Does High-Risk Human Papilloma Virus Play a Role in the Development of Squamous Cell Carcinoma of the Bladder? - Expert Commentary 

Squamous cell carcinoma (SCC) is the second most common histologic variant of bladder cancer. These tumors have pure squamous histology in the absence of any in situ urothelial component and are traditionally associated with conditions that cause chronic inflammation/irritation. A recent study published in Urology investigated the association between bladder SCC and Human Papilloma Virus (HPV).

The investigators included cases of SCC of the bladder. Smoking (133/207, 64%) and chronic bladder irritation (83/207, 40%) were identified as risk factors. The majority of patients had muscle-invasive disease, and 17%) patients had lymph node metastases. The investigators also quantified p16 by IHC was positive in 52/204 (25%) cases. However, there was no association between p16 expression and any clinical outcome measure.

The investigators one case had high-risk HPV when tested with in situ hybridization (ISH), which provides direct evidence of the presence of transcriptionally active HPV. This patient had other risk factors, including a history of n neurogenic bladder secondary to spinal cord injury with a bladder augment, continent catheterizable stoma, and bladder stones.

Oncogenic viruses are detected in a small number of conventional urothelial cancer. The role of HPV in SCC of the cervix is well established. This study suggests no association between HPV and SCC of the bladder. It is possible that more sensitive molecular methods could identify viral DNA integration in a subset of bladder SCC patients.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York


  1. Gordetsky J, Spieker AJ, Pena MDCR, et al."Squamous Cell Carcinoma of the Bladder is Not Associated with High-Risk HPV." Urology. 2020 Jul 15:S0090-4295(20)30832-3. doi: 10.1016/j.urology.2020.06.065. Online ahead of print. PMID: 32681917
Read the Abstract 
email news signup