Italian observational study on HPV infection, E6, and p16 expression in men with penile cancer (original) (raw)
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Human papillomavirus genotypes and HPV16 variants in penile carcinoma
International journal of cancer. Journal international du cancer, 2008
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 si...
BMC Infectious Diseases
Background: Approximately 50% of cases of penile carcinoma (PeCa), a rare neoplasm worldwide, are associated with human papillomavirus (HPV). However, the detection of HPV-DNA is not sufficient to consider it the etiological factor in the development of this type of cancer. Currently, the overexpression of P16INK4A is used as a surrogate biomarker of HPV carcinogenesis. Information on PeCa in Mexico is scarce, particularly regarding cases related to HPV and genotype frequency. Objective: To evaluate the presence of HPV, its genotypes, and the presence of multiple genotypes, and the expression of P16INK4A, as well as its clinical and histopathological parameters. Methods: For HPV-DNA detection and P16INK4A expression, we used the INNO-LiPA® test and immunohistochemistry, respectively. Results: Sixty cases of PeCa were evaluated, of which 75% were HPV-non-related histological variants. We found that 58.9% (33/56) of PeCa cases were HPV-DNA positive, while 30.9% of the cases evaluated (17/55) were positive for P16INK4A. HPV16 was the main genotype in 42.9% of the cases, followed by HPV52 in 7.1% and HPV18 in 5.4%. Within the HPV-positive cases, 27.3% had multiple genotypes. All HPV-positive patients under the age of 45 years were positive only for HPV16. Conclusions: HPV16 was the most commonly detected genotype in PeCa. HPV 31, 35 and 39 were infrequent; however, they were related to a single infection and P16INK4A overexpression; thus, they seem to be relevant in PeCa carcinogenesis. Our results suggest that P16INK4A overexpression could be useful for the classification of HPV-related PeCa. The role of multiple HPV genotypes in the development and prognosis of PeCa is still not completely understood. Thus, it is necessary to define criteria to establish reliable ways to classify HPV-related PeCa that could lead to optimal therapeutic approaches.
PLOS ONE, 2020
Background In Brazil, penile cancer (PC) is not uncommon. The highest incidence of PC is in the North and Northeast of the country. In addition to phimosis, the Human Papillomavirus (HPV) and Epstein-Baar Virus (EBV) infections are also related as risk factors for PC. The overexpression of p16 INK4a is a surrogate sensitive marker of HPV infection in PC. Objectives To correlate p16 INK4a overexpression and HPV infection status with EBV infection in a series of PC patients from the Amazon region. Methods Tumor tissues from 47 PC cases were analyzed for the presence of HPV and EBV DNA by PCR. All PC patients were diagnosed between 2013 and 2018 at a public reference cancer center hospital in Manaus, Amazonas-Brazil. HPV was genotyped using E7 HPV16/ HPV18 type-specific real-time PCR and the PapilloCheck ® HPV-Screening assay. p16 INK4a expression was evaluated by immunohistochemistry using the automated Ventana ® BenchMark Ultra.
Human Pathology, 2014
Approximately 50% of penile squamous cell carcinomas (SCC) are associated with high-risk human papillomavirus (HR-HPV) infection. We evaluated the correlation of p16 INK4a expression and HR-HPV with clinicopathological features and outcome in a cohort of patients with penile SCC. Two tissue microarrays were constructed from 53 invasive penile SCC at our hospital. p16 INK4a expression was assessed by immunohistochemistry (CINtec Kit). High-risk human papillomavirus status was assessed by in situ hybridization (INFORM HPV III family 16 probe B cocktail). High-risk human papillomavirus was detected in 8 cases (15%), and p16 INK4a overexpression was found in 23 cases (44%). Both markers showed a significant association with histologic subtype (P = .017 and P = .01, respectively) and lymphovascular invasion (P = .015 and P = .015, respectively). Regarding outcome analyses, neither HPV infection nor p16 INK4a overexpression significantly predicted overall survival or cancer-specific survival using Cox proportional hazards regression model. High-risk human papillomavirus positivity and p16 INK4a overexpression were significantly associated with histologic subtype and presence of lymphovascular invasion. Human papillomavirus status was not predictive of outcome in our cohort.
