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HPV and Squamous Cell Carcinoma of the Bladder - Expert Commentary

Squamous cell carcinoma represents 5% of lower urinary tract tumors in the U.S. Several factors are linked to squamous cell carcinoma of the bladder (BSCC), such as Schistosoma infection, recurrent urinary tract infections (UTIs), bladder calculi, pelvic radiation, antecedent intravesical Bacillus Calmette-Guérin (BCG), and indwelling catheters. Human papillomavirus (HPV) is also known to contribute to SCC, but there has been limited data on the association between HPV and advanced BSCC (aBSCC). Ghelani et al. conducted a retrospective study to determine whether patient outcomes correlated with HPV status.

Of 171 patients with aBSCC, 160 were negative for HPV, and 11 were positive for HPV. HPV positivity was more frequent in women and younger patients. There were fewer genomic alterations in HPV-positive aBSCC tumor samples than in HPV-negative samples (p < 0.0001). HPV-positive samples exhibited more inactivating alterations in RB1 (p = 0.032) and fewer inactivating alterations in CDKN2A (p < 0.0001), CDKN2B (p = 0.05), TERT promoter (p = 0.0004), and TP53 (p < 0.0001) compared to HPV-negative samples. Whereas 28% of HPV-negative aBSCC samples exhibited MTAP loss, it was not present in any of the HPV-positive samples (p < 0.0001). Expression of treatment-related biomarkers and PD-L1 and genomic alterations in FGFR2 and FGFR3 were similar in both groups.

Molecular findings associated with HPV status can help guide treatment decisions for patients with aBSCC. Understanding the mechanisms by which HPV viral infections influence the biology of bladder cancer and squamous differentiation is an important area for investigation.

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

References:

  1. Ghelani GH, Zerdan MB, Jacob J, et al. HPV-positive clinically advanced squamous cell carcinoma of the urinary bladder (aBSCC): A comprehensive genomic profiling (CGP) study [published online ahead of print, 2023 Oct 9]. Urol Oncol. 2023;S1078-1439(23)00298-3. doi:10.1016/j.urolonc.2023.09.001

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