Squamous Cell Carcinoma of the Bladder is Not Associated with High-Risk HPV.

To evaluate the clinical features, pathologic features, and prevalence of human papilloma virus (HPV) in squamous cell carcinoma (SCC) of the bladder. SCC of the bladder is known to be associated with conditions that cause chronic inflammation/irritation.

The literature is inconsistent regarding the association of HPV with pure SCC of the bladder.

A multi-institutional study identified cases of SCC of the bladder. Pure squamous histology and the absence of urothelial carcinoma in situ was required for inclusion. Clinical and pathologic features were collected, and tissues were evaluated for high-risk HPV using p16 immunohistochemistry (IHC) and in situ hybridization (ISH).

We identified 207 cases of SCC of the bladder. Risk factors for bladder cancer included smoking (133/207, 64%) and chronic bladder irritation (83/207, 40%). The majority (155/207, 75%) of patients had > pT2 disease. Mean tumor size was 5.6±3.0 cm and 36/207 (17%) patients had lymph node positive disease. p16 IHC was positive in 52/204 (25%) cases but high-risk HPV was identified with ISH in only 1 (0.5%) case. Tumor size, stage, number of lymph nodes removed, number of positive lymph nodes, lymphovascular invasion, perineural invasion, and positive margins each were associated with cancer-specific mortality when adjusted for demographic factors. A multivariate analysis of variable importance further revealed sex and race as important factors in predicting cancer-specific mortality.

SCC of the bladder is an aggressive histologic subtype. Although bladder SCC can express p16, it is not typically associated with high-risk HPV, although rare cases can occur.

Urology. 2020 Jul 15 [Epub ahead of print]

Jennifer Gordetsky, Andrew J Spieker, Maria Del Carmen Rodriguez Pena, Sonia Kamanda, Michele R Anderson, John Cheville, Steve Boorjian, Igor Frank, Carlos Prieto Granada, Eva Comperat, Michelle S Hirsch, Kenneth A Iczkowski, Brittney Imblum, Lauren Schwartz, Giovanna A Giannico, Soroush Rais-Bahrami

Department of Pathology, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Urology, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address: ., Department of Biostatistics, Vanderbilt University, Nashville, TN, USA., Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA., Department of Pathology, Vanderbilt University Medical Center, Nashville, TN, USA., Department of Pathology, Mayo Clinic, Rochester, MN, USA., Department of Urology, Mayo Clinic, Rochester, MN, USA., Department of Pathology, Tenon Hospital, Sorbonne University, Paris, France., Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA., Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, USA., Department of Pathology, University of Pennsylvania, Philadelphia, PA, USA., Department of Urology, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Radiology, University of Alabama at Birmingham, Birmingham, AL, USA; O'Neal Comprehensive Cancer Center at UAB, University of Alabama at Birmingham, Birmingham, AL, USA.

Read an Expert Commentary by Bishoy Faltas, MD

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