Human Genetics Unit, Indian Statistical Institute, Kolkata, India.
An inventory of HPV types and estimation of their prevalence across various parts of India among general population are crucial to development of optimal strategies for the prevention of cervical cancer (CaCx) either by HPV screening or vaccination. With the advent of vaccines, which eradicate the most prevalent of the viral types, HPV 16 and 18, it is speculated that the association between HPV infection and CaCx is likely to fall apart. However, the question that needs to be addressed is, will the generic drugs/vaccines that have been tried and tested on viral isolates found in western countries be as effective in India as well? India is socioculturally and genetically diverse. Therefore, the nature of host pathogen interaction across the various populations is likely to vary with an impact on HPV prevalence and CaCx development. It is planned to discuss some of our findings on the prevalence of HPV and HPV16/18 infections overall or age -related among cytologically normal women from four grossly different states, two from the north-east (Manipur and Sikkim) where ethnic populations prevail, West Bengal in the east and Chattisgarh in central India. The latter state harbors a pool of tribal populations. Besides, some interesting findings on HPV prevalence patterns within the two major religious groups, Hindus and Muslims in West Bengal, will also be discussed. Focus will then be shifted on HPV16 intratype variations observed among such isolates within CaCx cases and controls drawn from the general populations. A number of viral genes are likely to act in concert to evade the immune system (E2, L2, L1) and then to jeopardize the cell cycle regulation (E4, E5, E6, E7) causing cellular transformation. Thus sequence variations (common or rare) within biologically relevant regions of the HPV16 isolates, either singly or within the common haplotype background, might influence the causal pathway of CaCx development. Two evolutionary distinct HPV16 subtypes were identified viz. Asian- American (AA) and European (E) on the basis of sequence diversity considering all variations of frequency > 0.05. Within the highly prevalent E subtype, one particular haplotype (E-1) seemed to be most prominent both among cases and controls, justifiably being the oldest haplotype. Similar analysis of the controls revealed that the E-1 haplotype was shared amongst subjects from all the four states. Thus population sub-structure within our country does not seem to affect the prevalence of viral subtypes. Hence a common vaccine is likely to be substantial for our population to combat HPV16, though with a number of variations from the reference haplotype chiefly involving the E2 and L2 regions, apart from few changes E5, E6 and L1 within ORFs and LCR of HPV16 genome. However, it remains to be ascertained whether the vaccines available in the market would effectively work wonders.
