Penile and Scrotal Cancer

Penile cancer is a rare malignancy, the great majority of which are squamous cell carcinomas arising on the glans, foreskin, or shaft of the penis. A substantial fraction of cases are linked to human papillomavirus (HPV) infection, while others are driven by chronic inflammation and poor preputial hygiene. Scrotal cancer is rarer still and holds a notable place in the history of occupational medicine as the first cancer recognised to have an occupational cause.

Definition

Penile cancer is a malignant neoplasm of the penis, most often squamous cell carcinoma, classified histologically under the WHO scheme into HPV-associated and HPV-independent types; scrotal cancer is a separate, rarer squamous malignancy of the scrotal skin.

Scope

This entry covers the epidemiology, risk factors, and classification of penile cancer, with a brief note on scrotal cancer. It addresses the HPV-related and HPV-independent pathways, the principal risk factors, and the WHO histological framework. It is a reference-educational overview and does not provide diagnostic or treatment recommendations.

Core questions

• What are the main histological types and HPV-related pathways of penile cancer?
• What are the established risk factors for penile cancer?
• What proportion of penile cancers are attributable to HPV?
• Why is scrotal cancer historically important in occupational medicine?

Key concepts

• Squamous cell carcinoma of the penis
• HPV-associated vs HPV-independent carcinogenesis
• Penile intraepithelial neoplasia (precursor lesion)
• Phimosis and chronic inflammation
• p16INK4a as an HPV surrogate marker
• Inguinal lymph node involvement
• Scrotal cancer and occupational carcinogens

Mechanisms

Penile squamous cell carcinoma arises through two broad pathways: an HPV-associated pathway, driven by oncogenic human papillomavirus types and often marked by p16INK4a overexpression, and an HPV-independent pathway linked to chronic inflammation, lichen sclerosus, and phimosis (Thomas, 2021; Olesen, 2019). Both can be preceded by penile intraepithelial neoplasia. The WHO classification distinguishes these subtypes histologically (Moch, 2016). Historically, scrotal cancer was the disease in which Percivall Pott identified an occupational cause in eighteenth-century chimney sweeps, establishing the concept of occupational carcinogenesis.

Clinical relevance

Penile cancer typically presents as a non-healing lesion, ulcer, or mass on the glans or foreskin, and spread to the inguinal (groin) lymph nodes is a key determinant of how the disease is staged (Thomas, 2021). The HPV status and histological subtype are increasingly used to characterise tumours. This entry describes how the disease is classified and is not a basis for individual diagnostic or treatment decisions.

Epidemiology

Penile cancer is rare in high-income countries but more common in parts of South America, Africa, and Asia, with incidence rising with age (Bray, 2024; Thomas, 2021). Established risk factors include the presence of a foreskin with phimosis, poor hygiene, chronic inflammatory conditions such as lichen sclerosus, tobacco use, and HPV infection; neonatal circumcision is associated with reduced risk. A pooled analysis estimated that roughly a third to a half of penile cancers carry HPV DNA, with higher proportions in certain histological subtypes (Olesen, 2019).

Evidence & guidelines

Histological classification follows the WHO classification of tumours of the urinary system and male genital organs, which separates HPV-associated from HPV-independent penile squamous carcinomas (Moch, 2016), and anatomical extent is described by the TNM staging system. Disease-specific guidelines are published by professional bodies such as the European Association of Urology and the American Urological Association; readers should consult the current versions.

History

Scrotal cancer occupies a foundational place in the history of cancer epidemiology: in 1775 the English surgeon Percivall Pott described an unusually high occurrence of scrotal cancer among chimney sweeps and attributed it to soot, the first recognition of an occupational cause of cancer. This observation is widely cited as the origin of occupational and chemical carcinogenesis as fields of study; the present entry notes it as historical context rather than current clinical guidance.

Seminal works

• thomas-2021
• olesen-2019
• moch-2016

Frequently asked questions

What is the most common type of penile cancer?

The large majority of penile cancers are squamous cell carcinomas, which the WHO classification divides into human papillomavirus (HPV)-associated and HPV-independent subtypes.

Why is scrotal cancer historically significant?

In 1775 Percivall Pott linked scrotal cancer in chimney sweeps to soot exposure, the first identification of an occupational cause of cancer and a founding observation of carcinogenesis research.