The management and prevention of premalignant penile lesions.

Abstract

Although penile cancer may arise de novo, there are evidence-based observations defining recognizable conditions preceding squamous cell carcinoma (SCC). It seems that many cases of penile SCC may either be prevented or at least diagnosed early enough to avoid invasion. The fact that the frequency of previous or concomitant penile symptoms or manifestations in various series of SCC varies within the range 7.6–42.2% may be due to some degree to ignorance. However, it is more likely that cultural, educational and/or professional factors cause considerable diagnostic and therapeutic delay (1, 2). Patients may disregard the condition merely because symptoms are only mild, if they occur at all. Furthermore, there is a broad range of clinical presentations and suboptimal diagnostic attention or initial misclassification by the physician can delay the proper diagnosis and therapy. At one end of the spectrum disorders exist that are generally considered to be medically benign, such as inflammatory conditions and warts; at the other end, penile intraepithelial neoplasia (PIN), clinically known as bowenoid papulosis (BP), morbus Bowen (MB) or erythroplasia of Queyrat (EQ), occurs. A diagnostic problem is that apparently benign warts, inflammatory conditions and PIN lesions coexist and overlap. Men suffering from penile warts (“condylomas”) generally attend a physician because of physical complaints or psychosexual disturbances (3, 4). Condyloma therapy, whether based on self-therapy with podophyllotoxin or imiquimod or on surgical wart eradication, is not necessarily associated with viral clearance. Condylomas, induced by non-oncogenic HPVs (6/11), coexist epidemiologically with oncogenic HPV infection (16/18). Therefore, this review of the therapy of premalignant lesions addresses the proper management of preceding or concurrent condylomatous disease. A vigilant diagnostic approach, including histopathological evaluation, is required as part of the therapeutic strategy in cases of clinical diagnostic uncertainty in order to detect premalignant lesions. This is particularly true in males >35–40 years and in immunosuppressed patients. A biopsy is also always recommended when severe intraepithelial neoplasia is suspected. While the risk of transformation of BP into invasive SCC is considered extremely rare in patients <35 years, transformation of PIN III in older men is estimated to occur in 10–20% of cases. Rational prevention and therapeutic measures against progression of premalignant disease include: (1) topical therapy of condylomas with non-mutagenic drugs, such as podophyllotoxin or imiquimod, and/or surgical destruction; (2) surgical excision or destruction of PIN lesions and long-lasting warts that have not responded to previous therapy; (3) adequate topical therapy and careful clinical follow-up of inflammatory conditions, in particular lichen sclerosus et atrophicus (LSA); and (4) early surgical correction of congenital or acquired phimosis. We present an updated review of topical and surgical therapy, as based on recent recommendations (5–8). The principles of evidence-based medicine have been applied and guidelines are based on grading strength and quality of evidence as suggested by the British Agency for Health Care Policy and Research (see Appendix) (9). For each therapeutic modality the strength of recommendations (A–E) and the quality of evidence (I–IV) are presented within parentheses for each therapeutic modality suggested for the respective diagnosis. We also address the current belief that early therapy against genital LSA using the ultrapotent steroid