Lung Cancer Detection by Screening - Presenting Circulating miRNAs as a Promising Next Generation Biomarker Breakthrough

Ramshankar, Vijayalakshmi,Krishnamurthy, Arvind Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.4

Lung cancer remains a major cause of morbidity and mortality worldwide, accounting for more deaths than any other cause. All the clinical practice guidelines recommended against routine screening for lung cancer have cited lack of robust evidence, at least until a few years back. However, the potential to screen lung cancers has received renewed interest due to superior performance of low dose CT (LD-CT) in detecting early stage cancers. The incremental costs and risks involved due to the invasive procedures in the screened population due to a high false positivity rate questions the use of LD-CT scan as a reliable community based screening tool. There is therefore an urgent need to find a less invasive and a more reliable biomarker that is crucial to increase the probability of early lung cancer detection. This can truly make a difference in lung cancer survival and at the same time be more cost and resource utilization effective. Sampling blood serum being minimally invasive, low risk and providing an easy to obtain biofluid, needs to be explored for potential biomarkers. This review discusses the use of circulatory miRNAs that have been able to discriminate lung cancer patients from disease free controls. Several studies conducted recently suggest that circulating miRNAs may have promising future applications for screening and early detection of lung cancer.

Risk Stratification of Early Stage Oral Tongue Cancers Based on HPV Status and p16 Immunoexpression

Ramshankar, Vijayalakshmi,Soundara, Viveka T.,Shyamsundar, Vidyarani,Ramani, Prathiba,Krishnamurthy, Arvind Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.19

Background: Recent epidemiological data have implicated human papilloma virus (HPV) infection in the pathogenesis of head and neck cancers, especially oropharyngeal cancers. Although, HPV has been detected in varied amounts in persons with oral dysplasia, leukoplakias and malignancies, its involvement in oral tongue carcinogenesis remains ambiguous. Materials and Methods: HPV DNA prevalence was assessed by PCR with formalin fixed paraffin embedded sections (n=167) of oral tongue squamous cell carcinoma patients and the physical status of the HPV16 DNA was assessed by qPCR. Immunohistochemistry was conducted for p16 evaluation. Results: We found the HPV prevalence in tongue cancers to be 51.2%, HPV 16 being present in 85.2% of the positive cases. A notable finding was a very poor concordance between HPV 16 DNA and p16 IHC findings (kappa<0.2). Further molecular classification of patients based on HPV16 DNA prevalence and p16 overexpression showed that patients with tumours showing p16 overexpression had increased hazard of death (HR=2.395; p=0.005) and disease recurrence (HR=2.581; p=0.002) irrespective of their HPV 16 DNA status. Conclusions: Our study has brought out several key facets which can potentially redefine our understanding of tongue cancer tumorigenesis. It has emphatically shown p16 overexpression to be a single important prognostic variable in defining a high risk group and depicting a poorer prognosis, thus highlighting the need for its routine assessment in tongue cancers. Another significant finding was a very poor concordance between p16 expression and HPV infection suggesting that p16 expression should possibly not be used as a surrogate marker for HPV infection in tongue cancers. Interestingly, the prognostic significance of p16 overexpression is different from that reported in oropharyngeal cancers. The mechanism of HPV independent p16 over expression in oral tongue cancers is possibly a distinct entity and needs to be further studied.

Use of Fast Transfer Analysis Cartridges for Cervical Sampling and Real Time PCR Based High Risk HPV Testing in Cervical Cancer Prevention - a Feasibility Study from South India

Vijayalakshmi, Ramshankar,Viveka, Thangaraj Soundara,Malliga, JS,Murugan, Kothandaraman,Kanchana, Albert,Arvind, Krishnamurthy Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.14

