Penile cancer has no single cause. It develops from a combination of risk factors, with HPV infection, chronic inflammation, and tobacco use playing the most significant roles. It’s rare in the United States, diagnosed in fewer than 1 in 100,000 men each year and accounting for less than 1% of all male cancers. About 2,260 new cases are expected in 2026. Understanding the specific factors that drive it can help you assess your own risk.
HPV Infection
Human papillomavirus is one of the strongest known risk factors for penile cancer, though the exact percentage of cases linked to HPV varies across studies. Some research puts the figure around 33%, while other analyses find HPV present in 46 to 48% of penile tumors. High-risk strains of HPV have been detected in up to 40% of cases, with HPV-16 carrying the highest risk of progressing to cancer. HPV-18 is the next most common type found in penile tumors.
HPV is a sexually transmitted infection that’s extremely common. Most men who contract it clear the virus without ever knowing they had it. But in some cases, the virus persists in the skin cells of the penis and gradually causes genetic changes that push those cells toward uncontrolled growth. This process typically takes years or even decades, which is why penile cancer is most often diagnosed in men over 50.
The HPV vaccine was approved for use in males in 2009, with demonstrated efficacy of about 90% for preventing genital warts. However, direct data on the vaccine’s ability to prevent penile cancer specifically is still limited. Because HPV-driven penile cancers depend on the same high-risk strains the vaccine targets, vaccination in adolescence is expected to reduce risk, but large-scale confirmation studies haven’t been completed yet.
Phimosis and Circumcision Status
Phimosis, a condition where the foreskin is too tight to retract fully, is consistently linked to higher rates of penile cancer. The mechanism is straightforward: when the foreskin can’t be pulled back, the area underneath stays warm, moist, and difficult to clean. This creates an environment where infections, irritation, and chronic inflammation can persist for years. That ongoing inflammation damages cells at the DNA level and increases the chance of cancerous changes.
Circumcision performed in childhood or adolescence has a strong protective effect against invasive penile cancer. A systematic review and meta-analysis found that early circumcision reduced the odds of invasive disease by about 67%. Interestingly, circumcision performed in adulthood did not show the same benefit and may even be associated with a higher risk, though researchers suspect this is because men who get circumcised as adults often do so to treat an existing problem like phimosis, meaning they’ve already spent years with elevated risk.
It’s worth noting that circumcision did not appear to protect against precancerous changes (penile intraepithelial neoplasia) at any age. This suggests the protective effect of early circumcision works primarily by preventing decades of chronic irritation rather than by blocking the earliest cellular changes.
Tobacco Use
Smoking, chewing tobacco, and snuff use all independently increase the risk of penile cancer. A multivariate analysis found statistically significant associations for each form of tobacco, and the more tobacco a man used, the higher the risk. Men who used more than one form of tobacco had an even greater chance of developing the disease.
Tobacco’s cancer-causing chemicals circulate through the bloodstream and concentrate in body fluids, including those that contact penile skin. These chemicals damage DNA in the cells they reach. When combined with other risk factors like HPV or chronic inflammation, tobacco use accelerates the process of normal cells becoming cancerous.
Chronic Skin Conditions
Lichen sclerosus is a chronic inflammatory skin condition that causes white, patchy areas of thinning skin on the penis. Over time, it can lead to scarring, tightening of the foreskin, and persistent irritation. This long-term inflammation creates an environment where cells are constantly repairing themselves, increasing the odds of a DNA copying error that leads to cancer.
Other chronic conditions of the penile skin also contribute to risk. Any long-standing irritation, repeated infections, or poorly healing lesions on the penis can serve as a breeding ground for precancerous changes if left untreated for years.
Precancerous Lesions
Penile cancer doesn’t usually appear out of nowhere. It often starts as a precancerous condition called penile intraepithelial neoplasia, or PeIN. These lesions show up as flat patches on the penis that can be white, red, or sometimes pigmented and warty in texture. Red patches on the glans were historically called erythroplasia of Queyrat, while similar lesions on the shaft were called Bowen’s disease. Both are now understood as forms of the same precancerous process.
Without treatment, genital precancerous lesions progress to invasive squamous cell carcinoma in roughly 10% of cases. That’s notably higher than the 3 to 5% progression rate seen with similar lesions on other parts of the body. The warm, moist environment of the genitals and exposure to HPV likely explain the difference. Identifying and treating these patches early is one of the most effective ways to prevent full-blown penile cancer.
Smegma and Hygiene
For decades, smegma (the natural buildup of oils, dead skin cells, and moisture under the foreskin) was blamed as a direct cause of penile cancer. This claim doesn’t hold up. A thorough review of the evidence concluded that assertions about smegma being carcinogenic cannot be justified on scientific grounds. Smegma itself does not cause cancer.
What matters is the broader picture: poor hygiene in uncircumcised men can lead to chronic irritation and recurring infections. It’s that persistent inflammation, not the smegma itself, that contributes to cancer risk over time. Regular cleaning under the foreskin eliminates this concern.
Age and Immune Health
Penile cancer is overwhelmingly a disease of older men, with most cases diagnosed after age 50 and the average age at diagnosis in the mid-60s. This reflects the slow nature of the disease. The cellular damage from HPV, inflammation, or tobacco accumulates over decades before a tumor forms.
A weakened immune system also raises risk. Men with HIV or those taking immunosuppressive medications after organ transplants are less able to clear HPV infections and less able to detect and destroy abnormal cells before they become cancerous. The combination of immune suppression and HPV is particularly dangerous.
How Multiple Risk Factors Interact
Most men who develop penile cancer have more than one risk factor working against them. A man with phimosis who also smokes and has a persistent HPV infection faces a much higher cumulative risk than someone with just one of those factors. The damage pathways overlap: HPV disrupts the cell’s ability to regulate growth, tobacco chemicals cause additional DNA mutations, and chronic inflammation keeps damaged cells dividing instead of dying off. Each factor compounds the others, which is why penile cancer clusters in populations where several risk factors are common simultaneously.