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De Martino S, Capasso B, Cis L, D'Orsi L, Canali G, Capasso P, De Gaetano A, Mercantini P, Mascagni D, Gaetano C, Farsetti A, Lo Presti E. Role of innate immunity in tumor microenvironment of HPV-associated anal cancer: the hypothetical beneficial role of γδ T cells. Crit Rev Oncol Hematol 2025:104771. [PMID: 40412574 DOI: 10.1016/j.critrevonc.2025.104771] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2025] [Revised: 05/13/2025] [Accepted: 05/19/2025] [Indexed: 05/27/2025] Open
Abstract
HPV infection plays a crucial role in the formation of the tumor microenvironment, especially in tumors associated with the genital tract, anus, and oropharyngeal region. In this manuscript, we will discuss the main genetic characteristics of HPV and its transmission mechanisms, with a specific focus on the expression of the oncogenes E6 and E7. We will also address the major tumors HPV can generate and their associated epidemiology. In particular, persistent HPV infection induces the release of pro-inflammatory cytokines (such as IL-6 and IL-8), which promote angiogenesis and the recruitment of immunosuppressive immune cells. We will describe on the immune response to the infection, specifically in adaptive immunity, where the virus reduces the expression of MHC class I molecules on infected cells, preventing recognition by cytotoxic T cells. The innate immune response against HPV infection is often ineffective, allowing the virus to persist and contribute to tumor progression. The focus of this work will be on the innate response mediated by γδ T lymphocytes, a subset of CD3+ T cell. Indeed, they recognize HPV-infected cells without the need for antigen presentation by MHC molecules, secrete pro-inflammatory cytokines like IFN-γ and TNF-α, and directly kill HPV-infected cells through cytotoxic mechanisms. In summary, γδ T lymphocytes play an important role in the innate and adaptive immune response against HPV, but the effectiveness of their action can be reduced by the immune evasion mechanisms mediated by the virus. This may occur through the creation of an immunosuppressive environment with the release of immunosuppressive cytokines (such as IL-10 and TGF-β) that inhibit the function of these cells, allowing the virus to persist and contribute to tumor progression. This mechanism has not been well studied in the emerging anal cancer induced by HPV infection, so tracing the state of the art on these aspects could lead to an increase in research in this area and promote the creation of specific immunotherapies that enhance the role of these cells.
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Affiliation(s)
- Sara De Martino
- National Research Council of Italy, Institute for Systems Analysis and Computer Science "A. Ruberti, " BioMatLab (Biomathematics Laboratory), UCSC Largo A. Gemelli 8, 00168 Rome, Italy
| | - Biagio Capasso
- Department of Surgical Sciences, La Sapienza University of Rome, Rome, Italy
| | - Luca Cis
- National Research Council of Italy, Institute for Systems Analysis and Computer Science "A. Ruberti, " BioMatLab (Biomathematics Laboratory), UCSC Largo A. Gemelli 8, 00168 Rome, Italy
| | - Laura D'Orsi
- National Research Council of Italy, Institute for Systems Analysis and Computer Science "A. Ruberti, " BioMatLab (Biomathematics Laboratory), UCSC Largo A. Gemelli 8, 00168 Rome, Italy
| | - Giulia Canali
- Department of Medical Surgical sciences and translational medicines, Sapienza University of Rome, 00185 Rome, Italy
| | - Pasquale Capasso
- Medical Polyspecialistic Department, Cardarelli Hospital, Via Antonio Cardarelli, 9, 80131 Naples NA
| | - Andrea De Gaetano
- National Research Council of Italy, Institute for Systems Analysis and Computer Science "A. Ruberti, " BioMatLab (Biomathematics Laboratory), UCSC Largo A. Gemelli 8, 00168 Rome, Italy; National Research Council of Italy (CNR), Institute for Biomedical Research and Innovation (IRIB), 90146 Palermo, Italy; Department of Biomatics, Óbuda University, Bécsi Road 96/B, H-1034 Budapest, Hungary
| | - Paolo Mercantini
- Department of Medical Surgical sciences and translational medicines, Sapienza University of Rome, 00185 Rome, Italy
| | - Domenico Mascagni
- Department of Surgical Sciences, La Sapienza University of Rome, Rome, Italy
| | - Carlo Gaetano
- Epigenetics Laboratory - Maugeri Scientific Clinical Institutes, Pavia, Italy
| | - Antonella Farsetti
- National Research Council of Italy, Institute for Systems Analysis and Computer Science "A. Ruberti, " BioMatLab (Biomathematics Laboratory), UCSC Largo A. Gemelli 8, 00168 Rome, Italy
| | - Elena Lo Presti
- National Research Council of Italy (CNR), Institute for Biomedical Research and Innovation (IRIB), 90146 Palermo, Italy.
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Williams GA, Wu AA, Eugene HC, Tsai YC, Wong M, Nonogaki H, Roden RB, Hung CF, Wu TC, Vang R, Xing D. Clinicopathologic Features and Viral Status of Low-risk HPV6 and HPV11-Associated Squamous Cell Carcinoma of the Uterine Cervix and Vulva. Am J Surg Pathol 2025; 49:458-470. [PMID: 39886739 PMCID: PMC12003062 DOI: 10.1097/pas.0000000000002367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2025]
Abstract
Despite being designated as "noncarcinogenic" human papillomavirus (HPV) types, mono-infection with HPV6 or HPV11 has been found in squamous cell carcinomas (SCCs) at specific sites, including the larynx, penis, anus, and rarely, the lower female genital tract. The association between clinicopathologic features, viral status, and the carcinogenic mechanisms related to these low-risk HPVs remains unclear. The current study characterizes a series of low-risk HPV6 and HPV11-associated SCCs of the uterine cervix (6 cases) and vulva (2 cases). The diagnosis of SCC was made through the identification of stromal invasion in 6 cases. In case 2, the diagnosis of cancer was made after metastases to the sigmoid colon and liver. The patient in case 6 was diagnosed with intramucosal papillary SCC given multiple recurrences. While all tumors displayed a similar verruco-papillary architecture, the cytologic features, and immunostaining patterns suggest 2 groups of lesions: one with high-grade cytology and a high Ki-67 proliferation index (>60% of lesional cells), and the other with low-grade cytology and a low Ki-67 (20% to 30% of lesional cells). The detection of HPV6 in 7 of 8 cases underscores its critical role in carcinogenesis at these anatomic sites. Case 8 represented the only patient who was infected with HPV11 and who had a well-controlled human immunodeficiency virus infection. Correlating with viral status, all cases, except case 7, demonstrated a negative or focal p16 staining pattern. In case 7, despite a block pattern of p16 staining often seen in predicting high-risk HPV, we employed several methods to confirm HPV6 as the sole HPV infection. Although this descriptive study does not establish an etiological mechanism for how HPV6/11 leads to malignant transformation, our results exclude the possibility of viral integration through a quantitative polymerase chain reaction-based analysis of the E2/E6 ratio. Our study highlights and expands upon the clinicopathologic features of a distinct group of low-risk HPV6/11-associated SCCs in the cervix and vulva. Although rare, recognizing this group of lesions is important for pathologists and oncologists, as it provides a basis for guiding appropriate prevention strategies and treatment modalities based on the viral type.
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Affiliation(s)
- Guy A. Williams
- Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD
| | - Annie A. Wu
- Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD
| | - Henrietta C. Eugene
- Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD
| | - Ya-Chea Tsai
- Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD
| | - Margaret Wong
- Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD
| | - Hiro Nonogaki
- Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD
| | - Richard B.S. Roden
- Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD
- Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD
- Department of Gynecology and Obstetrics, The Johns Hopkins Medical Institutions, Baltimore, MD
| | - Chien-Fu Hung
- Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD
- Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD
| | - Tzyy-Choou Wu
- Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD
- Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD
- Department of Gynecology and Obstetrics, The Johns Hopkins Medical Institutions, Baltimore, MD
| | - Russell Vang
- Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD
- Department of Gynecology and Obstetrics, The Johns Hopkins Medical Institutions, Baltimore, MD
| | - Deyin Xing
- Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD
- Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD
- Department of Gynecology and Obstetrics, The Johns Hopkins Medical Institutions, Baltimore, MD
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Dorofte L, Davidsson S, Carlsson J, Larsson GL, Karlsson MG. New histological risk grading system for prediction of lymph node metastasis in patients with penile cancer. Virchows Arch 2025; 486:759-767. [PMID: 39251424 PMCID: PMC12018598 DOI: 10.1007/s00428-024-03916-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Revised: 07/07/2024] [Accepted: 08/27/2024] [Indexed: 09/11/2024]
Abstract
Inguinal lymph node surgery is a standard treatment for penile cancer patients with intermediate or high risk for lymph node metastasis (LNM) according to European Association of Urology (EAU) risk grading. We are proposing a more objective histological prognostic grading system for inguinal LNM in these patients. We assessed worst pattern of invasion, lymphocytic host response, lymphovascular invasion, and perineural invasion in a population-based cohort of 306 penile cancer patients. Patients were classified into low, intermediate, and high risk for inguinal LNM. There was a significant association both between risk groups and pT stage (p < 0.001) and between risk groups and LNM. Univariate logistic regression showed 25.43 times higher odds of LNM for patients in the intermediate risk group compared with the low risk group (odds ratio (OR) 25.43; 95% confidence interval (CI): 5.94-108.97) and a 177.13 times higher odds in the high risk group compared to the low risk group (OR 177.13; 95% CI: 40.09-782.51). When comparing our histological risk grading with the EAU grading, we found a higher sensitivity, of 51.28% (95% CI: 45.68-56.88) versus 37.09% (95% CI: 31.68-42.50), as well as a higher area under the curve (0.86; 95% CI: 0.81-0.89; versus 0.65; 95% CI: 0.58-0.71) with our grading system. While our grading classified 111 patients as low risk, only 31 were considered low risk for LNM according to the EAU risk classification. The new histological risk grading system shows a higher sensitivity and includes a higher number of patients in the low risk group in whom lymph node surgery could be avoided, reducing morbidity and costs.
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Affiliation(s)
- Luiza Dorofte
- Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
| | - Sabina Davidsson
- Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Jessica Carlsson
- Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Gabriella Lillsunde Larsson
- Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
- School of Health Sciences, Örebro University, Örebro, Sweden
| | - Mats G Karlsson
- Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
- School of Health Sciences, Örebro University, Örebro, Sweden
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Balgovind P, Aung E, Shilling H, Murray GL, Molano M, Garland SM, Fairley CK, Chen MY, Hocking JS, Ooi C, McNulty A, McCloskey J, McNamee K, Bateson D, Owen L, Tabrizi SN, Machalek DA. Human Papillomavirus Prevalence Among Australian Men Aged 18-35 Years in 2015-2018 According to Vaccination Status and Sexual Orientation. J Infect Dis 2025; 231:451-461. [PMID: 39213380 DOI: 10.1093/infdis/jiae412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Revised: 08/09/2024] [Accepted: 08/28/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND Australia introduced a national human papillomavirus (HPV) vaccination program for girls in 2007 and boys in 2013, achieving high coverage. We assessed HPV prevalence among men who have sex with women (MSW) and men who have sex with men (MSM) aged 18-35 years and examined program effects. METHODS Between 2015-2018, men self-collected a penile or intra-anal swab for HPV genotyping. Vaccination status was confirmed with the National Register. HPV prevalence was examined by age groups and vaccination status. RESULTS Prevalence of quadrivalent vaccine-targeted HPV types (6, 11, 16, 18) was 10.6% (95% confidence interval [CI], 8.7%-12.8%) in unvaccinated MSW and 10.7% (95% CI, 5.7%-19.3%) in vaccinated MSW (P = .96). Prevalence was 40.3% (95% CI, 36.0%-44.8%) in unvaccinated MSM and 29.9% (95% CI, 23.1%-37.8%) in vaccinated MSM (P = .02). Among those with confirmed doses, quadrivalent types were detected in 0% (95% CI, 0%-7.7%; n = 46) of men who had their first dose at 13-19 years and 37.2% (95% CI, 27.5%-47.8%; n = 94) in those who received their first dose at 20 years or older. CONCLUSIONS Our data demonstrate the importance of universal adolescent HPV vaccination to ensure MSM receive the same benefits as MSW.
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Affiliation(s)
- Prisha Balgovind
- Centre for Women's Infectious Diseases, The Royal Women's Hospital
- Molecular Microbiology, Murdoch Children's Research Institute
| | - Eithandee Aung
- Centre for Women's Infectious Diseases, The Royal Women's Hospital
- Molecular Microbiology, Murdoch Children's Research Institute
| | - Hannah Shilling
- Centre for Women's Infectious Diseases, The Royal Women's Hospital
- Molecular Microbiology, Murdoch Children's Research Institute
| | - Gerald L Murray
- Centre for Women's Infectious Diseases, The Royal Women's Hospital
- Molecular Microbiology, Murdoch Children's Research Institute
- Department of Obstetrics, Gynaecology, and Newborn Health, University of Melbourne
| | - Monica Molano
- Centre for Women's Infectious Diseases, The Royal Women's Hospital
- Molecular Microbiology, Murdoch Children's Research Institute
| | - Suzanne M Garland
- Centre for Women's Infectious Diseases, The Royal Women's Hospital
- Molecular Microbiology, Murdoch Children's Research Institute
- Department of Obstetrics, Gynaecology, and Newborn Health, University of Melbourne
| | - Christopher K Fairley
- Melbourne Sexual Health Centre, Alfred Health
- School of Translational Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University
| | - Marcus Y Chen
- Melbourne Sexual Health Centre, Alfred Health
- School of Translational Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University
| | - Jane S Hocking
- Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria
| | - Catriona Ooi
- Western Sydney Sexual Health Centre, Western Sydney Local Health District
- Sexual Health Service, Northern Sydney Local Health District Sexual Health Service
- Northern Clinical School, Faculty of Health and Medicine, University of Sydney
| | - Anna McNulty
- Sydney Sexual Health Centre, South Eastern Sydney Local Health District, Sydney, New South Wales
| | - Jenny McCloskey
- School of Biomedical Sciences, University of Western Australia
- Department of Sexual Health, Royal Perth Hospital, Perth, Western Australia
| | - Kathleen McNamee
- Department of Obstetrics, Gynaecology, and Newborn Health, University of Melbourne
- Sexual Health Victoria, Melbourne, Victoria
| | - Deborah Bateson
- The Daffodil Centre, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales
- Statewide Sexual Health Service, Hobart, Tasmania
| | - Louise Owen
- Statewide Sexual Health Service, Hobart, Tasmania
| | - Sepehr N Tabrizi
- Centre for Women's Infectious Diseases, The Royal Women's Hospital
- Molecular Microbiology, Murdoch Children's Research Institute
| | - Dorothy A Machalek
- Centre for Women's Infectious Diseases, The Royal Women's Hospital
- The Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia
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Li X, Jiao G, Chen Y. A case-control study based on the National Health and Nutrition Examination Survey to evaluate the effects of human papilloma virus on bone health in women. BMC Med 2025; 23:75. [PMID: 39920637 PMCID: PMC11806905 DOI: 10.1186/s12916-025-03909-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Accepted: 01/24/2025] [Indexed: 02/09/2025] Open
Abstract
BACKGROUND Human papillomavirus (HPV) infection and osteoporosis (OP) are global health concerns, with higher prevalence observed in women compared to men. However, the impact of HPV infection on bone health remains uncertain. METHODS This case-control study utilized data from the National Health and Nutrition Examination Survey (NHANES). Comparable datasets were created using nearest neighbor propensity score matching (PSM) at a ratio of 1:1. The association between HPV infection and bone mineral density (BMD) was analyzed using the Welch two-sample t-test. Furthermore, linear mixed models were employed for validation purposes. Restricted cubic spline (RCS) analysis and Kendall's tau-b tests were performed to explore the effect of different types of HPV infection on BMD. RESULTS Individuals with HPV infection (mean age 38.11 ± 11.32 years) had lower BMD in the femur and lumbar spine compared to uninfected individuals (mean age 37.92 ± 11.42 years). RCS analysis revealed that an increasing number of cooccurring HPV types in women was associated with lower BMD. Specifically, four HPV types were negatively associated with femur BMD, while 14 HPV types were negatively associated with lumbar spine BMD. Additionally, HPV types 53, 59, and 89 exhibited effects on both femur and lumbar spine BMD. CONCLUSIONS HPV infection is associated with a decrease in BMD, and co-infection with multiple types of HPV implies even lower BMD. Appropriately designed trials are needed to determine if interventions targeted at preventing HPV infection can have a protective effect on BMD.
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Affiliation(s)
- Xiang Li
- Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250000, China
- Department of Orthopedics, Qilu Hospital of Shandong University, No.107, Wenhuaxi Road, Jinan, Shandong, 250000, China
| | - Guangjun Jiao
- Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250000, China.
- Department of Orthopedics, Qilu Hospital of Shandong University, No.107, Wenhuaxi Road, Jinan, Shandong, 250000, China.
| | - Yunzhen Chen
- Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250000, China.
- Department of Orthopedics, Qilu Hospital of Shandong University, No.107, Wenhuaxi Road, Jinan, Shandong, 250000, China.
