Penile Squamous Cell Carcinoma

Penile squamous cell carcinoma is a rare but serious form of cancer that affects the penis, representing about 95% of all penile cancers. While uncommon in developed countries, early detection and modern treatment approaches can often lead to successful outcomes and preserve quality of life.

Table of contents

• What is Penile Squamous Cell Carcinoma?
• How Common is This Cancer?
• Risk Factors and Causes
• Signs and Symptoms
• Diagnosis and Testing
• Types and Grades
• Treatment Options
• Outlook and Survival
• Prevention

What is Penile Squamous Cell Carcinoma?

Penile squamous cell carcinoma is a type of cancer that develops when healthy cells in the penis change and grow out of control^[1]. The cancer forms in the squamous cells, which are flat, thin cells that line the surface of the penis^[2].

This cancer most commonly begins on the head of the penis (called the glans) or on the foreskin in men who are not circumcised^[1]. The cancer may also develop in the area where the head meets the shaft, known as the coronal sulcus^[1].

Penile squamous cell carcinoma accounts for approximately 95% of all penile cancers^[9]. The remaining cases include other rare types such as melanoma, basal cell carcinoma, adenocarcinoma, and sarcoma^[2].

How Common is This Cancer?

Penile squamous cell carcinoma is rare in the United States and other developed nations. In 2015, the American Cancer Society predicted 1,820 new cases with 310 deaths from penile cancer in the United States^[1]. The condition makes up less than 1% of cancers among men in the U.S.^[2].

However, the disease is more common in developing countries, where it may represent up to 10% of cancers in males^[1]. Higher rates are observed in parts of Asia, Africa, and South America^[2]. In Europe, penile squamous cell carcinoma accounts for approximately 0.7% of all malignant tumors in men^[6].

The disease most commonly affects older men. About 80% of penile cancer diagnoses in the U.S. occur in men aged 55 or over^[2].

Risk Factors and Causes

While researchers do not know exactly what causes healthy penile cells to become cancerous, they have identified several risk factors that may increase the chance of developing penile squamous cell carcinoma^[10].

Human papillomavirus (HPV) infection is one of the most significant risk factors. High-risk strains of HPV, particularly types 16 and 18, have been found in 70% to 100% of penile carcinoma in situ cases and in 30% to 50% of invasive forms of the disease^[6]. The virus works through viral proteins called E6 and E7, which interfere with important tumor suppressor genes in cells, potentially leading to uncontrolled cell growth and cancer^[1].

Being uncircumcised is associated with increased risk. Men who were not circumcised at birth may have a higher risk of developing penile cancer^[10]. Circumcision may help prevent HPV infection and removes the possibility of certain other risk factors^[10].

Phimosis, a condition in which the foreskin of the penis cannot be pulled back over the head, increases risk^[10]. This condition can create an environment where poor hygiene leads to the buildup of smegma, a substance made of dead skin cells and oils that can irritate and inflame penile tissues^[7].

Chronic inflammation conditions such as balanitis (swelling and irritation of the head of the penis) and lichen sclerosus are often associated with penile cancer^[13].

Tobacco use is another well-established risk factor. Smokers may be three to four and a half times more likely to develop this cancer compared to non-smokers^[7].

Other risk factors include poor personal hygiene, having many sexual partners, and having HIV/AIDS^[10].

Signs and Symptoms

Penile squamous cell carcinoma usually causes visible changes to the penis. The most common symptoms include^[2]:

• A painless lump or sore that may bleed
• Flat growths that look bluish-brown
• Foul-smelling fluid underneath the foreskin
• A rash on the penis
• Skin thickening or changing skin color
• Small, crusty bumps
• Swelling and irritation, especially in the head of the penis

The cancer often begins as a small red area that may be limited to the skin for a long time^[7]. These cancers can grow to become either raised and growing outward or forming deep ulcers^[7].

Many patients do not notice the cancer or do not report it promptly^[7]. Pain is uncommon in early stages^[7]. Sometimes, enlarged lymph nodes in the groin may be present due to inflammation and secondary infection^[7].

It is important to note that less serious conditions like infections and allergic reactions can also cause these symptoms. However, any unusual changes should be evaluated by a healthcare provider, as early detection is crucial^[2].

Diagnosis and Testing

If penile cancer is suspected, a biopsy is required to confirm the diagnosis. During a biopsy, a small sample of tissue is removed and examined under a microscope^[7]. The biopsy may be a punch biopsy, incisional biopsy, or excisional biopsy, and when possible, tissue under the lesion should be sampled^[7].

Physical examination includes careful inspection of the penis and palpation of the lymph nodes in the groin area^[9]. The lymph nodes are important because penile cancer often spreads first to these nearby nodes.

Once cancer is diagnosed, additional tests are done to determine if cancer cells have spread. These staging tests may include^[7]:

• CT (computed tomography) scan or MRI (magnetic resonance imaging) to check for invasion into deeper tissues and to evaluate lymph nodes
• PET-CT scan to investigate spread to deep lymph nodes^[9]
• Ultrasound of the groin lymph nodes

A specialized procedure called Dynamic Sentinel Node Biopsy (DSNB) may be performed. A radioactive liquid is injected into the tumor, and the first lymph nodes that the tumor drains to are identified and removed for careful testing^[21]. This helps determine if cancer has spread without removing all lymph nodes.

Types and Grades

More than 95% of penile cancers are squamous cell cancers^[4]. These cancers develop from squamous cells which are flat, skin-like cells that cover the surface of the penis^[4].

Verrucous carcinoma is a rare type of squamous cell penile cancer. It looks like a large wart and is a slow-growing tumor that rarely spreads to other parts of the body^[4]. Verrucous carcinoma is usually curable with surgery^[4].

