Role of Human Papillomaviruses (HPV) in Penile Carcinoma among Patients from the Indian Subcontinent

This study looked at the role of HPV in penile carcinoma and the types associated with this malignancy in men from the Indian subcontinent. This study also attempted to assess the presence of HPV in asymptomatic men to assess the baseline prevalence in this population. We also looked at alternate or HPV independent mechanisms in the causation of penile cancer. The major results from this study are: ➤ Human papillomavirus was not associated with penile carcinoma (squamous cell type) in men from the Indian subcontinent. ➤ Despite an earlier report of 40% HPV positivity in Indian men with penile carcinoma, only 1.42% of our study subjects with penile carcinoma showed HPV positivity. ➤ The only histological type of penile carcinoma in this study was squamous cell type. ➤ HPV 16 and HPV 18 were the types detected in the two positive HPV DNA biopsy specimens taken from the primary tumour. ➤ This is the first Indian study that has looked at mRNA transcripts of E6/E7 by real time PCR. HPV 18 mRNA transcript was detected and quantified by this assay in a single biopsy specimen. ➤ In lieu of low HPV positivity, role of mRNA viral load as a prognostic marker could not be assessed. Also, its role across the three stages of cancer could not be ascertained. ➤ In asymptomatic men, the HPV DNA was detected in 8.6% using the PGMY09/11 primers suggesting that HPV is a common STI in men in this geographic region. Risk factors like circumcision, smoking and phimosis were also analysed. We did not find any significant correlation between any of these risk factors and asymptomatic men. ➤ The HPV types detected in decreasing order of frequency were HPV16, HPV 31, HPV 68, HPV 42, HPV 55, HPV 51, HPV 52, HPV 58, HPV 66, HPV 69 and HPV 73. ➤ Gene expression analysis of p53, BAX, BCl-2, p21, p16, EGFR, PTEN and HER-4 were studied by real time PCR to study candidate genes and their dysregulation in penile carcinoma for the first time in India. There was a significant upregulation of all the eight candidate genes studied across the three stages of cancer. ➤ A network map of the eight genes was performed by using online software to establish the relationship among them. p53, BCL-2, EGFR, p21 and p16 were all upregulated in advanced stage of cancer (T3). ➤ HER-4 and PTEN were down regulated across the three stages of the cancer. ➤ A correlation between upregulated cellular genes and nodal involvement and/or metastases could not be established. ➤ Protein expression of the studied candidate genes in the different stages of penile cancer would have shed more light on their role in penile carcinogenesis. CONCLUSION: • In men from the Indian subcontinent with penile cancer, the prevalence of HPV is very low. This may be due to all penile carcinoma biopsy specimens being of squamous cell type. • There is a paucity of basaloid and warty type histology in cases of penile carcinoma from this region. • However, there was a higher prevalence of HPV, including high risk HPV in asymptomatic men in a cross-sectional analysis of them. Long term follow up studies in such individuals are needed. • This study clearly shows that HPV independent molecular mechanisms play a significant role in penile carcinoma in men from the Indian subcontinent