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Davis EN, Doyle PC. An Assessment of Young Adults' Awareness and Knowledge Related to the Human Papillomavirus (HPV), Oropharyngeal Cancer, and the HPV Vaccine. Cancers (Basel) 2025; 17:344. [PMID: 39941716 PMCID: PMC11816247 DOI: 10.3390/cancers17030344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Revised: 01/08/2025] [Accepted: 01/16/2025] [Indexed: 02/16/2025] Open
Abstract
BACKGROUND/OBJECTIVES The human papillomavirus (HPV) is a prevalent sexually transmitted infection that is a known cause of morbidities such as genital warts and cancers of the cervix, anus, and oropharynx. Non-cervical HPV-related cancers have been a developing problem in North America, increasing in incidence by up to 225% in some instances over a span of two decades. METHODS This study investigated levels of awareness and knowledge of HPV, oropharyngeal cancer (OPC), and the HPV vaccine using a self-administered web-based survey designed specifically for this research. University students (n = 1005) aged 18-30 completed a 42-item questionnaire that included demographic information, awareness questions, and a series of "true/false/I don't know" knowledge questions. RESULTS The data gathered revealed that participants had relatively high levels of awareness. However, many respondents had significant gaps in their knowledge of HPV, OPC, and the HPV vaccine. Collectively, the data indicate that awareness and knowledge of HPV and the value of vaccination may place younger individuals at risk for HPV-related infections. CONCLUSIONS Although a relatively high level of awareness concerning HPV was observed, the gaps in knowledge suggest that further efforts are necessary to educate young adults. While all risk factors cannot be reduced, the present data may guide future efforts directed toward better education on HPV and related health concerns and associated risks.
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Affiliation(s)
- Eric N. Davis
- Laboratory for Quality of Life and Well-Being in Oncology, Rehabilitation Sciences, Western University, London, ON N6G 1H1, Canada
| | - Philip C. Doyle
- Otolaryngology Head and Neck Surgery, Division of Laryngology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA
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Sun D, Zhang H, Diao T, Zhang K, Wang J. Comparison of antegrade and retrograde laparoscopic bilateral inguinal lymphadenectomy for penile cancer. J Cancer Res Ther 2024; 20:2061-2065. [PMID: 39792416 DOI: 10.4103/jcrt.jcrt_1281_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Accepted: 11/01/2024] [Indexed: 01/12/2025]
Abstract
PURPOSE To investigate and compare the feasibility, safety, and clinical outcomes of antegrade and retrograde laparoscopic bilateral inguinal lymphadenectomy for penile cancer. METHODS We retrospectively analyzed the clinical data of 32 patients with penile cancer admitted between 2018 and 2022. Among them, 17 patients underwent antegrade laparoscopic inguinal lymphadenectomy (ALIL group) and 15 underwent retrograde laparoscopic inguinal lymphadenectomy (RLIL group). The key surgical procedures and techniques are described. Operative time, intraoperative blood loss, hospital stay, drainage duration, postoperative complications, and follow-up data in both groups were statistically analyzed. RESULTS Surgery in both groups was successfully completed without the need for intraoperative conversion to open surgery. The operative time was significantly shorter for ALIL than for RLIL (P < 0.001). Significantly less intraoperative blood loss was reported with ALIL than with RLIL (P < 0.001). The ALIL group had a significantly shorter hospital stay than the RLIL group (P = 0.027). The number of removed lymph nodes in the ALIL group differed insignificantly from that in the RLIL group (P = 0.360). Postoperative drainage duration, recurrence, short-term survival, and postoperative complications were similar between both groups. CONCLUSION In the patients with penile cancer, ALIL and RLIL yielded similar perioperative outcomes. However, ALIL was associated with shorter operative time, less blood loss, and shorter hospital stays. ALIL did not require repositioning of the laparoscopic instruments, thereby simplifying the procedure and minimizing patient trauma. Additionally, if needed, pelvic lymphadenectomy could be performed simultaneously from the same trocar position used in ALIL.
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Affiliation(s)
- Dingqi Sun
- Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People's Republic of China
| | - Hui Zhang
- Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People's Republic of China
| | - Tongxiang Diao
- Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People's Republic of China
| | - Keqin Zhang
- Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People's Republic of China
| | - Jinhua Wang
- Department of Radiotherapy, Shandong Second Provincial General Hospital, Jinan, Shandong, People's Republic of China
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Ge S, Zheng L, Li Y, Gan L, Wang Z, Zeng Z, Meng C, Li K, Ma J, Wang D, Ren Y. Comparing the safety and effectiveness of minimally invasive surgery and open inguinal lymph node dissection in penile cancer: A systematic review and meta-analysis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 50:108553. [PMID: 39059191 DOI: 10.1016/j.ejso.2024.108553] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2024] [Revised: 06/04/2024] [Accepted: 07/18/2024] [Indexed: 07/28/2024]
Abstract
OBJECTIVE To compare the safety and effectiveness of minimally invasive surgery (MIS) with open inguinal lymph node dissection (O-ILND) in penile cancer. METHODS We performed a systematic reviews and cumulative meta-analyses of primary results of interest according to PRISMA criteria, and quality assessment followed AMSTAR. The system searched five databases, including Zhiwang, Embase, PubMed, Cochrane Library and Web of Science. The search period ranged was from database creation until September 2023. The statistical analysis software used Stata16. RESULTS A total of 16 studies, including 898 patients. Compared to O-ILND, MIS is superior in length of stay (WMD = -2.96, 95%CI [-4.38, -1.54], P < 0.05), drainage time (WMD = -3.24, 95%CI [-4.70, -1.78], P < 0.05) and estimated blood loss (WMD = -35.70, 95%CI [-46.27, -25.14], P < 0.05), while operation time, recurrence rate and 5-year overall survival rate are the same. The number of lymph nodes dissection between the two groups are not statistically significant. Subgroup analyses found that there are more lymph nodes dissection in robotic-assisted inguinal lymph nodes dissection (WMD = 0.50, 95%CI [0.20, 0.80], P < 0.05). The overall complication rate of MIS was lower (OR = 0.26, 95%CI [0.09, 0.70], P < 0.05). CONCLUSION Minimally invasive inguinal lymph nodes dissection appears to be a better option for penile cancer cases. But more large samples and multicenter studies are needed to further confirm.
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Affiliation(s)
- Si Ge
- Department of Urology, Nanchong Central Hospital, The Second Clinical College, North Sichuan Medical College (University), Nanchong, 63700, Sichuan, China; Department of Urology, School of Clinical Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Lei Zheng
- Department of Urology, Nanchong Central Hospital, The Second Clinical College, North Sichuan Medical College (University), Nanchong, 63700, Sichuan, China
| | - Yunxiang Li
- Department of Urology, Nanchong Central Hospital, The Second Clinical College, North Sichuan Medical College (University), Nanchong, 63700, Sichuan, China; Department of Urology, School of Clinical Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China.
| | - Lijian Gan
- Department of Urology, Nanchong Central Hospital, The Second Clinical College, North Sichuan Medical College (University), Nanchong, 63700, Sichuan, China
| | - Zuoping Wang
- Department of Urology, Nanchong Central Hospital, The Second Clinical College, North Sichuan Medical College (University), Nanchong, 63700, Sichuan, China
| | - Zhiqiang Zeng
- Department of Urology, School of Clinical Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Chunyang Meng
- Department of Urology, School of Clinical Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Kangsen Li
- Department of Urology, Nanchong Central Hospital, The Second Clinical College, North Sichuan Medical College (University), Nanchong, 63700, Sichuan, China
| | - Jiakai Ma
- Department of Urology, Nanchong Central Hospital, The Second Clinical College, North Sichuan Medical College (University), Nanchong, 63700, Sichuan, China
| | - Deyu Wang
- Department of Urology, Nanchong Central Hospital, The Second Clinical College, North Sichuan Medical College (University), Nanchong, 63700, Sichuan, China
| | - Yuan Ren
- Department of Urology, School of Clinical Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China
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Amicuzi U, Grillo M, Stizzo M, Olivetta M, Tammaro S, Napolitano L, Reccia P, De Luca L, Rubinacci A, Della Rosa G, Lecce A, Coppola P, Papi S, Trama F, Romano L, Sciorio C, Spirito L, Crocetto F, Manfredi C, Del Giudice F, Ferro M, Rocco B, Tataru OS, Balsamo R, Lucarelli G, Del Biondo D, Barone B. Exploring the Multifactorial Landscape of Penile Cancer: A Comprehensive Analysis of Risk Factors. Diagnostics (Basel) 2024; 14:1790. [PMID: 39202278 PMCID: PMC11353487 DOI: 10.3390/diagnostics14161790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 08/10/2024] [Accepted: 08/14/2024] [Indexed: 09/03/2024] Open
Abstract
Penile cancer, while rare, is a critical public health issue due to its profound impact on patients and the complexities of its management. The disease's multifactorial etiology includes risk factors such as HPV infection, poor hygiene, smoking, genetic predispositions, and socioeconomic determinants. This article provides a comprehensive review and analysis of these diverse risk factors, aiming to enhance understanding of the disease's underlying causes. By elucidating these factors, the article seeks to inform and improve prevention strategies, early detection methods, and therapeutic interventions. A nuanced grasp of the multifactorial nature of penile cancer can enable healthcare professionals to develop more effective approaches to reducing incidence rates and improving patient outcomes.
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Affiliation(s)
- Ugo Amicuzi
- Division of Urology, Department of Surgical Sciences, AORN Sant’Anna e San Sebastiano, 81100 Caserta, Italy;
| | - Marco Grillo
- Department of Urology, Ospedale del Mare, ASL NA1 Centro, 80147 Naples, Italy; (M.G.); (D.D.B.)
| | - Marco Stizzo
- Urology Unit, Department of Woman, Child and General and Specialized Surgery, University of Campania Luigi Vanvitelli, 80131 Naples, Italy; (M.S.); (L.S.); (C.M.)
| | - Michelangelo Olivetta
- Urology Unit, Gaetano Fucito Hospital, AOU San Giovanni di Dio e Ruggi d’Aragona, 84085 Mercato San Severino, Italy;
| | - Simone Tammaro
- Department of Neurosciences and Reproductive Sciences and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy; (S.T.); (L.N.); (A.R.); (G.D.R.); (A.L.); (P.C.); (S.P.); (L.R.); (F.C.)
| | - Luigi Napolitano
- Department of Neurosciences and Reproductive Sciences and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy; (S.T.); (L.N.); (A.R.); (G.D.R.); (A.L.); (P.C.); (S.P.); (L.R.); (F.C.)
| | - Pasquale Reccia
- Urology Unit, AORN Ospedali dei Colli, Monaldi Hospital, 80131 Naples, Italy; (P.R.); (R.B.)
| | - Luigi De Luca
- Division of Urology, Department of Surgical Multispecialty, AORN Antonio Cardarelli, 80131 Naples, Italy;
| | - Andrea Rubinacci
- Department of Neurosciences and Reproductive Sciences and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy; (S.T.); (L.N.); (A.R.); (G.D.R.); (A.L.); (P.C.); (S.P.); (L.R.); (F.C.)
| | - Giampiero Della Rosa
- Department of Neurosciences and Reproductive Sciences and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy; (S.T.); (L.N.); (A.R.); (G.D.R.); (A.L.); (P.C.); (S.P.); (L.R.); (F.C.)
| | - Arturo Lecce
- Department of Neurosciences and Reproductive Sciences and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy; (S.T.); (L.N.); (A.R.); (G.D.R.); (A.L.); (P.C.); (S.P.); (L.R.); (F.C.)
| | - Paola Coppola
- Department of Neurosciences and Reproductive Sciences and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy; (S.T.); (L.N.); (A.R.); (G.D.R.); (A.L.); (P.C.); (S.P.); (L.R.); (F.C.)
| | - Salvatore Papi
- Department of Neurosciences and Reproductive Sciences and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy; (S.T.); (L.N.); (A.R.); (G.D.R.); (A.L.); (P.C.); (S.P.); (L.R.); (F.C.)
| | - Francesco Trama
- Urology Complex Unit, ASL Napoli 2 Nord ‘Santa Maria delle Grazie’ Hospital, 80078 Pozzuoli, Italy;
| | - Lorenzo Romano
- Department of Neurosciences and Reproductive Sciences and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy; (S.T.); (L.N.); (A.R.); (G.D.R.); (A.L.); (P.C.); (S.P.); (L.R.); (F.C.)
| | | | - Lorenzo Spirito
- Urology Unit, Department of Woman, Child and General and Specialized Surgery, University of Campania Luigi Vanvitelli, 80131 Naples, Italy; (M.S.); (L.S.); (C.M.)
| | - Felice Crocetto
- Department of Neurosciences and Reproductive Sciences and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy; (S.T.); (L.N.); (A.R.); (G.D.R.); (A.L.); (P.C.); (S.P.); (L.R.); (F.C.)
| | - Celeste Manfredi
- Urology Unit, Department of Woman, Child and General and Specialized Surgery, University of Campania Luigi Vanvitelli, 80131 Naples, Italy; (M.S.); (L.S.); (C.M.)
| | | | - Matteo Ferro
- 2nd Unit of Urology, Department of Health Science, University of Milan, ASST Santi Paolo and Carlo, Via A. Di Rudini 8, 20142 Milan, Italy (B.R.)
| | - Bernardo Rocco
- 2nd Unit of Urology, Department of Health Science, University of Milan, ASST Santi Paolo and Carlo, Via A. Di Rudini 8, 20142 Milan, Italy (B.R.)
| | - Octavian Sabin Tataru
- Department of Simulation Applied in Medicine, The Institution Organizing University Doctoral Studies (I.O.S.U.D.), George Emil Palade University of Medicine, Pharmacy, Sciences, and Technology from Târgu Mureș, 540142 Târgu Mureș, Romania;
| | - Raffaele Balsamo
- Urology Unit, AORN Ospedali dei Colli, Monaldi Hospital, 80131 Naples, Italy; (P.R.); (R.B.)
| | - Giuseppe Lucarelli
- Urology, Andrology and Kidney Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy;
| | - Dario Del Biondo
- Department of Urology, Ospedale del Mare, ASL NA1 Centro, 80147 Naples, Italy; (M.G.); (D.D.B.)
- Department of Urology, Ospedale San Paolo, ASL NA1 Centro, 80125 Naples, Italy
| | - Biagio Barone
- Department of Urology, Ospedale San Paolo, ASL NA1 Centro, 80125 Naples, Italy
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10
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AlMesbah N, Maatoug J, Selim N, Bougmiza I. Human papillomavirus prevalence and genotypes in Gulf Cooperation Council countries: A scoping review 2017-2024. Qatar Med J 2024; 2024:33. [PMID: 39131793 PMCID: PMC11311752 DOI: 10.5339/qmj.2024.33] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2024] [Accepted: 06/09/2024] [Indexed: 08/13/2024] Open
Abstract
Background Cervical cancer remains a global health challenge, claiming the lives of millions annually and having a significant impact on Gulf Cooperation Council (GCC) countries. Human papillomavirus (HPV), the primary causative agent, plays a central role, with regional variations in prevalence.1 The process from HPV infection to neoplastic changes takes 5-25 years to occur, hence, knowing its prevalence in our community is vital.2. Methods PubMed and SCOPUS were searched to identify articles related to cervical and anogenital HPV prevalence and genotypes in Qatar, Kuwait, Bahrain, Oman, the United Arab Emirates (UAE), and the Kingdom of Saudi Arabia (KSA) published between 2017 and 2024. Results A total of 19 articles were included in this review. Eight studies were from KSA, four were from Kuwait, three were from the UAE, one was from Qatar, Oman, and Bahrain, and one presented data collectively from the KSA, UAE, Qatar, and Bahrain. The prevalence of HPV ranged between 4.7% and 77% in studies from the KSA, between 15% and 54.3% in studies from Kuwait, between 14.7% and 88% in studies from the UAE, was 8.1% and 31.3% in the two studies from Qatar, and was 17.8% and 20% in the studies from Oman and Bahrain, respectively. HPV 16 was the most prevalent high-risk genotype found in studies conducted in the KSA, UAE, Kuwait, and Qatar. In Oman, HPV 82 predominated. In Bahrain, the majority had other non-HPV 16/18/45 genotypes. In the UAE and Kuwait, HPV 11 was the predominant low-risk type, followed by HPV 6. In Qatar, HPV 81 was the most common low-risk type, followed by HPV 11. In Oman, HPV 54 was the most common low-risk type, followed by HPV 42. Conclusion There are no studies with data on HPV prevalence and genotypes among women who have been vaccinated against HPV in GCC countries.