Background: Molecular testing for human papillomavirus (HPV) is the most objective and reproducible of all cervical cancer screening tests and also less demanding in terms of training and quality assurance. However, there is an impending need for cost effective molecular HPV testing methods with sampling ease, easy storage measures and minimum turn around times suitable for a low resource setting. Objective : Our aim was to evaluate the feasibility of using a fast transfer analysis (FTA) mini elute cartridge for cervical sampling to identify high risk HPV by real time PCR and to compare molecular HPV testing and Pap cytology testing to predict histologically confirmed cervical precancer (CIN 2+ lesions) in a cervical cancer prevention program. Materials and Methods: This was conducted as a pilot study (n=200) on women sampled using FTA mini elute cartridges, genotyped by two different real time PCR assays, detecting 13 high risk HPV (HR HPV) species, including HPV16 along with its physical DNA status. Results obtained from each of the tests were compared and analysed using suitable statistical tests. Results: With FTA mini elute cartridge samples HR HPV positivity was seen in 48/200 (24%). Of these, presence of HPV 16 DNA was observed in 28/48 (58.3%) women. High risk HPV was positive in 20% (37/185) of women with benign cytology and 73.3% (11/15) of women with abnormal cytology findings. A very significant correlation (${\chi}^2=22.090$ ; p=0.000) was observed between cytology and HR HPV findings showing an increasing trend of HR HPV prevalence in 50% (1/2) of LSIL, 75% (3/4) of HSIL and 100% (3/3) of SCC. Of the CIN 2+ lesions identified by histopathology, 88.9% (8/9) had HR HPV. A significant association (${\chi}^2=11.223$ ; p=0.001) of HR HPV and histopathologically confirmed CIN 2+ lesions was found. Sensitivity of the two tests were comparable but specificity of Pap testing was better (90.7% vs 70.4%) to predict histopathologically diagnosed cervical precancers. Conclusions: The current study explored the feasibility of using a FTA mini elute cartridge for cervical sampling for the first time in India as a part of a community based cervical cancer prevention program. We suggest that FTA based sampling is suitable and feasible for real time based HPV testing. Molecular HR HPV testing can be more sensitive and useful to identify high risk women requiring Pap testing which is more specific to detect histologically confirmed cervical precancer.

Early Stage Oral Tongue Cancer among Non-Tobacco Users - An Increasing Trend Observed in a South Indian Patient Population Presenting at a Single Centre

Krishnamurthy, Arvind,Ramshankar, Vijayalakshmi Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.9

Background: Oral tongue squamous cell carcinoma (OTSCC) is the most common cancer diagnosed within the oral cavity worldwide. Many studies in India report OTSCC ranking among the top two most common subsites within the oral cavity. India is often labeled the oral cancer capital of the world. The incidence of tongue cancers in the population-based cancer registry (PBCR) of Chennai is showing an increasing trend. A majority of the oral cavity cancers (85%) in our cancer center present in advanced stages (III and IV). In contrast, early tongue cancers (stages I and II) constitute nearly 45% of all OTSCCs. Aim: The aim of this study was to analyze the clinical profile and epidemiological trends in our early stage tongue cancer patients with an emphasis on tobacco and alcohol habits. Materials and Methods: This retrospective analysis was based on a prospectively collected database of 458 consecutive early stage OTSCC in-patients at a tertiary care oncology centre in Chennai between 1995 and 2008. Results: Our study suggests that the earlier trends have clearly changed whereby nearly half of our patients are now never-tobacco users. The findings of the study indicate that a majority of the patients were never alcohol users (86.4%) and nearly half of them were never tobacco users (49.3%), and they had the best survival outcomes. This increasing trend of OTSCC among non-tobacco users is in contrast to our earlier experience of tongue cancer more than five decades ago.The median age of patients in our study was 53.3 years; the male to female ratio was approximately 2:1. The median follow up for the 458 patients was 53 months. Conclusions: Our study importantly as well as interestingly shows a conspicuous absence of association with the traditional risk factors, tobacco and alcohol.

