These data reinforce the need for detailed analyses of immune dysregulation in CIN patients. They also suggest the potential usefulness of the cytokine assays for determining prognosis or deciding whether cytokine-based therapy is indicated.

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.

No abstract

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. Infections with certain types of human papillomaviruses (HPV) have been strongly and consistently associated with the development of cervical intraepithelial neoplasia (CIN) and cervical cancer worldwide. 1-5 The more than 40 HPV genotypes infecting the genital mucosa can be divided into 3 groups: 'high-riskÕ or 'carcinogenicÕ types (16,18,31,33,35,39,45,51,52,56, 58, 59) associated with a high relative risk of cervical cancer; 'low riskÕ viruses (6,11,40,42,43,44,54, 61, 70, 72, 81, 89) associated with benign epithelial proliferations in the genital area, but not associated with invasive cervical cancer; and a group of 6 types (26,53, 66, 68, 73, 82) that is classified as 'probably carcinogenicÕ since there is limited data associating these HPV types with cervical cancer. 6,7 Additionally, carcinogenic HPVs are involved in the development of a subset of other carcinomas arising from mucosal squamous epithelial cells including penile carcinoma. 8 Penile cancer is a relatively rare disease in Europe and United States with incidence rates varying from 0.5 to 1.5 per 100,000 men. In other parts of the world and particularly in developing countries, however, it is a common male cancer with an incidence of 2 to 5 per 100,000 men, constituting for example, 12-22% of all male cancers in countries like Brazil, Uganda and Puerto Rico, which are also communities with high rates of cervical neoplasia. 9 Epidemiological studies have indicated that HPVs are sexually transmitted pathogens infecting the male and female squamous epithelium of the anogenital tract with similar prevalence rates (28%) in symptom-less university students. 10 Moreover, sub-clinical penile lesions (flat penile lesions) are frequently found in male sexual partners of women with CIN, with HPV infection rates of 73% and genotype concordance of 36% within the couples. 11 The prevalence of HPV-related high-grade penile intraepithelial neoplasia, however, is very low suggesting that penile tissue is less prone to maintain persistent infection and to undergo neoplastic transformation. As for the cervical cancer pathogenesis, several additional risk factors have been reported, in conjunction with HPV infection, for the development of invasive penile cancer: (i) exogenous cofactors (lack of circumcision in childhood, phimosis, smoking, trauma), 12,13 (ii) host cofactors (genetic factors, immune response) 14,15 and (iii) viral cofactors (infection by specific types, viral load, viral integration status).The frequency of ...

The number of positive lymph nodes represents the strongest prognostic factor in melanoma of the vulva. Because of the lack of effective adjuvant therapies, such prognostic indicators might be used to define the timing and extent of the surgical approach.