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Affiliation(s)
- Nahlah AlMesbah
- Community Medicine Residency Program, Medical Education, Hamad Medical Corporation, Doha, Qatar *
| | - Jihene Maatoug
- Community Medicine Residency Program, Primary Health Care Corporation, Doha, Qatar
- Faculty of Medicine, Sousse University, Tunisia
| | - Nagah Selim
- Community Medicine Residency Program, Primary Health Care Corporation, Doha, Qatar
- Public Health and Preventive Medicine, Faculty of Medicine, Cairo University, Egypt
| | - Iheb Bougmiza
- Community Medicine Residency Program, Primary Health Care Corporation, Doha, Qatar
- Faculty of Medicine, Sousse University, Tunisia
- College of Medicine, QU Health, Qatar University, Doha 2713, Qatar
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Muneer A, Bandini M, Compérat E, De Meerleer G, Fizazi K, Gietema J, Gillessen S, Kirkham A, Sangar V, Alifrangis C, Powles T. Penile cancer: ESMO-EURACAN Clinical Practice Guideline for diagnosis, treatment and follow-up. ESMO Open 2024; 9:103481. [PMID: 39089768 PMCID: PMC11360427 DOI: 10.1016/j.esmoop.2024.103481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Revised: 04/26/2024] [Accepted: 04/29/2024] [Indexed: 08/04/2024] Open
Abstract
•This ESMO CPG provides recommendations for diagnosis, staging, pathology, treatment and follow-up of penile cancer. •Algorithms for the management of primary penile tumours and inguinal lymph nodes are provided. •The author group encompasses a multidisciplinary group of experts from different institutions and countries in Europe. •Recommendations are based on available scientific data and the authors’ collective expert opinion. •In clinical practice, all recommendations provided need to be discussed with patients in a shared decision-making approach.
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Affiliation(s)
- A Muneer
- Department of Urology and NIHR Biomedical Research Centre, University College London Hospitals NHS Foundation Trust, London; Division of Surgery and Interventional Science, University College London, UK
| | - M Bandini
- Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
| | - E Compérat
- Department of Pathology, Medical University Vienna, Austria
| | - G De Meerleer
- Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium
| | - K Fizazi
- Department of Cancer Medicine, Institut Gustave Roussy, University of Paris Saclay, Villejuif, France
| | - J Gietema
- Department of Medical Oncology, University Medical Center Groningen, Groningen, The Netherlands
| | - S Gillessen
- Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale (EOC), Bellinzona; Universita della Svizzera Italiana, Lugano, Switzerland
| | - A Kirkham
- Department of Radiology, University College London Hospitals NHS Foundation Trust, London
| | - V Sangar
- Department of Urology, The Christie NHS Foundation Trust, Manchester
| | - C Alifrangis
- Department of Oncology and NIHR Biomedical Research Centre, University College London Hospitals NHS Foundation Trust, London
| | - T Powles
- Barts Experimental Cancer Medicine Centre, Barts Cancer Institute, Queen Mary University of London, London, UK
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Nicolais O, Cummings M, Buchanan TR. Case Report: Low-Risk HPV associated Verruco-Papillary squamous cell carcinoma of the cervix. Gynecol Oncol Rep 2024; 53:101395. [PMID: 38646444 PMCID: PMC11031799 DOI: 10.1016/j.gore.2024.101395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Revised: 04/04/2024] [Accepted: 04/08/2024] [Indexed: 04/23/2024] Open
Abstract
•Cervical cancer plays a large role in morbidity and mortality for gynecologic cancer.•Most cases are involved with high-risk HPV, rare cases of low-risk HPV associated cancer exists.•Low risk HPV associated cervical cancers have increased difficulty in diagnosis.•No distinction exists in treatment between low and high risk HPV associated cervical cancer.
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Affiliation(s)
- Olivia Nicolais
- Department of Obstetrics and Gynecology, Abington Hospital-Jefferson Health, 1200 Old York Road, Price 109, Abington, PA 19001, United States
| | - Mackenzie Cummings
- Department of Obstetrics and Gynecology, Abington Hospital-Jefferson Health, 1200 Old York Road, Price 109, Abington, PA 19001, United States
| | - Tommy R Buchanan
- Hanjani Institute for Gynecologic Oncology, Asplundh Cancer Pavilion, Abington Hospital-Jefferson Health, 3941 Commerce Avenue, Willow Grove, PA 19090, United States
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13
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Karaoğlan BB, Ürün Y. Unveiling the Role of Human Papillomavirus in Urogenital Carcinogenesis a Comprehensive Review. Viruses 2024; 16:667. [PMID: 38793549 PMCID: PMC11125962 DOI: 10.3390/v16050667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 03/27/2024] [Accepted: 04/09/2024] [Indexed: 05/26/2024] Open
Abstract
Human papillomavirus (HPV), an oncogenic DNA virus, is the most common sexually transmitted virus and significant public health concern globally. Despite the substantial prevalence of HPV infection among men, routine testing remains elusive due to the lack of approved HPV tests and the complexity of detection methods. Various studies have explored the link between HPV and genitourinary cancers, revealing different associations influenced by geographic variation, histological subtype and methodological differences. These findings underscore the importance of further research to elucidate the role of HPV in male urogenital cancers. This comprehensive review delves into the intricate relationship between HPV and male genitourinary cancers, shedding light on the virus's oncogenic mechanisms and its reported prevalence. A deeper understanding of HPV's implications for male health is essential for advancing public health initiatives and reducing the burden of urogenital cancers worldwide.
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Affiliation(s)
- Beliz Bahar Karaoğlan
- Department of Medical Oncology, Ankara University Faculty of Medicine, 06620 Ankara, Türkiye;
- Faculty of Medicine, Department of Internal Medicine, Division of Internal Medicine, Ankara University Cancer Research Institute, 06620 Ankara, Türkiye
| | - Yüksel Ürün
- Department of Medical Oncology, Ankara University Faculty of Medicine, 06620 Ankara, Türkiye;
- Faculty of Medicine, Department of Internal Medicine, Division of Internal Medicine, Ankara University Cancer Research Institute, 06620 Ankara, Türkiye
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14
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Dorismond VG, Boscardin WJ, Sawaya GF. The association between YouTube use and knowledge of human papillomavirus-related cancers. PEC INNOVATION 2023; 3:100186. [PMID: 37457670 PMCID: PMC10339240 DOI: 10.1016/j.pecinn.2023.100186] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 06/28/2023] [Accepted: 06/29/2023] [Indexed: 07/18/2023]
Abstract
Objective To examine the association between YouTube usage and HPV-related cancer knowledge (cervical, anal, oral and penile). Study design Cross-sectional study using data from the Health Information National Trends survey conducted between 2017 and 2020 (N = 16,092). Logistic regression was used to analyze the independent effect of YouTube use on cancer knowledge, controlling for sociodemographic characteristics. Results Respondents' knowledge of HPV-related cancers varied: 49.9% about cervical, 18% anal, 20.1% oral and 20.4% penile cancers. YouTube use was associated with increased knowledge for all cancers (cervical: OR 2.66, 95% CI 2.04, 3.46; anal: OR 1.83, 95% CI 1.32, 2.53; oral: OR 1.89, 95% CI 1.37, 2.61; penile OR 2.00, 95% CI 1.44, 2.77) in models adjusted for all covariates. Other independent predictors of HPV-related cancer knowledge included female gender, younger age, a higher income, and higher education. Conclusions YouTube could play an important role in educating people about HPV-related cancers and should also target other populations, such as males and those with less formal education. Innovation The study provides novel insights into the potential of YouTube as an educational tool for promoting cancer knowledge with the goal of cancer prevention.
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Affiliation(s)
- Vanessa G. Dorismond
- Department of Obstetrics and Gynecology, University of California, San Francisco, CA, USA
| | - W. John Boscardin
- Department Epidemiology & Biostatistics, University of California, San Francisco School of Medicine, 490 Illinois St, San Francisco, CA 94158, USA
| | - George F. Sawaya
- Department of Obstetrics and Gynecology, University of California, San Francisco School of Medicine, 2356 Sutter St, San Francisco, CA 94115, USA
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Kusters JMA, Brouwer JGM, van Benthem BHB, Heijne JCM, Schim van der Loeff MF. Global Type-Specific Genital Human Papillomavirus Prevalence in Men, by Sexual Orientation: A Systematic Review and Meta-Analysis. J Infect Dis 2023; 228:1023-1032. [PMID: 37079383 PMCID: PMC10582913 DOI: 10.1093/infdis/jiad109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 03/16/2023] [Accepted: 04/18/2023] [Indexed: 04/21/2023] Open
Abstract
BACKGROUND Knowledge on genital type-specific human papillomavirus (HPV) prevalence among men is important for prevention of HPV-related cancers and other diseases. Men who have sex with men (MSM) have higher anal prevalence than men who have sex with women only (MSW) but for genital HPV this is unclear. We performed a systematic review and meta-analysis of type-specific genital HPV prevalence among men, by sexual orientation. METHODS MEDLINE and Embase were used for searching publications reporting on male genital HPV prevalence with data from November 2011 onwards. A random-effects meta-analysis was conducted estimating pooled type-specific and grouped external genital and urethral HPV prevalence. Subgroup analyses were conducted for sexual orientation. RESULTS Twenty-nine studies were eligible. Of those, 13 studies reported prevalence among MSM, 5 among MSW, and 13 studies did not stratify by sexual orientation. The most common genotypes were HPV-6 and HPV-16 for both anatomical locations, although heterogeneity was high. HPV prevalence was similar among studies reporting on MSW, MSM, and men with unknown sexual orientation. CONCLUSIONS Genital HPV is common among men, with HPV-6 and HPV-16 being the most common genotypes. Type-specific HPV genital prevalence appears to be similar among MSM and MSW, which contrasts with earlier findings on anal HPV.
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Affiliation(s)
- Johannes M A Kusters
- Centre for Infectious Diseases Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands
- Institute for Infection and Immunity, Amsterdam University Medical Centers, Amsterdam, the Netherlands
| | - Jesca G M Brouwer
- Centre for Infectious Diseases Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands
| | - Birgit H B van Benthem
- Centre for Infectious Diseases Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands
| | - Janneke C M Heijne
- Centre for Infectious Diseases Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands
| | - Maarten F Schim van der Loeff
- Institute for Infection and Immunity, Amsterdam University Medical Centers, Amsterdam, the Netherlands
- Department of Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, the Netherlands
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Morris VK, Jazaeri A, Westin SN, Pettaway C, George S, Huey RW, Grinsfelder M, Shafer A, Johnson B, Vining D, Guo M, Fellman B, Frumovitz M. Phase II Trial of MEDI0457 and Durvalumab for Patients With Recurrent/Metastatic Human Papillomavirus-Associated Cancers. Oncologist 2023:7146114. [PMID: 37104874 DOI: 10.1093/oncolo/oyad085] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 03/09/2023] [Indexed: 04/29/2023] Open
Abstract
BACKGROUND Human papillomavirus (HPV) types 16/18 drive oncogenesis for most patients with cervical, anal, and penile cancers. MEDI0457, a therapeutic DNA vaccine containing plasmids for E6 and E7 HPV-16/18 viral oncogenes and IL-12 adjuvant, is safe and provokes an immune response against E6/E7. We tested MEDI0457 with the anti-PD-L1 antibody durvalumab for patients with HPV-associated cancers. METHODS Patients with recurrent/metastatic, treatment-refractory HPV-16/18 cervical cancer, or rare HPV-associated (anal and penile) cancers were eligible. Prior immune checkpoint inhibition was not permitted. Patients received MEDI0457 7 mg intramuscularly (weeks 1, 3, 7, 12, and every 8 weeks thereafter) and durvalumab 1500 mg intravenously every 4 weeks. The primary endpoint was overall response (RECIST 1.1). In this Simon two-stage phase 2 trial (Ho: p < 0.15; Ha: p ≥ 0.35), ≥2 responses were needed in both cervical and non-cervical cohorts during the first stage for the trial to proceed to stage 2 with an additional 25 patients (34 total) enrolled. RESULTS Twenty-one patients (12 cervical, 7 anal, and 2 penile) were evaluable for toxicity and 19 for response Overall response rate was 21% (95% CI, 6%-46%) among evaluable patients. Disease control rate was 37% (95% CI, 16%-62%). Median duration of response among responders was 21.8 months (95% CI, 9.7%-not estimable). Median progression-free survival was 4.6 months (95% CI, 2.8%-7.2%). Median overall survival was 17.7 months (95% CI, 7.6%-not estimable). Grades 3-4 treatment-related adverse events occurred in 6 (23%) participants. CONCLUSIONS The combination of MEDI0457 and durvalumab demonstrated acceptable safety and tolerability in patients with advanced HPV-16/18 cancers. The low ORR among patients with cervical cancer led to study discontinuation despite a clinically meaningful disease control rate.
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Affiliation(s)
- Van K Morris
- Department of Gastrointestinal Medical Oncology, The University of Texas - MD Anderson Cancer Center, Houston, TX, USA
| | - Amir Jazaeri
- Department of Gynecologic Oncology, The University of Texas - MD Anderson Cancer Center, Houston, TX, USA
| | - Shannon N Westin
- Department of Gynecologic Oncology, The University of Texas - MD Anderson Cancer Center, Houston, TX, USA
| | - Curtis Pettaway
- Department of Urology, The University of Texas - MD Anderson Cancer Center, Houston, TX, USA
| | - Solly George
- Department of Gynecologic Oncology, The University of Texas - MD Anderson Cancer Center, Houston, TX, USA
| | - Ryan W Huey
- Department of Gastrointestinal Medical Oncology, The University of Texas - MD Anderson Cancer Center, Houston, TX, USA
| | - Michaela Grinsfelder
- Department of Gynecologic Oncology, The University of Texas - MD Anderson Cancer Center, Houston, TX, USA
| | - Aaron Shafer
- Department of Gynecologic Oncology, The University of Texas - MD Anderson Cancer Center, Houston, TX, USA
| | - Benny Johnson
- Department of Gastrointestinal Medical Oncology, The University of Texas - MD Anderson Cancer Center, Houston, TX, USA
| | - David Vining
- Department of Radiology, The University of Texas - MD Anderson Cancer Center, Houston, TX, USA
| | - Ming Guo
- Department of Pathology, The University of Texas - MD Anderson Cancer Center, Houston, TX, USA
| | - Bryan Fellman
- Department of Biostatistics, The University of Texas - MD Anderson Cancer Center, Houston, TX, USA
| | - Michael Frumovitz
- Department of Gynecologic Oncology, The University of Texas - MD Anderson Cancer Center, Houston, TX, USA
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17
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Armstrong HL, Scholfield C, Symonds Y, Nadarzynski T, Graham CA. Reasons for incomplete STI vaccination among men who have sex with men in an English sexual health service. Int J STD AIDS 2023:9564624231165078. [PMID: 36943686 DOI: 10.1177/09564624231165078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/23/2023]
Abstract
BACKGROUND In England, vaccination for human papillomavirus, hepatitis A, and hepatitis B is recommended for men who have sex with men (MSM). However, uptake is sub-optimal and some men do not complete all recommended vaccine doses. This service evaluation aimed to explore reasons for lack of uptake for each of these vaccines among MSM in one English sexual health service and to inform improvements in service delivery to increase full dose completion rates. METHODS MSM, ≥18 years, who had previously attended NHS Solent Sexual Health for at least one vaccination, and who had not completed the full dosing regimen for at least one of these vaccines, were invited to participate in an anonymous, online survey between 14/12/2020-11/04/2021. RESULTS Among 246 MSM (M = 42.1 years), the most common reason for non-vaccination was that participants thought it was unneeded and had not been recommended by a doctor or healthcare provider. None reported vaccine hesitancy. Likewise, the most common reasons for vaccination were doctor/healthcare provider recommendation (51.7-65.6%) and self-protection (60.9-68.1%). The most common reason for not having completed the full course of vaccination was being unaware that the next dose was due (30.0-37.8%). Many participants who had not completed vaccination indicated that a doctor/healthcare provider recommendation would be a motivating factor and that reminder messages and being able to book subsequent appointments in advance would facilitate vaccination. CONCLUSIONS Sexual health clinicians should be encouraged to discuss STI vaccination with MSM and services should explore possibilities to improve ease and access to vaccine appointments to increase uptake and completion rates.
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Affiliation(s)
- Heather L Armstrong
- Solent NHS Sexual Health Service, Southampton, UK
- 7423University of Southampton, Southampton, UK
| | | | - Ynez Symonds
- Solent NHS Sexual Health Service, Southampton, UK
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Ding L, Zhang C, Wang K, Zhang Y, Wu C, Xia W, Li S, Li W, Wang J. A machine learning-based model for predicting the risk of early-stage inguinal lymph node metastases in patients with squamous cell carcinoma of the penis. Front Surg 2023; 10:1095545. [PMID: 37009612 PMCID: PMC10063794 DOI: 10.3389/fsurg.2023.1095545] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Accepted: 02/07/2023] [Indexed: 03/19/2023] Open
Abstract
ObjectiveInguinal lymph node metastasis (ILNM) is significantly associated with poor prognosis in patients with squamous cell carcinoma of the penis (SCCP). Patient prognosis could be improved if the probability of ILNM incidence could be accurately predicted at an early stage. We developed a predictive model based on machine learning combined with big data to achieve this.MethodsData of patients diagnosed with SCCP were obtained from the Surveillance, Epidemiology, and End Results Program Research Data. By combing variables that represented the patients' clinical characteristics, we applied five machine learning algorithms to create predictive models based on logistic regression, eXtreme Gradient Boosting, Random Forest, Support Vector Machine, and k-Nearest Neighbor. Model performance was evaluated by ten-fold cross-validation receiver operating characteristic curves, which were used to calculate the area under the curve of the five models for predictive accuracy. Decision curve analysis was conducted to estimate the clinical utility of the models. An external validation cohort of 74 SCCP patients was selected from the Affiliated Hospital of Xuzhou Medical University (February 2008 to March 2021).ResultsA total of 1,056 patients with SCCP from the SEER database were enrolled as the training cohort, of which 164 (15.5%) developed early-stage ILNM. In the external validation cohort, 16.2% of patients developed early-stage ILNM. Multivariate logistic regression showed that tumor grade, inguinal lymph node dissection, radiotherapy, and chemotherapy were independent predictors of early-stage ILNM risk. The model based on the eXtreme Gradient Boosting algorithm showed stable and efficient prediction performance in both the training and external validation groups.ConclusionThe ML model based on the XGB algorithm has high predictive effectiveness and may be used to predict early-stage ILNM risk in SCCP patients. Therefore, it may show promise in clinical decision-making.
