.2008.06.003

The MDM2 SNP309 has been associated with increased expression of the protein which could suppress p53 function, and has been shown to modulate risk to cancer. We have previously shown that overexpression of MDM2 is a common event in oral cancers. In the present study, we determined the association between the MDM2 SNP309 polymorphism and oral cancer in 207 oral cancer patients and 116 normal subjects. We genotyped the MDM2 SNP309 by PCR-RFLP. Logistic regression was adapted to calculate odds ratios for MDM2 SNP309 polymorphism from univariate and multivariable adjusted models. Our results suggest that MDM2 SNP309 does not confer increased risk to oral cancer (OR=1.55, 95% CI=0.77-3.11). However, the GG/TG genotype was associated with later disease onset in women above 55 years of age. Collectively, our data suggests that MDM2 SNP309 may modulate the risk to oral cancer and is a modifier of the age at oral cancer onset in women above the age of 55 years.
Gene expression in human oral squamous cell carcinoma is influenced by risk factor exposure

Cheong SC, Chandramouli GV, Saleh A, Zain RB, Lau SH, Sivakumaren S, et al.

Oral Oncol, 2009 Aug;45(8):712-9.
PMID: 19147396 DOI: 10.1016/j.oraloncology.2008.11.002

Oral squamous cell carcinoma (OSCC) is a world health problem and is associated with exposure to different risk factors. In the west, smoking and alcohol consumption are considered to be the main risk factors whilst in India and southeast Asia, betel quid (BQ) chewing is predominant. In this study, we compared the gene expression patterns of oral cancers associated with BQ chewing to those caused by smoking using Affymetrix microarrays. We found that 281 genes were differentially expressed between OSCC and normal oral mucosa regardless of aetiological factors including MMP1, PLAU, MAGE-D4, GNA12, IFITM3 and NMU. Further, we identified 168 genes that were differentially expressed between the BQ and smoking groups including CXCL-9, TMPRSS2, CA12 and RNF24. The expression of these genes was validated using qPCR using independent tissue samples. The results demonstrate that whilst common genes/pathways contribute to the development of oral cancer, there are also other gene expression changes that are specific to certain risk factors. The findings suggest that different carcinogens activate or inhibit specific pathways during cancer development and progression. These unique gene expression profiles should be taken into consideration when developing biomarkers for future use in prognostic or therapeutic applications.
Cultural and dietary risk factors of oral cancer and precancer--a brief overview

Zain RB

Oral Oncol, 2001 Apr;37(3):205-10.
PMID: 11287272

This is an update on cultural and dietary risk factors for oral precancer and cancer. It is an overview on ethnic differences (where possible) and socio-cultural risk factors (tobacco/areca nut/betel quid, alcohol use and dietary factors) in relation to oral precancer and cancer. While studies were from Western countries, India and China, this update also attempts to include and highlight some studies conducted in the Asia-Pacific region.
Clinical interpretation of findings from a systematic review and a comprehensive meta-analysis on clinicopathological and prognostic characteristics of oral squamous cell carcinomas (OSCC) arising in patients with oral lichen planus (OLP)

Jayaraj R, Shetty SS, Kumaraswamy C, Gothandam KM, Ram MR, Shaw P

Oral Oncol, 2020 09;108:104974.
PMID: 32798186 DOI: 10.1016/j.oraloncology.2020.104974
Clinical comments on prognostic and clinicopathological significance of PD-L1 overexpression in oral squamous cell carcinoma (OSCC)

Jayaraj R, Shetty S, Kumaraswamy C, Raghul S, Gothandam KM, Raymond G, et al.

Oral Oncol, 2020 Dec;111:104886.
PMID: 32684328 DOI: 10.1016/j.oraloncology.2020.104886
Fulltext Diagnostic implications of miRNAs in Liquid Biopsy for Oral Squamous Cell Carcinoma (OSCC): Clinical validity and interpretation

Jayaraj R, Kumaraswamy C, Raymond G, Ravishankar Ram M, Govind SK, Chandramoorthy HC, et al.

Oral Oncol, 2020 10;109:104634.
PMID: 32171663 DOI: 10.1016/j.oraloncology.2020.104634
Fulltext Clinical validity of clinicopathological and prognostic significance of circulating tumor cells in head and neck squamous cell carcinoma

Jayaraj R, Shetty S, Kumaraswamy C, Raymond G, Ram M R, Govind SK, et al.