Preventive and Risk Reduction Strategies for Women at High Risk of Developing Breast Cancer: a Review

Krishnamurthy, Arvind,Soundara, Viveka,Ramshankar, Vijayalakshmi Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.3

Breast cancer is the most commonly diagnosed invasive cancer among women. Many factors, both genetic and non-genetic, determine a woman's risk of developing breast cancer and several breast cancer risk prediction models have been proposed. It is vitally important to risk stratify patients as there are now effective preventive strategies available. All women need to be counseled regarding healthy lifestyle recommendations to decrease breast cancer risk. As such, management of these women requires healthcare professionals to be familiar with additional risk factors so that timely recommendations can be made on surveillance/risk-reducing strategies. Breast cancer risk reduction strategies can be better understood by encouraging the women at risk to participate in clinical trials to test new strategies for decreasing the risk. This article reviews the advances in the identification of women at high risk of developing breast cancer and also reviews the strategies available for breast cancer prevention.

Halloysite Nanotubes (HNTs)-Reinforced Natural Rubber (NR)/Ethylene-Propylene-Diene Monomer (EPDM) Composites

P. Ganeshan,M. S. Ravi Theja,P. Ramshankar,K. Raja 한국고분자학회 2023 폴리머 Vol.47 No.4

Natural rubber/ethylene-propylene-diene monomer (NR/EPDM) rubber blends of composition 75/25 with 0, 2, 4, 6, 8, and 10 phr (parts per hundred rubber) halloysite nanotubes (HNTs) were prepared by two-roll mill. The effect of HNTs on the cure characteristics and mechanical properties of the NR/EPDM nanocomposites were studied. The effect of HNTs loading on the morphological, physical, swelling resistance and compression set of nanocomposites based on NR/EPDM was also investigated. Tensile strength tests revealed that the HNTs-reinforced NR/EPDM composite could resist 84% greater strength to break than the NR/EPDM blend without reinforcement. The introduction of HNTs into the NR/EPDM rubber matrix induced a rough morphology in the fracture surface, and a well-dispersed structure was obtained with the inclusion of up to 8 phr of HNTs, according to the morphological analyses.

p53 Expression Helps Identify High Risk Oral Tongue Premalignant Lesions and Correlates with Patterns of Invasive Tumour Front and Tumour Depth in Oral Tongue Squamous Cell Carcinoma Cases

Viveka, Thangaraj Soundara,Shyamsundar, Vidyarani,Krishnamurthy, Arvind,Ramani, Pratibha,Ramshankar, Vijayalakshmi Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.1

Oral tongue squamous cell carcinoma (OTSCC) is the most common oral cancer subtype with a maximum propensity for regional spread. Our objective was to study if p53 expression might have any correlation with aggressive patterns of invasion within oral tongue cancers as well as with the histologically identified degree of oral tongue dysplasia. p53 immunoexpression was studied using immunohistochemistry in early staged OTSCCs (n=155), oral tongue dysplasias, (n=29) and oral tongue normal specimens (n=10) and evaluated for correlations with histological and clinicopathological parameters. Our study (n=194) showed a pattern of p53 expression increasing with different grades of tongue dysplasia to different grades of invasive OTSCC (p=0.000). Among the OTSCC tumours, positive p53 expression was seen in 43.2% (67/155) and a higher p53 labelling index was significantly associated with increased Bryne's grade of the tumour invasive front (p=0.039) and increased tumour depth (p=0.018). Among the OTSCC patients with tobacco habits, (n=91), a higher p53 labelling index was significantly associated with increased risk of local recurrence (p=0.025) and with lymphovascular space involvement (p=0.014). Evaluation of p53 through varying degrees of dysplasia to oral tongue cancer indicates that p53 expression is linked to aggressive features of oral tongue cancers and tongue precancers entailing a closer monitoring in positive cases. Among the OTSCCs, p53 expression is associated with tumour aggressiveness correlating with increased grading of invasive tumour front and tumour depth.