Objectives. The prevalence of human papillomavirus deoxyribonucleic ac
id (DNA) in primary squamous cell carcinoma of the male urethra and co
rresponding control tissue was studied. Methods. The technique of poly
merase chain reaction DNA amplification was used to detect specific hu
man papillomavirus DNA sequences in archival pathologic and control ti
ssue. We analyzed 16 cases of primary squamous cell carcinoma of the m
ale urethra and 22 specimens of normal male urethra stratified by loca
tion within the urethra. Results. Primary squamous cell carcinoma of t
he pendulous urethra was significantly associated with human papilloma
virus type 16 DNA (6 of 6 cases), but the control tissue from the pend
ulous urethra was not (0 of 12, P<0.001). Primary squamous cell carcin
oma of the bulbous and posterior urethra was not associated with human
papillomavirus infection. Conclusions. Infection of the male urethra
with human papillomavirus type 16 may have a role in the pathogenesis
of primary squamous cell carcinoma of the pendulous urethra, for which
it has a strong predilection, vis-a-vis the bulbous and posterior ure
thra.