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Cancers
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Penile Carcinoma
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Penile Carcinoma

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (10 October 2023) | Viewed by 14771

Special Issue Editor

Prof. Dr. Kerstin Junker

E-Mail Website
Guest Editor
Department of Urology and Pediatric Urology, Saarland University, Kirrberger Straße 100, Gebäude 6, 66424 Homburg/Saar, Germany
Interests: tumor biomarkers; tumor microenvironment; miRNA; extracellular vesicles; urological malignancies
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Penile squamous cell carcinoma (PSCC) is a rare tumor disease with regionally heterogeneous incidences. HPV infection is the most important risk factor. About 50% of PSCC are HPV-related. It is of high clinical impact to establish prognostic parameters to identify patients who are likely to benefit from invasive surgical options such as lymph node dissection or adjuvant systemic therapy. Although TNM classification has been approved and additional parameters including HPV infection have been evaluated, individual risk assessment is still unsatisfactory. Furthermore, standardized effective systemic therapies for metastatic disease are missing. In this regard, molecular characterization and development of preclinical models are essential to improve patient care for this urological disease. The focus of this Special Issue is to present new developments in clinical as well as experimental research in penile cancer including original manuscripts and reviews.

Prof. Dr. Kerstin Junker
Guest Editor

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Published Papers (5 papers)

