What is Penile Cancer


Penile cancer is a rare cancer that mostly associates with squamous cell carcinoma of the glans and foreskin of the penis. The risk factors for penile cancer include HPV infection, smoking and also poor hygiene.


Penile cancer is a rare cancer with a prevalence of 0.1 to 1 per 100,000 men in high-income countries. However, global morbidity varies significantly between populations based on risk factors such as human papillomavirus (HPV) infection, smoking and poor hygiene, or protective factors such as infant circumcision. Penile cancer (95%) accounts for the majority of cases associated with squamous cell carcinoma of the glans and foreskin, which in other words is penile squamous cell carcinoma (PSCC). According to WHO recommendations, they can be further divided into papillary, sarcomatoid, adenosquamous, verrucous, and other rare forms and may not be caused by or associated with HPV​1​.


Penile cancer is a rare disease with approximately 26,000 cases per year worldwide, accounting for less than 1% of new cancers in men. In high-income countries, the prevalence of penile cancer is 0.1-1 per 100,000 men, but it is generally higher in low- and middle-income areas. In Islamic countries and Israel in particular, the incidence due to religious neonatal circumcision is low, while in Brazil and India, it affects 3 to 7 per 100 000 males. Up to 40% of men get a focal penile cancer diagnosis, with overall survival of ~90%. However, as the tumor metastasizes, the prognosis deteriorates dramatically​1​.

Pathology and pathogenesis of penile cancer

Almost 95% of all malignancies of the penis are squamous cell carcinomas. About half of them arise from the non-keratinized epithelium of the glans or the inner layer of the foreskin. However, other malignancies (melanoma, sarcoma) or penile metastasis are extremely rare. In the case of squamous cell carcinoma of the penis, there are distinguishing histological subtypes, according to the Union Internationale Contre le Cancer (UICC) classification.

Two distinct pathogenic pathways involve in the development of penile carcinoma. About a third of cases are related to human papillomavirus (HPV) infection. Immunohistochemical detection of p16 serves as a surrogate parameter for HPV association. The most commonly recognized HPV serotypes are HPV 16, 18, 31, 33, 45, 56 and 65. Penile cancer types associated with HPV can be distinguished from those not associated with HPV by polymerase chain reaction (PCR) or immunohistochemistry.

Another pathogenic pathway is the chronic inflammation of the foreskin with phimosis or the chronic inflammation associated with lichen sclerosus. Because of these two distinct pathogenic pathways, the new UICC classification differentiates between HPV-related and non-HPV-associated penile carcinoma​2​.


  1. 1.
    Thomas A, Necchi A, Muneer A, et al. Penile cancer. Nat Rev Dis Primers. Published online February 11, 2021. doi:10.1038/s41572-021-00246-5
  2. 2.
    Hakenberg O, Dräger D, Erbersdobler A, Naumann C, Jünemann K, Protzel C. The Diagnosis and Treatment of Penile Cancer. Dtsch Arztebl Int. 2018;115(39):646-652. doi:10.3238/arztebl.2018.0646