Relationship Between Human Papillomavirus and Penile Cancer

Implications for Prevention and Treatment

Laura C. Kidd; Sharon Chaing; Juan Chipollini; Anna R. Giuliano; Philippe E. Spiess; Pranav Sharma


Transl Androl Urol. 2017;6(5):791-802. 

In This Article

Abstract and Introduction


Penile cancer is a rare disease in the United States, but rates are increasing, causing concern. Several risk factors have been associated with the disease, including human papillomavirus (HPV) infection. Knowledge of HPV pathogenesis has led to the development of a vaccine, which has proven instrumental in reducing the incidence of female HPV-related cancers, but results in men have yet to be elucidated. Fortunately, rates of vaccination are up-trending in both males and females in the past several years. In addition, targeted therapies are the focus of several ongoing research efforts. Some of these therapeutics are currently in use, while several are in trials. With continued patient education and research, both treatment and prevention of HPV-related pre-malignant lesions and penile cancer will likely diminish.


Penile cancer is a rare disease with significant morbidity and mortality when present in the advanced stages of the disease. Its prevalence is highest in the developing countries of Africa, Asia, and South America, and its most common histology is squamous cell carcinoma (SCC).[1,2] The overall incidence in the United States is approximately 0.69 per 100,000 men with incidence associated with increasing age at diagnosis.[3] Traditionally, radical penile and inguinal surgery has been considered the mainstay treatment even though it can carry substantial physical and psychosexual morbidity for those treated. Recently, however, organ-sparing has become a widely accepted approach due to established equivalent oncologic control while achieving satisfactory somatic and sexual health outcomes.[4,5]

The etiology of penile cancer is multifactorial with many risk factors identified including phimosis, poor hygiene, smoking, and chronic inflammatory states such as balanitis xerotica obliterans (BXO).[2] Other risk factors for penile cancer include an increasing number of sexual partners, or history of genital warts or other sexually transmitted diseases. In particular, infection with human papillomavirus (HPV) has been linked to penile cancer carcinogenesis,[6] although exact pathways have not been fully elucidated to date. Nonetheless, the pathogenesis of HPV infection provides an actionable target for newer therapeutic agents to treat this rare and disfiguring disease. In this review, we provide a thorough update on the epidemiology of HPV infection, mechanisms of pathogenesis, as well as current and future therapeutic strategies against HPV-mediated penile carcinogenesis.