EAU & ASCO: Penile Cancer 2023

See Original Guidelines

Background

Uncommon in industrialized countries
More common in South America, Southeast Asia, and parts of Africa
Race
- Highest incidence in white Hispanics, followed by Alaskans and Native American Indians, African Americans, white non-Hispanics.
Increasing incidence in Western/developed countries most likely due to higher infection rates of HPV

Human papilloma virus (HPV)
- Most important risk factor
- Most frequent HPV genotypes: HPV16 followed by HPV6
- Risk of penile cancer is increased in patients with condyloma acuminata
- Female sexual partners of patients with penile cancer have not been found to have an increased incidence of cervical cancer
- No general recommendation (except in a few countries) for HPV vaccination in males because of the different HPV-associated risk patterns in penile- and cervical cancer
  - Since up to 50% of invasive penile carcinomas and 80% of preneoplastic lesions are HPV-associated, HPV vaccination is encouraged
Phimosis
- Strongly associated with invasive penile cancer, due to associated chronic infections
- Smegma is not a carcinogen
- Neonatal circumcision reduces the incidence of penile cancer, but does not reduce the risk of Penile Intraepithelial Neoplasia
Chronic penile inflammation
Lichen sclerosus
Ultraviolet A phototherapy
Cigarette smoking
Low level of education
Low socio-economic status

Usually arises from the epithelium of the inner prepuce or the glans
Subtypes
- HPV-independent
  - Usual
  - Pseudohyperplastic
  - Pseudoglandular
  - Verrucous
  - Caniculatum
  - Papillary
  - Sarcomatoid (Most aggressive and worse prognosis)
  - Mixed
- HPV-associated
  - Basaloid (most common among HPV-associated penile carcinomas)
  - Warty
  - Clear cell
  - Lymphoepithelioma-like
  - Mixed
Penile intraepithelial neoplasia is considered the precursor lesion of penile SCC
- Clinical terms such as ‘Erythroplasia of Queyrat, Bowenoid papulosis and Bowen’s disease’ are discouraged
- Penile intraepithelial neoplasia is also classified as HPV-independent and HPV-associated

The tumour, node, metastasis (TNM) classification for penile cancer includes tumour grade based on its prognostic relevance
Highly observer-dependent and can be problematic, especially in large tumours which may be heterogeneous
Based on
- Cytological atypica
- Keratinisation
- Intercellular bridges
- Mitotic activity
- Tumour margin
Classified into
- Grade 1
- Grade 2
- Grade 3
- Sarcomatoid
  - Grade 3 and sarcomatoid are considered poorly differentiated

Tissue sections determine the accuracy of histological diagnosis.
- Small lesions should be fully included
- Bigger lesions should have at least 3-4 blocks of tumour with the anatomical landmarks
Second-opinion pathology review is recommended given the rarity of this cancer
The pathology report must include
- Surgical procedure
- Anatomical site of the primary tumour
- Size of tumour
- Maximum thickness
- Histological type of SCC
- Grade
- Depth and extent of invasion
- Vascular invasion (venous/lymphatic)
- Perineural invasion
- Surgical margins
- HPV assessment