Human papillomavirus and non-muscle invasive urothelial bladder cancer: Potential relationship from a pilot study

Abstract

Abstract.The relationship between urothelial bladder cancer and high-risk human papillomaviruses (HR-HPV) is still a poorly understood entity, even if some studies have supposed a probably correlation. The aim of the present study was to assess the potential relationship between the presence of HR-HPV and non-muscle invasive urothelial bladder cancers (NMIBC). One hundred and thirty-seven subjects (78 patients affected by NMIBC and 59 controls) were recruited in this prospective study. HR-HPV DNA was evaluated both in urine and tumour tissues. Data from patients were compared with data from controls. The relationship between patients and controls, in terms of HR-HPV presence was performed. The relationship between all pathological data and HR-HPV presence in patient group was carried out. HR-HPV DNA in tissue was found in 27 of 78 (34.6%) tumour samples and in 6 of 59 (10.1%) specimens from TUR-P, with a statistically significant difference (p=0.0009; dF=1; 2 =10.98). HR-HPV DNA in urine was found in 36 of 78 (46.1%) samples obtained from patients, whereas in only 8 of 59 (13.5%) samples from controls (p<0.0001: dF=1; 2 =16.37). A statistical significant difference in terms of HR-HPV frequency between high-grade and low-grade urothelial bladder cancer, was found (p=0.032; RR=0.52 -95% CI 0.27-0.93; OR=0.34 -95% CI 0.13-0.90). In conclusion, this study highlights the correlation between urothelial bladder cancer and high-risk type HPV infection, suggesting the potential etiopathogenetic role of HR-HPV in urothelial bladder cancer development. IntroductionApproximately 67,160 new bladder cancer cases are expected in the United States in 2007 with 13,750 estimated deaths (1).Moreover, the high recurrence rate and the percentage of adjuvant intravesical therapy failure contribute to bladder carcinoma becoming a social problem (2). In addition, following aspects of the urothelial bladder carcinoma natural history are partially unknown: i) whether a genetic factor exists which determines its predisposition (although there are several oncogenes involved), ii) which are the major risk factors involved in its genesis preventing us from putting into practice an effective prevention campaign. Among all etiopathogenetic factors and co-factors that contribute to urothelial bladder cancer development, we focused our attention on the role of human papillomavirus (HPV), which has been considered as a possible aetiologic agent (3). HPV is one of the most common sexually transmitted infections worldwide and it is associated with lesions ranging from benign cutaneous warts to malignancies, like cervical, penile or anal cancers (4). About 13 different HPV genotypes are associated with malignancy and are referred to as high-risk HPV (HR-HPV) (5,6). The oncogenic potential of HR-HPV types lies in the oncoproteins E6 and E7, which bind to and modulate a number of different gene products, in particular, the tumour suppressors p53 and pRb. These interactions lead to a disturbance of cell cycle control and a deficiency in DNA repair, res...

p16 expression is not associated with human papillomavirus in urinary bladder squamous cell carcinoma

“…In contrast to our findings and the previously mentioned reports, others have shown a positive correlation between high-risk HPV infection and high-grade urothelial cancers of the bladder. [7][8][9]35,36 Cai et al 37 have proposed that HPV may have a causative role in the genesis of urothelial neoplasms, particularly in nonmuscle-invasive bladder cancer. In our study, we detected p16 expression in 31% (13/42) of cases of urinary bladder squamous cell carcinoma and in 33% (9/27) of cases of urinary bladder urothelial carcinoma with squamous differentiation.…”

Human Papillomavirus is Not an Etiologic Agent of Urothelial Inverted Papillomas

“…The reported findings have been conflicting and inconclusive. [17][18][19][20][21][22] It has also been proposed that HPV may play a role in the development of inverted papilloma, on the basis of detection of HPV strains 16 and 18 in a number of these lesions. 23,24 The primary aim of this study was to examine a relatively large population of urothelial inverted papillomas for the presence of HPV infection using in situ hybridization (ISH) methods to provide more definitive evidence as to the etiologic role HPV may play in urothelial cells.…”

Human papillomavirus detection in Moroccan patients with bladder cancer

“…In contrast, several studies stated that high risk-HPV (HR-HPV) should be considered as cofactor in urothelial bladder cancer. Cai et al have recently found a statistical significant difference in HR-HPV frequency between high-grade and lowgrade urothelial bladder cancer cases [40]. Also, Moonen et al found a higher infection rate in highgrade tumors and stated that the increase in infection rate in high-grade tumors suggests a relationship between tumor grade and high-risk HPV infection [29].…”