Journal of the American Academy of Dermatology, 2013
Background: Penile squamous cell carcinoma (PSCC) is a tumor with a high metastatic potential. In PSCC the attributable fraction to human papillomavirus (HPV) is not well established. Objective: We sought to provide novel data about the prevalence of HPV in a large series of penile intraepithelial neoplasia (PeIN) and invasive PSCC, correlating the results with the histologic subtype, p16 INK4a immunostaining, and prognosis. Methods: A total of 82 PSCC were included in the study, 69 invasive and 13 PeIN. HPV detection was performed by polymerase chain reaction with SPF-10 broad-spectrum primers followed by DNA enzyme immunoassay and genotyping with a reverse hybridization line probe assay. P16 INK4a immunohistochemical expression on tissue microarrays was also analyzed. Results: HPV DNA was identified in 31 of 77 (40.2%) PSCC (22 of 67 invasive and 9 of 10 PeIN). In 25 of 31 (80.6%) cases HPV-16 was identified. HPV detection was significantly associated with some histologic subtypes: most basaloid and warty tumors were high-risk HPV (hrHPV) positive, whereas only 15% of usual PSCC were hr-HPV positive. All hrHPV-positive PSCC had an adjacent undifferentiated PeIN. Strong p16 INK4a immunostaining correlated with hrHPV infection. Most undifferentiated PeIN showed p16 INK4a immunohistochemical overexpression. Both hrHPV-positive and p16 INK4a-positive tumors showed a better overall survival without reaching statistical significance. Limitations: This was a retrospective study. Conclusions: Our results suggest that most hrHPV-positive PSCC develop from undifferentiated hrHPVpositive PeIN. P16 INK4a immunostaining may be useful in identifying both etiologically related hrHPVpositive tumors and those with better outcome. The routine use of p16 INK4a staining should be incorporated in histologic evaluation of PSCC.
The role of human papillomavirus (HPV) infection in penile carcinoma (PeC) is currently reported and about half of the PeC is associated with HPV16 and 18. We used a PCR-based strategy by using HPV general primers to analyze 86 penile carcinomas paraffin-embedded tissues. Some clinical data, the histological subtype, growth pattern, and differentiation degree were also collected. The amplified fragments were then sequenced to confirm the HPV type and for HPV16/18 variants. DNA samples were also subjected to relative real time PCR for hTERC gene copy number. Some clinical data were also collected. Global HPV frequency was 77.9%. Relative contributions was for HPV16 (85%), 31 (4.4%), 11 (4.4%), 58, 33, 18, and 59 (1.4% each one). Sequence analysis of HPV16 identified European variants and Asian-American (AAb-c) variants in 92% and in 8% of the samples, respectively. Furthermore hTERC gene amplification was observed in only 17% of the cases. Our results suggest that some members of HPV A9 group (represented by HPV16, 58, and 31) are the most frequent among PeC patients studied with an important contribution from HPV16 European variant. The hTERC gene amplification could be poorly related to penile epithelial tissue.
International Journal of Molecular Sciences, 2021
The expression of p16 is a good surrogate of human papillomavirus (HPV) infection in HPV-associated cancers. The significance of p16 expression, HPV genotype and genera in the outcome of patients with HPV-associated cervical cancer (CC) is unclear. Our aim is to ascertain the prognostic significance of these factors. Data from 348 patients (median age: 47.5 years old) with CC, diagnosed in two referral centers, were retrospectively collected. Advanced disease (FIGO2018 IB2-IV) was present in 68% of patients. A single HPV genotype was identified in 82.8% of patients. The most common HPVs were HPV16 (69%) and HPV18 (14%). HPV genera reflected this distribution. HPV16 tumors presented at an earlier stage. P16 was negative in 18 cases (5.2%), 83.3% of which were squamous cell carcinomas. These cases occurred in older patients who tended to have advanced disease. In the univariate analysis, HPV16 (HR: 0.58; p = 0.0198), α-9 genera (HR: 0.37; p = 0.0106) and p16 overexpression (HR: 0.54; ...
Indonesian Journal of Cancer
Background: : Penile cancer is a rare type of cancer in men and was the highest in Bali compared to other regions in Indonesia. Around 95% of malignancies in the penis are squamous cell carcinoma (SCC) type. One of the risk factors associated with penile squamous cell carcinoma is an infection caused by Human Papillomavirus (HPV). Human Papillomavirus E6 and E7 oncoproteins play a significant role in penile squamous cell carcinoma carcinogenesis. Overexpression of p16 protein can be used as a marker of HPV infection. This study aims to determine the expression of p16 protein in penile squamous cell carcinoma.Methods: This study was conducted to determine the prevalence of p16 protein expression was assessed by immunohistochemical examination from paraffin block tumors of penile cancer patients. Expression of p16 was observed to be positive when stained with a strong brown color in the nucleus and cytoplasm of tumor cells. The analysis method used in this study is a descriptive stati...
Role of Human Papillomavirus in Penile Carcinomas Worldwide
Background: Invasive penile cancer is a rare disease with an approximately 22 000 cases per year. The incidence is higher in less developed countries, where penile cancer can account for up to 10% of cancers among men in some parts of Africa, South America, and Asia. Objective: To describe the human papillomavirus (HPV) DNA prevalence, HPV type distribution, and detection of markers of viral activity (ie, E6*I mRNA and p16 INK4a) in a series of invasive penile cancers and penile high-grade squamous intraepithelial lesions (HGSILs) from 25 countries. A total of 85 penile HGSILs and 1010 penile invasive cancers diagnosed from 1983 to 2011 were included. Design, setting, and participants: After histopathologic evaluation of formalin-fixed paraffin-embedded samples, HPV DNA detection and genotyping were performed using