The grade of cancer tells how much the cancer cells look like normal cells^[4]. Squamous cell cancers are graded by the World Health Organization classification system:

• Grade 1 (low grade): Cancer cells look very much like normal cells
• Grade 2: Cancer cells look somewhat like normal cells
• Grade 3 (high grade): Cancer cells look very abnormal and not like normal cells

Low-grade cancers usually grow very slowly, while high-grade cancers tend to grow more quickly^[4].

Penile cancer may evolve from penile intraepithelial neoplasia (PIN), also called carcinoma in situ, or arise directly without this precursor^[1]. PIN represents cancer cells confined to the top layers of skin^[18].

Treatment Options

The primary goal in managing penile squamous cell carcinoma is to eliminate the cancer while preserving as much of the penis as possible to maintain its appearance and function^[17]. Treatment depends on the size and location of the tumor, whether it has spread, and the patient’s general health^[16].

Treatment for Early-Stage Cancer

For cancer confined to the top layers of skin (penile intraepithelial neoplasia), treatment options include^[17]:

• Chemotherapy creams such as fluorouracil (5-fluorouracil or 5FU) or imiquimod, which uses the immune system to fight cancer. These creams will not cause hair loss^[18]
• Laser therapy, which uses a strong beam of light to destroy cancer cells^[16]
• Cryotherapy, which uses freezing to kill cancer cells^[16]
• Glans resurfacing surgery, where the top layers of tissue from the glans are removed and covered with a skin graft^[18]

Circumcision may be recommended before using creams to make monitoring and application easier^[18].

Surgery for Invasive Cancer

Surgery is the main treatment for cancer that has grown deeper into the penis^[13]. Modern surgical approaches focus on removing as little tissue as possible while ensuring complete cancer removal. Current standards allow for safety margins of no more than a few millimeters, because local recurrence, if it occurs, can still be treated with curative intent^[13].

Surgical options include^[16]:

• Circumcision for cancers of the foreskin
• Wide local excision, removing the cancer and a surrounding area of tissue
• Mohs micrographic surgery, a specialized technique that removes cancer layer by layer while immediately examining tissue under a microscope^[1]
• Partial removal of the head of the penis (partial glansectomy) or total removal (total glansectomy)
• Removal of part of the penis (partial penectomy), reserved for more advanced cases
• Reconstructive surgery using skin grafts to rebuild the penis after cancer removal^[16]

Radiation Therapy

Radiation therapy uses high-energy rays to kill cancer cells. It can be used instead of surgery for small, early-stage cancers, or in combination with other treatments^[16]. One advantage is the potential to maintain sexual function^[17].

Two types of radiation may be used^[17]:

• External beam radiation therapy, delivered from outside the body
• Brachytherapy, where radioactive material is placed directly into or near the cancer

Radiation therapy has disadvantages, including potential complications such as urethral strictures, penile necrosis, pain, and swelling^[17].

Management of Lymph Nodes

Proper management of regional lymph nodes is crucial because lymph node involvement strongly predicts survival^[13]. Even when lymph nodes feel normal during examination, there is a high rate of microscopic cancer spread^[13].

Treatment of lymph nodes may include^[15]:

• Careful monitoring with physical examination and ultrasound
• Sentinel lymph node biopsy to check the first lymph nodes that drain the tumor
• Radical lymph node dissection (removal of lymph nodes) if cancer is found
• Adjuvant chemotherapy after lymph node surgery if cancer has spread

Chemotherapy

Chemotherapy uses medicines to kill cancer cells throughout the body. It may be given^[16]:

• With radiation therapy (chemoradiotherapy)
• Before surgery to shrink the tumor
• After surgery to kill any remaining cancer cells
• For cancer that has spread to other parts of the body

A single superior treatment regimen has not been defined, but cisplatin-based combinations are commonly used^[15].

Outlook and Survival

When found early, penile cancer can usually be cured^[3]. Penile cancer is curable in all early stages with appropriate treatment^[13].

The prognosis depends crucially on whether cancer has spread to lymph nodes. Survival is directly related to lymph node involvement^[13][6]. Squamous cell cancers that are found early are usually curable^[4].

Untreated invasive penile cancer typically progresses and may cause death within 2 years^[7]. However, this underscores the importance of early detection and treatment.

The cancer generally grows slowly over many years, though occasionally it can grow more quickly^[4]. If local recurrence occurs after treatment, it can still often be treated successfully with curative intent^[13].

Advanced cancer that has spread to distant parts of the body is harder to treat^[2]. In these cases, treatment focuses on slowing the cancer’s growth, managing symptoms, and helping patients live longer^[16].

Prevention

While there is no sure way to prevent penile squamous cell carcinoma, several measures may lower the risk^[8]:

Circumcision in infancy or childhood lowers the risk of penile cancer. Studies show that circumcision decreases the risk significantly, with a hazard ratio of 0.33^[13]. It may help prevent HPV infection and eliminates the possibility of phimosis and smegma accumulation^[10].

HPV vaccination is a powerful preventive measure. Vaccination against HPV significantly reduces the risk of penile cancer associated with the virus^[1]. Early vaccination is recommended and can provide protection against all HPV-related cancers^[3].

Good personal hygiene is important, especially for uncircumcised men. Regular, careful cleaning under the foreskin can reduce the risk of inflammation and smegma buildup^[8].

Not smoking or using tobacco products is crucial, as tobacco use substantially increases risk^[10].

Practicing safe sex reduces the risk of HPV and other sexually transmitted infections^[8].

Men should also be alert to any changes in their penis and seek medical attention promptly if they notice unusual symptoms. Early diagnosis is critical for successful treatment^[1].