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Research

Jump to: Review

27 pages, 12196 KiB  
Article
Evaluation of Prognostic Parameters to Identify Aggressive Penile Carcinomas
by Jan Niklas Mink, Oybek Khalmurzaev, Alexey Pryalukhin, Carol Immanuel Geppert, Stefan Lohse, Kristof Bende, João Lobo, Rui Henrique, Hagen Loertzer, Joachim Steffens, Carmen Jerónimo, Heiko Wunderlich, Julia Heinzelbecker, Rainer M. Bohle, Michael Stöckle, Vsevolod Matveev, Arndt Hartmann and Kerstin Junker
Cancers 2023, 15(19), 4748; https://doi.org/10.3390/cancers15194748 - 27 Sep 2023
Viewed by 1301
Abstract
Background: Advanced penile carcinoma is characterized by poor prognosis. Most data on prognostic factors are based on small study cohorts, and even meta-analyses are limited in patient numbers. Therefore, there is still a lack of evidence for clinical decisions. In addition, the most [...] Read more.
Background: Advanced penile carcinoma is characterized by poor prognosis. Most data on prognostic factors are based on small study cohorts, and even meta-analyses are limited in patient numbers. Therefore, there is still a lack of evidence for clinical decisions. In addition, the most recent TNM classification is questionable; in line with previous studies, we found that it has not improved prognosis estimation. Methods: We evaluated 297 patients from Germany, Russia, and Portugal. Tissue samples from 233 patients were re-analyzed by two experienced pathologists. HPV status, p16, and histopathological parameters were evaluated for all patients. Results: Advanced lymph node metastases (N2, N3) were highly significantly associated with reductions in metastasis-free (MFS), cancer-specific (CS), and overall survival (OS) rates (p = <0.001), while lymphovascular invasion was a significant parameter for reduced CS and OS (p = 0.005; p = 0.007). Concerning the primary tumor stage, a significant difference in MFS was found only between pT1b and pT1a (p = 0.017), whereas CS and OS did not significantly differ between T categories. In patients without lymph node metastasis at the time of primary diagnosis, lymphovascular invasion was a significant prognostic parameter for lower MFS (p = 0.032). Histological subtypes differed in prognosis, with the worst outcome in basaloid carcinomas, but without statistical significance. HPV status was not associated with prognosis, either in the total cohort or in the usual type alone. Conclusion: Lymphatic involvement has the highest impact on prognosis in penile cancer, whereas HPV status alone is not suitable as a prognostic parameter. The pT1b stage, which includes grading, as well as lymphovascular and perineural invasion in the T stage, seems questionable; a revision of the TNM classification is therefore required. Full article
(This article belongs to the Special Issue Penile Carcinoma)
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12 pages, 1337 KiB  
Article
Prognostic Significance of p16 and Its Relationship with Human Papillomavirus Status in Patients with Penile Squamous Cell Carcinoma: Results of 5 Years Follow-Up
by Jad Chahoud, Niki M. Zacharias, Rachel Pham, Wei Qiao, Ming Guo, Xin Lu, Angelita Alaniz, Luis Segarra, Magaly Martinez-Ferrer, Frederico Omar Gleber-Netto, Curtis R. Pickering, Priya Rao and Curtis A. Pettaway
Cancers 2022, 14(24), 6024; https://doi.org/10.3390/cancers14246024 - 7 Dec 2022
Cited by 17 | Viewed by 2957
Abstract
Penile Squamous Cell Carcinoma (PSCC) is associated with high-risk human papillomavirus (HR-HPV). The immunohistochemical (IHC) test for p16INK4a (p16) is highly correlated with HR-HPV expression in other SCCs. To investigate whether the expression of p16 IHC or HR-HPV is associated with survival [...] Read more.
Penile Squamous Cell Carcinoma (PSCC) is associated with high-risk human papillomavirus (HR-HPV). The immunohistochemical (IHC) test for p16INK4a (p16) is highly correlated with HR-HPV expression in other SCCs. To investigate whether the expression of p16 IHC or HR-HPV is associated with survival in PSCC, we conducted a single institution analysis of 143 patients with a diagnosis of PSCC and, available tissue were tested for p16 IHC staining patterns, histological subtype, tumor grade, and lymphovascular invasion (LVI) by an experienced pathologist. HR-HPV status using the Cobas PCR Assay or the RNAScope high-risk HPV in situ hybridization kit were also assessed. Patient characteristics were summarized using descriptive statistics of clinico-pathologic variables. Kaplan–Meier was used to estimate median overall survival (OS), cancer specific survival (CSS) and correlated with HPV, p16, and other study variables. Patients with p16+ tumors had a significantly longer median CSS in comparison to the p16– group (p = 0.004), with respective 5-year CSS probability of 88% (95% CI; 0.84, 1) versus 58% (95% CI; 0.55, 0.76; p = 0.004). HPV status did not predict survival outcomes. Multivariable analysis with respect to OS and CSS, showed that p16+ status was associated with a lower risk of death (HR = 0.36, 95%CI; 0.20–0.67, p = 0.001), and improved CSS (HR = 0.20, 95% CI; 0.07–0.54, p = 0.002) after adjusting for covariates. In conclusion, tumor p16 status via IHC was an easy to perform independent prognostic factor for OS and CSS that correlates with HR-HPV expression. Full article
(This article belongs to the Special Issue Penile Carcinoma)
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11 pages, 1971 KiB  
Article
Penile Squamous Cell Carcinomas in Sub-Saharan Africa and Europe: Differential Etiopathogenesis
by Carolina Manzotti, Laurina Chulo, Ricardo López del Campo, Isabel Trias, Marta del Pino, Ofélia Saúde, Iracema Basílio, Nelson Tchamo, Lucilia Lovane, Cesaltina Lorenzoni, Fabiola Fernandes, Adela Saco, Maria Teresa Rodrigo-Calvo, Lorena Marimon, Mamudo R. Ismail, Carla Carrilho, Inmaculada Ribera-Cortada, Jaume Ordi and Natalia Rakislova
Cancers 2022, 14(21), 5284; https://doi.org/10.3390/cancers14215284 - 27 Oct 2022
Cited by 3 | Viewed by 1998
Abstract
Penile squamous cell carcinomas (PSCC) are classified by the World Health Organization into two categories based on their relationship with the human papillomavirus (HPV): HPV-associated and HPV-independent. We compared a cohort of PSCC from Mozambique, a sub-Saharan country in southeast Africa with a [...] Read more.
Penile squamous cell carcinomas (PSCC) are classified by the World Health Organization into two categories based on their relationship with the human papillomavirus (HPV): HPV-associated and HPV-independent. We compared a cohort of PSCC from Mozambique, a sub-Saharan country in southeast Africa with a high prevalence of HPV and HIV infection, and Spain, a country in southwestern Europe with a low prevalence of HPV and HIV, to study the distribution of the etiopathogenic categories of these tumors in both sites. A total of 79 PSCC were included in the study (28 from Mozambique and 51 from Spain). All cases underwent HPV-DNA polymerase chain reaction (PCR) testing, genotyping, and immunohistochemistry for p16 and p53. Any PSCC showing either p16 overexpression or HPV-DNA in PCR analysis was considered HPV-associated. Overall, 40/79 (50.6%) tumors were classified as HPV-associated and 39 (49.4%) as HPV-independent. The two sites showed marked differences: 25/28 (89.3%) tumors from Mozambique and only 15/51 (29.4%) from Spain were HPV-associated (p < 0.001). HPV16 was the most frequent HPV type identified in 64.0% (16/25) of the HPV-associated tumors from Mozambique, and 60.0% (9/15) from Spain (p = 0.8). On average, patients from Mozambique were almost two decades younger than those from Spain (mean age 50.9 ± 14.9 and 69.2 ± 13.3, respectively [p < 0.001]). In conclusion, significant etiopathogenic differences between PSCC in Mozambique and Spain were observed, with a remarkably high prevalence of HPV-associated tumors in Mozambique and a relatively low prevalence in Spain. These data may have important consequences for primary prevention of PSCC worldwide. Full article
(This article belongs to the Special Issue Penile Carcinoma)
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13 pages, 4687 KiB  
Article
Evaluation of the Cellular Dissociation Grading, Based on Tumor Budding and Cell Nest Size, in Squamous Cell Carcinoma of the Penis
by Hayel Derani, Anne-Sophie Becker, Oliver Hakenberg and Andreas Erbersdobler
Cancers 2022, 14(19), 4949; https://doi.org/10.3390/cancers14194949 - 9 Oct 2022
Cited by 2 | Viewed by 1980
Abstract
The “Cellular Dissociation Grade” (CDG) is based on tumor cell budding and cell nest size. Many studies have examined the CDG in squamous cell carcinomas of other organs such as the lungs, oral cavity, pharynx, larynx, cervix and esophagus. In this study, the [...] Read more.
The “Cellular Dissociation Grade” (CDG) is based on tumor cell budding and cell nest size. Many studies have examined the CDG in squamous cell carcinomas of other organs such as the lungs, oral cavity, pharynx, larynx, cervix and esophagus. In this study, the CDG was examined in 109 cases of invasive penile squamous cell carcinoma that were treated at the University Medicine Rostock between 2014 and 2022. Furthermore, its correlation with the pathologic status of regional lymph nodes (pN) as the main prognostic factor was verified. Finally, cellular dissociation grading was compared with classic WHO grading. The results showed that pN in penile squamous cell carcinoma showed a highly significant association with the CDG and no statistically significant association with WHO grading. These results support the notion that cellular dissociation grading is an important prognostic factor for squamous cell carcinoma. Full article
(This article belongs to the Special Issue Penile Carcinoma)
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Review

