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

Abstract

Squamous cell carcinoma of the urinary bladder is unusual and of unknown etiology. There is a wellestablished association between human papillomavirus (HPV) infection and the development of cervical and head/neck squamous cell carcinomas. However, the role of HPV in the pathogenesis of squamous cell carcinoma of the urinary bladder is uncertain. The purposes of this study were to investigate the possible role of HPV in the development of squamous cell carcinoma of the urinary bladder and to determine if p16 expression could serve as a surrogate marker for HPV in this malignancy. In all, 42 cases of squamous cell carcinoma of the urinary bladder and 27 cases of urothelial carcinoma with squamous differentiation were investigated. HPV infection was analyzed by both in situ hybridization at the DNA level and immunohistochemistry at the protein level. p16 protein expression was analyzed by immunohistochemistry. HPV DNA and protein were not detected in 42 cases of squamous cell carcinoma (0%, 0/42) or 27 cases of urothelial carcinoma with squamous differentiation (0%, 0/15). p16 expression was detected in 13 cases (31%, 13/42) of squamous cell carcinoma and 9 cases (33%, 9/27) of urothelial carcinoma with squamous differentiation. There was no correlation between p16 expression and the presence of HPV infection in squamous cell carcinoma of the bladder or urothelial carcinoma with squamous differentiation. Our data suggest that HPV does not play a role in the development of squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation. p16 expression should not be used as a surrogate marker for evidence of HVP infection in either squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation as neither HVP DNA nor protein is detectable in these neoplasms.

Human Papillomavirus is Not an Etiologic Agent of Urothelial Inverted Papillomas

“…30 These findings in squamous cell carcinoma are FIGURE 1. Inverted papilloma of the urinary bladder.…”

“…Our work and a growing body of evidence indicate that HPV plays little to no etiologic role in neoplastic processes of the urinary bladder. 17,18,22,[30][31][32] The cell cycle protein p16 is critical in the pathogenesis of HPV-induced carcinoma of the uterine cervix or oropharynx. The normal inhibition of p16 by the retinoblastoma tumor suppressor gene (RB) is reversed by high-risk HPV early genes.…”

P16INK4aImmunostaining but Lack of Human Papilloma Virus Type 16 in Cutaneous Squamous Cell Carcinoma and Basal Cell Carcinoma: a Report from West Iran

“…HPV-DNA and protein were not detected in 42 cases of SCC of the urinary bladder (0%) or 27 cases of urothelial carcinoma with squamous differentiation (0%). There was no correlation between p16 expression and the presence of HPV infection in SCC of the bladder or urothelial carcinoma with squamous differentiation (Alexander et al, 2012). P16INK4A IHC seems to be a superior marker for the detection of HPV-associated penile SCC compared to in-situ hybridization (Aumayr et al, 2013).…”

“…In a number of studies, p16 overexpression was observed in SCC patients (30-35%) (Alexander et al, 2012;Zhu et al, 2015), gastric carcinomas (0%) ( Bashir et al, 2010), esophageal SCC (22%) (Kumar et al, 2015), oral SCC (86.66%) (Patil et al, 2014), head and neck SCCs (56%) (Klussmann et al, 2003), oropharyngeal SCC (78%) (Lewis et al, 2011), BCC (94.3%) (Paolini et al, 2011), and urothelial carcinoma with squamous differentiation (33%) (Alexander et al, 2012. One study (Conscience et al, 2006), reported that p16 overexpression was significantly observed in 58% of cutaneous carcinomas (SCC:60% and BCC:50%) versus 0% of normal human skin.…”

Low prevalence of HPV detection and genotyping in non-muscle invasive bladder cancer using single-step PCR followed by reverse line blot

“…Furthermore, high-risk HPV has been suggested to contribute to malignant progression in head and neck, lung, breast and also bladder cancer [1]. Various epidemiological studies evaluated the relationship between HPV infection and bladder cancer with controversial results regarding HPV prevalence between 0 and 60 % [2][3][4]. A recent meta-analysis included 2855 cases of bladder cancer confirming that the HPV incidence varied by region (highest rate in Asia), types of HPV-DNA specimen (higher in fresh samples than in fixed tissues) as well as PCR primers used [5].…”