Bibhu Ranjan Das

Cyclin D1 overexpression and upregulation has been reported largely in Oral Squamous Cell Carcinoma (OSCC) but the mechanism behind it is not clear. Here, the transcription and translational upregulation of cyclin D1 was observed in most of the tobacco chewing oral cancer patients where as the gene amplification was limited to only small group (20%) of patients. A transcription factor (TF) binding site has been detected from −483 to −451 by using DNase I foot printing analysis and confirmed by electrophoretic mobility shift assay by using oral tumour nuclear extract (NE). This is a STAT binding sequence and confirmed as STAT5a by supershift assay. The binding of STAT5 was observed in 80% (24/30) oral cancer samples. The co-expression of cyclin D1 with STAT5 binding was observed in 90% (27/30) of the samples. STAT family of proteins is emerging to play role in oral carcinogenesis. Here, the binding of STAT5 might up regulate cyclin D1 in most of the samples whereas; the gene amplification events are sporadic in oral carcinogenesis. Our study provides the first evidence of the constitutive activation of STAT5-cyclin D1 pathway in chewing tobacco mediated OSCC.

Background Infection with human papilloma virus (HPV) is an important etiological factor in the development of cervical cancer and it has been proposed that individuals homozygous for Arg/Arg at codon‐72 of p53 are seven times more susceptible to HPV‐mediated cancer. In this study, we have analyzed the genetic predisposition of the India population to HPV infection and cervical carcinogenesis.Methods We investigated 71 cases of squamous cell carcinoma of the cervix, 14 cases of low‐grade squamous intraepithelial lesions, 25 cases of high‐grade squamous intraepithelial lesions and 29 noncancer controls for presence of HPV16/18 infections by L‐1‐specific PCR assay and Southern hybridization, and its association with polymorphism at p53 codon 72.Results We observed that 69·1% (76/110) of the cervical cancer patients were HPV positive, among which the presence of HPV16, 18 and 16/18 coinfection was 40·9%, 8·2% and 13·6%, respectively. The allele frequencies of the three p53 genotypes Arg/Arg, Arg/Pro and Pro/Pro in the HPV‐positive tumour samples were 0·34, 0·57 and 0·09 in comparison with frequencies of 0·18, 0·44 and 0·38 for HPV‐negative tumours. Hence, there is a significant difference in the allelic frequency of p53 Arg/Arg in high‐risk HPV‐infected cervical carcinoma cases (0·34) and HPV‐negative carcinomas (0·18).Conclusion Our results indicate a striking over‐representation of homozygous arginine at codon 72 of p53 in HPV‐associated cervical carcinogenesis. We conclude that women with Arg/Arg homozygous allele are more prone to infection by HPV16/18, which leads to cervical carcinomas having poor prognosis.

The present review is an attempt to summarize the important advances made during the last decade in the molecular approach to oral cancer and its application for early, sensitive diagnosis, effective treatment, and improved prognosis. Cancer of the oral cavity is more prevalent in developing countries, where many people are addicted to tobacco chewing and maintain poor oral hygiene. Despite extensive research on the biological and molecular aspects of oral SCC, the problems of local-regional recurrence and distant metastasis still persist. Among the more pressing problems in clinical management is the lack of early detection, due to the absence of a potential diagnostic marker. Oncologists are now more aware of the challenges associated with the treatment of cancer of the oral cavity, and survival percentages are improving significantly. More trials are need in the area of improved surgical procedures, variations in dosages of radiotherapy, and the use of various combinations of chemotherapeutic agents with minimal side effects. Moreover, progress in the elucidation of the molecular genetic changes that lead to the development of these tumors should soon bring novel diagnostic and therapeutic procedures into clinical practice. The case of ONYX-015 is one example of success, which has shown the great potential in Phase-I and II clinical trials. Finally, the legislator should also impose some restrictions and bans on the easy availability of various forms of tobacco.

Human papillomavirus (HPV) infects the squamous epithelial cells of oral cavity and cervix leading to formation of warts that develops into the cancer. Human papillomavirus (HPV)‐16 and 18 encode E6 oncoprotein, which binds to and induces degradation of the tumour suppressor protein p53. A common polymorphism of p53, encoding either proline (Pro) or arginine (Arg) at position 72, affects the susceptibility of p53 to E6 mediated degradation in vivo. Oral cancer is a pressing problem in India due to the widespread habit of chewing betel quid, which plays an important role in etiology of this disease. In the present study an attempt has been made to analyze the genetic predisposition of the Indian population to HPV infection and oral carcinogenesis. In our study a total of 110 cases of Oral Cancer highly addicted to betel quid and tobacco chewing are analyzed for HPV 16/18 infection and its association with polymorphism at p53 codon 72. Of these a total number of 37 patients (33.6%) have shown the presence of HPV, among which the presence of HPV‐16, 18 and 16/18 coinfection is 22.7%, 14.5% and 10%, respectively. Our results also indicate that the p53 codon 72 genotype frequencies in Indian Oral Cancer patients are 0.55 (Arg) and 0.45 (Pro) as per Hardy‐Weinberg equilibrium. In our study, striking reduction in Pro/Pro allele frequency has been found in HPV positive cases, indicating Arg/Arg genotype to be more susceptible to HPV infection and oral carcinogenesis.