Etiology of squamous cell carcinoma of the penis

Objective: To review the epidemiology of invasive cancer of the penis based on scientific publications identified by a Medline search from 1966-2000 f or the keywords penis/penile, cancer/carcinoma and risk as well as the cite d references in the identified papers. Results: Strong risk factors (OR >10 ) identified by case-control studies included phimosis, chronic inflammator y conditions such as balanopostitis and lichen sclerosus et atrophicus and treatment with psoralen and ultraviolet A photo-chemotheraphy (PUVA). A con sistent association was found between penile cancer and smoking that was do se-dependent and not explained by investigated confounding factors such as sexual history. Sexual history and self-reported history of condyloma were associated with a 3-5-fold increased penile cancer risk. Cervical cancer in the wife was not consistently associated with cancer of the penis in the h usband. Circumcision was associated with penile cancer risk in ecological s tudies. In a case-control study, circumcision neonatally, but not after the neonatal period, was associated with a 3-fold decreased risk, albeit 20% o f penile cancer patients had been circumcised neonatally. In a large number of case series, human papillomavirus (HPV) DNA was identified in penile ne oplastic tissue. In penile intraepithelial neoplasia, between 70 and 100% o f lesions were HPV DNA positive, whereas invasive penile cancer was positiv e in only 40-50% of cases. A few serological case-control studies and one p rospective study also identified an association between HPV type 16 and pen ile cancer risk. An association between penile cancer risk and HPV prevalen ce in the population was also suggested by ecological studies. Conclusion: The evidence on risk factors for penile cancer suggests that preventive mea sures that could be considered include prevention of phimosis, treatment of chronic inflammatory conditions, Limiting PUVA treatment, smoking cessatio n and prophylactic prevention of HPV infection.