BackgroundTwo clinically relevant high-risk HPV (HR-HPV) types 16 and 18 are etiologically associated with the development of cervical carcinoma and are also reported to be present in many other carcinomas in extra-genital organ sites. Presence of HPV has been reported in breast carcinoma which is the second most common cancer in India and is showing a fast rising trend in urban population. The two early genes E6 and E7 of HPV type 16 have been shown to immortalize breast epithelial cells in vitro, but the role of HPV infection in breast carcinogenesis is highly controversial. Present study has therefore been undertaken to analyze the prevalence of HPV infection in both breast cancer tissues and blood samples from a large number of Indian women with breast cancer from different geographic regions.MethodsThe presence of all mucosal HPVs and the most common high-risk HPV types 16 and 18 DNA was detected by two different PCR methods - (i) conventional PCR assays using consensus primers (MY09/11, or GP5+/GP6+) or HPV16 E6/E7 primers and (ii) highly sensitive Real-Time PCR. A total of 228 biopsies and corresponding 142 blood samples collected prospectively from 252 patients from four different regions of India with significant socio-cultural, ethnic and demographic variations were tested.ResultsAll biopsies and blood samples of breast cancer patients tested by PCR methods did not show positivity for HPV DNA sequences in conventional PCRs either by MY09/11 or by GP5+/GP6+/HPV16 E6/E7 primers. Further testing of these samples by real time PCR also failed to detect HPV DNA sequences.ConclusionsLack of detection of HPV DNA either in the tumor or in the blood DNA of breast cancer patients by both conventional and real time PCR does not support a role of genital HPV in the pathogenesis of breast cancer in Indian women.

Our previous study showed that p53 protein is accumulated in >60% of cases of oral squamous cell carcinoma (OSCC) and its overexpression is related to poor prognosis. However, the mechanism behind this is still elusive. The present study attempts to dissect p53 alterations at various levels from gene to function in tumor biopsies to understand whether molecular alterations have any relationship with the accumulation of p53 protein in OSCC. Protein-stabilizing mutations were observed in only 13.8% of the samples. Neither p53 polymorphisms nor human papillomavirus (HPV) infection (<2%) has any major role in augmented expression of p53 protein. Analysis of the p53 transcript demonstrated that alteration in the level of p53 mRNA (10%) is not the major mechanistic cause for accumulation of p53 protein, and p21 transcript status showed that the overexpressed p53 protein is functionally inactive. Immunoprecipitation studies demonstrated that the known interactors of p53, such as MDM2 and HSP70, have no significant role in stabilizing p53 and the significant presence of some unknown interactors, sequestering p53, and leading to the aberrant accumulation of p53. Our study suggests that overexpression of inactive p53 protein could be manifested as a result of sequestering from degradation by an unknown interacting protein rather than by gene or transcript level of alteration.