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Affiliation(s)
| | | | | | | | | | | | | | - Wang Li
- Correspondence: Wang Li Junqi Wang
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19
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Dufour L, Carrouel F, Dussart C. Human Papillomaviruses in Adolescents: Knowledge, Attitudes, and Practices of Pharmacists Regarding Virus and Vaccination in France. Viruses 2023; 15:v15030778. [PMID: 36992485 PMCID: PMC10058809 DOI: 10.3390/v15030778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2023] [Revised: 03/13/2023] [Accepted: 03/16/2023] [Indexed: 03/31/2023] Open
Abstract
Human papillomaviruses (HPVs) are responsible for one of the most common sexually transmitted diseases in the world, and their oncogenic role has been well demonstrated in genital, anal, and oropharyngeal areas. However, a certain distrust and a lack of knowledge about this vaccine are perceptible among French adolescents and their parents. Thus, health professionals and, more particularly, pharmacists appear to be key persons to promote HPV vaccination and restore confidence in the target population. The present study aims to assess the knowledge, attitudes, and practices regarding HPV vaccination among pharmacists, particularly in boys, following the 2019 recommendation to vaccinate them. The present study was designed as a cross-sectional, quantitative, and descriptive survey that was conducted from March to September 2021 among pharmacists in France. 215 complete questionnaires were collected. Gaps in knowledge were found, only 21.4% and 8.4% obtained a high level of knowledge related to, respectively, HPV and vaccination. Pharmacists were confident in the HPV vaccine (94.4%), found it safe and useful, and felt that the promotion of the vaccine was part of their role (94.0%). However, only a few have already advised it, which they justify due to a lack of opportunity and forgetfulness. Faced with this, training, computerized reminders, or supportive materials could be implemented to improve the advice and thus the vaccination coverage. Finally, 64.2% were in favor of a pharmacy-based vaccination program. In conclusion, pharmacists are interested in this vaccination and the role of promoter. However, they need the means to facilitate this mission: training, computer alerts, supportive materials such as flyers, and the implementation of vaccination in pharmacies.
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Affiliation(s)
- Lucas Dufour
- Laboratory "Health, Systemic, Process" (P2S), UR4129, University Claude Bernard Lyon 1, University of Lyon, 69008 Lyon, France
| | - Florence Carrouel
- Laboratory "Health, Systemic, Process" (P2S), UR4129, University Claude Bernard Lyon 1, University of Lyon, 69008 Lyon, France
| | - Claude Dussart
- Laboratory "Health, Systemic, Process" (P2S), UR4129, University Claude Bernard Lyon 1, University of Lyon, 69008 Lyon, France
- Hospices Civils of Lyon, 69003 Lyon, France
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20
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Sarier M, Sepin N, Emek M, Konuk EY, Kaplan T, Yuksel BA, Barut Z, Cakcak DS, Hoscan MB. Evaluation of the optimal sampling approach for HPV genotyping in circumcised heterosexual men with genital warts. J Infect Chemother 2023; 29:475-480. [PMID: 36731776 DOI: 10.1016/j.jiac.2023.01.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Revised: 12/17/2022] [Accepted: 01/25/2023] [Indexed: 02/03/2023]
Abstract
BACKGROUND Human papillomavirus (HPV) causes a serious socioeconomic burden globally. However, there is currently no consensus on the optimal sampling method for HPVDNA genotyping in circumcised heterosexual men. This study aimed to determine the diagnostic efficacy of 6 different anatomic sampling sites in HPV DNA polymerase chain reaction (PCR) testing of circumcised heterosexual men with genital warts. METHODS The study included circumcised heterosexual men who presented to our clinic with complaints of genital warts. Swab samples were obtained from the penile shaft (PS), scrotum, coronal sulcus (CS), and external urethral meatus (EUM). First-void urine (FVU) and genital wart biopsy (GWB) were also tested for HPV DNA by PCR. RESULTS A total of 32 patients (mean age: 36.9 ± 6.9 years) were included. None of the six samples studied was sufficient on its own to reveal all HPV types detected in a patient. When the samples were analyzed individually, GWB detected an average of 49.5% of total HPV types in a patient. This rate was 50.5% for PS, 40.4% for CS, 31.6% for scrotum, 26.3% for EUM, and 15.8% for FVU samples. The detection rate increased to 75.8% with combined testing of GWB and PS samples, 83.2% with GWB/PS/CS, 90.5% with GWB/PS/CS/scrotum, and 98.9% with GWB/PS/CS/scrotum/EUM samples. CONCLUSION No single anatomic region or sample type can detect all HPV types present in circumcised heterosexual men by PCR assay. The detection rate approaches 99% when wart biopsy is combined with swab sampling of the penile shaft, coronal sulcus, scrotum, and external urethral meatus.
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Affiliation(s)
- Mehmet Sarier
- Department of Urology, Istinye University, Istanbul, Turkiye; Department of Urology, Medical Park Hospital, Antalya, Turkiye.
| | - Nevgun Sepin
- Department of Clinical Microbiology and Infectious Disease, Training and Research Hospital Antalya Turkiye.
| | - Mestan Emek
- Department of Public Health, Akdeniz University, Antalya, Turkiye.
| | | | - Tugrul Kaplan
- Department of Obstetrics and Gynaecology, Medical Park Hospital, Antalya, Turkiye.
| | - Burcu Aykan Yuksel
- Department of Obstetrics and Gynaecology, Training and Research Hospital, Antalya, Turkiye.
| | - Zerrin Barut
- Department of Basic Medical Sciences Antalya Bilim University, Antalya, Turkiye.
| | | | - Mustafa Burak Hoscan
- Department of Dialysis, Vocational School of Health Services, Antalya Bilim University, Antalya, Turkiye.
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21
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Epidemiology, Diagnosis and Management of Penile Cancer: Results from the Spanish National Registry of Penile Cancer. Cancers (Basel) 2023; 15:cancers15030616. [PMID: 36765574 PMCID: PMC9913503 DOI: 10.3390/cancers15030616] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 01/11/2023] [Accepted: 01/17/2023] [Indexed: 01/20/2023] Open
Abstract
INTRODUCTION Penile cancer (PC) is a rare malignancy with an overall incidence in Europe of 1/100,000 males/year. In Europe, few studies report the epidemiology, risk factors, clinical presentation, and treatment of PC. The aim of this study is to present an updated outlook on the aforementioned factors of PC in Spain. MATERIALS AND METHODS A multicentric, retrospective, observational epidemiological study was designed, and patients with a new diagnosis of PC in 2015 were included. Patients were anonymously identified from the Register of Specialized Care Activity of the Ministry of Health of Spain. All Spanish hospitals recruiting patients in 2015 were invited to participate in the present study. We have followed a descriptive narration of the observed data. Continuous and categorical data were reported by median (p25th-p75th range) and absolute and relative frequencies, respectively. The incidence map shows differences between Spanish regions. RESULTS The incidence of PC in Spain in 2015 was 2.55/100,000 males per year. A total of 586 patients were identified, and 228 patients from 61 hospitals were included in the analysis. A total of 54/61 (88.5%) centers reported ≤ 5 new cases. The patients accessed the urologist for visually-assessed penile lesions (60.5%), mainly localized in the glans (63.6%). Local hygiene, smoking habits, sexual habits, HPV exposure, and history of penile lesions were reported in 48.2%, 59.6%, 25%, 13.2%, and 69.7%. HPV-positive lesions were 18.1% (28.6% HPV-16). The majority of PC was squamous carcinoma (95.2%). PC was ≥cT2 in 45.2% (103/228) cases. At final pathology, PC was ≥pT2 in 51% of patients and ≥pN1 in 17% of cases. The most common local treatment was partial penectomy (46.9% cases). A total of 47/55 (85.5%) inguinal lymphadenectomies were open. Patients with ≥pN1 disease were treated with chemotherapy in 12/39 (40.8%) of cases. CONCLUSIONS PC incidence is relatively high in Spain compared to other European countries. The risk factors for PC are usually misreported. The diagnosis and management of PC are suboptimal, encouraging the identification of referral centers for PC management.
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22
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Gamboa-Hoil SI. Human papillomavirus in men. Rev Int Androl 2023; 21:100325. [PMID: 36257902 DOI: 10.1016/j.androl.2021.09.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 06/11/2021] [Accepted: 09/19/2021] [Indexed: 01/26/2023]
Abstract
OBJECTIVE To describe the clinical behavior of human papillomavirus in men. MATERIALS AND METHODS Current international literature was reviewed to describe the clinical behavior of human papillomavirus in men. RESULTS Internationally, the overall prevalence of HPV DNA is 50.8%, HPV considered high risk are 14 types. Prevalence of HPV DNA in invasive penile cancer ranges from 33.1% to 47%. HPV-16 has been the most frequent (68.3%), followed by HPV-6 (8.1%) and HPV-18 (6.9%). Positive HPV is described as an independent prognostic factor for cancer-specific survival. CONCLUSION It is not clear why HPV infection has a predilection in specific areas of the genital tract. However, it is important to note that there are factors that increase the risk of HPV infection.
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Chen HX, Lin CC, Lin CH, Yang CR. Combination of Durvalumab and Chemotherapy to Potentially Convert Unresectable Stage IV Penile Squamous Cell Carcinoma to Resectable Disease: A Case Report. Curr Oncol 2022; 30:326-332. [PMID: 36661675 PMCID: PMC9857427 DOI: 10.3390/curroncol30010026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 12/19/2022] [Accepted: 12/21/2022] [Indexed: 12/28/2022] Open
Abstract
Penile squamous cell carcinoma is a rare disease entity with poor overall survival in an advanced stage. Few studies have investigated the role of immunotherapy in advanced penile squamous cell carcinoma. Herein, we report a case of stage IV unresectable penile squamous cell carcinoma presenting with anal bleeding and urethra obstruction who responded dramatically to combination therapy of durvalumab and cisplatin-based chemotherapy. The patient had HPV-positive penile squamous cell carcinoma, cT3N3M0, with concomitant anus squamous cell carcinoma. After 2 months of the combination treatment, almost all bulky inguinal lymph nodes shrank, and the main tumor of the anus and penis responded completely. A durable response was seen 16 months after initiating the combination therapy. This case report highlights the potential role of the combination of immunotherapy and chemotherapy in patients with advanced penile cancer. The promising results of this combination resulted in the conversion of unresectable disease to a potentially curable disease.
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Affiliation(s)
- Hao Xiang Chen
- Department of Urology, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan
| | - Ching-Chan Lin
- Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung 404, Taiwan
- Division of Hematology and Oncology, Department of Internal Medicine, An Nan Hospital, China Medical University, Tainan 709, Taiwan
| | - Che-Hung Lin
- Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung 404, Taiwan
| | - Chi-Rei Yang
- Department of Urology, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan
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24
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Prognostic Significance of p16 and Its Relationship with Human Papillomavirus Status in Patients with Penile Squamous Cell Carcinoma: Results of 5 Years Follow-Up. Cancers (Basel) 2022; 14:cancers14246024. [PMID: 36551510 PMCID: PMC9775956 DOI: 10.3390/cancers14246024] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 12/02/2022] [Accepted: 12/05/2022] [Indexed: 12/13/2022] Open
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 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.
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25
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Tang Y, Hu X, Wu K, Li X. Immune landscape and immunotherapy for penile cancer. Front Immunol 2022; 13:1055235. [PMID: 36524123 PMCID: PMC9745054 DOI: 10.3389/fimmu.2022.1055235] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Accepted: 11/15/2022] [Indexed: 11/30/2022] Open
Abstract
Penile cancer is a rare malignancy and usually refers to penile squamous cell carcinoma (PSCC), which accounts for more than 95% of all penile malignancies. Although organ-sparing surgery is an effective treatment for early-stage PSCC, surgical intervention alone is often not curative for advanced PSCC with metastases to the inguinal and/or pelvic lymph nodes; thus, systemic therapy is required (usually platinum-based chemotherapy and surgery combined). However, chemotherapy for PSCC has proven to be of limited efficacy and is often accompanied by high toxicity, and patients with advanced PSCC usually have poor prognosis. The limited treatment options and poor prognosis indicate the unmet need for advanced PSCC. Immune-based therapies have been approved for a variety of genitourinary and squamous cell carcinomas but are rarely reported in PSCC. To date, several studies have reported high expression of PDL1 in PSCC, supporting the potential application of immune checkpoint inhibitors in PSCC. In addition, human papillomavirus (HPV) infection is highly prevalent in PSCC and plays a key role in the carcinogenesis of HPV-positive PSCC, suggesting that therapeutic HPV vaccine may also be a potential treatment modality. Moreover, adoptive T cell therapy (ATC) has also shown efficacy in treating advanced penile cancer in some early clinical trials. The development of new therapeutics relies on understanding the underlying biological mechanisms and processes of tumor initiation, progression and metastasis. Therefore, based on the interest, we reviewed the tumor immune microenvironment and the emerging immunotherapy for penile cancer.
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Affiliation(s)
| | | | | | - Xiang Li
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
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26
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Kristiansen S, Bjartling C, Torbrand C, Grelaud D, Lindström M, Svensson Å, Forslund O. Increased prevalence of human papillomavirus in fresh tissue from penile cancers compared to non-malignant penile samples: a case-control study. BMC Cancer 2022; 22:1227. [PMID: 36443686 PMCID: PMC9703753 DOI: 10.1186/s12885-022-10324-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 11/16/2022] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND HPV has been detected in approximately 50% of invasive penile cancers but with a large span between 24 and 89%, most likely due to different types of tumors and various methods for HPV analysis. Most studies of HPV in penile cancer have been performed using paraffin-embedded tissue, argued to be at risk for contaminated HPV analysis. Viral activity of HPV, by the use of HPV mRNA expression is well studied in cervical cancer, but seldom studied in penile cancer. The aim was to determine prevalence of HPV types in fresh tissue of penile cancers compared to non-malignant age-matched penile controls. Additional aims were to analyze the viral expression and copy numbers of HPV16-positive tumors and 10 mm adjacent to the tumor. METHODS Fresh tissue from penile cancer cases was biopsied inside the tumor and 10 mm outside the tumor. Controls were males circumcised for non-malignant reasons, biopsied at surgery. PCR and Luminex assays were used for identification of HPV types. HPV16-positive samples were investigated for copy numbers and expression of HPV16-mRNA. RESULTS Among tumors (n = 135) and age-matched controls (n = 105), HPV was detected in 38.5% (52/135) and 11.4% (12/105), respectively (p < 0.001), adjusted odds ratio 12.8 (95% confidence interval 4.9-33.6). High-risk HPV types were found in 35.6% (48/135) of tumors and 4.8% (5/105) of controls (p < 0.001). Among tumors and controls, HPV16 was present in 27.4% (37/135) and 1% (1/105), respectively (p < 0.001). Among HPV16-positive penile cancers, mean HPV16 viral copy/cell was 74.4 (range 0.00003-725.4) in the tumor and 1.6 (range 0.001-14.4) 10 mm adjacent from the tumor. HPV16-mRNA analysis of the tumors and 10 mm adjacent from the tumors demonstrated viral activity in 86.5% (32/37) and 21.7% (5/23), respectively. CONCLUSIONS The prevalence of HPV was significantly higher in penile cancer (38.5%) than among age-matched non-malignant penile samples (11.4%). HPV16 predominates (27.4%) in penile tumors. HPV16 expression was more common in penile cancer than in adjacent healthy tissue, strongly suggesting an etiological role for HPV16 in the development of penile cancer.