Oral Oncol, 2020 10;109:104727.
PMID: 32327312 DOI: 10.1016/j.oraloncology.2020.104727
Fulltext Clinical approaches to interpreting the findings of systematic review and meta-analysis of the effectiveness of probiotics in the prevention and treatment of Cancer Therapy-Induced Oral Mucositis (CTIOM)

Jayaraj R, Kumaraswamy C, Shetty S, Raymond G, Ram M R, Govind SK, et al.

Oral Oncol, 2020 05;104:104622.
PMID: 32115371 DOI: 10.1016/j.oraloncology.2020.104622
Fulltext Clinical validity and conceptual interpretation of systematic review and meta-analysis on elective neck dissection (END) versus observation for early-stage oral squamous cell carcinoma (OSCC)

Jayaraj R, Shetty S, Kumaraswamy C, Raymond G, Ram M R, Govind SK, et al.

Oral Oncol, 2020 10;109:104764.
PMID: 32402654 DOI: 10.1016/j.oraloncology.2020.104764
Accelerated implementation of teleconsultation services for the monitoring of oral potentially malignant disorders as a result of the COVID-19 pandemic

Rajendran S, Mohamad Zaini Z, Lim YZ, Kallarakkal TG, Ramanathan A, Chan SW, et al.

Oral Oncol, 2022 Feb 14;126:105730.
PMID: 35176655 DOI: 10.1016/j.oraloncology.2022.105730
Humidification mitigates acute mucosal toxicity during radiotherapy when factoring volumetric parameters. Trans Tasman Radiation Oncology Group (TROG) RadioHUM 07.03 substudy

Macann A, Fauzi F, Simpson J, Sasso G, Krawitz H, Fraser-Browne C, et al.

Oral Oncol, 2017 12;75:75-80.
PMID: 29224827 DOI: 10.1016/j.oraloncology.2017.10.021

PURPOSE/OBJECTIVE(S): To model in a subset of patients from TROG 07.03 managed at a single site the association between domiciliary based humidification use and mucositis symptom burden during radiotherapy (RT) for head and neck cancer (HNC) when factoring in volumetric radiotherapy parameters derived from tumour and normal tissue regions of interest.
MATERIALS/METHODS: From June 2008 through June 2011, 210 patients with HNC receiving RT were randomised to either a control arm or humidification using the Fisher & Paykel Healthcare MR880 humidifier. This subset analysis involves patients recruited from Auckland City Hospital treated with a prescribed dose of ≥70 Gy. Regression models included control variables for Planning Target Volume 70 GY (PTV70Gy); Equivalent Uniform Dose (EUD) MOIST and TSV (surrogates of total mucosal and total swallowing volumes respectively).
RESULTS: The analysis included 39 patients (humidification 20, control 19). There was a significant odds reduction in CTCAE v3.0 functional mucositis score of 0.29 associated with the use of humidification (p
Fulltext Consensus recommendations for management of head and neck cancer in Asian countries: a review of international guidelines

D'cruz A, Lin T, Anand AK, Atmakusuma D, Calaguas MJ, Chitapanarux I, et al.

Oral Oncol, 2013 Sep;49(9):872-877.
PMID: 23830839 DOI: 10.1016/j.oraloncology.2013.05.010

Head and neck cancer (HNC) is a disease of the upper aerodigestive tract and is one of the most frequently diagnosed cancers worldwide. A high rate of cancers involving the head and neck are reported across the Asian region, with notable variations between countries. Disease prognosis is largely dependent on tumor stage and site. Patients with early stage disease have a 60-95% chance of cure with local therapy. Early diagnosis and appropriate treatment are important to increase the likelihood of cure and survival. However, the majority of patients present with locally advanced disease and require multimodality treatment. This necessitates, a multidisciplinary approach which is essential to make appropriate treatment decisions, particularly with regards to tolerability, costs, available infrastructure and quality of life issues. Unfortunately, majority of the studies that dictate current practice have been developed in the west where diseases biology, patient population and available infrastructure are very different from those in the Asian continent. With this in mind an expert panel of Head and Neck Oncologists was convened in May 2012 to review the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO) clinical practice guidelines and develop practical recommendations on the applicability of these guidelines on the management of head and neck cancer for Asian patients. The objective of this review and consensus meeting was to suggest revisions, to account for potential differences in demographics and resources, to the NCCN and ESMO guidelines, to better reflect current clinical management of head and neck cancer within the Asian region for health care providers. These recommendations, which reflect best clinical practice within Asia, are expected to benefit practitioners when making decisions regarding optimal treatment strategies for their patients.

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