One of the most common malignancies, especially in developing countries, is transitional cell carcinoma of the bladder. Several chemical agents have been suspected to have a role in its development. HPV plays an etiological role for genital tumors, but the exact effect of this virus in transitional cell carcinoma of bladder is still vague. More than a decade ago, a report of HPV-16 positive bladder carcinoma in a patient with attenuated natural killer cell function and aplastic anemia was published . In the same year, another paper briefed a transplant patient with bladder tumor in whom HPV 11 was detected . Agliano and colleagues investigated the presence of HPV types 16 and 18 DNA in formalin-fixed, paraffin-embedded tissues from the urinary bladder (46 transitional cell carcinomas and 10 non-neoplastic normal urinary samples) of non-immune deficient cases. HPV16 and/or HPV18 genomes were detected in 23 of 46 (50%) bladder carcinomas and in none of 10 (0%) non-neoplastic urinary samples. In 1995, Kamel et al. analyzed 47 bladder carcinomas for the presence of DNA-HPV subtypes 6, 11, 16, 18, 31 and 33 by nucleic acid in situ hybridization. HPV DNA was found in 27/47 (57%) bladder carcinomas, with multiple subtypes in 20 cases (76). To our knowledge, our study has one of the largest control groups of non-neoplastic bladder tissue specimens. The high prevalence of HPV infection in the present study demonstrates an association between HPV and TCC of the bladder.
Human papillomavirus seems to be related to the etiology of bladder tumor because of its high prevalence in samples obtained from bladder tumors in the present study and some previous researches. Our study demonstrated HPV-positivity rate in 35.6% of cases and 5% of controls. It seems that carcinoma development may be triggered by HPV infection. Inactivation of the tumor suppressor pRB by the human papillomavirus (HPV) oncoprotein E7 is a mechanism by which HPV promotes cell growth . Human papillomavirus type 16 proteins, E6 and E7, have been shown to cause centrosome amplification and lagging chromosomes during mitosis, leading to chromosomal instability. Genomic instability is thought to be an essential part of the conversion of a normal cell to a cancer cell  Kamel and colleagues demonstrated concurrent HPV positivity and abnormal p53 protein accumulation in 18 out of 47 cases, 14 showing the presence of HPV subtypes 16 and/or 18 DNA. In our study, HPV 18 was the most frequent type(81%) requiring more specific epidemiologic studies and experimental investigations.
HPV may have a great role in progression of TCCs toward higher stages and/or grades by inactivation of the tumor suppressors or other unknown mechanisms.
Larue et al. reported that sensitivity of detection of HPV is largely dependent on a series of technical factors such as tissue fixation, DNA preparation and amplification conditions. In their study, presence of HPV correlated with grade but not stage of the tumors. . Our specimens were formalin-fixed, paraffin-embedded tissues from the urinary bladder. Using fresh or frozen tumor material will probably increase the sensitivity. The high incidence demonstrated in the present study might be higher if fresh specimens were available and used in order to overcome the probability of qualitative loss of DNA in the material.
High rate of HPV positivity in present study suggests that other sexually transmissible viruses may play some roles in development and progression of transitional cell carcinoma of the bladder. As Gazzaniga et al demonstrated, there may be a high synergism between Human Papillomaviruses type 16 and 18 (HPV 16, HPV 18), Epstein-Barr virus (EBV), cytomegalovirus (CMV) and herpes simplex virus type 2 (HSV-2) and bladder carcinogenesis. In this regard, further investigation with a large number of patients sounds to be required.
On the basis of high rate of HPV positivity in TCC cases (35.6%), comparing with control group(5%), the present report supports an etiologic role of HPV in bladder carcinogenesis.