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Affiliation(s)
- Sinja Kristiansen
- grid.4514.40000 0001 0930 2361Department of Dermatology and Venereology, Lund University, Skane University Hospital, Jan Waldenströmsgata 16, 214 28 Malmö, Sweden
| | - Carina Bjartling
- grid.4514.40000 0001 0930 2361Department of Obstetrics and Gynecology, Lund University, Skane University Hospital, Malmö, Sweden
| | - Christian Torbrand
- grid.413823.f0000 0004 0624 046XLund University, Department of Urology, Helsingborg Hospital, Helsingborg, Sweden ,grid.4514.40000 0001 0930 2361Lund University, Institution of Translational Medicine, Malmö, Sweden
| | - Diane Grelaud
- grid.411843.b0000 0004 0623 9987Department of Pathology, Skane University Hospital and Regional Laboratories, Malmö, Sweden
| | - Martin Lindström
- grid.411843.b0000 0004 0623 9987Department of Pathology, Skane University Hospital and Regional Laboratories, Malmö, Sweden
| | - Åke Svensson
- grid.4514.40000 0001 0930 2361Department of Dermatology and Venereology, Lund University, Skane University Hospital, Jan Waldenströmsgata 16, 214 28 Malmö, Sweden
| | - Ola Forslund
- grid.4514.40000 0001 0930 2361Lund University, Department of Medical Microbiology, Laboratory Medicine, Lund, Sweden ,grid.426217.40000 0004 0624 3273Clinical Microbiology, Infection Prevention and Control, Office for Medical Services Region Skane, Kristianstad, Sweden
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Teixeira Júnior AAL, da Costa Melo SP, Pinho JD, Sobrinho TBM, Rocha TMS, Duarte DRD, de Oliveira Barbosa L, Duarte WE, de Castro Belfort MR, Duarte KG, da Silva Neto AL, de Ribamar Rodrigues Calixto J, Paiva Paiva LC, do Nascimento FSMS, Alencar Junior AM, Khayat AS, da Graça Carvalhal Frazão Corrêa R, Lages JS, Dos Reis RB, Araújo WS, Silva GEB. A comprehensive analysis of penile cancer in the region with the highest worldwide incidence reveals new insights into the disease. BMC Cancer 2022; 22:1063. [PMID: 36243680 PMCID: PMC9569053 DOI: 10.1186/s12885-022-10127-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Accepted: 09/13/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Although penile cancer (PC) is uncommon in developed countries, it is widespread in developing countries. The state of Maranhão (Northeast, Brazil) has the highest global incidence recorded for PC, and, despite its socioeconomic vulnerability, it has been attributed to human papillomavirus (HPV) infection. This study aimed to determine the histopathological features, the prevalence of HPV infection, and the immunohistochemical profile of PC in Maranhão. METHODS A retrospective cohort of 200 PC cases were evaluated. HPV detection was performed using nested-PCR followed by direct sequencing for genotyping. Immunohistochemistry (IHC) was performed using monoclonal antibodies anti-p16INK4a, p53, and ki-67. RESULTS Our data revealed a delay of 17 months in diagnosis, a high rate of penile amputation (96.5%), and HPV infection (80.5%) in patients from Maranhão (Molecular detection). We demonstrated the high rate of HPV in PC also by histopathological and IHC analysis. Most patients presented koilocytosis (75.5%), which was associated with those reporting more than 10 different sexual partners during their lifetime (p = 0.001). IHC revealed frequent p16INK4a overexpression (26.0%) associated with basaloid (p < 0.001) and high-grade tumors (p = 0.008). Interestingly, p16 appears not to be a better prognostic factor in our disease-free survival analysis, as previously reported. We also demonstrated high ki-67 and p53 expression in a subset of cases, which was related to worse prognostic factors such as high-grade tumors, angiolymphatic and perineural invasion, and lymph node metastasis. We found a significant impact of high ki-67 (p = 0.002, log-rank) and p53 (p = 0.032, log-rank) expression on decreasing patients' survival, as well as grade, pT, stage, pattern, and depth of invasion (p < 0.05, log-rank). CONCLUSIONS Our data reaffirmed the high incidence of HPV infection in PC cases from Maranhão and offer new insights into potential factors that may contribute to the high PC incidence in the region. We highlighted the possible association of HPV with worse clinical prognosis factors, differently from what was observed in other regions. Furthermore, our IHC analysis reinforces p16, ki-67, and p53 expression as important diagnosis and/or prognosis biomarkers, potentially used in the clinical setting in emerging countries such as Brazil.
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Affiliation(s)
- Antonio Augusto Lima Teixeira Júnior
- Department of Genetics and Postgraduate Program in Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.,Postgraduate Program in Adult Health, Federal University of Maranhão, São Luís, Brazil
| | - Syomara Pereira da Costa Melo
- Laboratory of Immunofluorescence and Electron Microscopy, University Hospital of the Federal University of Maranhão, São Luís, Brazil
| | | | - Thaís Bastos Moraes Sobrinho
- Laboratory of Immunofluorescence and Electron Microscopy, University Hospital of the Federal University of Maranhão, São Luís, Brazil
| | - Thalita Moura Silva Rocha
- Postgraduate Program in Adult Health, Federal University of Maranhão, São Luís, Brazil.,Laboratory of Immunofluorescence and Electron Microscopy, University Hospital of the Federal University of Maranhão, São Luís, Brazil
| | - Denner Rodrigo Diniz Duarte
- Laboratory of Immunofluorescence and Electron Microscopy, University Hospital of the Federal University of Maranhão, São Luís, Brazil
| | - Liseana de Oliveira Barbosa
- Laboratory of Immunofluorescence and Electron Microscopy, University Hospital of the Federal University of Maranhão, São Luís, Brazil
| | - Wesliany Everton Duarte
- Postgraduate Program in Adult Health, Federal University of Maranhão, São Luís, Brazil.,Laboratory of Immunofluorescence and Electron Microscopy, University Hospital of the Federal University of Maranhão, São Luís, Brazil
| | - Marta Regina de Castro Belfort
- Laboratory of Immunofluorescence and Electron Microscopy, University Hospital of the Federal University of Maranhão, São Luís, Brazil.,Postgraduate Program in Health Science, Federal University of Maranhão, São Luís, Brazil
| | - Kelly Gomes Duarte
- Postgraduate Program in Clinical Surgery, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - Antonio Lima da Silva Neto
- Laboratory of Immunofluorescence and Electron Microscopy, University Hospital of the Federal University of Maranhão, São Luís, Brazil
| | | | - Lúcio Cristiano Paiva Paiva
- Laboratory of Immunofluorescence and Electron Microscopy, University Hospital of the Federal University of Maranhão, São Luís, Brazil
| | | | - Antonio Machado Alencar Junior
- Postgraduate Program in Health Science, Federal University of Maranhão, São Luís, Brazil.,University Hospital of the Federal University of Maranhão, São Luís, Brazil
| | | | | | - Joyce Santos Lages
- University Hospital of the Federal University of Maranhão, São Luís, Brazil
| | - Rodolfo Borges Dos Reis
- Postgraduate Program in Clinical Surgery, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - Wilson Silva Araújo
- Department of Genetics and Postgraduate Program in Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - Gyl Eanes Barros Silva
- Postgraduate Program in Adult Health, Federal University of Maranhão, São Luís, Brazil. .,Laboratory of Immunofluorescence and Electron Microscopy, University Hospital of the Federal University of Maranhão, São Luís, Brazil. .,Postgraduate Program in Health Science, Federal University of Maranhão, São Luís, Brazil.
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28
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Straub Hogan MM, Spieker AJ, Orejudos M, Gheit T, Herfs M, Tommasino M, Sanchez DF, Fernandez-Nestosa MJ, Pena MDCR, Gordetsky JB, Epstein JI, Canete-Portillo S, Gellert LL, Prieto Granada CN, Magi-Galluzzi C, Cubilla AL, Giannico GA. Pathological characterization and clinical outcome of penile intraepithelial neoplasia variants: a North American series. Mod Pathol 2022; 35:1101-1109. [PMID: 35190664 DOI: 10.1038/s41379-022-01020-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Revised: 01/24/2022] [Accepted: 01/25/2022] [Indexed: 11/08/2022]
Abstract
Penile intraepithelial neoplasia (PeIN) is classified as human papillomavirus (HPV)- and non-HPV-related. This classification is associated with distinct morphologic subtypes. The natural history and prognosis of PeIN subtypes are not well known. This study aims to evaluate clinicopathological features, HPV status, and outcome of PeIN subtypes. Eighty-two lesions from 64 patients with isolated PeIN were retrospectively reviewed. Mean age was 59 years. Lesions were multicentric in 34% of patients and affected glans (33%), shaft (26%), and foreskin (20%). Histologically, 22% of patients had coexisting lesions, classified as hybrid and mixed. HPV-related PeIN (97%) included basaloid (59%), warty (8%), warty-basaloid (8%), hybrid (19%) and mixed (3%) types. P16 and HPV positivity occurred in 99% and 82% of lesions, respectively. HPV 16 was more common in basaloid PeIN. Multiple genotypes were detected in 35%, more commonly in hybrid PeIN (P = 0.051). Positive margins occurred in 63% of excisions. PeIN recurred in 48% of excisions and 30% of overall repeated procedures, and progression to invasive carcinoma occurred in 2%. At follow-up, 86% of patients had no evidence of disease and 12% were alive with disease. Lichen sclerosus occurred in non-HPV and HPV-related PeIN (100% and 47%).In conclusion, HPV-related and, more specifically basaloid PeIN were the predominant types and preferentially associated with HPV 16. While PeIN had a high recurrence rate, there was a slow and infrequent progression to invasive or metastatic carcinoma with multimodal treatments. Additional studies are needed to understand biology and natural history of PeIN.
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Affiliation(s)
- Melissa M Straub Hogan
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Andrew J Spieker
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Michael Orejudos
- Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Tarik Gheit
- Infections and Cancer Biology Group, International Agency for Research on Cancer, Lyon, France
| | - Michael Herfs
- Laboratory of Experimental Pathology, University of Liège, Liège, Belgium
| | - Massimo Tommasino
- Instituto de Patología e Investigación, Universidad Nacional de Asunción, Asunción, Paraguay
| | - Diego F Sanchez
- Instituto de Patología e Investigación, Universidad Nacional de Asunción, Asunción, Paraguay
- School of Medicine, National University of Asunción, San Lorenzo, Paraguay
| | | | | | - Jennifer B Gordetsky
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Jonathan I Epstein
- Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | | | | | | | | | - Antonio L Cubilla
- Instituto de Patología e Investigación, Universidad Nacional de Asunción, Asunción, Paraguay
| | - Giovanna A Giannico
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
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Trimmel B, Oszwald A, Diemand C, Ertl IE, Lemberger U, Bruchbacher A, Brettner R, Korn S, Resch I, Comperat E, Shariat SF, Hassler MR. Evaluation of APOBEC3 expression as prognostic marker in squamous cell carcinoma of the penis. Sci Rep 2022; 12:12911. [PMID: 35902635 PMCID: PMC9334367 DOI: 10.1038/s41598-022-17056-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Accepted: 07/20/2022] [Indexed: 11/29/2022] Open
Abstract
Squamous cell carcinoma of the penis (PSC) is a rare disease with limited information on the molecular events leading to malignant transformation. In a third of PSC cases, presence of human papilloma virus (HPV) is found. The APOBEC3 family of proteins is known to play a significant role in defense against HPV infection, but their role in PSC is largely unknown. In this study, we aim to assess mRNA expression levels of APOBEC3 family members in HPV+ and HPV− PSC to get insight into their association with clinicopathological features and to evaluate their prognostic impact. Expression levels of six APOBEC3 family members in tissue from 50 patients with PSC were determined by RT-PCR and correlated with clinical and histopathological features. Lower expression of APOBEC3A, APOBEC3B, and APOBEC3C was observed in advanced PSC stages. Except for APOBEC3D, HPV+ samples showed higher expression of APOBEC3s compared to HPV− samples. In univariate analyses, APOBEC3A and APOBEC3C expression tended to be associated with disease-free survival and APOBEC3A expression with overall survival; however, multivariable analyses failed to confirm these associations with outcome. More extensive external validation and functional laboratory studies are needed to evaluate further their role in PSC development and progression.
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Affiliation(s)
- Bettina Trimmel
- Department of Pathology, Medical University of Vienna, Vienna, Austria
| | - Andre Oszwald
- Department of Pathology, Medical University of Vienna, Vienna, Austria
| | - Christoph Diemand
- Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Iris E Ertl
- Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Ursula Lemberger
- Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Andreas Bruchbacher
- Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Robert Brettner
- Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Stephan Korn
- Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Irene Resch
- Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Eva Comperat
- Department of Pathology, Medical University of Vienna, Vienna, Austria
| | - Shahrokh F Shariat
- Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.,Hourani Center for Applied Scientific Research, Al-Ahliyya Amman University, Amman, Jordan.,Department of Urology, The University of Texas Southwestern Medical Center, Dallas, TX, USA.,Department of Urology, Weill Cornell Medical College, New York, NY, USA.,Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic.,Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russia
| | - Melanie R Hassler
- Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
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30
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Fu L, Tian T, Yao K, Chen XF, Luo G, Gao Y, Lin YF, Wang B, Sun Y, Zheng W, Li P, Zhan Y, Fairley CK, Grulich A, Zou H. Global Pattern and Trends in Penile Cancer Incidence: Population-Based Study. JMIR Public Health Surveill 2022; 8:e34874. [PMID: 35793140 PMCID: PMC9301560 DOI: 10.2196/34874] [Citation(s) in RCA: 68] [Impact Index Per Article: 22.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 03/01/2022] [Accepted: 05/26/2022] [Indexed: 12/16/2022] Open
Abstract
Background
Penile cancer is a relatively rare genital malignancy whose incidence and mortality are rising in many countries.
Objective
This study aims to assess the recent incidence and mortality patterns and incidence trends of penile cancer.
Methods
The age-standardized incidence and mortality rates (ASIR and ASMR, respectively) of penile cancer in 2020 were estimated from the Global Cancer Registries (GLOBOCAN) database. Incidence trends of penile cancer from 1973 to 2012 were assessed in 44 populations from 43 countries using the Cancer Incidence in Five Continents plus (CI5plus) and the Nordic Cancer Registries (NORDCAN) databases. Average annual percentage change was calculated to quantify trends in ASIR using joinpoint regression.
Results
Globally, the estimated ASIR and ASMR of penile cancer were 0.80 (per 100,000) and 0.29 (per 100,000) in 2020, equating to 36,068 new cases and 13,211 deaths in 2020, respectively. There was no significant correlation between the ASIR (P=.05) or ASMR (P=.90) and Human Development Index. In addition, 15 countries saw increasing ASIR for penile cancer, 13 of which were from Europe (United Kingdom, Lithuania, Norway, Estonia, Finland, Sweden, Cyprus, Netherlands, Italy, Croatia, Slovakia, Russia, and the Czech), and 2 from Asia (China and Israel).
Conclusions
Although the developing countries still bear the higher incidence and mortality of penile cancer, the incidence is on the rise in most European countries. To mitigate the disease burden resulting from penile cancer, measures to lower the risk for penile cancers, including improving penile hygiene and male human papillomavirus vaccination, may be warranted.
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Affiliation(s)
- Leiwen Fu
- School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Tian Tian
- School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Kai Yao
- Department of Urology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Xiang-Feng Chen
- Center for Reproductive Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China
- Shanghai Human Sperm Bank, Shanghai, China
| | - Ganfeng Luo
- School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yanxiao Gao
- School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yi-Fan Lin
- School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Bingyi Wang
- School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yinghui Sun
- School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Weiran Zheng
- School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Peiyang Li
- School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yuewei Zhan
- School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Christopher K Fairley
- Central Clinical School, Monash University, Melbourne, Australia
- Melbourne Sexual Health Centre, Alfred Health, Melbourne, Australia
| | - Andrew Grulich
- Kirby Institute, University of New South Wales, Sydney, Australia
| | - Huachun Zou
- School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong, China
- Kirby Institute, University of New South Wales, Sydney, Australia
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31
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Sun H, Cai R, Zhai C, Song W, Sun J, Bi Y. Primary Mucoepidermoid Carcinoma of the Lacrimal Apparatus. Am J Ophthalmol 2022; 239:170-179. [PMID: 35288069 DOI: 10.1016/j.ajo.2022.03.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Revised: 02/21/2022] [Accepted: 03/01/2022] [Indexed: 11/20/2022]
Abstract
PURPOSE In this study, we evaluated the clinicopathologic and molecular characteristics of lacrimal apparatus mucoepidermoid carcinoma (MEC) to define its typical diagnostic features. DESIGN Retrospective observational case series. METHODS Institutional pathology records between 2011 and 2021 were searched for all cases of lacrimal apparatus MEC. RESULTS A total of 2 male and 6 female patients ranging in age from 18 to 83 years (median 56, mean 54) were included. Six lacrimal apparatus MECs were found in the lacrimal gland, and 2 cases occurred in the lacrimal sac and nasolacrimal duct. Histologically, there were 6 cases of conventional MEC, 1 clear-cell variant of MEC, and 1 oncocytic variant of MEC for a total of 8 cases. There were 3 low-grade cases and 5 high-grade cases. All 8 cases were evaluated via immunohistochemistry, and the results were positive (scores 1-4) for pankeratin, 34betaE12, p63, p40, CK7, CK8, and CK19, with a relatively higher expression of p63 observed in high-grade MEC. The presence of human papillomavirus (HPV) type 6 DNA was found in 4 patients. MAML2 fluorescence in situ hybridization was positive for MAML2 rearrangement in 3 lacrimal gland tumors (2 low-grade and 1 high-grade). Six tumors were managed with radical resection, and 2 patients underwent orbital exenteration. Postoperative radiation therapy was delivered to 6 patients, and chemotherapy was administered to 1 patient. CONCLUSIONS MECs of the lacrimal apparatus are rare tumors, and the rate of MAML2 translocations is lower than that in salivary MECs. Lacrimal gland and lacrimal sac MECs may not be of the same subtypes intrinsically because of the difference in MAML2 translocation, anatomy, and clinical course. The etiologic function of HPV type 6 infection should be explored in lacrimal apparatus MECs. Radical surgery is the treatment of choice. The description of these unique findings may assist in the definitive diagnosis of and improve our understanding of lacrimal apparatus MEC.
