HPV-16 variant analysis of E6, E7, L1 genes and long control region in cervical cancer patients from North India

Abstract

High risk human papillomaviruses particularly, HPV types 16 and 18 play a cardinal role in the aetiology of cervical cancer. The most prevalent HPV type 16 shows intratypic sequence variants which are known to differ in oncogenic potential and geographic distribution. This study is designed to analyze sequence variations in E6, E7, L1 and LCR regions of HPV 16 in cervical cancer patients to identify most prevalent and novel HPV 16 variants and to correlate them with the severity of the disease. Cervical biopsies from sixty HPV16 positive cancer cases were analyzed by PCR and DNA sequencing. The most frequently observed variations were T350G (100%) in E6, T789C (87.5%) in E7, A6695C (54.5%) in L1 and G7521A (91.1%) in LCR. In addition, only one novel variant (T527A) in E6 and four new variants each in L1 (A6667C, A6691G, C6906T, A6924C) and in LCR (C13T, A7636C, C7678T, G7799A) were identified. While E7 was found to be highly conserved, the variant 350G of E6 was most prevalent in all the histopathological grades. Majority of LCR variants were found at the YY1 transcription factor binding sites. Interestingly, a complete absence of Asian Lineage and a high prevalence of European lineages in E6, E7, L1 and LCR (85%, 86.7%, 67.7% and 63.3% respectively) indicate possible epidemiological linkage between Europe and India with regard to the dissemination of HPV 16 infections in India.