The biological behavior of invasive cervical cancer, a leading cause of cancer related deaths in women is not always predictable. Even when the disease is localized to the cervix, 15-20% patients have recurrences. The present study is designed as a multi-centric one with 4 leading centers-ACTREC/TMC (Navi-Mumbai), ICPO (Noida), NCBS (Bangalore) and RGCB (thiruvananthapuram), to analyze the expression of select markers, which have been shown in isolated studies to be of relevance in the HPV mediated cervical carcinogenesis.
Infection with HPV-16 is strongly associated with squamous cell carcinoma of the oropharynx and is detected in approximately 50% of these tumors. In a small study of patients with squamous carcinomas of the head and neck as well as studies of women with cervical cancer, detection of HPV-16 DNA in peripheral blood appears to be a strong predictor of tumor recurrence.
Local-regional relapse after definitive therapy is a major cause of morbidity and mortality in patients with oral squamous cell carcinoma and has prompted substantial efforts in identifying molecular biomarkers that accurately predict patients at risk for disease recurrence.
An altered apoptotic response represents a pivotal feature of cancer, contributing to carcinogenesis and resistance to therapy. Our recent studies demonstrate high expression of Mcl-1, bclxL and bclw transcripts in oral cancer cell lines (Gurav, Dwivedi) and in immortalized fetal buccal mucosa cell line (FBM) using the Ribonuclease Protection assay. In addition 65% of the oral tumor samples examined by RPA assay also exhibited upregulation of Mcl-1(L) transcript which is an anti-apoptotic form.
Defects in cellular apoptosis and proliferation play an important role in tumor pathogenesis allowing neoplastic cells to survive beyond their normal intended lifespan. Our earlier studies indicate an inhibition of cell death, enhancement of proliferation and frequent overexpression of p53, bcl-2 and bax, members of the p53-dependent apoptotic pathway in the transition from oral lesions to oral cancer. The present project proposes to determine the expression pattern of apoptotic genes involved in the intrinsic and extrinsic cell death pathways (Fig.1) (viz.