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Affiliation(s)
- Hui Sun
- From the Department of Pathology, Eye and ENT Hospital, Fudan University (H.S., R.C., C.Z., W.S., J.S., Y.B.); Department of Pathology, Fudan University Shanghai Cancer Center (H.S.), Shanghai, China
| | - Rongrong Cai
- From the Department of Pathology, Eye and ENT Hospital, Fudan University (H.S., R.C., C.Z., W.S., J.S., Y.B.)
| | - Changwen Zhai
- From the Department of Pathology, Eye and ENT Hospital, Fudan University (H.S., R.C., C.Z., W.S., J.S., Y.B.)
| | - Wanjing Song
- From the Department of Pathology, Eye and ENT Hospital, Fudan University (H.S., R.C., C.Z., W.S., J.S., Y.B.)
| | - Ji Sun
- From the Department of Pathology, Eye and ENT Hospital, Fudan University (H.S., R.C., C.Z., W.S., J.S., Y.B.)
| | - Yingwen Bi
- From the Department of Pathology, Eye and ENT Hospital, Fudan University (H.S., R.C., C.Z., W.S., J.S., Y.B.).
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Alencar AM, Sonpavde G. Emerging Therapies in Penile Cancer. Front Oncol 2022; 12:910335. [PMID: 35800050 PMCID: PMC9253417 DOI: 10.3389/fonc.2022.910335] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Accepted: 05/04/2022] [Indexed: 11/25/2022] Open
Abstract
Advances in the treatment of rare tumors like penile cancer were always hampered by the lack of deep comprehension of the molecular biology and genomic and epigenomic alterations involved in carcinogenesis and tumor progression, as well as by the difficulty in recruitment of patients for prospective clinical trials. Despite the high rates of cure in early localized penile cancers with surgery or other local procedures, locally advanced and metastatic tumors require systemic treatment, with chemotherapy being the current standard, but with high toxicity and no proven real impact on survival. Recent important findings of frequent genomic alterations and mutation signatures in penile cancer have motivated several trials in new modalities of systemic treatments, especially immunotherapy. This review aims to present the most recent advances and the prospect of new modalities of systemic therapies with ongoing studies in penile cancer.
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Affiliation(s)
- Antonio Machado Alencar
- Grupo de Estudos em Patologia Molecular, Hospital Universitário da Universidade Federal do Maranhão, São Luís, Brazil
- Department of Clinical Oncology, Hospital São Domingos/Dasa, São Luís, Brazil
| | - Guru Sonpavde
- Department of Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, United States
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33
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Deng X, Liu Y, Zhan X, Chen T, Jiang M, Jiang X, Chen L, Fu B. Trends in Incidence, Mortality, and Survival of Penile Cancer in the United States: A Population-Based Study. Front Oncol 2022; 12:891623. [PMID: 35785206 PMCID: PMC9248743 DOI: 10.3389/fonc.2022.891623] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Accepted: 05/18/2022] [Indexed: 11/13/2022] Open
Abstract
Purpose The aim of this study is to investigate the trends in incidence and mortality, and explore any change in survival of penile cancer in the United States. Methods We obtained data from the Surveillance, Epidemiology, and End Results (SEER) database (2000-2018) utilizing the SEER Stat software. The joinpoint regression was used to analyze the secular trend of incidence and incidence-based mortality (IBM) stratified by age, race, and summary stage. The 5-year relative survival rate was also calculated. Result The age-adjusted rates of penile cancer patients were 0.38 (0.37-0.39) and 0.21 (0.2-0.21) for overall incidence and IBM, respectively. The 5-year relative survival rates were 67.7%, 66.99%, and 65.67% for the calendar periods of 2000-2004, 2005-2009, and 2010-2014, respectively. No significant changes in incidence by era were observed from 2000 to 2018 [annual percentage change (APC) = 0.5%, p = 0.064]. The IBM rate of penile cancer showed an initial significant increase from 2000 to 2002 (APC = 78.6%, 95% CI, -1.7-224.6) followed by a deceleration rate of 4.6% (95% CI, 3.9-5.3) during 2002 to 2018. No significant improvement in 5-year relative survival was observed. The trends by age, race, and summary stage in incidence and IBM were significantly different. Conclusion This study, using population-level data from the SEER database, showed an increasing trend in IBM and no significant improvement in the 5-year relative survival rate. Meanwhile, the incidence of penile cancer exhibited a relatively stable trend during the study period. These results might be due to the lack of significant progress in the treatment and management of penile cancer patients in the United States in recent decades. More efforts, like increasing awareness among the general population and doctors, and centralized management, might be needed in the future to improve the survival of this rare disease.
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Affiliation(s)
- Xinxi Deng
- Department of Urology, Jiu Jiang No.1 People’s Hospital, Jiujiang, China
- Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yang Liu
- Department of Cardiology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Xiangpeng Zhan
- Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Tao Chen
- Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Ming Jiang
- Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Xinhao Jiang
- Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Luyao Chen
- Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Bin Fu
- Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, China
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Development and Verification of Prognostic Nomogram for Penile Cancer Based on the SEER Database. BIOMED RESEARCH INTERNATIONAL 2022; 2022:8752388. [PMID: 35419456 PMCID: PMC9001101 DOI: 10.1155/2022/8752388] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 02/28/2022] [Accepted: 03/08/2022] [Indexed: 11/25/2022]
Abstract
Aim We aimed to establish a prognostic nomogram for penile cancer (PC) patients based on the Surveillance, Epidemiology, and End Results Program (SEER) database. Methods Data from 1643 patients between 2010 and 2015 were downloaded and extracted from the SEER database. They were randomly divided into the development group (70%) and the verification group (30%), and then, univariate and multivariate Cox proportional hazards regression, respectively, was used to explore the possible risk factors of PC. The factors significantly related to overall survival (OS) and cancer-specific survival (CSS) were used to establish the nomogram, which was assessed via the concordance index (C-index), receiver operating characteristic (ROC) curve, and calibration curve. An internal validation was conducted to test the accuracy and effectiveness of the nomogram. Kaplan–Meier calculation was used to predict the further OS and CSS status of these patients. Results On multivariate Cox proportional hazards regression, the independent prognostic risk factors associated with OS were age, race, marital status, N/M stage, surgery, surgery of lymph nodes, and histologic type, with a moderate C-index of 0.737 (95% confidence interval (CI): 0.713–0.760) and 0.766 (95% CI: 0.731–0.801) in the development and verification groups, respectively. The areas under the ROC (AUC) of 3- and 5-year OS were 0.749 and 0.770, respectively. While marital status, N/M stage, surgery, surgery of lymph nodes, and histologic type were significantly linked to PC patients' CSS, which have better C-index of 0.802 (95% confidence interval (CI): 0.771–0.833) and 0.82 (95% CI: 0.775–0.865) in the development and verification groups, and the AUC of 3- and 5-year CSS were 0.766 and 0.787. Both of the survival calibration curves of 3- and 5-year OS and CSS brought out a high consistency. Conclusion Our study produced a satisfactory nomogram revealing the survival of PC patients, which could be helpful for clinicians to assess the situation of PC patients and to implement further treatment.
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Comparison of different surgical methods and strategies for inguinal lymph node dissection in patients with penile cancer. Sci Rep 2022; 12:2560. [PMID: 35169241 PMCID: PMC8847572 DOI: 10.1038/s41598-022-06494-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Accepted: 01/27/2022] [Indexed: 02/05/2023] Open
Abstract
To compare the clinical feasibility and oncological outcome of different surgical techniques for inguinal lymphadenectomy (ILND) in patients suffering from penile cancer. This study included data from 109 cN0-2 patients diagnosed with penile cancer who received ILND. 80 laparoscopic ILND were performed on 40 patients, while 138 open surgeries were performed on 69 patients. Perioperative complications and prognosis were compared between different surgical techniques. Compared with the open surgery group, the laparoscopy group had a shorter hospital stay (8.88 ± 7.86 days vs. 13.94 ± 10.09 days, P = 0.004), and a lower wound healing delay rate (8.75% vs. 22.46%, P = 0.017), but also had longer drainage time (10.91 ± 9.66 vs. 8.70 ± 4.62, P = 0.002). There were no significant differences in terms of other intraoperative parameters, complications, and survival between open and laparoscopic group. Compared with saphenous vein ligated subgroup, preserved subgroup showed no significant reducing of complication rate. There was no significant difference among complication between different open surgery subgroup. Immediate ILND showed no prognostic advantage over delayed ILND regardless of clinical lymph node status. Compared with open surgery, the minimally invasive ILND technique has similar oncological efficiency and a lower complication rate. Saphenous vein preservation has limited value in reducing complications. Delayed lymphadenectomy might be a more reasonable option for ILND.
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Deacon M, Muir G. What is the medical evidence on non-therapeutic child circumcision? Int J Impot Res 2022; 35:256-263. [PMID: 34997197 DOI: 10.1038/s41443-021-00502-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Revised: 10/24/2021] [Accepted: 11/15/2021] [Indexed: 01/02/2023]
Abstract
Non-therapeutic circumcision refers to the surgical removal of part or all of the foreskin, in healthy males, where there is no medical condition requiring surgery. The arguments for and against this practice in children have been debated for many years, with conflicting and conflicted evidence presented on both sides. Here, we explore the evidence behind the claimed benefits and risks from a medical and health-related perspective. We examine the number of circumcisions which would be required to achieve each purported benefit, and set that against the reported rates of short- and long-term complications. We conclude that non-therapeutic circumcision performed on otherwise healthy infants or children has little or no high-quality medical evidence to support its overall benefit. Moreover, it is associated with rare but avoidable harm and even occasional deaths. From the perspective of the individual boy, there is no medical justification for performing a circumcision prior to an age that he can assess the known risks and potential benefits, and choose to give or withhold informed consent himself. We feel that the evidence presented in this review is essential information for all parents and practitioners considering non-therapeutic circumcisions on otherwise healthy infants and children.
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Affiliation(s)
| | - Gordon Muir
- Urology Department, King's College Hospital, London, UK.
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Jakobsen JK. Sentinel Node Methods in Penile Cancer - a Historical Perspective on Development of Modern Concepts. Semin Nucl Med 2021; 52:486-497. [PMID: 34933740 DOI: 10.1053/j.semnuclmed.2021.11.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Accepted: 11/23/2021] [Indexed: 02/06/2023]
Abstract
Malignant penile tumors are of squamous cell origin in more than 95% of cases and the occurrence of a distant metastasis without prior inguinal lymph node metastatic deposits is very rare. This makes inguinal lymph node staging very reliable and of great prognostic significance since undiscovered and untreated inguinal metastases may lead to a fatal clinical course. In lack of a sufficiently accurate noninvasive lymph node staging modality, penile cancer relies on surgical lymph node removal for regional staging. In this respect sentinel node biopsy offers a favourable minimally invasive alternative to prophylactic inguinal lymph node dissection which is associated with significant surgery-related morbidity. Today sentinel node biopsy is widely used in surgical oncology within high volume cancers such as breast cancer and melanoma. In rare cancers sentinel node biopsy is also emerging as a minimal invasive staging tool in patients with no obvious lymph node involvement. At several specialized units across Europe sentinel node biopsy has been practiced by dedicated specialist within vulva and penile cancer for more than two decades. In fact, the rare disease penile cancer was a model entity for development of the original sentinel node concept as early as the 1970'es due to work by the Paraguayan penile cancer pioneer, Cabañas, the sentinel node concept was subsequently successfully adapted in breast cancer and melanoma. This turned out mutually beneficial since the sequential development of sentinel node biopsy in penile cancer in the 1990s eventually adopted new insights and added conceptual details from the experiences harvested in the broader clinical application possible in these high-volume diseases. The prerequisite to conceptualising the sentinel node approach was the gradual anatomical and functional understanding of the lymphatic system which in western medicine rooted in ancient Greece and gradually increased in details and comprehension with significant contributions from many great notabilities during the last centuries including Hippocrates, Galen, Fallopio, Malpighi, Virchow, Starling, Cabañas, Hodgkin and Horenblas. Sentinel node biopsy in penile cancer is a complex multimodality procedure involving inguinal ultrasonography by radiologists, precise tracer-injection and interpretation of nuclear images by nuclear medicine physicians, radio-tracer- and dye guided open surgical biopsies by urologists and thorough step-sectioning, immunostaining and accurate lymph node specimen analysis by pathologists. This team effort requires well-tested protocols, experience and good collaboration and in rare diseases this calls for centralization of service.
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Thomas A, do Canto Alvim LM, Rainho CA, Juengel E, Blaheta RA, Spiess PE, Rogatto SR, Tsaur I. Systemic treatment of penile squamous cell carcinoma-hurdles and hopes of preclinical models and clinical regimens: a narrative review. Transl Androl Urol 2021; 10:4085-4098. [PMID: 34804850 PMCID: PMC8575571 DOI: 10.21037/tau-20-945] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Accepted: 10/07/2020] [Indexed: 01/06/2023] Open
Abstract
Despite contemporary research efforts, the prognosis of penile squamous cell carcinoma (PeSCC) has not significantly improved over the past decade. Despite frequently encountered patient-related delayed medical consultations impairing outcomes, several other aspects contribute to the lack of advancement in the treatment of this condition. One essential reason is that translational research, a prerequisite for the clinically successful disease management, is still at an early stage in PeSCC as compared to many other malignancies. Preclinical experimental models are indispensable for the evaluation of tumor biology and identification of genomic alterations. However, since neither commercial PeSCC cell lines are available nor xenograft models sustainably established, such analyses are challenging in this field of research. In addition, systemic therapies are less effective and toxic without decisive breakthroughs over recent years. Current systemic management of PeSCC is based on protocols that have been investigated in small series of only up to 30 patients. Thus, there is an unmet medical need for new approaches necessitating research efforts to develop more efficacious systemic strategies. This review aims to highlight the current state of knowledge in the molecular alterations involved in the etiology and ensuing steps for cancer progression, existing preclinical models of translational research, clinically relevant systemic protocols, and ongoing clinical trials.
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Affiliation(s)
- Anita Thomas
- Department of Urology and Pediatric Urology, University Medicine Mainz, Mainz, Germany
| | - Luisa Matos do Canto Alvim
- Department of Clinical Genetics, University Hospital of Southern Denmark, Vejle, Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark
| | - Claudia Aparecida Rainho
- Department of Chemical and Biological Sciences, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Eva Juengel
- Department of Urology and Pediatric Urology, University Medicine Mainz, Mainz, Germany
| | | | - Philippe E Spiess
- Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, Florida, USA
| | - Silvia Regina Rogatto
- Department of Clinical Genetics, University Hospital of Southern Denmark, Vejle, Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark
| | - Igor Tsaur
- Department of Urology and Pediatric Urology, University Medicine Mainz, Mainz, Germany
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Shen J, Zhou H, Liu J, Zhang Z, Fang W, Yang Y, Hong S, Xian W, Ma Y, Zhou T, Zhang Y, Zhao H, Huang Y, Zhang L. Incidence and risk factors of second primary cancer after the initial primary human papillomavirus related neoplasms. MedComm (Beijing) 2021; 1:400-409. [PMID: 34766131 PMCID: PMC8491207 DOI: 10.1002/mco2.43] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2020] [Revised: 11/01/2020] [Accepted: 11/03/2020] [Indexed: 12/16/2022] Open
Abstract
Comprehensive studies in second primary cancer (SPC) after the initial primary human papillomavirus (HPV)-related cancer still remain warranted. We aimed to analyze the incidence and risk factors of SPC after HPV-related cancer. We identified 86 790 patients diagnosed with initial primary HPV-related cancer between 1973 and 2010 in the SEER database. Standardized incidence ratio (SIR) and cumulative incidence were calculated to assess the risk of SPC after HPV-related cancer. The SIR of SPC after HPV-related cancer was 1.60 (95% confidence interval [CI], 1.55-1.65) for male and 1.25 (95% CI, 1.22-1.28) for female. SIR of second primary HPV-related cancer (7.39 [95% CI, 6.26-8.68] male and 4.35 [95% CI, 4.04-4.67] female) was significantly higher than that of HPV-unrelated cancer (1.54 [95% CI, 1.49-1.60] male and 1.16 [95% CI, 1.13-1.19] female). The 5-year cumulative incidence of SPC was 7.22% (95% CI, 6.89-7.55%) for male and 3.72% (95% CI, 3.58-3.88%) for female. Risk factors for SPC included being married and having initial primary cancer (IPC) diagnosed at earlier stage for both genders, and IPC diagnosed at older age as well as surgery performed for female. Patients diagnosed with HPV-related cancer are more likely to develop another primary cancer, compared with the age-specific reference population.
