Penile Cancer - Causes and Pathogenesis

Causes of Penile Cancer

The exact causes of penile cancer have not been fully established. It is known that chronic irritation of the skin of the preputial sac with smegma and products of bacterial decomposition of exfoliated epithelial cells plays a negative role, therefore, circumcised men have a lower probability of developing penile cancer than men with preserved foreskin. This is most evident in phimosis, when smegma accumulates in significant quantities and chronic inflammation is more pronounced. Thus, phimosis is detected in 44-90% of cases in patients with penile cancer.

Long-term exposure to smegma affects the likelihood of developing penile cancer, as indicated by the different incidence rates depending on cultural and religious customs in different countries. For example, penile cancer is extremely rare among Jewish men, who are usually circumcised on the 8th day after birth for religious reasons. However, penile cancer is more common among Muslims, who are circumcised at an older age. It should be noted that circumcision in adults does not reduce the risk of developing the disease.

There are a number of precancerous conditions. These include:

• diseases sporadically associated with penile cancer (cutaneous horn, bowenoid papulosis);
• diseases with a high risk of developing into cancer (leukoplakia, xerous obliterating balanitis, genital warts, Buschke-Lowenstein tumor, erythroplasia of Queyrat).

Data have been obtained on the possible involvement of the human papilloma virus in the etiopathogenesis of penile cancer. A number of authors believe that the development of tumors is caused by infection with human papillomavirus types 16 and 18: they are found in 60-80% of patients with malignant neoplasms of the penis. The carcinogenic effect of these viruses is associated with the inactivation of tumor suppressor genes p53 and pRb by viral proteins E6 and E7, respectively. However, there is no convincing data confirming the reliability of this theory.

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Morphology of penile cancer

In 95% of cases, penile cancer is represented by squamous cell keratinizing (91.3%) or nonkeratinizing (8.7%) cancer.

There are different morphological forms of squamous cell carcinoma of the penis.

By growth type:

• classical squamous cell;
• basal cell;
• verrucous and its varieties:
• sarcomatoid;
• adenosquamous.

By growth pattern:

• with superficial distribution;
• with nodular or vertical growth;
• warty.

By degree of differentiation:

• highly differentiated;
• moderately differentiated;
• poorly differentiated;
• undifferentiated.

It has been established that with low- and moderately differentiated forms of cancer, by the time of diagnosis, almost all patients already have metastases in the lymph nodes. With highly differentiated tumors, the lymph nodes are affected in 50% of cases.

The frequency of cancer localization in the area of the glans penis, foreskin and body is 85.15 and 0.32% of cases, respectively. More frequent localization of the tumor in the area of the glans and foreskin is associated with constant contact of the skin with smegma and decay products of exfoliated epithelial cells.

Penile cancer is characterized by lymphogenous metastasis to the inguinal and iliac lymph nodes. Hematogenous metastases appear in the late stages of the disease and can affect the lungs, liver, bones, brain, and heart. Lymph drainage from the penis occurs in the superficial and deep inguinal and pelvic lymph nodes. The superficial inguinal nodes, 4-25 in number, lie in Scarpa's triangle on the surface of the deep fascia and along the great saphenous vein. The sentinel node is located medial to the femoral vein. The deep inguinal nodes, from one to three in number, lie under the broad fascia also medial to the femoral vein. Due to the strong development of the lymphatic network, metastases may affect the inguinal regions of both sides. Lymph from the base of the penis flows through the vessels of the femoral canal into the external iliac and pelvic lymph nodes. It should be taken into account that the appearance of palpable dense regional lymph nodes does not always indicate their metastatic lesion and may be associated with inflammatory changes. That is why many authors emphasize that clinical examination does not allow to reliably establish the degree of involvement of lymph nodes in the tumor process. Thus, inguinal lymph nodes can be palpated in 29-96% of patients with penile cancer. At the same time, in 8-65% of cases, morphological examination of lymph nodes does not reveal signs of metastatic lesion. On the other hand, in 2-66% of patients with non-enlarged inguinal nodes, micrometastases are detected after lymphadenectomy.