INTRODUCTION — Primary urethral cancer is a rare malignancy in women [1-4]. Unlike other tumors arising in the urinary tract, urethral cancer is more common in women than in men. Differences in anatomy and etiology lead to important differences in the clinical presentation, diagnosis, and treatment of urethral cancer in women compared to men.
The diagnosis and treatment of urethral cancer in women will be reviewed here. Urethral cancer in men is discussed separately. (See “Urethral cancer in men”).
ETIOLOGY AND PATHOGENESIS — Although the etiology of urethral cancer is not well understood, several factors have been associated with its development:
• Transitional cell carcinoma of the proximal urinary tract — Transitional cell carcinoma (TCC) of the urothelium is often multifocal, and similar lesions can develop in the female urethra. Urethral TCC may occur simultaneously with, precede, or follow lesions of the bladder, ureters, or renal pelves.
• Human papillomavirus (HPV) infection — A close association exists between infection with HPV and squamous cancers of the anogenital tract, including cancers of the cervix and anus. (See “Virology of human papillomavirus infections and the link to cancer”, see “Anal squamous intraepithelial lesions (ASIL): Diagnosis, screening, and treatment”, section on HPV infection and see “Cervical intraepithelial neoplasia: Etiology, diagnosis, and natural history”, section on Human papillomavirus infection).
HPV also appears to play a role in causing female urethral cancer. This was illustrated by a series in which HPV was identified in tumors from 11 of 18 patients (61 percent) [5]. HPV 16, which has been causally linked to cervical and anal cancers, was present in 9 of the 11 cases.
• Urethral diverticuli — Cancers can arise in urethral diverticuli. Most typically, these have been clear cell carcinomas, although TCCs and squamous cell carcinomas (SCCs) have also been reported [6,7]. Urinary stasis and infection may be contributing factors.
ANATOMY AND PATHOLOGY — The female urethra averages 3 to 4 cm in length. The proximal 30 percent is composed of transitional epithelium, while the distal 70 percent is stratified squamous epithelium

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