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Affiliation(s)
- Jiayi Shen
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangzhou China.,Zhongshan School of Medicine Sun Yat-sen University Guangzhou China
| | - Huaqiang Zhou
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangzhou China
| | - Jiaqing Liu
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangzhou China.,Zhongshan School of Medicine Sun Yat-sen University Guangzhou China
| | - Zhonghan Zhang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangzhou China
| | - Wenfeng Fang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangzhou China
| | - Yunpeng Yang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangzhou China
| | - Shaodong Hong
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangzhou China
| | - Wei Xian
- Zhongshan School of Medicine Sun Yat-sen University Guangzhou China
| | - Yuxiang Ma
- Department of Clinical Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangzhou China
| | - Ting Zhou
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangzhou China
| | - Yaxiong Zhang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangzhou China
| | - Hongyun Zhao
- Department of Clinical Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangzhou China
| | - Yan Huang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangzhou China
| | - Li Zhang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangzhou China
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Shao Y, Tu X, Liu Y, Bao Y, Ren S, Yang Z, Hu X, Wu K, Zeng H, Wei Q, Li X. Predict Lymph Node Metastasis in Penile Cancer Using Clinicopathological Factors and Nomograms. Cancer Manag Res 2021; 13:7429-7437. [PMID: 34594135 PMCID: PMC8478162 DOI: 10.2147/cmar.s329925] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2021] [Accepted: 09/14/2021] [Indexed: 02/05/2023] Open
Abstract
Objective To investigate the predictive factors of lymph node metastasis (LNM) and evaluate the usefulness of prediction nomograms. Methods This study included 300 patients diagnosed with penile squamous cell carcinoma at West China Hospital (WCH) of Sichuan University (Chengdu, China) and 412 cases acquired from the Surveillance, Epidemiology, and End Results (SEER) program. Logistic regression analysis was performed on these cohorts to investigate the predictive factors of LNM. We evaluated a recently developed prediction nomogram for LNM, which was established based on the National Cancer Database (NCDB). Moreover, we developed a novel nomogram using cases from the WCH for the prediction of lymphatic metastasis. Results Logistic analysis identified that younger age at diagnosis, invasion of the penis body, poorer pT stage, cN stage, nuclear grade and the presence of lymph vascular invasion (LVI) were significantly correlated with LNM in WCH cases; however, only race, poorer T stage and cN stage were significantly associated with LNM among the cases from the SEER. Multivariate analysis demonstrated that younger age, poorer T stage, cN stage and nuclear grade were independent predictors of LNM. Receiver operating characteristic curve analysis of WCH cases showed that the tumor T stage 8th edition has better area under the curve than 7th stage (0.672 vs 0.636, respectively). Moreover, well AUC was seen in external validation of NCDB nomogram in WCH cohorts and SEER series (0.833 vs 0.795). The new nomogram included the aforementioned independent predictors and the bootstrap-corrected concordance was 0.876. Conclusion Younger diagnose age, poorer pT stage, cN stage, nuclear grade and LVI were the most important predictors of LNM in patients with penile cancer. 8th T stage performed better than 7th version in predicting LNM. NCDB nomogram has some application values in both WCH and SEER cases, and our novel model further improved the predictive accuracy.
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Affiliation(s)
- Yanxiang Shao
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Xiang Tu
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Yang Liu
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Yige Bao
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Shangqing Ren
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, People's Republic of China.,Robotic Minimally Invasive Surgery Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, People's Republic of China
| | - Zhen Yang
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, People's Republic of China.,Department of Urology, Chengdu Second People's Hospital, Chengdu, People's Republic of China
| | - Xu Hu
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Kan Wu
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Hao Zeng
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Qiang Wei
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Xiang Li
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, People's Republic of China
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Li X, Xiang F, Chen Z, Zhang T, Zhu Z, Zhang M, Wu R, Kang X. Genital Human Papillomavirus Prevalence and Genotyping Among Males in Putuo District of Shanghai, China 2015-2019. Med Sci Monit 2021; 27:e932093. [PMID: 34475371 PMCID: PMC8422898 DOI: 10.12659/msm.932093] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Accepted: 05/17/2021] [Indexed: 11/28/2022] Open
Abstract
BACKGROUND Reports of human papillomavirus (HPV) infection and genotype distribution in Chinese men are limited, and HPV vaccination has not yet been recommended for men in China. MATERIAL AND METHODS We retrospectively reviewed the prevalence and genotyping of male genital HPV. A total of 1227 male patients (aged 17 to 81 years) attending the dermatology and sexually transmitted disease clinics at Putuo District Center Hospital in Shanghai from 2015 to 2019 were included. Genital exfoliated specimens were obtained for detection and genotyping of 27 HPV types by Luminex-based multiplex assay. RESULTS The prevalence of any HPV was 65.5% (804/1227). The rate of multiple infection was 25.8% (317/1227). The 5 main HPV types were 6 (32.0%), 11 (23.2%), 16 (5.6%), 43 (4.3%), and 59 (4.0%). Among all detected HPV genotypes, 65.5% (875/1336) were 9-valent HPV genotypes. No significant differences were observed in the detection rate of HPV infection over 5 years (P>0.05). Age groups ≤24 years (70.7%) and ≥55 years (72.9%) showed higher infection rates, and significant differences were detected in rates of low-risk HPV infection in different age-stratified groups (P<0.05). Prevalence of HPV infection among patients with warts (74.4%) was significantly higher than that of patients with other clinical characteristics (40.4%) and physical examination (63.6%). CONCLUSIONS Our study suggested that more than half of Chinese male patients have detectable HPV infections, and penis-genital and anogenital warts were the most common clinical manifestations. Moreover, the available 9-valent HPV vaccine covers the most frequently observed HPV types among men.
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Ivanovski O, Saidi S, Shabani B, Gurmeshevski S, Pejkov R, Komina S, Gavrilovska-Brazanov A. Penile cancer after a tick bite: A possible association. SAGE Open Med Case Rep 2021; 9:2050313X211036779. [PMID: 34377488 PMCID: PMC8323426 DOI: 10.1177/2050313x211036779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 07/12/2021] [Indexed: 11/18/2022] Open
Abstract
Penile cancer is a rare cancer in Western countries, but is more common in parts of the
developing world. Usually, it is associated with older uncircumcised men who have a
long-term phymotic preputium. Here, we report a case of penile cancer in a circumcised
patient, occurring 3 months after a tick bite on the head of the penis. To the best of our
knowledge, this is the first report that suggests a possible association between Lyme
disease and occurrence of “de novo” penile cancer. Further studies are needed to confirm
this hypothesis.
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Affiliation(s)
- Ognen Ivanovski
- University Clinic of Urology, Medical Faculty, University "SS Cyril and Methodius," Skopje, Macedonia
| | - Skender Saidi
- University Clinic of Urology, Medical Faculty, University "SS Cyril and Methodius," Skopje, Macedonia
| | - Bashkim Shabani
- University Clinic of Urology, Medical Faculty, University "SS Cyril and Methodius," Skopje, Macedonia
| | - Slobodan Gurmeshevski
- University Clinic of Urology, Medical Faculty, University "SS Cyril and Methodius," Skopje, Macedonia
| | - Risto Pejkov
- University Clinic of Urology, Medical Faculty, University "SS Cyril and Methodius," Skopje, Macedonia
| | - Selim Komina
- Institute of Pathology, University "SS Cyril and Methodius," Skopje, Macedonia
| | - Aleksandra Gavrilovska-Brazanov
- University Clinic for Traumatology, Orthopaedic Diseases, Anaesthesia, Reanimation, Intensive Care and Emergency Centre, Medical Faculty, University "SS Cyril and Methodius," Skopje, Macedonia
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43
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Shao Y, Lia T, Wang Y, Wu K, Hu X, Liu Y, Feng S, Ren S, Yang Z, Xiong S, Yang W, Wei Q, Zeng H, Li X. Prognostic Values of Different Clinicopathological Factors and Predictive Models for Penile Carcinoma. Cancer Manag Res 2021; 13:5623-5632. [PMID: 34285582 PMCID: PMC8285520 DOI: 10.2147/cmar.s323321] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Accepted: 07/07/2021] [Indexed: 02/05/2023] Open
Abstract
Objective To evaluate the prognostic factors of penile cancer and the utility of prognostic models. Methods We analyzed postoperatively collected data of 311 patients diagnosed with penile cancer. Survival analysis (Kaplan–Meier and cox regression methods) was performed on this cohort. The c-index was used to determine the predictive accuracies of potential prognostic factors. The accuracies of four prognostic models were also evaluated, which were AJCC prognostic stage group for three recent editions, and four nomograms constructed by the Surveillance, Epidemiology, and End Results program (SEER). Two novel nomograms using our data were created and AUC of 2-year survival were determined to compare existing and newly established models. Results Tumor site, T and N stages, nuclear grade and lymph vascular invasion (LVI) significantly influenced prognosis. The 8th T and N stages had better c-indexes than former editions, while no improvement was seen in the 8thAJCC stage group. 6th AJCC+grade nomogram had a higher c-index than other three nomograms (SEER+grade, 6th TNM+grade, and 6th T1-3N0-3+grade nomograms; c-index: 0.831 vs 0.738, 0.792 and 0.781). New nomogram 1 included the 8th T and N stages, tumor site, nuclear grade, and LVI, with a c-index of 0.870. Novel nomogram 2 replaced the T and N stages with the AJCC stage group, which had a lower c-index of 0.855. The order of prediction accuracy of 2-year survival in the old and new models is consistent with the c-index results. Conclusion Tumor site, stages, grade, and LVI play important roles in predicting survival of penile cancer. The 8th stages have better predictive accuracy than former editions. We proposed two models with better predictive accuracy than former models; specifically, nomogram 1 may be a more precise and convenient tool for predicting penile cancer outcomes.
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Affiliation(s)
- Yanxiang Shao
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China
| | - Thongher Lia
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China
| | - Yaohui Wang
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China
| | - Kan Wu
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China
| | - Xu Hu
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China
| | - Yang Liu
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China
| | - Shuyang Feng
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China
| | - Shangqing Ren
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.,Robotic Minimally Invasive Surgery Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, 610072, People's Republic of China
| | - Zhen Yang
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.,Department of Urology, Chengdu Second People's Hospital, Chengdu, 610021, People's Republic of China
| | - Sanchao Xiong
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China
| | - Weixiao Yang
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China
| | - Qiang Wei
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China
| | - Hao Zeng
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China
| | - Xiang Li
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China
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Mohanty SK, Mishra SK, Bhardwaj N, Sardana R, Jaiswal S, Pattnaik N, Pradhan D, Sharma S, Kaushal S, Baisakh MR, Das S, Pradhan MR, Satapathy K, Pattnaik A, Sharma SK, Khadenga CR, Das S, Rath D, Nanda B, Parwani AV. p53 and p16 ink4a As Predictive and Prognostic Biomarkers for Nodal metastasis and Survival in A Contemporary Cohort of Penile Squamous Cell Carcinoma. Clin Genitourin Cancer 2021; 19:510-520. [PMID: 34348854 DOI: 10.1016/j.clgc.2021.07.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Revised: 05/30/2021] [Accepted: 07/02/2021] [Indexed: 11/16/2022]
Abstract
BACKGROUND Human papilloma virus (HPV) infection is implicated in a proportion of invasive squamous cell carcinoma of the penis (PC). A subset of PC involves dysregulation of the p53 pathway. HPV in situ hybridization (ISH) and p16ink4a positivity are surrogate markers for HPV infection, and p53 immunohistochemistry (IHC) denotes abnormality in the p53 pathway. There remains an ambiguity with regard to the contribution of both the pathways in the prognosis of PC. We sought to analyze the clinicopathologic characteristics of a cohort of Indian PC patients with respect to p16 ink4a and p53 expression. PATIENTS AND METHODS A cohort of 123 PC patients was studied for p16ink4aand p53IHC and HPVISH. The results of these biomarkers were correlated with various clinicopathologic parameters. RESULTS p16ink4a and HPV ISH were positive in 47% and 53% of the tumors, respectively. The proportion of warty, basaloid, or mixed warty-basaloid tumor subtypes showed significant p16ink4apositivity (P < .0001) compared to other subtypes. Twenty-eight patients were dual negative (p53- /p16ink4a-), 32 were dual positive (p53+/p16ink4a+), 38 were p53+/p16ink4a-, and 25 were p53-/p16ink4a +. In patients where p16ink4a was negative, a p53-positive phenotype had a higher propensity for lymph node metastases (OR, 5.42; 95% CI, 1.75-16.80; P = .003). Similarly, p53 positivity dictates nodal involvement in the p16ink4a-positive subset of tumors (OR, 5.00; 95% CI, 1.23-20.17; P = .024). On multivariate analyses, pathologic subtypes (warty, warty-basaloid, and basaloid) (P < .0001), p16ink4aexpression (P < .0001), and absence of nodal metastasis (P < .0001) were significant predictors of improved overall (OS) and cancer specific survival (CSS). In Kaplan-Meier analysis, the OS was significantly longer in patients with p16ink4a + tumors (P < .0001), as was the CSS (P < .0001). Patients with dual positive tumors had a significantly higher OS (P < .001) and CSS (P = .012), in the entire cohort. In the node positive patients, dual positivity was associated with significantly higher OS (P < .0001); however, the median CSS for p53+/p16ink4a+tumors were not significantly different compared to p53- /p16ink4a- tumors (P = .064), although there was a trend towards improved CSS. CONCLUSIONS There is a strong concordance between p16ink4aIHC and HPV ISH results. p16ink4a status is an independent predictor of survival (OS and CSS) in our cohort of PCs. p53 is a predictor of nodal metastasis irrespective of p16 status. Dual positive tumors have a significantly better outcome in comparison to dual negative tumors.
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Affiliation(s)
- Sambit K Mohanty
- Department of Pathology and Laboratory Medicine, Advanced Medical Research Institute, Bhubaneswar, India; Department of Pathology and Laboratory Medicine, CORE Diagnostics, Gurgaon, India
| | - Sourav K Mishra
- Department of Medical Oncology, Advanced Medical Research Institute, Bhubaneswar, India
| | - Nitin Bhardwaj
- Department of Pathology and Laboratory Medicine, CORE Diagnostics, Gurgaon, India
| | - Ruhani Sardana
- Department of Pathology and Laboratory Medicine, Advanced Medical Research Institute, Bhubaneswar, India
| | - Sunil Jaiswal
- Department of Surgical Oncology, Advanced Medical Research Institute, Bhubaneswar, India
| | - Niharika Pattnaik
- Department of Pathology and Laboratory Medicine, Advanced Medical Research Institute, Bhubaneswar, India
| | | | - Shivani Sharma
- Department of Pathology and Laboratory Medicine, CORE Diagnostics, Gurgaon, India
| | - Seema Kaushal
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Manas R Baisakh
- Department of Pathology and Laboratory Medicine, Prolife Diagnostics, Bhubaneswar, India
| | - Suren Das
- Department of Urology, Institute of Medical Sciences and SUM Hospital, Bhubaneswar, India
| | - Manas R Pradhan
- Department of Urology, Advanced Medical Research Institute, Bhubaneswar, India
| | | | - Ashis Pattnaik
- Department of Pathology and Laboratory Medicine, Advanced Medical Research Institute, Bhubaneswar, India
| | - Shailendra K Sharma
- Department of Pathology and Laboratory Medicine, Advanced Medical Research Institute, Bhubaneswar, India
| | - Chira R Khadenga
- Department of Radiation Oncology, Institute of Medical Sciences and SUM Hospital, Bhubaneswar, India
| | - Subodh Das
- Department of Urology, Advanced Medical Research Institute, Bhubaneswar, India
| | - Debadarshi Rath
- Department of Urology, Institute of Medical Sciences and SUM Hospital, Bhubaneswar, India
| | - Biswajit Nanda
- Department of Urology, Institute of Medical Sciences and SUM Hospital, Bhubaneswar, India
| | - Anil V Parwani
- Department of Pathology, Wexner Medical Center, Columbus, OH.
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Smith JS, Backes DM, Hudgens MG, Mei W, Chakraborty H, Rohner E, Moses S, Agot K, Meijer CJLM, Bailey RC. Male Circumcision Reduces Penile HPV Incidence and Persistence: A Randomized Controlled Trial in Kenya. Cancer Epidemiol Biomarkers Prev 2021; 30:1139-1148. [PMID: 33972367 PMCID: PMC8172477 DOI: 10.1158/1055-9965.epi-20-1272] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Revised: 01/24/2021] [Accepted: 03/22/2021] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Male circumcision reduces the risk of human immunodeficiency virus infection in men. We assessed the effect of male circumcision on the incidence and natural history of human papillomavirus (HPV) in a randomized clinical trial in Kisumu, Kenya. METHODS Sexually active, 18- to 24-year-old men provided penile exfoliated cells for HPV DNA testing every 6 months for 2 years. HPV DNA was detected via GP5+/6+ PCR in glans/coronal sulcus and in shaft samples. HPV incidence and persistence were assessed by intent-to-treat analyses. RESULTS A total of 2,193 men participated (1,096 randomized to circumcision; 1,097 controls). HPV prevalence was 50% at baseline for both groups and dropped to 23.7% at 24 months in the circumcision group, and 41.0% in control group. Incident infection of any HPV type over 24 months was lower among men in the circumcision group than in the control group [HR = 0.61; 95% confidence interval (CI), 0.52-0.72]. Clearance rate of any HPV infection over 24 months was higher in the circumcision group than in the control group (HR = 1.87; 95% CI, 1.49-2.34). Lower HPV point-prevalence, lower HPV incidence, and higher HPV clearance in the circumcision group were observed in glans but not in shaft samples. CONCLUSION Male circumcision reduced the risk of HPV acquisition and reinfection, and increased HPV clearance in the glans. IMPACT Providing voluntary, safe, and affordable male circumcision should help reduce HPV infections in men, and consequently, HPV-associated disease in their partners.