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22 pages, 38928 KiB  
Review
Multiparametric Magnetic Resonance Imaging of Penile Cancer: A Pictorial Review
by Marta D. Switlyk, Andreas Hopland, Edmund Reitan, Shivanthe Sivanesan, Bjørn Brennhovd, Ulrika Axcrona and Knut H. Hole
Cancers 2023, 15(22), 5324; https://doi.org/10.3390/cancers15225324 - 8 Nov 2023
Cited by 3 | Viewed by 5556
Abstract
The role of multiparametric magnetic resonance imaging (mpMRI) in assessing penile cancer is not well defined. However, this modality may be successfully applied for preoperative staging and patient selection; postoperative local and regional surveillance; and assessments of treatment response after oncological therapies. Previous [...] Read more.
The role of multiparametric magnetic resonance imaging (mpMRI) in assessing penile cancer is not well defined. However, this modality may be successfully applied for preoperative staging and patient selection; postoperative local and regional surveillance; and assessments of treatment response after oncological therapies. Previous studies have been mostly limited to a few small series evaluating the accuracy of MRI for the preoperative staging of penile cancer. This review discusses the principles of non-erectile mpMRI, including functional techniques and their applications in evaluating the male genital region, along with clinical protocols and technical considerations. The latest clinical classifications and guidelines are reviewed, focusing on imaging recommendations and discussing potential gaps and disadvantages. The development of functional MRI techniques and the extraction of quantitative parameters from these sequences enables the noninvasive assessment of phenotypic and genotypic tumor characteristics. The applications of advanced techniques in penile MRI are yet to be defined. There is a need for prospective trials and feasible multicenter trials due to the rarity of the disease, highlighting the importance of minimum technical requirements for MRI protocols, particularly image resolution, and finally determining the role of mpMRI in the assessment of penile cancer Full article
(This article belongs to the Special Issue Penile Carcinoma)
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