Relationship among human papillomavirus infection, p16INK4a, p53 and NF-κB activation in penile cancer from northern Thailand

Abstract

Abstract. Human papillomavirus (HPV) E6 and E7 oncoproteins are essential factors for HPV oncogenesis. These E6 and E7 gene products play a central role in the induction of malignant transformation by interacting with several cellular regulatory proteins such as p16 INK4a , p53 and nuclear factor κB (NF-κB). In the present study, conducted in northern Thailand, HPV-DNA was detected in penile cancer cases using an in situ hybridization procedure and p16 INK4a , p53 and NF-κB were detected by immunohistochemistry. Using the cell cycle regulatory proteins p16 INK4a (61.5%) and p53 (71.8%), it was found that of the 51 cases, 39 (76.5%) were HPV-DNApositive in penile cancer. On the other hand, 25% p16 INK4a and 75% p53, respectively, were found in HPV-negative cases. Prevalence of HPV infection (76.5%) was shown in penile cancer cases in northern Thailand. No difference was found between HPV-positive and HPV-negative cases with respect to the presence of the cell cycle regulatory protein p53. On the other hand, p16 INK4a was found to be different between HPV-positive and HPV-negative cases. Inactivation of tumor suppressor genes, such as p16 INK4a and p53, to genetic instability, cell immortalization, accumulation of mutations and cancer formation, with or without HPV and irrespective of HPV infection, is therefore suggested. Of the 39 HPV-positive cases, 35 (89.7%) were NF-κB-positive in the nucleus, 29 (74.4%) in the cytoplasm and 37 (94.9%) in the nucleus and/or cytoplasm. NF-κB was detected in 4 (33.3%) of the 12 HPV-negative cases. Therefore, we propose that penile cancer cases with HPV infection are more likely to activate NF-κB than those without HPV infection.

DNA Copy Number Aberrations, and Human Papillomavirus Status in Penile Carcinoma. Clinico-Pathological Correlations and Potential Driver Genes

“…We have provided a detailed characterization of the genetic landscape of prostate cancer by DNA copy number aberrations found in HPV-positive and HPV-negative PSCCs, and demonstrated that these tumors display similar patterns of genetic aberrations despite the distinct pathogenetic mechanisms, with statistically significant changes in only a few small loci. It has been documented that HPV changes cell physiology inactivating RB and p53 pathways [ 28 , 29 ] and our genomic data shows copy number loss at 13q12.11-q34 (80% of HPV positive cases) and 17p13.3-p11.1 (63% of HPV positive cases), harboring RB1 and TP53 genes, respectively. However, these changes were not statistically significant in their difference from the HPV negative cohort.…”

Human papillomavirus infection induces NF-κB activation in cervical cancer: A comparison with penile cancer

“…We demonstrated the correlation between HPV infection and nuclear and/or cytoplasmic NF-κB expression using the Fisher's exact probability test. HPV infection was considered to activate NF-κB resulting in cell transformation (11,12,24).…”

Human Papilloma Virus (HPV) Infection and Non-Cervical Oncogenic Disease States

“…Finally, upregulation of cyclooxygenase (COX-2) expression, implicated in the pathogenesis of cancers at other sites [46,47], has been demonstrated in some specimens [48]. Molecular correlates of disease outcome have been found with p53 expression inversely correlating with regional lymph node metastasis and survival [49] while others have found that p16INK4a allelic loss or promotor hypermethylation and not p53 was associated with negative clinical outcomes [50,51]. (Table 3) Observed survival differences has led to the postulate that HPV-positive and negative tumors represent different clinical entities [34,43].…”