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Affiliation(s)
- Jennifer S Smith
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina.
- Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina
| | - Danielle M Backes
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina
| | - Michael G Hudgens
- Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina
| | - Wenwen Mei
- Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina
| | | | - Eliane Rohner
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina
- Institute of Social and Preventive Medicine, University of Bern, Switzerland
| | - Stephen Moses
- Department of Community Health Sciences, University of Manitoba, Winnipeg, Canada
| | - Kawango Agot
- Impact Research and Development Organization, Kisumu, Kenya
| | - Chris J L M Meijer
- Department of Pathology, Amsterdam UMC, location VUmc, Amsterdam, the Netherlands
| | - Robert C Bailey
- Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago, Illinois
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Sasidharanpillai S, Ravishankar N, Kamath V, Bhat PV, Bhatt P, Arunkumar G. Prevalence of Human Papillomavirus (HPV) DNA among Men with Oropharyngeal and Anogenital Cancers: A Systematic Review and Meta-Analysis. Asian Pac J Cancer Prev 2021; 22:1351-1364. [PMID: 34048162 PMCID: PMC8408381 DOI: 10.31557/apjcp.2021.22.5.1351] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Accepted: 05/10/2021] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE The term ''Human Papillomavirus'' or ''HPV'' has become synonymous with uterine cervical cancer leading to feminisation of all the preventive measures, especially immunisation. Taking into consideration the rising number of HPV associated cancers among men in many developed countries and the risk of transmission to women, male HPV infection is a serious concern. A systematic review and meta-analysis of literature was performed to determine the global prevalence of HPV among men with oropharyngeal and anogenital cancers. METHODS A systematic review and meta-analysis of literature was performed searching electronic databases for published articles in English between January 1984- April 2020 based on standard systematic review guidelines. The meta-analysis component was modified appropriately for the synthesis of prevalence study results. National Institutes of Health checklist for observational, cohort and cross-sectional studies was used to assess the quality of the studies selected after the abstract and content review. The meta-analysis was performed in STATA version 13.0 (College Station, Texas 77,845 USA) and the forest plots were constructed using metan package in STATA. RESULTS Through the electronic search of databases, 3486 original articles were screened for eligibility. Fifty-eight articles were systematically reviewed and 42 articles were qualified for meta-analysis including 4,250 men with oropharyngeal, penile and prostate cancers. The pooled prevalence of HPV DNA in oropharyngeal cancers was 45% (95%CI 24.0%-66.0%). Meanwhile the pooled prevalence rates of 48% (CI 40.0%- 57.0%) and 19% (CI 10.0%-29.0%) were observed in penile and prostate cancers respectively. Even though, articles regarding HPV prevalence in anal cancers were systematically reviewed, none of the studies were qualified for meta-analysis. CONCLUSION Higher pooled prevalence of HPV DNA was observed among men with oropharyngeal and penile cancers. Multicentric molecular studies investigating the prevalence of HPV in prostate cancers have to be planned in future.
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Affiliation(s)
| | - Nagaraja Ravishankar
- Department of Biostatistics, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.
| | - Veena Kamath
- Department of Community Medicine, Centre for Vaccine Studies-In Charge, Kasturba Medical College, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, India.
| | - Parvati V Bhat
- Department of Obstetrics and Gynecology, Dr T M A Pai Hospital, Manipal Academy of Higher Education, Manipal, Karnataka, India.
| | - Puneet Bhatt
- Manipal Institute of Virology, Manipal Academy of Higher Education, Manipal, Karnataka, India.
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Zito Marino F, Sabetta R, Pagliuca F, Brunelli M, Aquino G, Perdonà S, Botti G, Facchini G, Fiorentino F, Di Lauro G, De Sio M, De Vita F, Toni G, Borges Dos Reis R, Neder L, Franco R. Discrepancy of p16 immunohistochemical expression and HPV RNA in penile cancer. A multiplex in situ hybridization/immunohistochemistry approach study. Infect Agent Cancer 2021; 16:22. [PMID: 33789689 PMCID: PMC8011184 DOI: 10.1186/s13027-021-00361-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Accepted: 03/19/2021] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND The high-risk human papillomavirus (HPV) infection represents one of the main etiologic pathways of penile carcinogenesis in approximately 30-50 % of cases. Several techniques for the detection of HPV are currently available including Polymerase chain reaction-based techniques, DNA and RNA in situ hybridization (ISH), p16 immunohistochemistry (IHC). The multiplex HPV RNA ISH/p16 IHC is a novel technique for the simultaneous detection of HPV E6/E7 transcripts and p16INK4a overexpression on the same slide in a single assay. The main aim of this study was to evaluate the discrepancy of p16 IHC expression relatively to HPV RNA ISH in penile cancer tissue. METHODS We collected a series of 60 PCs. HPV has been analysed through the RNA ISH, p16 IHC and the multiplex HPV RNA ISH/p16 IHC. RESULTS The multiplex HPV RNA ISH /p16 IHC results in the series were in complete agreement with the previous results obtained through the classic p16 IHC and HPV RNA scope carried out on two different slides. The multiplex HPV RNA ISH /p16 IHC showed that HPV positivity in our series is more frequently in usual squamous cell carcinoma than in special histotypes (19 out of 60 - 15 %- versus 6 out of 60 - 10 %-), in high-grade than in moderate/low grade carcinomas (6 out of 60 - 10 %- versus 4 out of 60 - 6.7 %-). In addition, our data revealed that in 5 out of 20 cases with p16 high intensity expression is not associated with HPV RNA ISH positivity. CONCLUSIONS Our findings emphasize that the use of p16 as a surrogate of HPV positivity was unsuccessful in approximatively 8 % of cases analysed in our series. Indeed, p16 IHC showed a sensitivity of 100 % and a specificity of 71 %, with a positive predictive value (PPV) of 54 % and a negative predictive value of 100 %; when considering high intensity, p16 IHC showed a sensitivity of 100 %, a specificity of 89 %, with a PPV of 75 % and NPV of 100 %. Since HPV positivity could represent a relevant prognostic and predictive value, the correct characterization offered by this approach appears to be of paramount importance.
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Affiliation(s)
- Federica Zito Marino
- Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania "L. Vanvitelli", Complesso di Santa Patrizia, Via Luciano Armanni, 5, 80138, Naples, Italy
| | - Rosalaura Sabetta
- Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania "L. Vanvitelli", Complesso di Santa Patrizia, Via Luciano Armanni, 5, 80138, Naples, Italy
| | - Francesca Pagliuca
- Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania "L. Vanvitelli", Complesso di Santa Patrizia, Via Luciano Armanni, 5, 80138, Naples, Italy
| | - Matteo Brunelli
- Department of Pathology, University of Verona, Verona, Italy
| | - Gabriella Aquino
- Pathology Unit, Istituto Nazionale Tumori, Fondazione G. Pascale, IRCCS, 80131, Naples, Italy
| | - Sisto Perdonà
- Department of Urology, Istituto Nazionale Tumori, Fondazione G. Pascale, IRCCS, 80131, Naples, Italy
| | - Gerardo Botti
- Pathology Unit, Istituto Nazionale Tumori, Fondazione G. Pascale, IRCCS, 80131, Naples, Italy
| | - Gaetano Facchini
- Medical Oncology Unit, S.M. delle Grazie Hospital, Via Domitiana, 80078, Pozzuoli, NA, Italy
| | - Francesco Fiorentino
- Pathology Unit, S.M. delle Grazie Hospital, Via Domitiana, 80078, Pozzuoli, NA, Italy
| | - Giovanni Di Lauro
- Urology Unit, S.M. delle Grazie Hospital, Via Domitiana, 80078, Pozzuoli (NA), Italy
| | - Marco De Sio
- Urology Unit, Department of Woman, Child and General and Specialized Surgery, University of Campania 'Luigi Vanvitelli, 80138, Naples, Italy
| | - Ferdinando De Vita
- Division of Medical Oncology, Department of Precision Medicine, School of Medicine, "Luigi Vanvitelli" University of Campania, Naples, Italy
| | - Giorgio Toni
- Laboratoire Central d'Anatomie pathologique, Hôpital universitaire de Nice, Université Côte d'Azur, 06000, Nice, France
| | - Rodolfo Borges Dos Reis
- Department of Surgery and Anatomy, Urology Division, Ribeirao Preto School Medicine, University of São Paulo, 14049 900, Ribeirao Preto, Brazil
| | - Luciano Neder
- Department of Pathology and Forensic Medicine, Ribeirão Preto Medical School, University of São Paulo, 14049 900, Ribeirão Preto, SP, Brazil
- Molecular Oncology Research Center, Barretos Cancer Hospital, 14784400, Barretos, SP, Brazil
| | - Renato Franco
- Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania "L. Vanvitelli", Complesso di Santa Patrizia, Via Luciano Armanni, 5, 80138, Naples, Italy.
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PD-L1 expression in anogenital and oropharyngeal squamous cell carcinomas associated with different clinicopathological features, HPV status and prognosis: a meta-analysis. Biosci Rep 2021; 41:228067. [PMID: 33704390 PMCID: PMC8011230 DOI: 10.1042/bsr20203669] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 02/19/2021] [Accepted: 02/25/2021] [Indexed: 12/17/2022] Open
Abstract
Background: Little research has been done on clinicopathological
characteristics and human papillomavirus (HPV) status of anogenital and
oropharyngeal squamous cell carcinomas (SCC) with a strong expression of
programmed death ligand 1 (PD-L1) in tumor cells. Therefore, we conducted this
meta-analysis. Methods: We performed a comprehensive research in
PubMed, Embase and Cochrane databases up to 30 September 2020. The effect size
was hazard ratio (HR) with 95% confidence interval (CI) for overall
survival (OS), cancer-specific survival (CSS), disease-free survival (DFS). The
pooled odds ratio (OR) with 95% CI were used to assess the association
between PD-L1 expression and clinicopathological features along with HPV status.
Results: A total of 2003 cases (944 anogenital and 1059
oropharynx SCC patients) were included. High PD-L1 expression in anogenital SCC
cases were associated with advanced age (OR = 1.63, 95% CI:
1.04–2.58) and HPV negativity (OR = 0.47, 95% CI:
0.31–0.71). Besides, PD-L1 positive anogenital SCC cases held a
significantly declined OS (HR = 2.18, 95% CI: 1.37–3.47)
and CSS (HR = 2.45, 95% CI: 1.30–4.65). For oropharynx SCC,
PD-L1 was more frequent in younger and HPV positive patients (OR = 0.60,
95% CI: 0.37–0.98; OR = 3.01, 95% CI:
1.78–5.09) and PD-L1 expression was relevant to better OS and DFS (HR
= 0.76, 95% CI: 0.60–0.97; HR = 0.50, 95% CI:
0.33–0.75). Conclusions: The meta-analysis demonstrated that
in anogenital SCC, PD-L1 positivity had to do with a worse outcome, which might
attribute to advanced age, higher tumor grade, lymph node metastasis and HPV
negativity, while in oropharynx cancer, PD-L1 expression was related to better
prognosis for the reason that PD-L1 was less frequent in the aged and negative
HPV status.
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Chen WK, Wu ZG. Adding radiotherapy based on chemotherapy can improve cancer-specific survival in N3 penile cancer: a SEER-based study. Transl Androl Urol 2021; 9:2587-2595. [PMID: 33457231 PMCID: PMC7807347 DOI: 10.21037/tau-20-1044] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Abstract
Background Controversial effectiveness of chemotherapy and still poor prognosis prompt us to find better treatment options. This study targeted at investigating whether adding radiotherapy based on chemotherapy can effectively improve the prognosis of patients, especially for advanced penile cancer. Methods Data were obtained from the Surveillance, Epidemiology, and End Results database (SEER*Stat software V.8.3.5; USA; Accession numbers: 13693-Nov2015 and lh8N79l2), and the survival curves were conducted using the Kaplan-Meier method. Univariate and multivariate cox regression models were performed in order to determine the hazard ratios (HRs) with 95% confidence intervals (CIs) for penile cancer-specific survival (PCSS). Subgroup analysis via multivariate Cox models were conducted to discovery the different effect in population with different features. Results The median follow-up time was 25 months, the 2-year PCSS was 52.98% in the chemoradiotherapy group and 55.81% in the chemotherapy group. In multivariate analysis of all patients, combined chemoradiotherapy was not associated with PCSS (HR =0.90, 95% CI: 0.63–1.29, P=0.572). In subgroup analysis, chemoradiotherapy improved the PCSS in N3 patients compared to these patients without therapy of radiotherapy (HR =0.54, 95% CI: 0.30–0.98, P=0.043). Conclusions Our study demonstrated a significant correlation of chemoradiotherapy with improved cancer-specific survival of penile cancer (PeCa) in N3 patients. Prospective international multicenter studies are necessary in order to improve prognosis for patients with advanced penile cancer.
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Affiliation(s)
- Wei-Kang Chen
- Department of andrology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Zhi-Gang Wu
- Department of andrology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
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50
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Soares A, de Carvalho IT, da Fonseca AG, Alencar AM, Leite CHB, Bastos DA, Soares JPH, Leite KRM, Filho MRB, Coelho RWP, Cavallero SRDA, de Cassio Zequi S, de Ribamar Rodrigues Calixto J. Penile cancer: a Brazilian consensus statement for low- and middle-income countries. J Cancer Res Clin Oncol 2020; 146:3281-3296. [PMID: 33104884 PMCID: PMC7679332 DOI: 10.1007/s00432-020-03417-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Accepted: 09/29/2020] [Indexed: 02/05/2023]
Abstract
PURPOSE Penile cancer is highly prevalent in low- and middle-income countries, with significant morbidity and mortality rates. The first Brazilian consensus provides support to improve penile cancer patients' outcomes, based on expert's opinion and evidence from medical literature. METHODS Fifty-one Brazilian experts (clinical oncologists, radiation oncologists, urologists, and pathologists) assembled and voted 104 multiple-choice questions, confronted the results with the literature, and ranked the levels of evidence. RESULTS Healthcare professionals need to deliver more effective communication about the risk factors for penile cancer. Staging and follow-up of patients include physical examination, computed tomography, and magnetic resonance imaging. Close monitoring is crucial, because most recurrences occur in the first 2-5 years. Lymph-node involvement is the most important predictive factor for survival, and management depends on the location (inguinal or pelvic) and the number of lymph nodes involved. Conservative treatment may be helpful in selected patients without compromising oncological outcomes; however, surgery yields the lowest rate of local recurrence. CONCLUSION This consensus provides an essential decision-making orientation regarding this challenging disease.
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Affiliation(s)
- Andrey Soares
- Department of Oncology, Centro Paulista de Oncologia-Oncoclínicas, Av. Brigadeiro Faria Lima, 4300, Vila Olímpia, São Paulo, SP, 01452-000, Brazil.
- Department of Oncology, Hospital Israelita Albert Einstein, Av. Albert Einstein, 627, Morumbi, São Paulo, SP, 05652-900, Brazil.
- Latin American Cooperative Oncology Group, Porto Alegre, Rio Grande do Sul, Brazil.
| | - Icaro Thiago de Carvalho
- Department of Radiotherapy, Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil
- Instituto Abathon, São Paulo, São Paulo, Brazil
| | | | - Antonio Machado Alencar
- Department of Oncology, Hospital Universitário da Universidade Federal do Maranhão, São Luís, Maranhão, Brazil
- Department of Oncology, Hospital São Domingos, São Luís, Maranhão, Brazil
| | | | - Diogo Assed Bastos
- Latin American Cooperative Oncology Group, Porto Alegre, Rio Grande do Sul, Brazil
- Department of Oncology, Hospital Sírio-Libanês, São Paulo, São Paulo, Brazil
| | | | - Katia Ramos Moreira Leite
- Medical Research Laboratory of the Discipline of Urology, Faculdade de Medicina da USP, São Paulo, São Paulo, Brazil
| | | | - Ronald Wagner Pereira Coelho
- Latin American Cooperative Oncology Group, Porto Alegre, Rio Grande do Sul, Brazil
- Department of Oncology, Hospital do Câncer Aldenora Bello, São Luís, Maranhão, Brazil
| | - Sandro Roberto de A Cavallero
- Latin American Cooperative Oncology Group, Porto Alegre, Rio Grande do Sul, Brazil
- Department of Oncology, Hospital Adventista de Belém, Belém, Pará, Brazil
- Department of Oncology, Centro de Tratamento Do Pará, Belém, Pará, Brazil
| | - Stênio de Cassio Zequi
- Department of Urology, AC Camargo Cancer Center, São Paulo, São Paulo, Brazil
- National Institute for Science and Technology in Oncogenomics and Therapeutic Innovation, AC Camargo Cancer Center, São Paulo, São Paulo, Brazil
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