Squamous Cell Carcinoma of the Penis: Premalignant Lesions

Abstract

Of all cancers affecting the penis >95% are squamous cell carcinoma (SCC). The disease is rare, representing only 1% of male cancers, and incidence rates vary across the world. The highest rates are found in Africa and South America and the lowest rates in Israel. Penile intraepithelial neoplasia (PIN) is considered to be a precursor of SCC but only a small proportion (estimated rate 5-15%) of cases of PIN will develop into invasive SCC. The evolution from low-grade PIN to invasive cancer may take as much as 15-20 years.Research into the etiology of cervical cancer has pointed to the role of oncogenic HPV-types, mainly HPV 16. The etiological significance of these oncogenic HPV types has also been established in SCC of the penis: in %50% of cases of SCC of the penis, HPV-DNA is detected (again mainly from HPV 16). Depending on the grade of differentiation of the PIN lesion, 70-100% of cases of PIN will show the presence of HPV-DNA. However, only oncogenic HPV types (16/18) have the ability to transform infected tissue into SCC. HPV types 6/11 lead mainly to the formation of benign warts. Some explanations can be given for the discrepancy between the high incidence of HPV-DNA in highgrade PIN lesions and the much lower incidence in SCC of the penis. Firstly, the sensitivity of the various tests for demonstrating HPV-DNA differs. Secondly, progression to SCC may occur concomitantly with disappearance of HPV. A third reason could be that an HPV-negative precursor lesion has not yet been recognized. Other risk factors associated with SCC are phimosis, recurrent balanoposthitis, lichen sclerosus et atroficus (LSA), smoking, PUVA treatment and HIV infection (see Dillner et al, p. 189).HPV infection is a sexually transmitted disease with a very high rate of acquisition. The infection is characterized by a high rate of spontaneous clearance (!70%). The prevalence of HPV DNA in healthy men is estimated to be 5%, with a peak of 8-11% occurring between 16 and 35 years of age.In almost 60% of male partners of women with cervical intraepithelial neoplasia (CIN), the presence of HPV (mostly the high-risk type HPV 16) has been shown. The etiological role of HPV is supposed to act through binding of the viral oncogene products E6 and E7 to the gene products of the tumor suppressor genes p53 and pRb.HPV infection elicits serum antibody response against HPV capsid. The antibody response is highly HPV type-specific. Because of its stability over time, even after clearance of the infection, this provides a useful marker of cumulative HPV exposure. Seropositivity is strongly correlated with the lifetime number of sexual partners (see Dillner et al, p. 194).The clinical presentation of HPV lesions is paradoxical. Most lesions, and in particular those induced by oncogenic HPV, tend to remain asymptomatic, while symptomatic lesions are mostly caused by lowrisk HPV and are usually self-limiting. Clinical entities histologically identified as PIN III are Bowen's disease, erythroplasia of Qeyrat and bowenoid papulosis.The role of inflammat...

Penile intraepithelial neoplasia: Nomenclature, incidence and progression to malignancy in the Netherlands

“…In the case of a longer follow up, we would expect a higher percentage of malignant progression. Malignant progression can occur after an interval of as long as 20 years …”

“…Histologically, these low‐grade lesions are easily misinterpreted as mild atypia because of inflammation and are therefore named “low grade PeIN”. However, these lesions are often found in the periphery of non‐HPV‐related penile carcinomas and must be interpreted as premalignant . In the VIN nomenclature according to the International Society for Study on Vulvovaginal Diseases, the term VIN I therefore no longer exists .…”

Malignant Tumors of the Penis

“…The presence of HPV DNA in penile SCC in situ ranges from 70% to 100%, and the overall presence of HPV DNA in invasive penile SCC is 22% to 45% . Only high‐risk oncogenic HPV types have the ability to transform infected epithelium into carcinoma, whereas low‐risk HPV types lead mainly to the formation of condyloma acuminata (Figure ) . The most commonly associated HPV type in penile SCC is HPV type 16 .…”

Contemporary diagnosis and management of squamous cell carcinoma (SCC) of the penis

“…Alternatively, positron‐emission tomography (PET)/CT allows for functional and morphological evaluation of the lymph nodes. While this would appear promising, PET/CT only has 20% sensitivity [31] and hence it does not enhance nodal staging accuracy in the early diagnostic period [36]. Recently, lymphotrophic nanoparticle‐enhanced MRI (LNMR) was introduced for lymph node staging [37].…”

“…Treatment of PIN includes either ablation or topical therapy. Topical treatment with 5‐fluorouracil (5‐FU) and imiquimod have been used alone and shown to be effective [31]. Using 5‐FU 5% cream alone or alternating with corticosteroids has been used before various ablative therapies [46].…”