HPV and penile cancer: 60% of cases linked to these strains

According to the American Cancer Society (ACS), in 2018 there were over 2000 new cases of penile cancer diagnosed and 410 deaths from penile cancer in the United States. Penile cancer accounts for less than 1% of cancers in men in the U.S (ACS, 2018). 

Penile cancer occurs when healthy cells grow out of control. Because there are different types of cells in the penis, there are several types of penile cancers that can develop. Almost all (approximately 95%) penile cancers start in the skin cells of the penis; these are squamous cell penile cancers (ACS, 2018).  Most of these cancers begin on the glans (head) of the penis or in the foreskin (in uncircumcised men). The other 5% of penile cancers consist of melanoma, basal cell carcinomas, adenocarcinomas, and sarcomas.

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Human papillomavirus (HPV) is the most common sexually transmitted infection (STI) and is found in approximately 63% of all penile cancers (CDC, 2019). HPV has also been linked to other cancers like cervical cancer, oropharyngeal cancer, and anal cancer. The exact mechanism is not known, but HPV affects the DNA of infected cells by changing how the cells regulate their growth. This lack of regulation allows cells to grow out of control and can lead to invasive cancer over time. HPV is common; over 80% of sexually active adults will have it at some point in their lives. Most of the time, HPV does not cause any symptoms; sometimes it can cause genital warts on the penis, around the anus, and in other genital areas. In some people, the infection can linger and potentially lead to cancer.

The HPV types that lead to cancer are the “high-risk” HPV types. In penile cancer, the strains most associated with HPV are types 16 and 18.

While infection with one of the high-risk HPV types is a significant risk factor for getting penile cancer, there are several other factors to consider.

• Tobacco use — Harmful chemicals from tobacco get into your bloodstream and can damage the DNA in your cells, including penile cells, and lead to uncontrolled cell growth. Tobacco users who also have an HPV infection are at an even higher risk.

• Being uncircumcised — It is unclear why, but men who get circumcised as infants have a lower risk of penile cancer than uncircumcised men. This may be because circumcised men do not have issues with smegma or phimosis (see below).

• Smegma — This is a thick buildup of secretions under the foreskin that occurs when the foreskin is not pulled back regularly to clean the head of the penis properly. It is not clear how smegma leads to penile cancer, but it may be because the smegma causes chronic inflammation.

• Phimosis— This happens when you have a tight foreskin that is difficult to pull back; men with this condition often accumulate smegma. The reason behind the increased risk of penile cancer is unknown.

• Age — As with many cancers, the risk of penile cancer increases with age. The average age of men with penile cancer in the U.S. is 68, with 80% of penile cancers diagnosed in men over 55 years old (ACS, 2018).

• AIDS — Men with a weakened immune system from AIDS are at higher risk for penile cancer. This is not surprising as a healthy immune system works to fight off an HPV infection and kill abnormally growing cancer cells. 

• UV light in the treatment of psoriasis — One of the treatments for psoriasis is to take a medication, called psoralens, followed by exposure to ultraviolet A (UVA) light; this is called PUVA therapy. Men who have undergone PUVA have an increased risk of penile cancer. In response, men getting PUVA now have their genitals covered during the treatments.

Since most penile cancers start in the skin cells of the penis, one of the first signs of the disease is a change in the penis skin; this is usually on the tip of the penis or the foreskin. Skin changes to look for include:

• Variations in color

• Area of skin thickening

• New lumps or bumps

• Rash under the foreskin

• A sore that may bleed

• Discharge or bleeding under the foreskin

Other signs and symptoms include swelling of the head of the penis or enlargement of the lymph nodes in the groin. Most of these symptoms are not specific to penile cancer; penile cancer is rare and these symptoms are likely due to some other problem. However, if you experience any of these, you should see your healthcare provider right away to be evaluated. 

Most of the known risk factors for penile cancer are avoidable; hence, you can potentially decrease your risk by avoiding those factors. However, it is possible to get penile cancer even if you don’t have any of those risk factors, so complete prevention is likely not possible. You can lower your risk with behavioral changes like avoiding tobacco use and having good genital hygiene, especially if you are uncircumcised, to prevent smegma buildup. It is debatable whether circumcision is protective against penile cancer; the decision to circumcise is usually a social and/or religious one.

We know that HPV infection plays a role in the majority of penile cancers. Therefore, taking precautions against getting HPV infections decreases your risk of penile cancer as well. Getting the HPV vaccine is likely the most effective way to prevent HPV infection, especially since the vaccine protects against the high-risk strains most associated with penile cancer (Stratton, 2016).

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Current version

September 18, 2019

Written by

Chimene Richa, MD

Fact checked by

Tzvi Doron, DO

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About the medical reviewer

Tzvi Doron, DO

Dr. Tzvi Doron is Board Certified in Family Medicine by the American Board of Family Medicine.