Pathogenesis (development of disease)
More than 95% of all malignancies of the penis are squamous cell carcinomas (PEK).
| Premalignant changes/preliminary stages of PEK. | Obligate precancerous lesions (precancerous lesions): high risk (approximately 10%) of developing penile carcinoma |
| Cutaneous keratinization of the penis | Penile intraepithelial neoplasia (carcinoma in situ) |
| Bowenoid papulosis of the penis (occurs mainly in younger men) | Buschke-Löwenstein tumor (so-called giant condyloma with locally invasive growth but without metastasis) |
| Balanitis xerotica obliterans (lichen sclerosus et atrophicus). | Erythroplasia quéyrate (flat erythematous plaques (“area-like or plate-like substance proliferation of the skin accompanied by redness of the skin”) on the inner preputial leaf (foreskin leaf) and glans penis (glans)) |
| Leukoplakia (whitish coatings that cannot be wiped off). | Bowen’s disease (affects mostly older men; raised, brownish-red, scaly plaques on penile shaft skin) |
| Paget carcinoma |
The World Health Organization (WHO) pathologic distinction of penile squamous cell carcinoma types is as follows:
- HPV-dependent carcinogenesis (carcinogenesis) of basaloid, warty, or similar mixed types of penile carcinoma.
- Basaloid HPV-associated subtype (5-10% of cases).
- Largely HPV-independent carcinogenesis of the usually, well-differentiated and keratinized squamous cell carcinomas (70-75% of cases).
In approximately one-third of all penile carcinomas, an association with an existing HPV infection is detectable. HPV can be detected in approximately 30-60% of all conventional penile carcinomas
Chronic inflammation (inflammation) is a cause of increased incidence of squamous cell carcinoma of the penis.
Chronic inflammation is a cause of the increased incidence of squamous cell carcinomas of the penis.
Micro RNA (RNA: ribonucleic acid) expression also plays a major role in tumorigenesis and progression.
Etiology (Causes)
Biographic Causes
- Socioeconomic factors – low socioeconomic status.
- Countries – African, in South America and in countries of Southeast Asia.
- Unmarried men
- Multiple sexual partners
- Early age of first sexual intercourse
Behavioral causes
- Consumption of stimulants
- Poor sexual hygiene (e.g., accumulation of smegma under the foreskin, which can cause inflammation).
Disease-related causes
- Chronic balanoposthitis (associated with phimosis (narrowing of the foreskin)); often associated with chronic inflammation and dermatoses (e.g., lichen sclerosus et atrophicus).
- Bowenoid papulosis; severe intraepithelial neoplasia in the penile region in the form of flat, reddish-brownish maculo-papular skin lesions, usually with evidence of HPV 16.
- Diseases with condylomata (synonyms: condylomata, wet warts, genital warts).
- Erythroplasia Queyrat (see below pathogenesis).
- HPV infection (in penile carcinoma subtypes 16 and 18 are detectable in up to 80% of cases).
- Leukoplakia (see below pathogenesis).
- Lichen sclerosus et atrophicus (also known as balanitis xerotica obliterans; benign chronic inflammatory precursor lesion; whitish atrophic scarring with foreskin adhesions).
- Bowen’s disease an intradermal carcinoma
- Phimosis (narrowing of the foreskin), not reducible
Other causes
- PUVA (psoralen plus UV-A phototherapy/UV-A) for psoriasis – 286-fold increase in the incidence of invasive penile carcinoma compared with the general population.