Squamous cell carcinoma of the penis (SCCP) is a rare malignancy, especially in developed nations, yet it represents a significant health concern globally. This type of cancer accounts for over 95% of all penile malignancies, making it the most common form of cancer to affect the organ. The disease is characterized by the uncontrolled growth of epithelial cells, which are the flat, scale-like cells that make up the surface of the skin. While the overall incidence is low in the United States and Europe, typically less than 2 cases per 100,000 men annually, rates are considerably higher in parts of South America, Africa, and Asia. This disparity points to the influence of environmental and socioeconomic factors on the disease’s development.
Understanding Squamous Cell Carcinoma of the Penis
Squamous cell carcinoma of the penis originates from the superficial layers of the skin and mucosal surfaces, most commonly appearing on the glans (head of the penis) or the inner layer of the foreskin (prepuce). This anatomical predilection is significant because these areas consist of squamous epithelium, the cell type from which the cancer arises. The tumor begins as abnormal cell growth, potentially starting as a pre-cancerous condition known as penile intraepithelial neoplasia (PeIN), which can progress to invasive cancer over time.
In Western countries, the incidence remains low, though the average age of diagnosis tends to be later, often after 60 years of age. The majority of these tumors are classified as Grade 1 or 2, meaning they are well or moderately differentiated. However, they are known to be aggressive, with a propensity for early metastatic spread to the lymphatic system.
SCCP is categorized into several histological subtypes that influence prognosis. The usual subtype is the most common (45% to 75% of cases) and is not always associated with the Human Papillomavirus (HPV). Other variants, such as basaloid and warty carcinomas, are strongly associated with high-risk HPV types, particularly HPV-16. The verrucous carcinoma subtype is characterized by a warty, non-invasive appearance, is well-differentiated, and rarely metastasizes.
Identifying Key Risk Factors and Preventive Measures
Chronic inflammation is a significant driver, frequently stemming from poor genital hygiene. This allows for the accumulation of smegma—a substance composed of dead skin cells and secretions—under the foreskin. This chronic irritation creates a microenvironment conducive to cellular changes and malignant transformation.
Phimosis, the inability to fully retract the foreskin, is considered one of the strongest risk factors. It exacerbates poor hygiene and chronic inflammation, correlating with up to 90% of SCCP diagnoses. The presence of phimosis, especially when accompanied by chronic inflammatory conditions like balanitis, significantly increases the risk profile.
Infection with high-risk subtypes of the Human Papillomavirus (HPV), specifically HPV-16 and HPV-18, is another major factor, implicated in approximately 50% to 60% of penile cancer cases. The viral proteins produced by HPV interfere with the body’s natural tumor suppressor genes, promoting uncontrolled cell growth. Tobacco use is also an established, independent risk factor, with the chemicals in tobacco smoke thought to contribute to carcinogenesis, particularly when combined with an HPV infection.
Primary preventive measures focus on managing identifiable risks. Circumcision, especially when performed early in life, is highly protective, as it eliminates the foreskin where most tumors originate and prevents chronic inflammation and smegma buildup. For uncircumcised individuals, rigorous and regular cleaning beneath the foreskin is necessary to reduce chronic irritation. The HPV vaccine is also a valuable tool for primary prevention, protecting against the high-risk types of the virus linked to SCCP.
Clinical Presentation and Diagnostic Staging
Early symptoms can be subtle, often leading to delayed diagnosis and negatively affecting prognosis. The most common initial presentation is a change in the skin, typically appearing as a persistent lump, a red or velvety patch, or an ulcerated sore that fails to heal. These lesions are most frequently found on the glans or under the foreskin and may be accompanied by a foul-smelling discharge or bleeding.
In some cases, the cancer may present as persistent inflammation or swelling at the tip of the penis, particularly in men with phimosis, where the lesion is hidden from view. The physical examination includes careful inspection and palpation of the entire penis to note the size, location, and extent of the primary tumor. The regional lymph nodes in the groin (inguinal nodes) are also thoroughly assessed, as involvement of these nodes is the single most important factor for predicting survival.
The definitive diagnostic tool is a biopsy, where a small tissue sample is taken for microscopic examination to confirm cancer and determine its subtype and grade. Once confirmed, imaging studies are used to stage the disease and determine how far the cancer has spread. Magnetic resonance imaging (MRI) is often utilized to assess the depth of the tumor’s invasion into internal structures, such as the corpus spongiosum or corpora cavernosa.
Staging is performed using the TNM (Tumor, Node, Metastasis) system. The ‘T’ component describes the size and depth of invasion of the primary tumor, while the ‘N’ component indicates whether the cancer has spread to the regional lymph nodes. The ‘M’ component specifies the presence or absence of distant metastases. Detecting lymphatic spread early is important because even clinically non-palpable nodes can harbor microscopic disease, which necessitates further invasive staging.
Core Treatment Strategies
Treatment for squamous cell carcinoma of the penis depends primarily on the stage of the disease, the tumor’s location, and the patient’s overall health. The overarching principle for managing localized disease is to achieve complete cancer removal while preserving as much penile structure and function as possible. For early-stage tumors that are small and superficial, organ-sparing techniques are the preferred approach to maintain sexual and urinary function.
These conservative treatments include topical therapies using creams like 5-fluorouracil or imiquimod, which are applied directly to the lesion for carcinoma in situ. Local ablative techniques, such as laser ablation or cryotherapy, and specialized surgical procedures like Mohs micrographic surgery (MMS) or wide local excision (WLE), are also employed for early-stage tumors. MMS offers superior outcomes in terms of local recurrence rates compared to WLE, due to its precise, layer-by-layer removal of cancerous tissue until clear margins are confirmed.
For more advanced tumors that have invaded deeper tissues, such as the corpus spongiosum or corpora cavernosa, surgical removal remains the cornerstone of treatment. This often requires a partial penectomy, where the distal portion of the penis is removed, or, in extensive cases, a total penectomy. Lymph node management is a decisive factor for prognosis, as survival rates are closely tied to whether the cancer has spread to the inguinal lymph nodes.
For patients with clinically negative lymph nodes but high-risk features in the primary tumor, a sentinel lymph node biopsy is often performed to detect microscopic disease without removing all nodes. If the nodes are clinically positive or the sentinel biopsy is positive, a full inguinal lymphadenectomy (surgical removal of the lymph nodes) is necessary to control the regional spread. Radiation therapy and chemotherapy are generally reserved for locally advanced or metastatic disease, often used in combination with surgery or as palliative care.
Platinum-based chemotherapy regimens are the most common systemic treatment, sometimes used before surgery (neoadjuvant) to shrink bulky lymph node metastases, which can improve the chance of a curative outcome. Long-term surveillance and regular follow-up are necessary post-treatment to monitor for local recurrence or the development of new lesions, especially in patients who underwent organ-sparing procedures.