Epidemiology & Risk Factors
Invasive squamous cell carcinoma accounts for >95% of penile malignancies, with an abrupt rise in incidence in the 6th decade of life.
Risk factors:
- Lack of circumcision — neonatal circumcision almost eliminates the risk of invasive penile cancer (it removes roughly half the tissue that can become cancer) but offers less protection against CIS; adult circumcision offers little to no protection.
- HPV — subtype 16 most frequent; oncogenic subtypes 16 and 18, non-oncogenic 6 and 11.
- Phimosis.
- Lichen sclerosus and chronic penile inflammation.
- Tobacco (smoking or chewing).
- Poor hygiene, rural residence, low socioeconomic status, being unmarried.
- Number of sexual partners and early age of first intercourse.
- Penile trauma.
- PUVA (psoralen + UVA phototherapy) for dermatologic conditions such as psoriasis.
TNM Staging (AJCC 8th)
Primary tumour (T):
| Category | Definition |
|---|---|
| Tis | Carcinoma in situ |
| Ta | Non-invasive SCC (basaloid, warty, verrucous, papillary, or mixed) |
| T1 | Invades subepithelial connective tissue — T1a without LVI/perineural invasion and not high grade; T1b with LVI, perineural invasion, or high grade (grade 3–4 or sarcomatoid) |
| T2 | Invades corpus spongiosum |
| T3 | Invades corpus cavernosum |
| T4 | Invades other adjacent structures |
Regional lymph nodes (N):
| Stage | Clinical (cN) | Pathologic (pN) |
|---|---|---|
| N1 | Unilateral, solitary, mobile node | Up to 2 unilateral positive nodes |
| N2 | ≥2 unilateral mobile nodes, or bilateral nodes | ≥3 unilateral nodes, or bilateral nodes |
| N3 | Fixed nodal mass (any size, uni- or bilateral) | Extranodal extension or pelvic node(s) |
cN0 means no palpable or visibly enlarged inguinal nodes. A node >4 cm is often associated with extranodal extension.
Distant metastasis (M): M1 = metastasis to nodes outside the true pelvis, or to visceral or bone sites. (There is no pathologic M0; clinical M completes the stage group.)
Natural History
- Tumour architecture — flat tumours metastasize to nodes earlier and carry worse survival than papillary tumours.
- The earliest route of spread is to the regional inguinal then pelvic nodes:
- Superficial lymphatics drain the foreskin and shaft skin → superficial inguinal nodes.
- Deep lymphatics drain the glans → superficial and deep inguinal nodes (femoral triangle).
- Symphyseal crossover allows spread to contralateral inguinal nodes.
- Drainage then proceeds to ipsilateral pelvic nodes (external iliac, internal iliac, obturator).
- Untreated nodal enlargement leads to skin necrosis, chronic infection, and death from sepsis or hemorrhage (femoral vessel erosion).
- Distant metastasis — most often lung, bone, and liver; clinically detectable distant disease is uncommon, occurs late after the local lesion is treated, and most untreated patients die within 2 years.
Self-Test
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What histologic type accounts for the majority of penile cancers, and its major modifiable risk factor? Squamous cell carcinoma (>95%); lack of (neonatal) circumcision is the major modifiable factor, along with HPV and smoking.
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What distinguishes T1a from T1b penile cancer? Both invade subepithelial connective tissue; T1b has lymphovascular or perineural invasion or is high grade (grade 3–4/sarcomatoid), whereas T1a has none of these.
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What separates T2 from T3? T2 invades the corpus spongiosum; T3 invades the corpus cavernosum.
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Which tumour architecture carries a worse prognosis? Flat tumours — earlier nodal metastasis and worse survival than papillary tumours.