Analysis of TP53 codon 72 polymorphism in HPV-positive and HPV-negative penile carcinoma.

The association of the p53 polymorphism at codon 72 and susceptibility to develop human papillomavirus (HPV)-related cancer has been investigated in several studies with controversial results. In this study, 78 penile squamous cell carcinoma biopsies (n=17 from Uganda, n=61 from Italy) and blood samples from 150 healthy controls (n=57 from Uganda, n=93 from Italy) have been analyzed for the arginine and proline allele distribution. Among Ugandan cases the heterozygous, proline homozygous and arginine homozygous genotype frequency was 41.2%, 52.9% and 5.9%, respectively, and among controls was 40.3%, 54.4%, and 5.3%, respectively (P=0.9917). Conversely, among Italian cases genotype distribution was 42.6%, 4.9%, and 52.5%, and among controls was 34.4%, 7.5%, and 58.1%, respectively (P=0.5343). No significant differences in arginine and proline allele distribution were observed when the cases were stratified by HPV status. Therefore, no evidence of association between homozygosity for p53 arginine and HPV-related or HPV-unrelated penile squamous cell carcinoma was observed neither among Ugandan nor among Italian populations.

Peniscopically controlled CO2 laser excision for conservative treatment of in situ and T1 penile carcinoma: report on 224 patients.

OBJECTIVE: To evaluate the outcome of peniscopically controlled laser excision of early-stage penile carcinoma. METHODS: Patients treated from 1982 to 2006 were investigated. The primary treatment was excisional surgery alone for in situ or initially invasive flat tumors, and reductive chemotherapy followed by surgery for the exophytic lesions. All excisional procedures were conducted by CO(2) laser under peniscopic control. RESULTS: Of a total of 224 patients, 111 underwent partial excision of the glans and/or coronal sulcus surface, and 113 total surface excision. Forty patients underwent reductive chemotherapy. Complete excision was obtained in 221 cases (98.7%) at lateral margins and in 217 cases (96.9%) at deep margin. Postoperative complications were negligible. Overall, the 10-yr recurrence rate was 17.5% (95% confidence interval, 16.4-18.6%), and apparently was not affected by the in situ or invasive nature of the lesion. Amputation was required in nine patients, for a 10-yr amputation rate of 5.5% (range, 5.2-5.7%). In the remaining cases, organ form and curvature were preserved, with satisfactory cosmetic and functional results. CONCLUSIONS: Early-stage penile carcinomas can be effectively treated with the organ-sparing strategy described here. Because local recurrences occur in a minority of patients and can be safely treated, organ preservation is compatible with local disease control. Reductive systemic chemotherapy in selected exophytic cases broadens the indication for our conservative approach.

Human papillomavirus genotypes and HPV16 variants in penile carcinoma.

The causative role of human papillomaviruses (HPV) and HPV16 variants has been extensively studied in uterine cervix dysplastic lesions and invasive carcinoma; few such studies, however, have been performed in penile tumors. We have investigated HPV genotype and HPV16 variant distribution on 41 penile cancer biopsies from Italian patients. Cases were extracted from the respective pathology departments databases of National Cancer Institutes in Naples and Milan. HPV sequences were detected by PCR and characterized by direct sequence analysis. Among the 19 HPV-positive cases (46.3%) 2 viral genotypes were identified (HPV16 and 18) with HPV16 accounting for 94.7% (18 out of 19) of the infections. Sequence analysis of E6, E7 genes and long control region (LCR) of 18 HPV16 isolates allowed the identification of European (E-G-350) and non-European (AA and Af-1) variants in 44.4% and in 55.6% of the samples, respectively. The AA variant alone represented 44.4% of all HPV16 infections, a significantly higher frequency of that observed in cervical carcinoma from Italian women (Tornesello et al., J Med Virol 2004;74:117-26). Our results suggest that HPV16 has a very high prevalence among penile cancer patients in Italy and the increased frequency of HPV16 non-European classes, particularly the AA, suggests that they are more oncogenic than European variants in penile tissue.

Analysis of human papillomavirus type-16 variants in Italian women with cervical intraepithelial neoplasia and cervical cancer.

Human papillomavirus type 16 (HPV-16) classes (E, AA, As, Af1, Af2) and their variants have different geographic distribution and different degrees of association with cervical lesions. This study was designed to examine HPV-16 variants among Italian women and their prevalence in case patients (affected by invasive cervical carcinoma or cervical intraepithelial neoplasia grade 2-3 and cervical intraepithelial neoplasia grade 1), versus control subjects with normal cervical epithelium (controls). A total of 90 HPV-16 positive cervical samples from women of Italian Caucasian descent have been tested, including 36 invasive cervical carcinomas, 21 with cervical intraepithelial neoplasias grade 2-3, 17 with cervical intraepithelial neoplasia grade 1 and 16 controls. HPV-16 was detected with an E6/E7 gene-specific polymerase chain reaction, and variant HPV-16 classes and subclasses were identified by direct nucleotide sequencing of the region coding for the E6 and the E7 oncoproteins, the MY09/11-amplified highly conserved L1 region, and the long control region (LCR). Among the 90 HPV-16 samples, nine viral variants have been identified belonging to the European (Ep-T350 and E-G350) and non-European (AA and Af-1) branches. The E-G350 is the prevalent variant in all analyzed different disease stages being present in 55.5% of ICC, 52.4% of cervical intraepithelial neoplasias 2-3, 47.1% of cervical intraepithelial neoplasia grade 1, and 50.0% of control samples. The non-European variants AA and Af1, rarely detected in control samples, represent 33.3% of all HPV-16 infections in invasive cervical carcinoma (with a peak of 19.4% and 13.9%, respectively), showing a statistically significant increase in frequency in more advanced lesions (chi(2) trend = 7.2; P < 0.05). The prevalence of HPV-16 Ep-T350, however, is higher in controls (43.7%) and in of cervical intraepithelial neoplasia grade 1 (41.2%) than in cervical intraepithelial neoplasia grade 2-3 (28.6%) and in invasive cervical carcinoma (11.1%) cases strongly suggesting lack of progression for pre-neoplastic lesions associated with such variant. The increased frequency of non-European variants in invasive lesions suggests that they are more oncogenic than European variants. This could have implications for future diagnostic and therapeutic strategies.