Penile Carcinoma

This is usually a squamous cell carcinoma (SCC). There is a well differentiated verrucous type called a Buschke-Löwenstein tumour.¹ There is a tendency for early signs to be ignored so that they often present late and conservative surgery is impossible. The psychological impact of the disease is highly significant. The cause of penile SCC is unclear but human papillomavirus (HPV) appears to be an important causative factor.

The risk of penile carcinoma shows marked geographical variation with high rates being reported in central and south America, parts of Asia and Africa. In western societies it represents about 2% of cancers of the male genital system and less than 1% of all male cancers. The rate is about 1 in 100,000. 95% of penile cancer is squamous cell carcinoma.

Risk factors and pre-malignant conditions

• Carcinoma in situ may progress to invasive carcinoma in 10 to 30% of cases. The problem is knowing which will progress.
• Bowen's disease is rare and most often occurs in elderly men. It is usually on the shaft of the penis and appears as a solitary, dull-red plaque with areas of crusting and oozing. Ulceration or papillomatous growth suggest that it has turned invasive as it does in approximately 5% of patients. Bowen's disease is treated with local excision.
• Erythroplasia of Queyrat also tends to affect elderly, uncircumcised men. It appears as a solitary, sharply defined, bright red, glistening, velvety, non-tender, plaque on the glans, the inner surface of the prepuce, or the coronal sulcus. Invasive transformation is commoner than in Bowen's disease, with an incidence of 10 to 33%. Ulceration or papillary outgrowths are signs of the disease. Treatment is with circumcision and 5FU cream.
• Bowenoid papulosis occurs mostly on the shaft of the penis in circumcised young men. It appears as multiple, small, slightly elevated, red or violet, slightly scaly or warty papules, which sometimes coalesce into large plaques. Histology is typical of Bowen's disease and it is associated with HPV infection. Lesions may remain static, spontaneously regress, or progress to Bowen's disease.
• HPV infection: PCR studies have shown a high incidence of HPV, especially type 16. It has been found in 50% of invasive cancer and 90% of carcinoma in situ. Subclinical infection is common, especially in the sexual partners of women with cervical carcinoma, invasive or in situ.²
• Other dermatological conditions: The role of such conditions as lichen planus and leukoplakia is disputed. There is an association between phimosis and risk of malignancy especially with balanitis xerotica obliterans.
• Other risk factors include exposure to chemicals such as insecticides, fertilizers, styrene and acrylonitrile as well as cigarette smoking.³ Ultraviolet radiation as in PUVA increases risk as does immune suppression.

Circumcision in early life appears to offer protection against penile malignancy, especially in those with poor personal hygiene. Retention of smegma causes phimosis and may lead on to malignant change. Those who are uncircumcised but attentive to personal hygiene are probably at no greater risk.

Carcinoma of the penis can occur at any age from 20 to 90 but is rare in children. About two thirds present before the age of 50. Around half have had the lesion for 6 months or more before presentation.

• It can occur anywhere on the penis but about 50% start on the glans, 20% on the prepuce and 10% on both
• Itching or a burning sensation especially under the prepuce are common features. There may be ulceration of the glans or prepuce and this may progress to a mass.
• Tumours may be papillary and single or multiple and likely to coalesce, raised and possibly necrose or ulcerate. Flat lesions appear as small superficial ulcers.
• If ignored the tumour will destroy the glans and prepuce and invade the shaft of the penis. It may obstruct the urethra and cause fistulae
• Lymphatic spread is first to the deep and superficial inguinal nodes and then the pelvic nodes. Distant metastasis is usually to liver or lung.
• Enlarged lymph nodes may also be due to secondary infection and a foul, purulent discharge may be noted.
• Verrucous carcinoma tends to grow and infiltrate rather than to produce distant spread.

Metastatic skin cancer and genital warts.

Biopsy is required to confirm the diagnosis. Imaging is required for staging and planning treatment.

Staging is important in planning treatment.
The histology is classified as grade I to IV based on cellular atypia and this dictates behaviour of the tumour and hence adds to prognosis.⁴ Staging may be by the Jackson classification or TNM.

• Surgical procedures may be local excision (Mohs micrographic surgery for small and superficial invasive carcinomas located on the glans or near the preputial sulcus has been used with good results), circumcision, glansectomy, partial penectomy, total penectomy, and demasculinisation. The psychological implications of all but the first two are enormous. The last 3 procedures may be accompanied by lymph node dissection.
• Verrucous carcinoma may be treated with cryosurgery, with or without 5 fluouracil.
• Medical therapy and radiotherapy may be needed. Medical therapy can be local or systemic. Drugs used include bleomycin, methotrexate, cisplatin, vincristine, 5 fluorouracil and interferons may be of value.
• Careful follow up is required, especially over the first year when the risk of recurrence is greatest.

Survival is very much related to lymph node status. It is unrelated to HPV status.⁵ The 5 years survival is:⁶

• Stage I, T1-3, N0, M0; 93%
• Stage II, T1-3, N1-2, M0; 55%
• Stage III, T4 or N3 or M1; 30%

Circumcision would appear to offer protection but personal hygiene is more important. Not only does circumcision protect against carcinoma of the penis but in men who have had multiple partners it reduces the risk of cervical carcinoma in the current partner.⁷ Preventive measures include prevention of phimosis, treatment of chronic inflammatory conditions, limiting PUVA treatment, smoking cessation and prophylactic prevention of HPV infection.⁸ Use of condoms may be a preventive factor.^9,10 Lesions should be reported early and the possibility of malignancy given due consideration.